[House Hearing, 105 Congress]
[From the U.S. Government Publishing Office]



 
                 DEPARTMENTS OF LABOR, HEALTH AND HUMAN
               SERVICES, EDUCATION, AND RELATED AGENCIES
                        APPROPRIATIONS FOR 1998

========================================================================

                                HEARINGS

                                BEFORE A

                           SUBCOMMITTEE OF THE

                       COMMITTEE ON APPROPRIATIONS

                         HOUSE OF REPRESENTATIVES

                       ONE HUNDRED FIFTH CONGRESS

                              FIRST SESSION
                                ________

  SUBCOMMITTEE ON THE DEPARTMENTS OF LABOR, HEALTH AND HUMAN SERVICES, 
                    EDUCATION, AND RELATED AGENCIES

                 JOHN EDWARD PORTER, Illinois, Chairman

C. W. BILL YOUNG, Florida        DAVID R. OBEY, Wisconsin
HENRY BONILLA, Texas             LOUIS STOKES, Ohio
ERNEST J. ISTOOK, Jr., Oklahoma  STENY H. HOYER, Maryland
DAN MILLER, Florida              NANCY PELOSI, California
JAY DICKEY, Arkansas             NITA M. LOWEY, New York
ROGER F. WICKER, Mississippi     ROSA L. DeLAURO, Connecticut
ANNE M. NORTHUP, Kentucky        

 NOTE: Under Committee Rules, Mr. Livingston, as Chairman of the Full 
Committee, and Mr. Obey, as Ranking Minority Member of the Full 
Committee, are authorized to sit as Members of all Subcommittees.

S. Anthony McCann, Robert L. Knisely, Susan E. Quantius, Michael K. Myers,
                  and Francine Mack, Subcommittee Staff
                                ________

                                 PART 4B

                            (Pages 1309-2552)

                      NATIONAL INSTITUTES OF HEALTH

                              

                                ________

                     U.S. GOVERNMENT PRINTING OFFICE

41-861 O                    WASHINGTON : 1997

------------------------------------------------------------------------

             For sale by the U.S. Government Printing Office            
        Superintendent of Documents, Congressional Sales Office,        
                          Washington, DC 20402                          







                       COMMITTEE ON APPROPRIATIONS                      

                   BOB LIVINGSTON, Louisiana, Chairman                  

JOSEPH M. McDADE, Pennsylvania         DAVID R. OBEY, Wisconsin            
C. W. BILL YOUNG, Florida              SIDNEY R. YATES, Illinois           
RALPH REGULA, Ohio                     LOUIS STOKES, Ohio                  
JERRY LEWIS, California                JOHN P. MURTHA, Pennsylvania        
JOHN EDWARD PORTER, Illinois           NORMAN D. DICKS, Washington         
HAROLD ROGERS, Kentucky                MARTIN OLAV SABO, Minnesota         
JOE SKEEN, New Mexico                  JULIAN C. DIXON, California         
FRANK R. WOLF, Virginia                VIC FAZIO, California               
TOM DeLAY, Texas                       W. G. (BILL) HEFNER, North Carolina 
JIM KOLBE, Arizona                     STENY H. HOYER, Maryland            
RON PACKARD, California                ALAN B. MOLLOHAN, West Virginia     
SONNY CALLAHAN, Alabama                MARCY KAPTUR, Ohio                  
JAMES T. WALSH, New York               DAVID E. SKAGGS, Colorado           
CHARLES H. TAYLOR, North Carolina      NANCY PELOSI, California            
DAVID L. HOBSON, Ohio                  PETER J. VISCLOSKY, Indiana         
ERNEST J. ISTOOK, Jr., Oklahoma        THOMAS M. FOGLIETTA, Pennsylvania   
HENRY BONILLA, Texas                   ESTEBAN EDWARD TORRES, California   
JOE KNOLLENBERG, Michigan              NITA M. LOWEY, New York             
DAN MILLER, Florida                    JOSE E. SERRANO, New York           
JAY DICKEY, Arkansas                   ROSA L. DeLAURO, Connecticut        
JACK KINGSTON, Georgia                 JAMES P. MORAN, Virginia            
MIKE PARKER, Mississippi               JOHN W. OLVER, Massachusetts        
RODNEY P. FRELINGHUYSEN, New Jersey    ED PASTOR, Arizona                  
ROGER F. WICKER, Mississippi           CARRIE P. MEEK, Florida             
MICHAEL P. FORBES, New York            DAVID E. PRICE, North Carolina      
GEORGE R. NETHERCUTT, Jr., Washington  CHET EDWARDS, Texas                 
MARK W. NEUMANN, Wisconsin             
RANDY ``DUKE'' CUNNINGHAM, California  
TODD TIAHRT, Kansas                    
ZACH WAMP, Tennessee                   
TOM LATHAM, Iowa                       
ANNE M. NORTHUP, Kentucky              
ROBERT B. ADERHOLT, Alabama            

                 James W. Dyer, Clerk and Staff Director








                            C O N T E N T S

                               __________

                     NATIONAL INSTITUTES OF HEALTH

                                VOLUME 4

                                                                   Page

National Institutes of Health Overview...........................     1

National Cancer Institute........................................   199

National Eye Institute...........................................   419

National Center for Human Genome Research........................   495

National Institute of Allergy and Infectious Diseases............   583

National Institute of Environmental Health Sciences..............   711

National Institute on Deafness and Other Communication Disorders.   805

National Heart, Lung, and Blood Institute........................   865

National Institute on Drug Abuse.................................   983

National Institute on Alcohol Abuse and Alcoholism...............  1091

National Institute of Diabetes, Digestive and Kidney Diseases....  1177

National Library of Medicine.....................................  1309

National Institute of Nursing Research...........................  1377

Fogarty International Center.....................................  1443

National Institute of Arthritis and Musculoskeletal and Skin 
  Diseases.......................................................  1491

National Center for Research Resources...........................  1573

National Institute of Child Health and Human Development.........  1635

National Institute of Dental Research............................  1737

National Institute of Mental Health..............................  1809

National Institute on Aging......................................  1915

National Institute of Neurological Disorders and Strokes.........  2001

National Institute of General Medical Sciences...................  2095

Office of AIDS Research..........................................  2155

Office of the Director and National Institutes of Health 
  Buildings and Facilities.......................................  2249







                                          Wednesday, March 5, 1997.

                      NATIONAL LIBRARY OF MEDICINE

                               WITNESSES

DONALD A.B. LINDBERG, M.D., DIRECTOR
KENT A. SMITH, DEPUTY DIRECTOR
DAVID J. LIPMAN, M.D., DIRECTOR, NATIONAL CENTER FOR BIOTECHNOLOGY 
    INFORMATION
DONALD C. POPPKE, EXECUTIVE OFFICER
SUSAN U. LEVINE, BUDGET OFFICER
HAROLD VARMUS, M.D., DIRECTOR, NIH
DENNIS P. WILLIAMS, DEPUTY ASSISTANT SECRETARY, BUDGET, DHHS
    Mr. Porter. The subcommittee will come to order.
    We're very pleased this afternoon to welcome Dr. Donald 
Lindberg, the Director of the National Library of Medicine, who 
will be the first of three institutes to appear this afternoon.
    Dr. Lindberg, why don't you introduce the people at the 
table with you and then proceed with your statement.

                       Introduction of Witnesses

    Dr. Lindberg. Yes, sir. We have on the far left Don Poppke, 
our Executive Officer, next, Sue Levine, our Budget Officer, 
next, Kent Smith, our noble Deputy Director of NLM, and on my 
right is Dr. David Lipman, who is the Director of the National 
Center for Biotechnology Information.

                           Opening Statement

    Mr. Chairman, I thank you very much for the privilege of 
appearing before you. My full statement for the record reports 
the status of many aspects of the Library's work in the past 
year and our plans for the new year. In this brief oral 
statement, I would like to highlight four items, with your 
permission--the Visible Humans, the Internet Grateful Med, our 
telemedicine projects, and the Human Gene Map.

                  National Information Infrastructure

    I should say that all four of those are the result of NLM's 
commitment to develop and support the best biomedical 
application of the National Information Infrastructure, NII. 
The NII was the result of the High Performance Computing and 
Communications program. As you will remember, the Congress 
authorized this program in 1991 permitting 12 Federal agencies 
to join forces and funds to develop improved computing and 
communications to address problems that are common to the 
agencies in the country.
    Inevitably, however, this work becomes dominated by the 
funds and the mission and concerns of what are called the ``Big 
Four'' science agencies--Department of Defense, Department of 
Energy, NASA, and NSF. Still, with the support of this 
Committee and HHS, the NLM and other NIH institutes have also 
participated. So there is a biomedical component, and I'm 
grateful for that.
    The developments I will show you today represent HPCC work 
from the National Library of Medicine. There are others, but I 
think these four highlight the developments.

                             visible humans

    First, the Visible Humans. This is a blow-up of the cover 
of the February issue of LIFE magazine. I should explain a 
little bit about the project. Visible Human is a fully 
computer-digitalization of the interior of a three-dimensional 
structure of a human being, one male and one female, including 
CAT scanning and MRI. This was originally designed to assist 
medical students and surgeons to learn and remember anatomy. 
Yet, now there are more than 750 licenses to individuals, 
institutions, and companies. This is in 26 countries I might 
say. So the applications far exceed what we originally 
imagined. You have before you the LIFE magazine. In this issue, 
they state my opinion correctly, ``Visible Humans forever 
change the way we see ourselves and the way doctors heal us.''
    [See figure 1.]

[Page 1311--The official Committee record contains additional material here.]


    The following are examples of applications that others have 
developed using this database. First, planning and rehearsing 
prostate and brain surgery; the same for radiotherapy of brain 
tumors; design and testing of automobile crash dummies; 
battlefield trauma management; a virtual or fly-through 
colonoscopy in place of the uncomfortable and less complete 
procedures with a rigid tube.
    In summary, this is a milestone development. It is 
relatively cheap, $1.4 million over the course of three to four 
years; it has stimulated good scientific ideas and commercial 
products; it is all in the public domain and it is available 
via the Internet; and it was made possible by the HPCC money, 
the improved networks and the improved computer capability.

                         internet grateful med

    Next, I would like to draw attention to our work in the 
Internet Grateful Med. Grateful Med is a system that allows 
doctors and, indeed, the public to search MEDLINE, the 
Library's largest and most consulted database, and other 
databases as well. Senator Bill Frist, who, as you know, is a 
physician, demonstrated Grateful Med at a recent TV broadcast. 
He said, ``MEDLINE can be critical for doctors in reaching the 
correct diagnosis and developing a soundtreatment plan, 
resulting in lives saved, limbs spared, and disease prevented, 
unnecessary treatment avoided, and hospitalization reduced.'' We agree. 
Internet Grateful Med is easy to use as well. The instant appeal of 
Internet Grateful Med has resulted in a dramatic increase in use, as 
you can imagine, and a little extra increase occurred after Ann Landers 
printed a letter from Dr. Michael DeBakey, a member of our Board of 
Regents, praising the new system. The display shows the letter.
    [See figure 2.]

[Page 1313--The official Committee record contains additional material here.]


    We are almost ready to introduce yet another MEDLINE-
related service. This is known as PUBMED, the name I attribute 
to my colleague Dr. David Lipman, who has a fertile 
imagination. This will allow the Nation's health professionals 
and the general public to request from publishers the full text 
of medical journal articles cited in the database. Congress has 
asked the Library to facilitate access to its health 
information at minimal cost. With this in mind, we're actually 
now exploring whether it might actually be possible to offer 
MEDLINE without charge in the U.S. to those who use our 
inexpensive Internet connection service. So it would be limited 
to the U.S. and those that come to us through Internet.

                              telemedicine

    Next, I want to highlight telemedicine. I'll talk about 
some projects that NLM has funded, but I should say first that 
this is really the best strategy for getting excellent health 
care applications onto the National Information Infrastructure. 
Telemedicine involves three things--information in support of 
decision-making, exchanging signals, which could be images or 
blood pressure, and, lastly, arrangements to practice medicine 
at a distance. With this in mind, it is obvious that these 
projects don't arise within the Library; they arise in 
competitive grant and research contract proposals from the 
universities and the great hospitals.
    About 70 such proposals were peer reviewed last year. We 
were able to fund 19 really good projects this past year. The 
map shows the country-wide distribution of the work in 13 
States and the District of Columbia. You have a listing of the 
detail of the projects, but I'll mention just a few things.
    [See figure 3.]

[Page 1315--The official Committee record contains additional material here.]


    The telemedicine projects include efforts to send vital 
signs from ambulances to the emergency room, to facilitate 
renal dialysis, to assist in home-care of high risk newborn 
infants, to give specialty consultation in rural areas, and to 
prevent drug interaction complications in the elderly. I could 
give you details on any of those. I should say, too, that NLM 
sponsored, along with HCFA and VA, a study by the National 
Research Council attempting to set out ways to evaluate 
telemedicine projects and the institutions that accepted these 
grants agreed to implement those NRC evaluation criteria.

                             human gene map

    Lastly, I want to draw attention to the Human Gene Map. 
Scientists at the NLM National Center for Biotechnology 
Information, which is headed by Dr. David Lipman, on my right, 
have recently released the Human Gene Map. This, too, is based 
on daily use of the high-speed Internet to exchange data 
between research centers around the world. The project uses 
high performance computers to compare each new sequence 
submitted to those already known, and to compute comparisons 
between all of the known information from the literature, other 
relevant molecular biology databases, and the known relevant 
chemical structure. Then, lastly, the use of Internet supports 
the tens of thousands of inquiries per day into this database.
    To see the gene map, one metaphorically dials up NLM and 
NCBI Home Pages on Internet. You see before you a picture of 
what that Home Page looks like. This display was, if you will, 
a centerfold of Science Magazine a month ago, its molecular 
biology issue. Here, we see graphical presentations of the 23 
human chromosome pairs and a picture plot of the number of 
genes at each point on the chromosome. This is of great use to 
the scientists who can kind of point and click and get down to 
the actual sequence that may characterize those genes. He or 
she can then see what that all looks like and even do searches 
and comparisons. Morethan one scientist has said that the 
existence of such a map would have saved years of research for any 
particular one of these genes.
    [See figure 4.]

[Page 1317--The official Committee record contains additional material here.]


    The Home Page also has information about the general nature 
of the disease, references to foundations and patient advocacy 
groups, and to the scientific and popular literature. Thus, the 
public and the scientist may use precisely the same database 
and each may pursue the topic to the extent he or she desires 
and in the fashion their interest and education permits. In 
many respects, the Human Gene Map tries to take a complex 
subject out of the lab to make it understandable in the 
classroom and the home.
    I should also say that in the work with these advanced 
information systems and our outreach, and the use of the new 
technology such as the Visible Human and Internet Grateful Med, 
we work in partnership with the National Network of Libraries 
of Medicine and particularly the medical library community.
    NLM's request is for $152,689,000 for fiscal year 1998. I 
would, of course, be pleased to attempt to answer any questions 
you might wish to raise.
    [The prepared statement follows:]

[Pages 1319 - 1323--The official Committee record contains additional material here.]


                                outreach

    Mr. Porter. Dr. Lindberg, thank you for your good 
statement. You might be interested to know that I was at a 
community health center in the inner-city in Chicago about 
three weeks ago, they were receiving an award from HRSA for 
working on an award-winning outreach program with Americorps 
volunteers, and as we went through the health center, there 
were television screens and NLM was on those screens.
    Dr. Lindberg. Great.
    Mr. Porter. They said they use your services all the time.
    Dr. Lindberg. Must be a good place. [Laughter.]

                            human genome map

    Mr. Porter. Excellent place. Dr. Lindberg, the publication 
last fall of the Human Genome Map with over 16,000 genes was an 
enormous technical feat. What were the major challenges in 
coordinating all the data from multiple sources and in setting 
up World Wide Web accessibility?
    Dr. Lindberg. Well, I'm going to give a quick answer and 
invite my colleague, Dr. Lipman, to answer you more fully, if 
you agree. It seems to me that looking at it slightly from the 
outside that his biggest challenge was to establish scientific 
credibility with a number of top genome research centers around 
the world. First, you have to have people trusting you and 
working with you, and then technology permitted the cooperation 
amongst those people that wanted to cooperate. So it was really 
a very international project, as I understand it. But I would 
like to invite Dr. Lipman to comment further.
    Dr. Lipman. As you know, collaboration is very important 
but it is not always achieved. In this particular case, our 
group, which had a very large collection of EST sequences, 
which are partial gene sequences, had done a lot of 
computational work to select particularly promising snippets of 
DNA sequence which could be used for mapping. We then contacted 
the groups who do the mapping and told them that we had done 
this work which would facilitate their work, and we got into 
sort of a quid pro quo situation where we would provide them 
with the agent, so to speak, to map and they would provide us 
back the information.
    Initially, in this mapping world, a lot of people have 
their own maps, their own sort of coordinate systems, and it is 
hard to integrate that information. In cross-checking trying to 
cross-validate the information we were getting, we could point 
out that there were errors at times and that it would benefit 
everybody if they would work with a single coordinate system. 
And so we managed to in fact get them all to do that and, in so 
doing, improve the accuracy of everybody's work.
    Dr. Lindberg is of course right that the collaboration 
happened because in fact we were really seen as scientists 
participating and not just technicians. And then I think the 
basis was really the basis of all scientific collaborations, 
which is that both parties could benefit.
    Mr. Porter. Once the genome map is five times as big when 
it includes all genes, will the map be too big to be 
manipulated on the Web?
    Dr. Lindberg. I think I can handle that one; that's easy. 
No, certainly not. Although I think part of the gamble is, of 
course, that the computing power keeps going up without our 
doing much of anything about it. There is enough of a market 
that the companies do that. The communications take a lot more 
effort. But, again, the country is pretty much committed to 
maintaining and advancing Internet. The President has announced 
the next generation Internet to go 100 times faster, and 1000 
times faster in some cases, with more security than the present 
ones. So we think NCBI and the others will keep out ahead of 
the problem.

                             bioinformatics

    Mr. Porter. The job prospects for those in the field of 
bioinformatics are extremely strong. Private industry is 
scrambling to find Ph.D's trained in computer science, 
information technology, and genetics to help them manage 
overwhelming quantities of data being produced from genetic 
sequencing. Is NLM participating in training these 
bioinformatics experts?
    Dr. Lindberg. Yes, sir. I think we saw the problem, Ican't 
say we're out ahead of it because I think it is a serious problem. The 
young men and women with knowledge of molecular biology and informatics 
are hot items and are definitely sought after. I should say that 20 
such individuals are training at NCBI, the National Center for 
Biotechnology Information, at NLM under Dr. Lipman. NSF funds another 
11. The Library of Medicine has supported training grants in medical 
informatics for over 20 years, 25 years. They are now renewed 
competitively every five years. There are 12 sites, 12 American 
universities with medical informatics training. About 100 post-docs 
total are supported by that program. We allocate slots especially 
toward molecular biology, so that adds another probably two dozen to 
the pool. The Department of Energy and the Sloan Foundation support 
another five. So these are smallish numbers, although they are very, 
very good people being produced.
    I think essentially the post-doc experience of working in 
Dr. Lipman's lab is really wonderful, and the systematic, I 
would say more formal, educational work in the universities is 
our best bet, those two combinations. But we are aware of the 
problem and certainly working it.
    Mr. Porter. Are you at all concerned that industry will 
lure these specialists out of academia, depleting the talent 
needed to educate the next generation?
    Dr. Lindberg. That's always a problem. In our country, we 
really don't assign people to their jobs; we let them go where 
they want to go. So I imagine that there will be attractive 
enough jobs in the Federal labs to attract a cadre.
    Mr. Porter. Provided we give you the resources you need to 
pay for them.
    Dr. Lindberg. Right. Exactly.
    Mr. Porter. Recently some pharmaceutical companies have 
begun to support academic informatics programs. Will this ease 
the problem of maintaining strong academic training programs?
    Dr. Lindberg. I think that they will. A lot of the people 
at least that I see in NCBI are really so thrilled to be there 
that we have to go around and ask them to turn the lights out 
every once in a while and go home and get some sleep. It's 
really an exciting place, an exciting time for people in that 
field. I think everybody realizes that, just as in former days 
when we were trying to discover and produce antibiotics, it 
will inevitably shift to an industrial base, as it must. Any 
drugs that result are multi-billion-dollar enterprises. So I 
think most people in the field welcome the participation of a 
profit-making company, a pharmaceutical company, especially 
those that have committed themselves to placing the results of 
these studies in the public domain. Merck particularly, as you 
know, has insisted that the ESTs that they paid for be placed 
in the public domain available to them and their competitors.

                             internet users

    Mr. Porter. You reported a 20 percent increase in users in 
1996 fueled by the popularity of your Internet service. Can you 
keep up with this level of user growth or do you risk having 
some of the same capacity problems as America Online?
    Dr. Lindberg. I'll tell you where they've got their 
problems is in the network and usually it is at local routers. 
We have actually studied this pretty carefully. We're not 
having those troubles, with the exception of our support of 
users overseas. There, an interesting proposition, but 
basically they don't have the good infrastructure that the U.S. 
has and of course there will always be difficulties in both 
places. But we've looked at it quite carefully and, generally 
speaking, the limit in capacity is not our computers or the raw 
capability of Internet, but rather local routers. The problem 
will correct itself in time.

                  next generation internet initiative

    Mr. Porter. Last October the administration announced its 
Next Generation Internet Initiative to create high-speed 
networks that are 100 to 1,000 times faster than today's 
Internet. NLM was originally included in the initiative but the 
President's budget doesn't seem to allocate funds for this 
purpose. Can you tell us what is the status of this initiative 
and NLM's involvement in it?
    Dr. Lindberg. I can tell you only what I know publicly, 
that the President made a release to the press announcing the 
next generation Internet. We were quite happy to read that it 
would involve $100 million a year in new money, and it would be 
managed by the four agencies I mentioned plus mine. I was sort 
of surprised when, as the budget subsequently was distributed, 
NIH dropped out and NIST dropped in. Obviously, I think that 
NIH and NLM as part of it have a great deal to contribute to at 
least the applications that will be part of this next 
generation Internet. I just don't think medicine will be 
included if there is nobody medical at the table. So the 
original level that was discussed of $5-$10 million a year 
certainly wouldn't be excessive, it might be an appropriate 
level to support biomedical applications. But we'll do the best 
we can with whatever budget we have and we'll give it as good a 
priority as we can.
    Mr. Porter. As an aside, Dr. Lindberg, let me say that we 
do not find it surprising at all that the President's budget 
doesn't reflect his rhetoric. In fact, two weeks before his 
State of the Union address and two weeks and a couple days 
before he submitted his budget, he was in my district saying 
how important biomedical research was and then submitted a 
budget that I think vastly underfunds the importance of 
priority of biomedical research. So I'm not surprised that you 
don't find the money in the President's budget. We're simply 
going to have to do a better job than the President has done in 
this regard and provide you the resources that you need.
    Mr. Bonilla.

                              telemedicine

    Mr. Bonilla. Thank you, Mr. Chairman. Before I ask Dr. 
Lindberg a couple of questions, I want to thank you, Mr. 
Chairman, for trying to delay and wait for me this morning. I 
could not attend this morning's hearing because we had a 
memorial service for Frank Tejeda, Congressman from my home 
town, and then I was unavoidably detained by a meeting with the 
Majority Leader and the Speaker on another issue. So I 
appreciate your patience with me today on these matters.
    Dr. Lindberg, I would like to start out by asking about 
telemedicine. According to a GAO study, there is no Federal 
strategy currently existing to maximize the Federal investment 
in telemedicine, which is amounting now to about $646 million 
spread across 9 Federal departments and agencies government-
wide. I have an interest in this not only because of this 
subcommittee, but also the National Security Subcommittee of 
which I'm also a member. The Department of Defense is the 
largest Federal investor in telemedicine with $262 million and 
is considered a leader in developing this technology. The GAO 
suggests that DOD is in the best position to develop a 
telemedicine strategy due to the major investment and that it 
manages the largest health care systems in the world.
    The major medical facility in my district is hundreds of 
miles away from those that need the medical attention the most. 
I represent an area that is 58,000 square miles, 600 miles of 
it the Texas-Mexico border. My district is larger than all 29 
States East of the Mississippi individually. The medical 
schools in my district tell me that they have the technology to 
implement telemedicine technology but lack a strategy at this 
time. Many in my district agree that this technology has the 
potential to overcome any professional isolation of rural 
doctors by allowing them to participate in immediate 
consultation with specialists.
    My question is, what is the level of cooperation and 
coordination with DOD? Do you have a shared vision on 
telemedicine's potential and its application?
    Dr. Lindberg. Right. Well, it's an interesting question. I 
think that I'm pretty well aware of the work in the DOD that 
you refer to. Certainly, I understand why it is highly 
appropriate for DOD to be interested in telemedicine. NASA also 
for similar reasons; you can't reach out in space to reach your 
astronauts.
    The GAO report you refer to I have read. We were, in fact, 
asked to comment on it before it was released. It is specific 
to DOD. It isn't really a careful study of the whole U.S. Some 
of the numbers, for instance, are a little bit jumbled because 
of the different ways of accounting. While I respect the DOD 
work, in fact, Rick Satava, one of their chiefs, is a good 
friend and I've seen his work up close, they have their mission 
that is different from problems of domestic U.S. nonmilitary 
medicine. Our problem will not be solved by battlefield 
management strategy. We'll benefit from their instrumentation, 
we pretty much know about that.
    So far as the exchange of information, there really is a 
joint working group on telecommunications within the Department 
of HHS and shared with Commerce. We meet very, very regularly. 
NIH and NLM have representatives on that group. So I think that 
the information is exchanged quite sufficiently. We do not have 
unnecessary duplication and/or waste, none of that.
    There's another factor that makes me say don't try to make 
a global plan for the whole country, particularly leading with 
DOD. The reason I think it is such a wonderful area is that 
every week I see a brand new, innovative, wise application that 
I wasn't smart enough myself to think of. So if I picture some 
small group going off making a plan and a strategy for the 
country, it worries me a whole lot that they will think about 
it as it is now rather than as it might come to be.
    There is one other area in which I have met with the DOD 
Acquisitions Deputy Secretary, and they are aware that they 
will need to get a commercial industrial component to 
telemedicine strategy. That doesn't take a highfalutin 
committee to come to that conclusion. Somebody has got to 
manufacture the instruments. The Pentagon has a program, which 
we have met with them and NASA, to look into considering 
whether we perhaps should be working with companies directly to 
enhance their ability to produce instruments that DOD then 
wants to use.
    So I think that we're on top of that problem. I don't 
advise that it should be this national strategy at the moment 
until we know how far and how good the field really is. The 
only part of the strategy I would say that should be national 
is the commitment to evaluation, which is why we work with the 
National Research Council. All this sounds newer than it is. As 
an idea, telemedicine was quite apparent in the 1965 regional 
medical program days and I have many, many pictures of friends 
and colleagues, including Mike DeBakey doing instruction in 
surgery from Texas to Geneva over the satellites. That's 
telemedicine. NLM worked also with NASA for a satellite that 
operated over the whole Western U.S., the WICHI and WAMI 
program. These were great ideas. They were pretty expensive. 
Everyone was enthusiastic.
    I personally believe telemedicine is a great strategy. I 
don't want to see it go away again the way of the hula hoop. I 
think that it will have the best outcome if we force ourselves 
to evaluate what's the medical benefit. Is there a dollar 
savings or additional expenses, and to whom? That's as far as I 
would recommend going on a national strategy.

                       nlm telemedicine projects

    Mr. Bonilla. It's interesting that you seem comfortable 
then with just the exchange of information. I can assure you 
that we're not going to let this go the way of the hula hoop 
either. I think it is very, very important. I'm not a medical 
expert, but from what my researchers and doctors tell me, this 
is something that is necessary not just to survive, but to 
thrive in the future.
    I have another question about that. How effective are the 
19 telemedicine projects currently funded by NLM? I guess you 
touched on that in general terms, but I would like to hear more 
specifics.
    Dr. Lindberg. I think the main appeal to me is that we 
didn't particularly set out to scatter them around the map of 
the U.S. That is the beautiful part of the United States and 
NIH, that if you just evaluate the scientific merit of these 
proposals, everybody kind of comes into play reasonably well. 
NLM actually funds a Circuit Librarian Program out of San 
Antonio, Texas, that is kind of long-lived and very useful I 
think.
    But if I look at those particular ones that are on the map 
and the little listing that you have, let me mention just a 
couple that struck me as innovative and surprising. One says 
``Massachusetts. Provide care to high risk newborns and their 
families.'' It seemed odd to me, first of all, because it comes 
out of Boston which is very much of a city, not a rural area. 
Yet, what they are actually doing is pretty inexpensive but 
good telecommunications sending equipment home with the 
families of high risk newborns so that they can essentially get 
a consultation with the hospital before they double panic and 
hop into a taxi cab or an ambulance to bring the baby back and 
forth to the emergency room, which is very, very common. 
They've actually made feasibility studies of this and it is a 
fairly low-cost proposition. So that in a sense you have the 
same communication difficulties within a big city as you do in 
a more rural area.
    We've done work in West Virginia. There, the application is 
attempting to get specialty consultation to very rural areas. 
We have quite a bit of experience with that. It works quite 
well.
    I know that the Congress is very receptive I think to the 
telemedicine ideas, I think rightly so. I think it is 
delivering a benefit back home where it is needed.
    Mr. Bonilla. There is a lot of interest not just on this 
subcommittee, but with members of other committees in this 
Congress on advancing telemedicine. I did notice that noneof 
these projects is in the State of Texas. I'm wondering if you see any 
future projects, starting any new ones, and, if so, what are the 
chances of having them in the State of Texas?
    Dr. Lindberg. I'm not sure that we got an application from 
Texas. We did not get an application from San Antonio which is 
where I would have expected it to come from. I should mention 
one other, if you'll permit.
    Mr. Bonilla. Sure.
    Dr. Lindberg. The one in Oregon is teledermatology, how to 
diagnose skin and so forth. That has an additional feature 
because in telemedicine typically you will expect to try to 
achieve very high band-width rate or speed of transmission so 
you can see high resolution, color, and sometimes even some 
applications require you see the patient walk in front of the 
camera. Of course, that's expensive. The cheapest of the 
applications would be if you could use ordinary telephone 
lines. That's what this one in Oregon does, the so-called 
``store and forward'' technology. The expert is at the Oregon 
Health Sciences University and then the users are in small 
towns in eastern and western Oregon where there are no 
dermatologists.
    We have had this young man come and give a presentation to 
our Board of Regents. It was quite amazing. The pictures were 
taken, of course with some training, of the patients out in the 
small places with a computer digital camera, then sent by 
ordinary phone line so the dermatologist can see it whenever he 
or she needs to as kind of an appendix to e-mail, and then he 
showed some of the diagnoses that were made. These are patients 
in some cases who had the same complaint for ten years who had 
seen three or four doctors without any relief. Once the picture 
arrived in Portland, it took three seconds to give a diagnosis 
of treatment. It was nothing. So what a grateful patient. In a 
couple of cases, they unfortunately were malignancies that had 
been missed and not diagnosed and treated correctly.
    So we were tremendously impressed that at the low end of 
the thing, the low cost end, it still was working very 
surprisingly nicely. That's another reason that I think we 
should not prematurely spell out exactly how it should be done, 
because these bright ideas are coming up all over the country.

                                outreach

    Mr. Bonilla. That's very interesting, doctor. I appreciate 
your examples. I have a question in another area, my last 
question, Mr. Chairman. I understand that NLM has made great 
strides in the past year with its Visible Human project and the 
Internet Grateful Med program. Can you tell us if the Library 
has engaged in active outreach activities designed to ensure 
that the Nation's health care providers and health information 
specialists are aware of these and other NLM services?
    Dr. Lindberg. Yes, sir. In the case of Visible Human, this 
is going rather well already on its own. We have made 
presentations at library associations which I think have in 
turn brought this to the attention of the hospitals and the 
doctors. The major users of Visible Human really have been 
surgeons and radiologists. So they are selling themselves. It 
was first introduced, actually, I did it at the Radiological 
Society of North America, RSNA. There were something like 
85,000 radiologists present and I think I met them all in one 
half hour.
    [Clerk's note. Later corrected to ``55,000'']
    It is, again, a case where the new applications are being 
discovered by those who are out in the world using it. We have 
a licensing agreement, although there is no exchange of money, 
so we do know how the applications are used. We share that 
information on a Home Page, and we've had one meeting with all 
those licensees. So I think that is probably our outreach 
there.
    The more traditional outreach work that we do is pointed at 
Internet Grateful Med. We have given actual grants to connect 
people to Internet and then to give training for health care 
professionals' use of these systems. There have been about 300 
such outreach awards. There are special areas of outreach, for 
instance in toxicology, in some areas of the country. I am 
reminded that the reason you don't see Texas on that particular 
map is that we just completed a project with the Texas 
Department of Health, that ended in March 1996 and that 
involved 10 public health sites, so that was an outreach area. 
And 70 percent of those participants who had training said that 
they would continue to use Grateful Med. So we think that's 
probably working. Participating sites I guess would probably be 
areas that would be familiar to you--San Angelo, Tom Green 
County Health District, Texas Department of Health Field Office 
in Fort Stockton, MARFA Rural Health Clinic, Guadalupe Valley 
Hospital, these are all I think pretty small places, Texas 
Department of Health Field Office in Beaville and Laredo, Rio 
Grande, Eagle Pass. So that's pretty rural and has met with 
success we think.
    Mr. Bonilla. Dr. Lindberg, thank you very much.
    Dr. Lindberg. Thank you, Mr. Bonilla.
    Mr. Porter. Thank you, Mr. Bonilla.
    Mrs. Lowey.

                         internet grateful med

    Mrs. Lowey. Thank you, Mr. Chairman, and thank you, Dr. 
Lindberg. I have been absolutely intrigued by the whole MEDLINE 
issue and the issues surrounding it. The availability of 
MEDLINE on the World Wide Web is just an amazing development. 
What it does is make a wealth of information available to the 
general public which was once the province of medical 
professionals only.
    Could you share with us your views about how will access to 
this information change health care. Will it make Americans 
better consumers? When you write your reports for the medical 
journals, do you keep in mind the fact that these are going to 
go on the Web and the average consumer is going to be reading 
it? Could you discuss that with us.
    Dr. Lindberg. Yes. I think those are very perceptive 
remarks. We are concerned about the opportunities that Internet 
Grateful Med offers for communicating starting out with 
patients and families and having as an ultimate goal the 
public. But there's a lot of the public, so we have to be a 
little bit modest.
    NLM has historically tried to serve the public through the 
health care profession. It is hard enough to do that but I 
think we're now doing a good job with it. I think you're right 
though that the public now is so much better educated and more 
receptive to medical knowledge than they were when even I was a 
medical student, the opportunities are much greater. We used to 
still have conversations about should the patient be told the 
truth. Most patients didn't want to be told the truth, we 
believed. I think that is all in the past. I think now you have 
a well-educated population that seeks information.
    As a library, we've always held to the tradition that no 
information is secret or privatized. It has always been opento 
anyone who wants to use it.
    The patient groups, the sort of help yourself groups or the 
disease-oriented groups we know to be very effective, starting 
out with ileostomy clubs and that sort of thing. We haven't 
been able to work effectively with them up until now because 
one of the things is that the literature gets out of date, they 
don't use bibliographical standards that even identify the date 
and the place things were published to know whether they're 
accurate and timely or not. All that is beginning to change as 
the Web allows the central creation and maintenance of a 
database and the access by others without having to physically 
be connected to it.
    A bigger problem we think is the highly variable quality of 
the information on the World Wide Web. I guess it is 
commonplace to say that, but you can get 1,000 hits but how 
many of them are actually worth reading? We wish that we could 
say that we have a plan whereby NLM would certify all the 
medical knowledge. We're trying an experiment that is not yet 
ready for a public test. I'm associated with a group in which 
an attempt has been made to issue a kind of a medallion 
agreeing that the site obeys a certain set of ethical 
constraints or discloses when they are commercially biased. 
This is working. There are 21,000 sites on the Web that 
actually say that they comply with this medical standard. The 
next issue of the Journal of the American Medical Association 
will have an editorial by George Lundberg urging that attention 
be directed to exactly that problem, although he doesn't spell 
out a prescription that solves the problem.
    So I guess I have to just agree with you that it is a 
wonderful challenge and opportunity. We're sort of barrelling 
in to try to find out how much work would be involved in doing 
a really excellent job. There are a certain set of areas that I 
would describe where we really are seeking to give information 
directly to the public. The first, because it had special 
appropriations, is AIDS. If you didn't give information to the 
people, what good would it be? The second is in our support of 
work of the National Cancer Institute in their PDQ. It has a 
formal section for the patient and for the doctor and either 
could go to either section. The Agency for Health Care Policy 
and Research produced clinical practice guidelines which, 
again, we worked with them on. It is modeled on the cancer 
model so that there is a formal section well-said for the 
patient and a formal section well-said for the doctor.
    We did another experiment starting four years ago, I guess 
almost five now, with EPA. EPA was given an authorization by 
the Congress to collect certain data about the release of 400 
toxic chemicals it turns out are released, amazing large 
amounts, in 45,000 places in the country and then the data are 
collected quarterly. We accepted EPA's request that we assist 
in making this available to the public. We do that through a 
computer database, CD-ROMs, and a variety of other things. The 
library community helps us greatly by trying to give 
instruction on how to use that as an outreach effort that I 
could describe in further detail with Historically Black 
Colleges and Universities.
    In any case, the attempt there is to bring the information 
to the public. We don't do it as well as we would like to be 
able to do it. You run up against the fundamental difficulty 
that the data are really about chemicals. If you will only talk 
to the machine about chemicals, it will love you and give you 
the information right away. But if you talk to it in ordinary 
terms, it is obtuse. To some extent we get around it by letting 
people enter their zip codes and it will immediately tell you 
where are the sites that are releasing chemicals and so forth. 
But ultimately it gets down to chemicals.
    Some of this is easier said than done. So there is a 
particular case, of course it's more difficult than other 
things, but if we really want it to be done right and to be 
understood and to be kept at a high quality, we really have a 
lot of work still to do on that.

              monitoring information on the world wide web

    Mrs. Lowey. I just wanted to follow up because I'm not sure 
if I heard correctly. You said something a couple of minutes 
ago about there is a stamp of approval. In other words, one of 
my concerns is, whether it is cancer or ileitis or any other 
illness, there can be, in addition to the group, some 50 
remedies, I don't want to call them witch doctor remedies or 
whatever. Could you back up and explain that to us. You said 
there is some kind of a----
    Dr. Lindberg. I agree with what you said. We do not feel 
that we could issue such a seal of approval.
    Mrs. Lowey. Oh, there is not one, then?
    Dr. Lindberg. Not from NLM. There are from some other 
groups.
    Mrs. Lowey. Like?
    Dr. Lindberg. Well, one outfit is called HON, Health On the 
Net. It is a foundation in Geneva. I am an advisor to that. But 
that is not U.S., it is not government, it is not world-wide. 
It is accepted by some 21,000 sites, so it is kind of a 
voluntary yielding to standards. But to do what you really want 
us to do, we don't know how to do it yet, how to say what is 
really valid, what is the best, what is reliable, what should 
the patient act on. I should say that part of this is getting 
the raw information to the patients. For instance, supposing 
that you get a citation to MEDLINE. Well, you have to go to the 
library, get out the article, try to understand it. A lot of 
times you just would like to see the full text and PUBMED is an 
attempt to do exactly that. So that would be available to the 
doctors, the patients, the families, anyone.
    Mrs. Lowey. Do you or does anybody monitor? I'm wondering, 
Mr. Chairman, if anyone really monitors what's on the Web. For 
example, if you see a proliferation of some kind of information 
cure that is suddenly everywhere on the Net and you know it is 
patently false, dangerous, whatever, is anybody monitoring 
this?
    Dr. Lindberg. Well, NIH is not a regulatory agency and FDA 
is. So I would guess that would fall under FDA jurisdiction and 
that they would look after such a matter.
    Mrs. Lowey. Then we will pursue it.
    Dr. Lindberg. I don't like to pass the buck to my 
colleagues in other agencies, but NIH is not a regulatory 
agency. I think when we include journals in MEDLINE, that is 
indication that they are of good quality, that they are peer 
reviewed, that they are acceptable and have a good track 
record. That is quite different from saying that everything in 
all those articles is quite correct. But at least they are peer 
reviewed and they are properly presented.
    We index something under 4,000 journals. We subscribe to 
around 27,000. The world probably has around 50,000 or 60,000. 
So what we present is sort of creme de la creme.
    Mrs. Lowey. Along with that, I don't know if I've used up 
my time or you've used up my time, but I think----
    Dr. Lindberg. I apologize. I'll give yes or no answers. 
[Laughter.]

                              telemedicine

    Mrs. Lowey. If the Chairman would indulge me, I was also 
very involved with telemedicine. I wonder if you care to 
briefly talk with us about that whole area. What are the limits 
of telemedicine? What do you think are its most effective 
applications? Or, Mr. Chairman, do you think we should leave 
that discussion for another day?
    Mr. Porter. I would just say to the gentlelady that Mr. 
Bonilla ventilated that subject very thoroughly but he did it 
before you came in.
    Mrs. Lowey. Oh, did he? Okay. I apologize.
    Mr. Porter. I think Dr. Lindberg would be willing to 
highlight it again.
    Mrs. Lowey. If there is anything that you didn't mention 
with regard to telemedicine--[Laughter.]
    Mrs. Lowey. For example, I was recently talking with some 
people at the Strang Clinic who were discussing the whole area 
of genetic counselling. They were telling me that there are so 
many people in need of genetic counselling and we can't 
possibly find enough doctors who can respond. He mentioned this 
as an area where telemedicine and use of the Internet and 
dispensing information through that is invaluable.
    Dr. Lindberg. I agree. I'm very enthusiastic personally 
about telemedicine projects. I think that is the very best 
strategy for getting good medical health-related use of the 
National Information Infrastructure. I think we all recognize 
that you want to amplify the powers of an expert, you want to 
deliver the care to remote areas or even hard to get to areas 
of big cities. The best is yet to come. We're not certain how 
to do this.
    I was describing a little bit before you came about some 
applications that require very high band-width and high 
resolution and, therefore, are expensive, others that are store 
and forward technology, like teledermatology, that are 
essentially very high benefit and very inexpensive. I think the 
cities are as interesting as are the rural areas. There, the 
challenges are just getting around, how big an obstacle is it 
to get from their apartment back to the hospital. So one of the 
applications that I mentioned in that respect is in Boston. 
There is an application in New York that has to do with chronic 
illness in home settings. There, too, this home care is an 
application that I must say I would not have thought of. I am 
pleased that innovative, good new applications come up every 
month or so. Chicago also has applications of telemedicine that 
are focused on outpatients. I just think it is a marvelous 
area.
    You speak about the genetic counseling. I don't know anyone 
who is doing that using telemedicine techniques, but I do know 
of a tremendous amount of worry that people have about the 
medical data privacy issues connected with genetic counseling 
and testing. We are looking into that as well but not as a 
telemedicine project.
    Mrs. Lowey. I was just thinking that between the Internet 
and telemedicine, I was talking recently to a parent who is 
desperately worried about a young adult, not even so young 
adult, with Crohn's Disease in London and worried about what is 
the treatment there, is it as sophisticated as ours. I wonder 
to what extent would a physician take a file and send it 
through whatever means you have now to someone at the National 
Institutes of Health, to a hospital where they're expert in 
that, and whether you can't essentially do a teleconference.
    Dr. Lindberg. Oh, sure.
    Mrs. Lowey. In the old days, you used to have to fly to New 
York, fly here, go to this clinic. I would imagine, or I should 
ask that in the form of a question, is this technology being 
used right now where you can essentially have a teleconference 
with a file remaining in London, for example, and let there be 
a conference with experts in several places?
    Dr. Lindberg. Yes. There are several good examples of that. 
In our country, Mayo Clinic operates in four places--Rochester, 
Minnesota, Florida, Arizona--and they set up exactly that sort 
of system for their own patients. They are already able to deal 
with this problem across state lines. Are the doctors licensed 
properly to do all this? Is there a secure line? There is, they 
own it. So working within that corporation, exactly what you 
describe is being done on a daily basis.
    In other cases, like Columbia Presbyterian, they actually 
have referral systems set up to the Middle East. So for special 
cases that is being done. But I think you want a more general 
solution. I think we want a solution that makes this available 
to really every American that needs it. That's coming.
    Mrs. Lowey. I thank you. Thank you for your indulgence, Mr. 
Chairman.
    Mr. Porter. Thank you, Mrs. Lowey.
    Dr. Lindberg, we have many more questions that we're going 
to have to ask you to answer for the record.
    Mr. Porter. We very much appreciate your good testimony, 
Dr. Lindberg, and your wonderful leadership at the National 
Library of Medicine. I think you are at the epicenter of this 
revolution of knowledge and technology that is happening across 
the world, and I am sure that you find your work fascinating 
every single day. We very much appreciate the leadership you 
are providing, and your good staff.
    Dr. Lindberg. It is kind of you to say that. Thank you very 
much.
    Mr. Porter. Thank you, sir.
    The committee will stand in recess briefly.
    [The following questions were submitted to be answered for 
the record.]

[Pages 1336 - 1376--The official Committee record contains additional material here.]

                               ----------

                                          Wednesday, March 5, 1997.

                 NATIONAL INSTITUTE OF NURSING RESEARCH

                               WITNESSES

DR. PATRICIA A. GRADY, DIRECTOR
MARY CUSHING, EXECUTIVE OFFICER
ELLEN MOUL, BUDGET OFFICER
DR. RUTH KIRSCHSTEIN, M.D., DEPUTY DIRECTOR, NIH
DENNIS P. WILLIAMS, DEPUTY ASSISTANT SECRETARY, BUDGET, DHHS

    Mr. Porter. The subcommittee will come to order.
    We would like to next welcome Dr. Patricia Grady, the 
Director of the National Institute of Nursing Research. Dr. 
Grady, if you will introduce the people you have brought with 
you, and then proceed with your statement.

                       Introduction of Witnesses

    Dr. Grady. Thank you, Mr. Chairman. On my left is Ms. Ellen 
Moul, our Budget Officer; Ms. Mary Cushing, our Executive 
Officer; Dr. Ruth Kirschstein of course you know well, and Mr. 
Williams, who is from the Department.

                           Opening Statement

    Mr. Chairman, it is a pleasure to be here today to describe 
for you NINR-supported research that demonstrates the relevance 
and the extent of our research endeavors. I look forward to 
discussing our current and planned research for fiscal year 
1998. These proposed programs reflect our prior research 
investment, emerging scientific needs, and opportunities 
available for pursuit.
    Nursing research focuses on the patient and involves 
clinical research directly related to the Nation's major health 
issues. Several changes are occurring in our society that 
underscore the importance of this. First, the mean age of our 
population is shifting to the upper decades of life. With 
longer lives, we can expect an increase in chronic illnesses 
which require more frequent and more costly health care. 
Second, the cost is requiring us to examine health care 
delivery. The demand for therapeutic innovations through 
nursing research discoveries has never been greater.

                             pain research

    Let me provide three examples for you of our unique 
contributions in the area of pain, irritable bowel syndrome, 
and reducing risk for cardiovascular disease. First, I would 
like to highlight a health concern that is common to all of us, 
that of pain. Pain generates nearly 40 million yearly visits to 
health care providers, can prolong hospital stays, and may 
impede recovery. Research on pain is complicated, because 
although we all share a basic common physiology, the responses 
to pain may differ.
    Recently, an NINR-supported study on pain generated a great 
deal of interest across the Nation. Investigators found that 
gender plays a key role in pain relief. Women in this study 
obtained satisfactory relief from seldom used kappa-opioid 
drugs while men received little benefit. An advantage of kappa-
opioids is that they have fewer side-effects compared to the 
more typically used morphine-like opioids. Additional work is 
needed to better understand the underlying reasons for this, 
such as the possible role of estrogen or testosterone in 
mediating pain, and whether or not women, for example, may have 
additional kappa receptors on certain nerve cells more than 
men, thus enabling kappa-opioids to block pain better in this 
population.
    This is an important area of research with many yet 
unanswered questions about better management of pain. This 
research also underscores the importance of including subjects 
of both genders in clinical studies.

                        irritable bowel syndrome

    Another health problem that affects 10 to 15 percent of 
Americans and two to three times more women than men involves 
understanding a cluster of symptoms known as irritable bowel 
syndrome, or IBS. Scientists found that women diagnosed with 
IBS have a heightened activity of the sympathetic nervous 
system, the so-called flight or fight system, which appears to 
be linked to higher levels of stress. This study's findings can 
impact positively in the area of cost-effectiveness.
    Currently, IBS is diagnosed indirectly through a process of 
excluding other causes. If a positive diagnosis were possible 
based on scientific methods, the result could be fewer doctors 
visits with subsequent savings in time for patients, and 
dollars to the health care system.

                         cardiovascular disease

    My third example is that of reducing risk for 
cardiovascular disease. The roots of adult cardiovascular 
disease often go back to childhood, making interventions early 
in life key to achieving a healthy adulthood. Researchers have 
designed and tested an eight-week intervention to reduce 
cardiovascular risk factors in more than 2,200 third and fourth 
graders in rural and urban areas, almost 20 percent of whom 
were African-American youngsters. By the study's end, students 
showed reductions in total cholesterol levels, body mass index, 
and body fat, as well as increased physical endurance. This 
type of study has a profound potential impact on the health of 
our future citizens.

                           cultural diversity

    As you can see, nursing research encompasses both 
behavioral and biological aspects of health. Threaded through 
NINR's research portfolio is an interest in the relationship 
between ethnic and cultural diversity and health. For example, 
if questionnaires and health assessments are in English only, 
non-English-speaking subjects will be excluded from health 
research findings and miss participating in studies which may 
benefit them. NINR-supported researchers successfully 
translated and tested an English language arthritis self-
management program into Spanish for Hispanic patients with 
arthritis. This program is now useful for Spanish-speaking 
arthritis patients, thus addressing their health needs and 
improving their quality of life.

                        future research emphases

    The continuing vitality of nursing research stems from the 
many questions that remain to be answered. To this end, future 
NINR research emphases include: research on symptoms associated 
with such neurological problems as stroke and traumatic brain 
injury, epilepsy, motor problems such as Parkinson's disease 
and spinal cord injury, chronic debilitating problems such as 
diabetes and AIDS, and studies of factors related to successful 
family caregiving. NINR, in collaboration with others at NIH, 
supports development of promising ways to prevent progressive 
deterioration caused by these problems.

                            transplantation

    With 12,000 organ transplantations each year and the 
improved technology available, many of these patients are 
surviving into their 50s and 60s, and face long-term drug 
regimens which can have serious side effects. These include 
osteoporosis, cancer, neurologic problems, and cardiac 
dysfunction. The NINR will explore ways to improve the quality 
of life of long-term transplantation survivors.

                              end of life

    End of life issues will encompass bioethical, biological, 
and behavioral studies. We plan to identify research needs in, 
and address the transition to: palliative care, management of 
pain and other symptoms, measurement of relief from symptoms, 
and documentation of financial burdens for patients and family 
caregivers.
    As NINR begins its second decade at the NIH, current and 
emerging research and societal issues intensify the need for 
nursing research. Clinically-based, patient-oriented nursing 
research is well positioned to make important contributions to 
improving the health and the quality of life for all our 
citizens.

                          fy 98 budget request

    Mr. Chairman, the fiscal year 1998 request for NINR is 
$55,692,000. I will be pleased to answer any questions you 
might have.
    [The prepared statement follows:]

[Pages 1380 - 1383--The official Committee record contains additional material here.]


                 justification of the budget estimates

    Mr. Porter. Thank you, Dr. Grady. Dr. Grady, you are a 
relatively new director of a relatively new institute. How 
would you feel if Congress gave you only 2.2 percent more than 
last year to work with this year?
    Dr. Grady. Mr. Chairman, we would be grateful for any 
increase over last year's budget.
    Mr. Porter. Dennis isn't listening. [Laughter.]
    Dr. Grady. But we do have big plans for growing. We have 
experienced growth in a constrained economy since we came on 
board. We have been very fortunate with the support of the NIH 
and the budget. But we also do have very large plans that we 
could implement in terms of training and in terms of 
initiatives. So the more that is available, we will promise to 
put it to good use.

                      professional judgment budget

    Mr. Porter. How much did you ask Ruth to provide to you 
initially?
    Dr. Grady. Well, our professional judgment budget was 
approximately 9 percent over this year. In fact, you mentioned 
being new, there's another aspect of the newness that I could 
add to that. That is the fact that the field of nursing 
research is still a relatively new and growing field. We are in 
the very interesting situation of funding nearly as many 
trainees as we fund active researchers. So you can see that 
what we're really dealing with is a field that is justabout to 
explode, and we have a number of people in the pipeline and a number of 
really good ideas to be able to fund.

                communication with health care providers

    Mr. Porter. It is important that the results of your 
research studies on patient care are communicated to major 
health care providers like hospitals and HMOs. What mechanisms 
have you established to encourage this transfer of information?
    Dr. Grady. We have several ways that we are attacking that 
situation. As you have mentioned, it is a very large audience. 
There are 2.2 million nurses across the country that we need to 
reach, as well as other team members, to inform them of the 
results of the research and to be able to implement them. We 
have a number of conferences that we participate in each year. 
We also have a Home Page and are using the Internet very 
actively in addition to the usual peer review publications. I 
also regularly write columns for the major publications in 
nursing and also interdisciplinary publications such as 
newsletters. We have a nursing outreach newsletter that we do 
have online. And we also are very responsive to the many 
inquiries that we get.
    Mr. Porter. Have you found that providers are reluctant to 
adopt your research findings if they have an adverse impact on 
their bottom line?
    Dr. Grady. An interesting thing about nursing research is, 
that compared to what you've been hearing about high 
technology, much of nursing research really is relatively low 
technology. There are interventions that are used that are 
patient-specific that tend to often effect better outcomes for 
patients but without being as expensive as some others. They 
are, however, somewhat more time intensive. That is an issue 
that we do need to deal with.
    We are funding a number of studies, for example, of nurses 
working with inner-city students who are at risk for HIV or, in 
fact, are HIV infected, counseling them to see if techniques 
with one-on-one counseling versus small group counseling would 
be more effective. In fact, we have found that working with 
small groups, which is much more effective in terms of time, 
has just as good outcomes as the one-on-one. So we're 
experimenting with ways to deal with these issues.

                      clinical research conference

    Mr. Porter. Your Institute co-sponsored a conference 
several weeks ago at the Clinical Center to explore the options 
available to maintain the continued health of clinical research 
given the changes in the health care marketplace. Can you share 
with us the ideas that were generated at this conference?
    Dr. Grady. Yes. There were a number of very interesting 
ideas generated at that conference. The major issue was 
attempting to deal with the changing health care landscape, 
that of managed care and HMOs coming into the marketplace. As 
it turns out really, a number of issues that are dealt with by 
nursing research, are very germane to, and would be helpful to 
the new circumstances in which we find ourselves. Much of what 
nurses do is to deal with reducing risk, promoting healthy life 
styles, and prevention. So that much of what we are engaged in 
is, in fact, very cost-effective and is something which used 
appropriately could be useful in the new circumstances.
    I will give you one example. One of our long-time funded 
researchers from University of Pennsylvania, who has moved to 
Ohio to Cleveland Clinic, has a model which is called a 
``transitional model'' of care in which patients using this 
model, which is a nurse-managed model, patients are able to 
leave the hospital earlier, have fewer unplanned return visits, 
and in general, fare quite well compared to patients discharged 
early without this type of model. The populations that have 
been addressed successfully are: mothers who would have low 
birth weight infants, resulting in follow-up ahead of time, 
resulting in a lower number of low birth weight babies; also, 
women who have come into the hospital for unplanned Cesarian 
sections, hysterectomies, and other moderate types of surgical 
interventions and/or illnesses. These patients have fared quite 
well with this model, and, in fact, it has turned out that it 
is cost-effective. So there was a great deal of interest in 
hearing the results of those particular research studies.

                          nursing publications

    Mr. Porter. Your Institute celebrated its tenth anniversary 
last fall. I'm sure you've seen an increasing maturity in the 
nursing research you supported during that period. In what 
journals does nursing research tend to be covered? Have nurse 
researchers broken into the ``big league'' journals?
    Dr. Grady. Yes. The lead study of the group that I just 
mentioned to you was published in the New England Journal of 
Medicine. There have been subsequent publications from that 
type of research published in that journal. Also, a number of 
other journals, Lung, and some of the physiology journals 
related to cardiovascular health, are also regularly published 
in by nurses. The major leading journal that nurses publish in, 
the research journal, is Nursing Research. However, the work is 
finding its way into many other journals.
    Much of what is going on now in the field is 
multidisciplinary and interdisciplinary. So many of these 
studies, in order to address the appropriate audience, need to 
be published in multidisciplinary journals. So we are covering 
the waterfront, as it were.

                         traumatic brain injury

    Mr. Porter. One of your areas of research priority is 
traumatic brain injury. New legislation focuses attention on 
brain injury throughout the Public Health Service both in terms 
of research and services. What is already known about managing 
the care of traumatic brain injury victims that could be useful 
for the service demonstrations being operated by HRSA?
    Dr. Grady. There are several studies in this area that are 
relevant. For several years, we have funded studies related to 
patients following traumatic brain injury in acute care 
settings relative to suctioning procedures and other intensive-
care procedures that result in an increase in intracranial 
pressure. As you may know from the background materials from 
that group, one of the major dangers in the early post-
traumatic period is a further increase in intracranial pressure 
resulting in further brain damage. That's an area in which 
several changes in care delivery as a result of these studies 
have shown the ability to either prevent the increase or 
actually result in a reduction of increase while care is being 
given.
    There are other areas of study which impact on this. One of 
our major initiatives is that of cognitive impairment, 
measuring changes in brain function as it relates to learning, 
memory, and awareness of one's environment. That is a major 
initiative of the Institute. The difference there now from 
earlier days is that the tools that are available to measure 
levels ofconsciousness and responsiveness of individuals 
following injury are much better. So that one can actually determine if 
an intervention or a way of caring for someone is actually beneficial. 
Earlier on, one could imagine that it might be or one could make an 
educated guess, but now one can actually measure that. In the coming 
year, we plan to encourage more applications in that area. We are 
collaborating with several institutes on campus in planning for that.

                         currency with research

    Mr. Porter. This is a question for both you and Dr. 
Kirschstein. All of the directors that have testified before us 
appear to us to be extremely knowledgeable in their fields, 
including Dr. Grady. I wonder, Dr. Kirschstein, if you could 
tell us how they receive their information. Is it sitting down 
with researchers who are working on particular projects and 
learning directly from them? Is it all read? How do they keep 
up with the expanding knowledge in each of their fields? It 
seems to me very difficult to keep up with, there is so much 
going on.
    Dr. Kirschstein. First of all, Mr. Porter, I think all of 
us find it is extremely difficult to keep up. But the best way 
they do it is by working very, very hard. They do, indeed, 
spend hours and days in all sorts of settings--meeting with 
researchers, going to research conferences, reading the 
literature, calling in groups of experts, interacting 
constantly, and then finding time, as they can, to think about 
it all, synthesize it, and put it into some planning effort and 
some sort of priority setting that you've been very interested 
in. It is a formidable task and they all do it extremely well.
    One of the reasons I think they are all so successful at it 
is that they have remarkable backgrounds to begin with. They 
have been well-trained, either as physicians or as research-
trained nurses, or as research scientists with other doctoral 
level degrees. They have probably all had quite distinguished 
careers, some more than others, nevertheless, as researchers, 
and have kept their interest and their enthusiasm and their 
excitement about science very current.
    Mr. Porter. I might add that applies to you and Doctor 
Varmus, obviously, more than perhaps anyone, because you have 
got to know all of the different fields and keep up with this 
vast amount of knowledge.
    Dr. Grady, would you like to add to that at all?
    Dr. Grady. Just that I would agree that Dr. Kirschstein 
never rests. In all honesty, to pick up on that, we do find 
ourselves in a number of settings. I think the best way I find 
to stay informed is to be able to collect the data from a 
number of sources, both from the literature, from meetings, in 
person, getting out to the sites. I find that it is often very 
helpful. If you are available on the Internet, or when I go to 
a scientific meeting I try to visit the nearby universities and 
speak while I'm there, people will bring concerns to you or 
they will bring the excitement of what they're doing in the 
clinic, in the laboratory to you. It helps, I think, to keep 
the vitality to hear it firsthand and to be able to share in 
that excitement. It makes it much more real.
    Mr. Porter. Thank you very much.
    Mrs. Lowey.
    Mrs. Lowey. Thank you very much, Mr. Chairman. I, too, 
would like to join the Chairman in welcoming you, Dr. Grady, 
and your colleagues. I have been a long time supporter and 
advocate for the nursing profession. I do feel that with our 
focus on quality yet cost-effective care the nursing profession 
has an extraordinary amount to contribute. So I really do 
appreciate it. And as we move forward, I think your work on the 
nursing profession will become even more invaluable and will be 
paid attention to. So I thank you very much.
    Dr. Grady. Thank you.

                        research training issues

    Mrs. Lowey. Along with that, the Nurse Education Act is a 
major source of support for programs for baccalaureate nurses 
who become the graduate students, nurses with advanced degrees, 
and faculty who perform nursing research. Would the NINR 
research agenda be hurt by a decrease in the number of nurses 
able to pursue a graduate degree or to move into faculty at 
schools of nursing? The administration's fiscal year 1998 
budget reduces spending for nursing education by 88 percent--88 
percent. If that budget were to become law, what would be its 
effect on nursing research?
    Dr. Grady. We depend for our research practitioners on 
those graduates of baccalaureate schools across the country. 
The average individual entering a doctoral program already has 
a bachelors and a masters degree in nursing. So we do rely on 
that. For us, it is a pipeline issue, that we do need to keep 
the supply coming.
    As you have implied by your question, the number of nurse 
researchers that are in demand exceeds the supply that is 
available. So we do very much need to keep that group coming. 
As I mentioned earlier, we are a young field and so the 
pipeline effect is really an important issue. We have many 
people who are entering training but we're just barely getting 
to where we need to be.

                         women's health issues

    Mrs. Lowey. Can you please update the subcommittee with 
regard to your work to improve women's health. For example, 
several years ago you were involved in an initiative with the 
Office of Research on Women's Health to examine whether women 
should undergo hysterectomies for noncancerous conditions. What 
is the status of that project, and could you please highlight 
your work on other women's health issues?
    Dr. Grady. Yes. Regarding the issue of hysterectomies in 
women, the report has now been published and it was found that 
there are fewer hysterectomies being performed on women for 
noncancerous conditions now than there were previously. There 
are a number of questions being asked before that is done. It 
is not the obvious first choice option which reportedly it had 
been in the past, although the data was more hearsay then than 
now.
    We are involved in a number of women's health areas. We, in 
fact, are one of the recipients of a fair number of resources 
from the Office of Research on Women's Health who co-funds 
through us to address several areas of women's health. Let me 
take the issue of screening for breast cancer for older women 
who are obviously at risk. This has been a problem group both 
in cities and also in rural areas. We are funding, for example, 
one study which is a, let me use the word, linkage study, 
meaning something different than you've heard earlier this 
week. Basically, this is a study to test whether linking up 
young women who are very aware of the risks and the dangers and 
accept this as an important tool, linking up younger women with 
older women to try to use a sort of mother-daughter approach to 
getting those women in for testing. The preliminary results are 
encouraging.
    We also are participating in the Swan-Study of Women Across 
the Nation, that is a consortium with the Aging Institute, 
addressing the health of older women.We fund one of the seven 
clinical sites. The area that we fund focuses primarily on the health 
needs of African-American older women.
    We also are funding a study looking at sleep disturbances 
in women with fibromyalgia. This, as you know, is a problem 
that has a much higher incidence in women than men. Sleep 
disturbance and pain are associated problems. We're funding a 
study in that area, one of only a few studies looking at those 
issues.
    We also are funding a number of studies looking at 
improvement in prenatal care to try to identify women at risk 
for low birth weight babies, women who are part of underserved 
rural populations, getting them in. We have one such study that 
is funded in Hawaii that resulted in a decrease in the number 
of low birth weight babies and also in a large increase in 
women in that group coming in for prenatal care. That was an 
interesting study in that what it did was to use specifically 
tailored approaches to the population so that it incorporated 
not just the well-known principles of promoting health in 
prenatal women and early child birth, but also looked at the 
cultural component and investigated the use of native healers 
in that population. By incorporating them on the team, there 
was a much larger response to that initiative.
    I could go on. Women's health is a major focus of many of 
our studies.

                           breast self-exams

    Mrs. Lowey. I was disturbed by the report yesterday that 
the results of a study that took place in Shanghai, China, 
challenged whether breast self-exams are effective in detecting 
cancer. News reports stated that there are few studies on the 
efficacy of breast self-exams. This would seem to be a 
necessary area of research, perhaps between your Institute and 
the National Cancer Institute. Could you please comment?
    Dr. Grady. I think that is an interesting observation. 
Because of the availability of many high technologies now, 
there has been a period of time when less attention has been 
paid to breast self-exam as a way of detecting small cancers. I 
think that for populations, as an adjunct to other 
technologies, that it still is thought by many to offer a 
useful screening approach. We do not currently fund studies 
that specifically are looking at the efficacy of that, although 
we do fund studies which are encouraging women to do breast 
self-exam along with the other healthy life style choices. In 
fact, we do co-fund with the Cancer Institute one such study 
which looks at a variety of screening methods to encourage 
people to use them, but it does not specifically look at the 
efficacy of one versus the other. But it is something that we 
do need to attend to.

                    counseling for genetic screening

    Mrs. Lowey. In the area of genetic screening, as we all 
know, genetic tests for breast cancer are available in the 
private market. Additional genetic tests for diseases such as 
Alzheimer's will be available soon. I am very concerned about 
the development of counseling strategies to help individuals 
and families decide whether or not to undergo these genetic 
tests. If they decide to, how do you deal with the possible 
results. Nurses, it would seem to me, can play, and should 
play, a significant role in helping to develop such counseling 
programs. Perhaps you could discuss with us the role the 
Nursing Institute is playing in this area. To what extent are 
you coordinating your work with the Human Genome and National 
Cancer Institute?
    Dr. Grady. We agree with you that nurses could, and should, 
play an important role in that area. We are collaborating with 
the National Human Genome Research Institute and the National 
Cancer Institute as well in this area. Specifically, we have 
collaborated with the Genome Institute in bringing nurses 
together from across the country who are involved in genetics 
in any way to look at what will ultimately be a core curriculum 
for nurses in genetics, and to look at the areas of need for 
counseling and to identify issues involved. We also participate 
with them in funding several grants under the ELSI program that 
is a part of the Genome Institute.
    We also fund several others along the lines of using a 
decision-making approach. One such grant is looking at the 
decision-making for those people who are considering BRCA-1 
testing. So we are addressing this from a number of areas and 
expect to continue to do that as time goes on.
    As you all have heard on several occasions from Dr. 
Collins, the percent of the genes that are identified as part 
of the Human Genome that actually are one gene-one disease is 
probably roughly as low as 10 percent. The other 90 percent of 
the genome will code for a predisposition. A misspelling in a 
particular gene will result in a predisposition to developing a 
disorder but not necessarily a certainty. The other factors 
that would play into it are factors such as diet, exercise, 
environment, and many others that we have not yet identified. 
As this body of information grows, the role of individuals, in 
this case it would be specifically the nurse, to identify what 
factors can be modified and to try to work with patients to 
intervene to either diminish the risk or introduce a healthy 
life style will become much more important as time goes on.
    Mrs. Lowey. I thank you, Dr. Grady. I think, as the 
population is getting older, the role of nurses working with 
chronic illness, with the patient, with the families will 
become increasingly important. I thank you again. I look 
forward to working with you. Thank you, Mr. Chairman.
    Dr. Grady. Thank you.
    Mr. Porter. Thank you, Mrs. Lowey.
    Dr. Grady, we have many more questions for you for the 
record that we would ask that you answer.
    Thank you for the fine job you're doing at NINR. We hope to 
do better by you than the President has done in his budget. 
That, of course, depends upon the overall budget and the budget 
allocations. Obviously, you, along with the other directors of 
the institutes, are doing wonderful work. You need resources to 
advance that work. You need resources to keep good people 
involved. We want to do the best that we possibly can to help 
you do that.
    Dr. Grady. Thank you, Mr. Chairman. We appreciate that.
    Mr. Porter. Thank you.
    The committee will stand in recess briefly.
    [The following questions were submitted to be answered for 
the record.]

[Pages 1391 - 1442--The official Committee record contains additional material here.]


                               ----------

                                          Wednesday, March 5, 1997.

                      FOGARTY INTERNATIONAL CENTER

                               WITNESSES

PHILIP E. SCHAMBRA, Ph.D., DIRECTOR
STEPHANIE J. BURSENOS, DEPUTY DIRECTOR
RICHARD MILLER, EXECUTIVE OFFICER
RUTH KIRSCHSTEIN, M.D., DEPUTY DIRECTOR, NATIONAL INSTITUTES OF HEALTH
DENNIS WILLIAMS, DEPUTY ASSISTANT SECRETARY, BUDGET, DEPARTMENT OF 
    HEALTH AND HUMAN SERVICES

    Mr. Porter. The subcommittee will come to order.
    Next we are pleased to welcome Dr. Philip Schambra, the 
Director of the Fogarty International Center. And Dr. Schambra, 
why don't you introduce the people you brought with you, and 
then proceed with your statement.

                       Introduction of Witnesses

    Dr. Schambra. Thank you very much, Mr. Porter.
    To my left is Mr. Richard Miller, the Executive Officer of 
the Fogarty Center. To my right is Ms. Stephanie Bursenos, the 
Deputy Director of the Fogarty Center. And of course, you know 
Dr. Kirschstein and Mr. Williams, to her right.

                           Opening Statement

    Mr. Chairman, if I may I'd like to submit my full statement 
for the record and give a brief oral presentation, starting out 
by commenting that once again it's my distinct privilege to 
present the programs and accomplishments of the Fogarty 
International Center.
    As you know, our namesake, John Fogarty, served as Chairman 
of this committee for 18 years, from 1949 to 1967. He was the 
first of a continuing lineage of Congressmen and women who have 
enabled NIH to become the world's leader in the pursuit of 
health through biomedical research. The Fogarty International 
Center was established by Congress specifically to improve 
health through international scientific cooperation. This broad 
mandate has required us to set priorities and concentrate our 
resources on strategic health areas.
    As an outcome of our long-range plan, we've identified 
scientific training programs with developing nations as our 
foremost priority to prepare the United States to meet urgent 
global health challenges.
    Our working principle is to coordinate our programs, not 
only across NIH, but across the Federal Government. In fact, 
almost 60 percent of the funds managed by the FIC, including 
AIDS funding allocated by the Office of AIDS research, are 
derived from other NIH or Federal components, who view FIC as a 
means of advancing their international goals. Moreover, these 
intra and interagency alliances reduce administrative costs and 
streamline management.
    The model for FIC's global health efforts is our AIDS 
International Training and Research Program. Since its 
inception in 1988, more than 1,000 scientists from over 80 
countries have received training in the United States, and now 
assist us in our international prevention efforts. This past 
year, the program documented a substantial decrease in the 
prevalence of HIV in the population of one foreign country as a 
result of a systematic prevention strategy.
    The long-range objective is to create these same 
partnerships to meet the challenges of new and emerging 
infectious diseases, environmental pollution and unsustainable 
population growth. The aim is to demonstrate a compelling 
leadership role for the United States in reaching global 
solutions to global problems through biomedical research 
training. Since the completion of our long-range plan, we have 
launched research training programs on population and health 
with the National Institute of Child Health and Human 
Development of NIH, and on environmental and occupational 
health with the National Institute of Environmental Health 
Sciences at NIH, and the Centers for Disease Control, and in 
new and emerging infectious diseases with the National 
Institute of Allergy and Infectious Diseases at NIH.
    These early investments are already yielding public health 
benefits. For example, in 1996, a scientist from Gabon received 
research training on Ebola virus at Yale University under our 
training program in new and emerging infectious diseases. Upon 
return to Gabon, he traced the origin of an Ebola-infected 
patient to a rural lumber camp. And because of his special 
training, he was able to perform the required laboratory 
studies in collaboration with CDC scientists.
    As a consequence, Gabon was able to confirm the Ebola 
outbreak, take appropriate treatment and prevention measures, 
and undertake a research program to identify the natural 
history of the virus.
    In addition to these research training programs, FIC 
undertakes concerted efforts to bring new resources and 
scientific perspectives to global health through allianceswith 
other Federal agencies. In cooperation with the National Science 
Foundation and the Agency for International Development, and with the 
strong endorsement of this Committee, in 1993 the FIC initiated the 
International Cooperative Biodiversity Groups Program. Its purpose is 
to discover new drugs from the earth's biological resources, while 
preserving national ecosystems and promoting economic growth through 
drug development.
    Since its inception, over 3,000 species of plants and 
insects have been examined for their potential therapeutic 
properties. Bioactive samples are now being tested as candidate 
drugs against certain cancers and viral diseases, malaria and 
degenerative neurological disorders.
    Finally, Mr. Chairman, last year, Dr. Varmus noted to the 
committee that a special panel would be established to review 
the ways in which the NIH carries out its commitments to 
international health. The report of the panel, co-chaired by 
Dr. Joshua Lederberg of Rockefeller University and Dr. Barry 
Bloom of Albert Einstein Medical College is now completed. And 
I'm pleased to note their strong recommendation of a 
strengthened international role for all NIH components.
    I'm particularly pleased that the panel endorsed the 
directions pursued in the FIC long-range plan. They cite the 
plan as a thoughtful and forward-looking approach for guiding 
FIC's future activities and commend the Center for 
demonstrating a leadership role. The report does recommend that 
FIC reassess several longstanding fellowship programs in light 
of its more recent global health priorities. This 
recommendation is consistent with internal discussions 
currently underway with Dr. Varmus and others within the NIH 
leadership.
    I'd like to conclude by noting that the political basis for 
public investment in biomedical research emerged from our 
Nation's critical needs during World War II. Today, the pursuit 
of health through research again is essential for our Nation's 
security. Scientific solutions to global health threats require 
a coordinated global response.
    Congressman Fogarty once remarked that our international 
health programs can be characterized as enlightened self-
interest, since it can be amply demonstrated that we receive as 
well as give.
    With the support of Congress, FIC will continue to advance 
this important mission through international cooperation.
    Thank you, Mr. Chairman. Our fiscal year 1998 budget 
request is $16,755,000. And I'll be pleased to answer any 
questions that you or members of the committee may have.
    [The prepared statement follows:]

[Pages 1446 - 1449--The official Committee record contains additional material here.]


             other countries leading in biomedical research

    Mr. Porter. Thank you, Dr. Schambra.
    I will forego my usual question about your 2.3 percent 
increase, because I think Mr. Williams has coached all of you 
to answer roughly the same way.
    Let me ask a general question that I'm just kind of curious 
about. What other countries, in the order of magnitude and 
quality, have research communities that are somewhat comparable 
to the United States? Japan, Germany, France?
    Dr. Schambra. That is certainly an easy one to answer, and 
you've started----
    Mr. Porter. There are none?
    Dr. Schambra. Japan has a superb biomedical research 
enterprise as a whole, indeed, in all fields of science, 
developed since the Second World War. Canada is certainly a 
leading scientific power. In fact, second to none as the 
largest foreign collaborator with the United States. A great 
number of our research grants given to foreign scientists, 
about half, go to Canadian scientists.
    Germany, France, very predominantly. The United Kingdom and 
other countries in Western Europe, Holland and the Netherlands 
are all leading countries in biomedical research. The 
Scandinavian countries are important powers in this field as 
well.
    Mr. Porter. Now, since World War II, 30 percent of the 
Nobel prizes awarded to scientists for research discoveries 
under NIH support were received by foreign researchers. This 
seems like quite a remarkable statistic, given that less than 1 
percent of NIH extramural grants in that period went to foreign 
investigators.
    How should we interpret this statistic? Should we assume 
that competition for NIH grants is so intense that only the 
very top international grantees win grants? Or should we be 
concerned about the competitive standing of U.S. researchers? 
Or is this a function of some other factors?
    Dr. Schambra. I think first and foremost, what it means is 
that NIH research administrators know how to pick winners. And 
in fact, it also illustrates, I think, very vividly, the 
importance of international collaboration between scientists, 
in this case, leading scientists who have made major 
discoveries that have led to the ultimate recognition of 
winning the Nobel prize. It is important for the NIH to support 
that type of international collaboration.
    Dr. Kirchstein. Mr. Chairman, if I may add something. There 
are policies at NIH that only a certain number of awards will 
be made to scientists abroad, so that the vast majority of the 
money can be provided to United States investigators.

                          fellowship programs

    Mr. Porter. Under the NIH Visiting Program, more than 2,000 
foreign scientists are supported each year in fellowships and 
assignments to the NIH intramural program at a cost of more 
than $70 million. Does this large international training 
program swamp the impact of the smaller Fogarty training 
programs, which also bring foreign scientists to the United 
States?
    Dr. Schambra. Well, yes, I think in fact it does, Mr. 
Chairman. And the realization of that fact alone, in 
conjunction with other considerations, has led us to modify 
some of our fellowship programs in recent years. When I became 
Director of the Fogarty Center in 1988, our major investment, 
in fact, was in training foreign scientists in the United 
States.
    But it represented only about 130, at the most, foreign 
scientists coming to the United States, and them mostly from 
the developed regions of the world. About three-quarters of the 
scientists came from Western Europe and Japan, and other 
developed countries of the world. These were small numbers 
compared to the very large numbers you cited who come from 
abroad to work just in the intramural research program at NIH.
    So we felt that given that fact, and the much more 
demonstrable need to provide training for scientists from 
developing countries and countries that had just emerged into 
the democratic sphere of international life in EasternEurope 
and the former Soviet Union, that we would in fact reduce our programs 
and focus on those scientists to the preference of offering fellowships 
very broadly in competition with the intramural research program at 
NIH.
    Mr. Porter. Do you have any data on the number of trainees, 
or the proportion of trainees that stay in the U.S. after 
completing their training rather than returning to their home 
countries?
    Dr. Schambra. We looked at that question in connection 
with, in fact, a program I just cited a few years ago. I don't 
have up to date, that is current figures, but then in excess of 
90 percent of the fellows that we were training under our 
programs returned to their home country. Even today, the nature 
of the foreign scientists who we bring under our various 
training programs to the United States for training come under 
visa provisions that require them to return to their home 
country after finishing their training.
    In addition, we usually make it a condition of their 
training here that in fact they have a place to go back to, and 
they in fact intend to go back to their home country. But that 
can't, of course, be 100 percent. But I'd say 90, 95 percent is 
probably a pretty good batting average.
    Mr. Porter. Do you have data on the percentage of 
international trainees in Fogarty programs who go on to compete 
successfully for NIH research grants?
    Dr. Schambra. At one time, and in fact also in connection 
with this particular program, we did look at that question. 
Frankly, I don't remember what the data at that point showed, 
Mr. Porter, but I'd be pleased to provide that for the record.
    [The information follows:]

                          Fellowship Programs

    The study I have referred to focused on the percentage of 
fellows who returned to their home countries and the types of 
employment pursued following their return. However, we now have 
begun to monitor the number of FIC-supported fellows who are 
subsequently supported by other NIH institutes. Under the AIDS 
International Training and Research Program, an important share 
of former trainees now participate in international research 
projects supported by NIAID. These include, for example, 
studies of natural history of HIV in Haiti and in Senegal, 
prevention research in Thailand on vaginal microbicides and 
studies in Uganda on the relationship between HIV and 
tuberculosis.

    Dr. Schambra. As Dr. Kirchstein pointed out, the number 
would be extremely small, in view of the fact that about 1 
percent of NIH research grants in total go to foreign 
scientists.
    Mr. Porter. Yes, I understand that the number is relatively 
small. But you could still see how many go to ones that you've 
trained.
    Dr. Schambra. Right, absolutely.

                         external panel review

    Mr. Porter. As you mentioned, the Lederberg panel 
commissioned by Dr. Varmus to review the structure of the 
Fogarty Center recommended last September that the Center's 
current mission and structure be retained in large part. It 
did, however, suggest that three training programs, Scholars in 
Residence, Senior International Fellowships, and International 
Research Fellowships, be reduced significantly. The 1998 budget 
appears to straight line these three programs. Do you disagree 
with the panel's judgement?
    Dr. Schambra. Having developed a long-range plan, we have 
been looking particularly at those programs for their validity 
and relevance in today's situation.
    As far as the budget projections for fiscal year 1998 are 
concerned, some of the money that is in that straight line is 
for the purpose of paying for commitments that have been made 
in prior years. In the case of the International Research 
Fellowship Program, that is the program that I referred to a 
moment ago as having already been very substantially reduced to 
about a third of its size from some five years ago.
    We are in discussion with Dr. Varmus and the leadership at 
NIH about the future of these programs and alternatives that 
might be in fact more pertinent to today's needs on the 
international scene.
    Mr. Porter. The Lederberg panel also recommended that a 
critical review of Fogarty's functional units be undertaken in 
the near future to determine the most efficient use of its 
resources. Do you plan to follow up on this recommendation?
    Dr. Schambra. Yes. In fact, we do. I'm pleased to say that 
that, too, can be seen as an encouragement to continue the 
process that we've already started several years ago with our 
long-range plan, and which, in fact at that time, we did 
reorganize the Fogarty Center, reducing the number of operating 
branches from five to three divisions. As you know also, Dr. 
Varmus, with the support and encouragement of this committee, 
is arranging for a complete review of the administrative 
functions of the entire NIH. And we would certainly be a part 
of that process as well.
    Mr. Porter. Finally along this line, the Lederberg panel 
recommended that the Fogarty Center should take a more active 
role with the National Library of Medicine in exploiting 
contemporary methods of communication to facilitate 
international science. In what ways have you observed the 
Internet changing international research communication?
    Dr. Schambra. Well, clearly, this has been perhaps one of 
the most profound technical developments, even aside from the 
international aspects, in terms of communication between 
scientists. But now, when scientists can communicate with 
relative ease and relatively low expense over long distances, 
it brings a whole new perspective to the meaning of 
international collaboration.
    It is one of the topics that we again, I'm pleased to say, 
identified in our long-range plan as one that needs much closer 
analysis to see how it would, in fact, change the way we would 
go about supporting and conducting and encouraging 
international scientific collaboration.
    I'm very pleased that Dr. Lindberg invited me to be a 
member of a planning panel, chaired by Dr. Donald Frederickson, 
and on which Dr. Lederberg also sits, to look at the future 
international activities of the Library, and through that and 
subsequent discussions we hope to develop a joint approach to 
addressing exactly this question.

                     human frontier science program

    Mr. Porter. Dr. Schambra, the Human Frontier Science 
Program is an effort to encourage global science collaborations 
funded mostly by the Japanese government. Is the Fogarty Center 
involved in this project?
    Dr. Schambra. To the tune of a half a million dollars a 
year we are, which is currently a third of the NIHcontribution 
to that program.
    Mr. Porter. Should your resources be used--well, I guess 
you're saying yes.
    Dr. Schambra. I was going to say that also, in fact our 
involvement has been much more than that. That was sort of a 
flip answer.
    But when the program was first discussed among the various 
governments, following the proposal by the Japanese Prime 
Minister in 1987, the Fogarty Center, on behalf of NIH, played 
a leading role in developing the concept of the program and the 
mechanisms through which it would operate. And in fact, 
assisted them in setting up a grants program modeled very much 
along the lines of NIH's.
    We're certainly pleased to see the program prosper and 
grow, because we, the United States, have been the principal or 
predominant beneficiaries of the program. The decision for the 
Fogarty Center to contribute half a million dollars, I think it 
was made by the leadership of NIH. I have no argument with it. 
Because I think it's a very, excellent program and it ought to 
be supported in one fashion or another. And whether it comes 
from our budget or collectively from the Institutes, I think is 
an administrative judgment.
    Mr. Porter. Are there other similar programs funded outside 
of Fogarty and NIH that provide resources for international 
research collaboration?
    Dr. Schambra. Outside Fogarty and outside NIH, the answer 
is yes. I would say that probably every agency in the Public 
Health Service, in this Department, has an international office 
and is involved to a greater or lesser extent in international 
scientific collaboration.
    Every Department of the Government has a strong 
international presence and office. I would say that there are 
very few of them that have a direct appropriation to support 
international scientific collaboration, but would have to 
depend on funds that are appropriated to other components of 
the agency, for the most part.

                 former soviet union--state of science

    Mr. Porter. What is your assessment of the state of 
scientific enterprise in the former Soviet Union? From press 
reports, it sounds like a massive brain drain is occurring as 
government funding for science there evaporates.
    Dr. Schambra. Well, I think that's a very pertinent and 
very serious question for the Russians these days. There's no 
question that the state of science all told in the former 
Soviet Union is in a state of near disaster. It's a question of 
funds being made available to pay a payroll, it's funds being 
made available to keep the electric power on and the heating on 
in facilities, to buy supplies and reagents.
    I think that one of the things that we have been able to do 
and do very quickly through the appropriation of the Fogarty 
Center some years ago, in fact, was to provide small grants 
that were given to American scientists who wanted to 
collaborate with known competent Russian scientists, and help 
them through a period of time until other sources of funding 
could come to their support. George Soros, in the private 
sector, for example, the National Science Foundation, and other 
sources in the European Community as well.
    It is indeed a constant matter of concern that Russian 
science not disintegrate. Because there is a great deal of good 
science and good potential in the future. We just want to make 
sure that it goes into useful purposes.
    Mr. Porter. Are you training Russian scientists now as part 
of your program?
    Dr. Schambra. Yes, as part of our program, speaking very 
broadly, for NIH, we have about, I think six, they're number 
six in the order of countries with scientists in the NIH 
intramural research program. I think at the last count there 
are somewhere between 130 and 150 Russian scientists working in 
the intramural program at NIH.
    Mr. Porter. The problem is when they return, where do they 
get the resources to pursue any kind of research at home?
    Dr. Schambra. That is a concern. And one of the ways that 
they would get resources is through the Fogarty International 
Research Collaboration Award program, the FIRCA program. We 
have this program now, I believe it's in its fourth year, it 
started out as a program specifically focused on developing 
relations with Latin American scientists, but then when the 
opportunity arose in the former Soviet Union and Eastern 
Europe, it was made available to them as well.
    These grants, while given to American researchers who want 
to collaborate with Russian researchers, are intended to 
provide support principally for the foreign scientists, the 
Russian scientists, in the form of the types of materials, the 
types of supplies that he or she would need to conduct 
research, to travel and stay in contact with their American or 
foreign colleagues.
    Mr. Porter. Maybe in their case, for the short term, we 
ought to encourage them to stay here, the good ones.
    Dr. Schambra. Better here than some other places in the 
world.

                          biodiversity program

    Mr. Porter. Your budget justification states that a 
significant percentage of most prescribed drugs, such as 
antibiotics, have their origin in natural products. We are 
familiar with the cancer drug, taxol, which comes from the 
Pacific yew. But what are some other examples?
    Dr. Schambra. In fact, just to provide an overall figure, 
I'm not sure that I could provide the names of the prescription 
compounds, but our latest studies show that something like 57 
percent of the most commonly prescribed drugs in the United 
States today come originally from natural compounds. Quinine is 
originally from a natural compound, aspirin is from a natural 
compound. The rosy periwinkle, which was discovered in 
Madagascar, provides vincristine and vinblastine, which is a 
very effective treatment for certain types of cancer.
    Dr. Kirchstein. You may remember that many of the 
antibiotics came from fungi; penicillin was originally bread 
mold, streptomycin is from a fungus that was discovered in New 
Jersey many, many years ago. So large numbers of them came, 
many of them have not been synthesized and had custom designing 
done to them. But the source is there.
    Mr. Porter. How much funding does your budget include for 
the biodiversity program? How much is spent on this effort 
throughout NIH by other institutes like Cancer, which has a 
substantial drug testing program for natural products?
    Dr. Schambra. To answer your latter question, in fact, we 
did a survey when we began our biodiversity cooperative group's 
program several years ago. I think at that time we found out 
that there were 12 Institutes, about half of the Institutes at 
NIH, were involved in developing pharmaceuticals from natural 
products for their particular purposes. I think the total 
dollar amount was about $60 million. And a third of that 
represented the Cancer Institute.
    As far as our international biodiversity program is 
concerned, Mr. Porter, that is funded currently at the total 
level of $2.5 million a year, of which about $1.5 million comes 
in a direct appropriation to the Fogarty Center. And as you 
know, the remaining amount comes from other Institutes at NIH, 
Allergy and Infectious Diseases Institute, the Heart Institute, 
the Cancer Institute, from the National Science Foundation and 
at one time from the Agency for International Development. And 
we haven't given up trying to attract them back to that program 
when it's up for renewal.
    [Clerk's note.--Later corrected to ``$1.3 million'']
    Mr. Porter. Well, if we give them some resources, they 
could participate.
    Dr. Schambra. That's right.
    Mr. Porter. Some of the drug companies are participating in 
your biodiversity program. How much do they invest in this on 
their own each year, independent of the Fogarty program?
    Dr. Schambra. We've estimated that to date, they have 
invested in kind or in cash probably about $1.5 million in 
total that we can clearly identify.
    Mr. Porter. How does the technology transfer aspect of your 
biodiversity program work? Do you sell licenses to drug 
companies to develop the substances identified by the Fogarty 
research? And is this a source of royalty income for NIH?
    Dr. Schambra. The way the program works is through five 
cooperative agreements, which are neither contracts nor grants, 
but something in between. They fall under the provisions of the 
Bayh-Dole Act, in which any intellectual property developed 
under those agreements belongs to the grantee.
    Between the grantees themselves, where there is a 
university component, probably an academic component, and an 
industrial component, they will have developed among themselves 
an agreement for revenue sharing or income sharing for any 
product that arises.
    I might mention incidentally that in my opening remarks, I 
commented that we have about 3,000 samples that have been 
investigated for their pharmacologically active properties. 
Twenty-five of those have shown real promise and are in further 
tests right now. And we have one that has proceeded to the 
stage of applying for a patent.
    Mr. Porter. You tested 3,000 natural substances in two 
years. How many acres of rain forest are lost to development 
each day, and at the current pace, will you lose the race 
against deforestation before you can test the unique substances 
these forests contain?
    Dr. Schambra. That's a very good, hotly debated question. I 
think that one hears a wide range of answers to the question of 
how much are we losing on a daily basis.
    Let me try to answer it from the point of view of 
biological species, many of which, in fact, probably most of 
the undiscovered species are found in these tropical rain 
forests. It's estimated that there are somewhere between 10 
million and 30 million species of various diversity around the 
world. Of that number, perhaps 10 percent are known to science, 
of that total number of 10 million to 30 million species, only 
1 percent or less have actually been explored for their 
pharmaceutical potential.
    It's estimated that in the next 30 years, that we could 
lose as much as 20 percent of the planet's biological diversity 
at the rate that it is disappearing today. I think that will 
give you a sense of how quickly the rain forests and other 
natural environments are disappearing as well.
    Mr. Porter. And even our ability to clone won't help this?
    Dr. Schambra. That's right. [Laughter.]
    Mr. Porter. Dr. Schambra, thank you very much, both for 
your good testimony this afternoon, for your very direct 
answers to our questions and for the excellent job you're doing 
at the Fogarty International Center. We thank you, sir.
    Dr. Schambra. Thank you very much, Mr. Porter.
    Incidentally, before we close, if I might give you one of 
the tangible products that has come from our international 
biodiversity program, it is a publication on biodiversity and 
human health that reflects the proceedings of a symposium that 
we ran in conjunction with the Smithsonian Institution. I think 
that you might find it very interesting reading. It makes the 
case very cogently for the importance of the relationship 
between biodiversity and human health and the health of all.
    Mr. Porter. Thank you very much. If it's informational, I 
can receive it under House rules.
    Dr. Schambra. Strictly informational, sir.
    Mr. Porter. Thank you, Dr. Schambra.
    The subcommittee will stand in recess until 10:00 a.m. 
tomorrow.
    [The following questions were submitted to be answered for 
the record.]

[Pages 1458 - 1489--The official Committee record contains additional material here.]

                               ----------

                                           Thursday, March 6, 1997.

 NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

                               WITNESSES

DR. STEPHEN I. KATZ, DIRECTOR
DR. STEVEN J. HAUSMAN, DEPUTY DIRECTOR
MARGARET S. KERZA-KWIATECKI, EXECUTIVE OFFICER
ROBYN J. STRACHAN, BUDGET OFFICER
DR. HAROLD VARMUS, DIRECTOR, NIH
DENNIS WILLIAMS, DEPUTY ASSISTANT SECRETARY, BUDGET, DEPARTMENT OF 
    HEALTH AND HUMAN SERVICES

    Mr. Porter. The subcommittee will come to order.
    Before we begin this morning, I want to make everybody 
aware of a change in our hearing schedule. The hearing 
scheduled for tomorrow will be postponed until later in the 
month. The House is not in session tomorrow. And I want to be 
sure that all members will have the opportunity to be here and 
to hear the testimony of the Office of AIDS Research, the 
Office of the Director and the Buildings and Facilities. And so 
we will announce when that hearing will be scheduled. It will 
be later this month.
    This morning we want to welcome Dr. Stephen Katz, the 
Director of the National Institute of Arthritis and 
Musculoskeletal and Skin Diseases for his testimony. And Dr. 
Katz, if you would introduce the people at the table with you 
and then proceed with your statement.

                       Introduction of Witnesses

    Dr. Katz. Good morning, and thank you very much.
    I'm pleased to introduce Ms. Kerza-Kwiatecki, who is our 
Executive Officer; Ms. Robyn Strachan, who is our Budget 
Officer; Dr. Steve Hausman, who's the Deputy Director; and of 
course, Dr. Varmus and Mr. Williams.

                           Opening Statement

    I'm delighted and honored to appear before this committee. 
Our research areas cover many common and very chronic diseases 
that affect our joints, bones, muscles and skin, and compromise 
daily life for many Americans. I would like to share some of 
the progress made in our plans for seizing upon scientific 
opportunities in four areas: osteoarthritis, autoimmunity, skin 
cancer and osteoporosis.

                             osteoarthritis

    Osteoarthritis is the most prevalent disease of the joints. 
It is characterized by progressive degeneration of the 
cartilage, which results in pain and dysfunction. It can affect 
any joint, but most commonly affects the hip or the knee joint. 
It takes a staggering toll in human suffering and economic 
costs. Osteoarthritis and related disorders account for more 
than half of all of the total hip replacements and over 85 
percent of all the total knee replacements that are done in 
this country.
    It is predicted that osteoarthritis will affect 70 percent 
of our over age 65 group in our country, an astounding number 
of Americans. We've developed a multi-pronged approach to 
osteoarthritis in terms of the research agenda. Recent research 
results have provided some important clues to help understand 
and develop new strategies or innovative strategies to the 
prevention and treatment of osteoarthritis, and also to the 
basic understanding of osteoarthritis.
    Highlights during this last year include finding that a 
normal cellular component, nitric oxide, can affect cartilage 
cells. Cartilage cells are the cells that line the joints. It 
can affect it in many ways. It can affect how it produces 
certain of its products. It can also kill these cells. By 
killing these cells, and not having any replacement for these 
cells, there's nothing left of the cartilage. So nitric oxide, 
from many different studies that have been reported this year, 
has been a central focus for many different laboratories as a 
potentially important molecule to look at as far as its causing 
destruction.
    Laboratory studies have supported these findings in that, 
if one takes antioxidants and uses antioxidants like vitamin C, 
vitamin E, beta carotene, in a test tube you can reverse some 
of these effects. Amplifying these findings, there are recent 
reports indicating that dietary factors, particularly 
antioxidants like vitamin C, may play an important role in the 
treatment of osteoarthritis of the knee. And we do have some 
preliminary clinical studies that have recently been reported.

                        total joint replacement

    A major advance also in the treatment of osteoarthritis is 
of course total joint replacement, in which damaged joint 
surfaces are replaced with metal and/or plastic components. 
These joint replacement procedures have generally been regarded 
as a very effective means of reducing pain and functional 
limitation associated with severe osteoarthritis. A NIAMS 
supported study verified the cost-effectiveness of total hip 
replacement.
    So if one takes a 60-year-old woman who needs total hip 
replacement, gets total hip replacement, over a 20-year period 
there is a cost savings of $117,000, just for medical costs. 
That has nothing to do with quality of life, and of course, 
quality of life is markedly improved in that she can then care 
for herself.
    Total joint replacements, however, are not without their 
problems, including concerns for the effect of the implant on 
the body. There is concern that a patient may develop 
osteolysis. Osteolysis is the disappearance of bone around the 
implant. And we are particularly interested in understanding 
why that happens. Because once it happens, it's very hard to do 
a second implant. The revision surgery becomes very, very 
expensive.
    We're also exploring the utility of non-surgical approaches 
to osteoarthritis. Since previous studiesindicated that certain 
antibiotics, such as doxycycline, inhibit the enzymes that are produced 
within the joint which destroy the cartilage, we are co-sponsoring an 
ongoing clinical trial on the effects of the antibiotic doxycycline on 
osteoarthritis. And I look forward to reporting progress about these 
studies to you next year.

                            genetic studies

    As you've heard in prior testimony during this past week, 
genetic studies have provided important insights in many areas 
of medicine. The same is true for us in the area of 
autoimmunity, that is, in lupus erythematosus and rheumatoid 
arthritis, as well as in skin cancer.

                      systemic lupus erythematosus

    In lupus, very recently UCLA scientists have provided the 
first evidence linking a particular chromosomal region to lupus 
susceptibility. This is a particularly important finding, 
because it's found across all ethnic groups, that is, in 
African-Americans, in Asians, and Caucasians. This should 
facilitate identifying the specific gene involved, and from 
there, the even more difficult step will be pursued, and that 
is, identifying the function of the gene.

                          rheumatoid arthritis

    This knowledge may open up new ideas regarding treatment or 
even prevention strategies. The same types of advances have 
been made in our intramural research program in rheumatoid 
arthritis. In this case, the genes have been identified in 
animal models rather than human beings. These animal models 
with rheumatoid arthritis show that susceptibility and severity 
is associated with certain gene types.
    I should say that we have made a major commitment to 
identifying susceptibility genes in lupus and in rheumatoid 
arthritis patients through various consortia that have been 
organized by extramural scientists since these studies require 
large numbers of patients and particularly important, families, 
to look at.

                              skin cancer

    Also in the area of gene study, in the skin cancer called 
basal cell carcinoma, which is the most common form of human 
cancer, scientists this year have discovered that there are 
mutations in the human version of a gene that has its analog in 
fruit flies. And it was the gene that was first identified in 
fruit flies that now has translated to our knowledge of human 
disease.
    This gene is thought to be important for controlling cell 
growth. And with the mutation of this gene, there is no longer 
control of cell growth. These studies were initially identified 
in a very rare disease, very, very rare disease that probably 
doesn't occur in a thousand people in the country. But these 
findings are now extrapolatable to the very common form of 
basal cell carcinoma, and should provide us with a better 
understanding of the molecular basis of these diseases, and 
potential new approaches to therapy.

                              osteoporosis

    Finally, I want to say a few words about new findings in 
osteoporosis, the leading cause of bone fractures. The clinical 
activity and mechanism of action of estrogens, which are 
important determinants in bone integrity in women, have been a 
major focus of our Institute's supported research. Since not 
all women are suitable candidates for estrogen replacement, it 
is important to determine the mechanism of estrogen action and 
determine alternative therapies. The effects of estrogen are 
complex, but there is much to be learned about the biochemical 
pathways through which they act.
    In recent research results, investigators have shown that 
estrogen induces death in the cells that actually break down 
bone. As you know, bone is a dynamic process, it's being broken 
down all the time, it's being built up all the time, and it's 
being broken down by cells called osteoclasts. And recent 
studies have demonstrated that estrogen and also estrogen 
analogs have an effect on these osteoclasts. They may produce 
premature death in the osteoclasts, which breaks down bone, and 
as a consequence, the buildup is much better. So that's one of 
the mechanisms by which estrogen produces good bone.
    These findings should provide us with new information on 
not only estrogen but also other drugs that may be used to 
produce the same types of effects.
    In conclusion, let me say that significant strides have 
been made in our understanding of diseases of bone, joints, 
muscles and skin. I am confident that the initiatives I have 
shared with you will do much to advance our knowledge of 
fundamental life processes and how they go awry in disease. 
Diseases that affect these tissues have the capacity to 
profoundly alter quality of life. The goal remains as always to 
improve the health of the American public, to reduce the burden 
of disease, and to enrich the quality of life of all Americans.

                         fy 1998 budget request

    The budget request for NIAMS for fiscal year 1998 is 
$258,932,000. I would be pleased to answer any questions you 
might have.
    [The prepared statement follows:]

[Pages 1495 - 1498--The official Committee record contains additional material here.]


    Mr. Porter. Dr. Katz, we're going to have to stand in 
recess because of a vote on the House Floor, so I'll leave you 
with a thought that you can ponder, your answer to my usual 
first question, what would you really like to have, rather than 
2.4 percent. And the subcommittee will stand in recess until I 
return.
    [Recess.]
    Mr. Bonilla [assuming chair]. Dr. Katz, I ran into Mr. 
Porter on the way out and he said to go ahead and begin 
questioning.
    Dr. Katz. Thank you.
    Mr. Bonilla. I did review your testimony in advance, and 
I'm sorry I wasn't here to actually hear you.
    But the committee will now resume order, and I'd like to 
ask you a couple of questions, if I can.
    Dr. Katz. Of course.

                       repetitive motion injuries

    Mr. Bonilla. Last year, Dr. Katz, you testified before this 
committee that there were important questions that remain 
unanswered about the causes of and preventive measures for 
repetitive motion injuries. Since your testimony last year, 
have we learned any more about the causes of these injuries?
    Dr. Katz. Yes. We are constantly learning more. At the 
National Institute of Arthritis and Musculoskeletal and Skin 
Diseases, we are supporting a broadarray of studies in terms of 
repetitive motion injuries that are looking at very molecular as well 
as clinical studies.
    So for example, in carpal tunnel syndrome, we've learned 
from a study in Boston the effect of certain types of surgery 
in terms of producing trigger fingers, which are often produced 
in carpal tunnel syndrome. We've learned that this type of 
surgical procedure is beneficial in patients with carpal tunnel 
syndrome. We have also learned since last year that certain 
types of repetitive injury, for example, thrust injury, can 
produce certain types of molecular changes in cellular 
components.
    So we're constantly learning more about repetitive motion 
disorders. We are supporting a broad portfolio of research that 
goes from the very fundamental to the clinical.
    Mr. Bonilla. You touched on a couple of specific causes and 
effects that result in injuries. Are the causes of these 
disorders clearly identified and quantitatively related to 
their occurrence? You touched on that and gave a couple of 
examples, but if you would elaborate a little bit more, I would 
appreciate it.
    Dr. Katz. In certain industries where there is repetition 
and high force and awkward posture, it is thought that there is 
very good evidence that there is association between repetitive 
motion disorders, which affect mainly upper extremities, from 
the wrists to the elbows to the tendons to the carpal tunnel 
syndrome, to the tension neck syndrome, all of that related to 
repetitive motion, and sometimes low back pain is thought to be 
due to repetitive motion.
    So in those industries, such as the meat and poultry 
industry or automobile manufacturing, where there is repetitive 
motion and also in data entry and computers, it is thought that 
there is an association between repetitive motion disorders and 
repetitive motion injury.
    Mr. Bonilla. Is it fair to say, Dr. Katz, that we need 
additional research before we can answer the fundamental 
questions about what causes both upper and lower body extremity 
complaints, and what measures we can use to manage and prevent 
them? I understand we're making progress, but do we have a long 
way to go?
    Dr. Katz. We are making progress as a consequence of a 
joint conference in 1994 that we supported along with the 
American Academy of Orthopedic Surgeons, and the National 
Institute of Occupational Safety and Health. As a consequence 
of recommendations from that conference, we have put out, or it 
will be out very shortly, a program announcement targeting many 
of the areas that you've talked about: in terms of learning, of 
gaining new information on the pathophysiology, that is the 
mechanisms involved in what these injuries are; the 
standardization of definition for disorders, identifying 
tissues that are injured, the nature of the injury, etc.; the 
diagnosis of the disorders; prospective studies of the value of 
functional capacity assessments, and predicting the successful 
return to work in patients who are affected; clinical studies 
to identify the optimal therapy; and the development of further 
delineation of ergonomic changes that are required in order to 
prevent these types of problems.
    Mr. Bonilla. There's a lot more to be done in the research 
area, based on this long list of questions that remain.
    Dr. Katz. There is a lot of research to be done.

                          ergonomics products

    Mr. Bonilla. I'd like to refer now to a recent Washington 
Post article on this subject. There's been a lot of conflicting 
information about so-called ergonomic products. You've probably 
seen some of those on the market that claim to do one thing, 
but you're not really sure what they can do when you wind up 
buying them and putting them in your home or office. Last 
week's Washington Post had an article about how confusing this 
information is for consumers. In particular, there seems to be 
a debate about keyboard design.
    What, in your view, Dr. Katz, is the state of the art 
regarding knowledge about the optimal design for a keyboard 
that would minimize an individual's risk of developing 
repetitive motion complaints, such as carpal tunnel syndrome? 
Are there other equally or more important factors that could 
contribute to that risk? If so, what are they, and can we 
distinguish among these causes as to their relative 
contribution to a specific individual's complaint?
    Dr. Katz. That's a difficult question for me to answer, 
because I'm not an expert in that particular area. In terms of 
the design of keyboards, I would have to leave that to the 
ergonomics experts.
    Mr. Bonilla. And there are ergonomic experts out there, 
Doctor?
    Dr. Katz. There are said to be ergonomics experts.

                       musculoskeletal disorders

    Mr. Bonilla. Who are some of the leading researchers in the 
field of MSDs who have received grants from NIAMS, Dr. Katz, 
and how are they selected?
    Dr. Katz. They're selected through a peer review process. 
Some of our experts on musculoskeletal disorders, when it comes 
to repetitive motion disorders, are supported through our 
centers program. We have a centers program in Boston, that is, 
at Harvard Medical School. Jeffrey Katz--no relationship--has a 
part of that project, and he is looking at the carpal tunnel 
syndrome. He's looking at all aspects of carpal tunnel 
syndrome, looking at outcomes of treatment, and also looking at 
studying the person's attitude towards work in terms of its 
effect on return to work from carpal tunnel syndrome.
    Other people around the country are also working on it. 
There are actually in some of our other centers, people who are 
looking at various aspects of carpal tunnel syndrome on a 
molecular basis. The names specifically, actually I can give 
you, if you give me one second. We do have a portfolio in that 
area.
    Mr. Bonilla. I only have about 10 minutes to go, Mr. 
Chairman--I'm kidding. [Laughter.]
    Dr. Katz. Let me give you a sense of what the people are 
doing in this area. Dr. Arthur Veis is an expert in the 
structure and assembly of collagen molecules and fibrils, and 
the project is being supported to understand the basic events 
involved in the formation of the supporting tissue in the body. 
Dr. Evan Flatow is supported on a career award to study the 
pathobiology of rotator cuff tendon injury. In other words, all 
of the injury of the rotator cuff is in the upper extremity, 
and all of these--tendonitis, rotator cuff injury--are thought 
to be related to this area.
    Arthur Olenick is an investigator at one of our centers. He 
is looking at the long-term goals of describing the 
epidemiology of musculoskeletal disorders in the State of 
Michigan,characterizing the resulting disability and to assess 
the role of various risk factors, that is, gender, age, source of 
injury, industry, occupation, etc. Dr. Julia Fawcett is looking at the 
disability of carpal tunnel syndrome. She's an investigator at one of 
our centers as well.
    I've already talked about the studies at Harvard, the 
outcomes of therapy for carpal tunnel syndrome, which 
investigators are looking at as a part of a centers project--
Drs. Vogel, Burke, Baines, and there are many others whom we 
are supporting through various mechanisms in the Institute.
    Now, how we make those decisions was the last part of your 
question. We make those decisions through the peer review 
process. Many of these grants are for research project grants 
which are submitted and reviewed by our Division of Research 
Grants study sections. They're given a high priority score and 
are consequently funded, because we think these are important 
areas of research to pursue.
    Mr. Bonilla. What studies does NIAMS currently have 
underway that could shed light on the issue of the cause or 
prevention of RMIs or MSDs, and when will those studies be 
completed? If no studies are underway, are there plans to 
initiate such studies? Is this an important avenue of research 
for NIAMS, or should it be, if it's not currently?
    Dr. Katz. Well, it is an important area, and that's the 
reason why we're putting out this program announcement. If it 
were not an important area for study, we wouldn't have 
supported and co-sponsored the meeting in 1994 on repetitive 
motion disorders. So we view it as a very important component 
of our work. We have recently hired an orthopedic surgeon who 
is in charge of our orthopedics program. And he interacts with 
NIOSH in terms of letting them know what we are doing in the 
way of this type of research.

                          ergonomic standards

    Mr. Bonilla. Thank you. As you know, Dr. Katz, I'm asking a 
lot of questions about this, because it's a question that we 
all have about ergonomics standards. I am willing to consider 
turning the entire issue over to science to look at perhaps 
developing some standards for workplaces down the road. My 
concern is that we're not at the point yet where science 
supports promulgating rules or standards by OSHA or any other 
regulatory body. And I just want to make sure that it's the 
scientists and the people who are experts at it that are 
involved, as opposed to anyone else who just may think they 
understand the issue and really don't understand it.
    Dr. Katz. I should tell you that my understanding is that 
NIOSH has recently done a comprehensive study, what's called a 
meta-analysis, in other words, an analysis of many studies. I 
have not seen the conclusion of that. But they have done that 
in order to assess what is the state of science in terms of the 
relationship with ergonomics.
    So I look forward to that, and I'm sure that that will be 
transmitted to you as well.
    Mr. Bonilla. Do you know when that's going to be complete, 
or is it already complete?
    Dr. Katz. I think it's under review now.
    Mr. Bonilla. Okay.
    Dr. Katz. I am in contact with Dr. Rosenstock, and she told 
me that it was under review now. So it shouldn't be too long.
    Mr. Bonilla. Thank you, Dr. Katz.
    Dr. Katz. Thank you.

                             human cloning

    Mr. Porter [resuming chair]. Thank you, Mr. Bonilla.
    Before I begin with questions for Dr. Katz, I want to ask a 
question of Dr. Varmus. I understand, Dr. Varmus, that over on 
the Senate side, Senator Frist is going to have Ian Wilmot in 
next week to testify from Scotland. I think we're going to be 
embroiled in this over a long period of time.
    But I want to give you an opportunity to clarify your 
remarks yesterday to the Science Committee about human cloning. 
Last week, before this subcommittee, you stated you found the 
notion of human cloning to be repugnant. You also cautioned 
against rapid legislative action before the scientific and 
ethical issues involved were thoroughly considered.
    From press reports yesterday, you reiterated your concern 
about precipitous legislation, but also opened the door to the 
possibility there might be some very limited circumstances in 
which human cloning would be ethically permissible. You cited 
as an example untreatable infertility in couples intent on 
having genetically related offspring. I think that particular 
circumstance is one that many people would include in your 
characterization as being repugnant.
    Did the Washington Post accurately report your comments 
before the Science Committee, and can you describe more fully 
what circumstances you feel might justify human cloning?
    Dr. Varmus. Mr. Porter, let me try to outline what I said 
and what I intended to say. My personal view is that there is a 
very clear case to be made against the use of human cloning for 
research purposes. I have an open mind about the possibility 
that in the minds of some, that's not myself, but in the minds 
of some, there might be a utility for the technology in certain 
very limited situations of reproductive incapacity.
    I don't presume to make a judgment. I haven't taken a stand 
on this. But I do feel that we have time for a debate in which 
all sides can be heard to address the issue. As I pointed out 
yesterday, my personal bias in situations of profound 
infertility is that there are other options, the most obvious 
being adoption or in vitro fertilization, in which, for 
example, a sperm donor's contribution replaces the contribution 
from the parent.
    I also think it's very important, as I tried to point out 
yesterday, to use this occasion to come to grips with what I 
perceive to be an excessive devotion to the idea of the gene, 
perhaps an idea that we as scientists, excited about genetics 
research, have fostered in public discussions. We ought to be 
more concerned with passing on our principles than passing on 
our genes.
    In the context of the family life, experience that 
generates human beings is most importantly carried out. I'm 
concerned that our current obsession with genes is diverting us 
from the need to focus on the experience and the education and 
the instruction that is involved in raising children. That 
having been said, some people still desire very strongly to 
have what they consider their own children. I sometimes find it 
difficult to see my genes in my own children, perhaps because I 
haven't spent enough time educating them, I don't know. But the 
point is that we need to reflect on some of the historical 
precedents here, in two contexts. First, we need to remember 
that about 20 years ago or so, when in vitro fertilization was 
introduced, there was a high degree of abhorrence of the idea 
of test tube babies. And yet in vitro fertilization is now 
commonly accepted by virtually everyone as a reasonable course 
in situations oflow sperm count or other obstacles to having 
children by the most natural process.
    I think it's also important to remember these historical 
precedents of in vitro fertilization, of gene therapy, and of 
recombinant DNA, when considering whether it's appropriate to 
proceed to legislation. I worry about legislation in the 
context of scientific issues because of the possibility that we 
will create laws that are difficult to reverse before we have 
had the kind of discussion of other kinds of voluntary or rule-
determined regulation processes that we've achieved regarding 
other controversial areas of research, such as gene therapy and 
recombinant DNA.

                     human cloning for transplants

    Mr. Porter. Luckily, the founders of our country made our 
legislative system so cumbersome that it's very unlikely we 
pass anything very quickly in any case.
    I was going to follow up with a question, then I'll 
recognize you, Mr. Miller.
    Dr. Varmus, would there be a situation where you had a need 
for a transplant, like bone marrow transplant, where cloning 
would ensure that there would be no rejection of the tissue? Is 
there any possibility, or would that be a gene that's already 
damaged, and you wouldn't want to deal with anyway? I'm not 
sure how it would work.
    Dr. Varmus. Let me expand on that a little bit. When you 
and I discussed these issues last week, I pointed out that the 
excitement in the scientific community about the results 
reported from Dr. Wilmot's lab are especially exciting because 
those experiments tell us that there may be ways to, in a 
sense, reprogram the genes. It might be possible, by making use 
of what we learn from a deeper study of the observations that 
Dr. Wilmot has made, to design tissues required for medical 
uses.
    So, for example, a patient who needs a bone marrow 
transplantation could conceivably, with a deeper understanding 
of those rules, receive a transplant in which the nucleus from 
some unaffected cell perhaps a skin cell, has been transferred 
into some neutral recipient cell under conditions that would 
instruct the reconstructed cell to become the cells that would 
normally be present in the blood, recreating bone marrow, but 
bone marrow in which every cell has the surface antigens of the 
recipient. That would be an ideal match.
    Mr. Porter. You're creating bone marrow, not an individual?
    Dr. Varmus. That's correct. That's point number one. I 
don't think anybody would have any reservations about that, 
although I could imagine legislation that created a fence 
around research that would prevent the use of human DNA, for 
example, to do such experiments. That worries me.
    The second issue is one that I think many people have 
talked about as a possible situation in which human cloning 
would be acceptable. I myself have grave reservations, for 
reasons I'll mention in a minute. But one could imagine, for 
example, parents who had, say, a three-year-old child who had 
leukemia. The child might be under treatment, doing all right, 
but the parents anticipate a need for a bone marrow 
transplantation at some point.
    The parents might indeed be trying to have another child, 
and they might say, well, why don't we have a child who is 
compatible antigenically with the child we already have. In a 
sense, the parents might think, we are going to give to our 
three-year-old child a twin, three years later, that he 
unfortunately did not already have. There are some children 
with leukemia who have a twin and have the advantage of 
receiving a bone marrow transplant that offers very little risk 
to the recipient.
    But our child doesn't have such a twin. So let's have one. 
That new child will be different in the way it's brought up and 
will have different experience. It will be a different child. 
We must get beyond the fantasy that it will be an instant new 
three-year-old that looks identical to and acts exactly like 
the three-year-old the parents already have.
    I can imagine that. I think there are some profound issues 
raised by that kind of a decision to have children. It creates 
an expectation for the marrow donation that requires the 
newborn child to be a willing donor. And I think that's the 
kind of ethical issue that does need to be discussed.
    This is not dramatically different from an ethical issue 
that has already been considered, and that is the possibility 
of parents having another child who might have a one in four 
chance of being a histo-compatible donor to an already living 
ill child. It raises the stakes a bit, because now there isn't 
the roll of the dice--the child would have a totally compatible 
set of genes.
    Now, I hasten to add with all this that there are still 
many unknowns in cloning, even in animals. The fact that Dolly 
is alive has not told us all we need to know about the 
efficiency of the process, whether mutations might have 
occurred in that famous udder cell used as a donor; whether 
changes have occurred in chromosomal structure, particularly at 
the ends of chromosomes, that would affect the aging process. 
All of those are unknowns, and I think any contemplation of 
human cloning, even if there were to be agreed-upon rare 
circumstances in which it might be permissible, is still going 
to be many, many years off.
    Mr. Porter. And we don't yet know, because I understand 
that this was one out of 270 some odd attempts, whether this 
can be replicated. This may be just something that----
    Dr. Varmus. We don't know.
    Mr. Porter. We don't know yet.
    Dr. Varmus. There could be considerable variation among 
species, there may be technical advances that allow it to occur 
more efficiently. I think we're still in an extremely early 
phase.

                       position on human cloning

    Mr. Porter. Well, we'll call this, your example, a late 
twin example.
    My last question is, do you know yet what Ian Wilmot will 
say when he comes to testify before Senator Frist's committee? 
Is his position on human cloning----
    Dr. Varmus. I have not discussed it with him, but he is 
going to be visiting NIH next week. It turns out that he was 
invited by the National Institute of Child Health and Human 
Development many months ago, based on his earlier work, to come 
and speak at the NIH next Thursday.
    Mr. Porter. I bet there won't be much interest in that. 
[Laughter.]
    Dr. Varmus. Well, we decided to move it to a smaller room. 
[Laughter.]
    But I look forward to meeting him then.
    Mr. Porter. Thank you, Dr. Varmus.
    I yield to you, Mr. Miller.

                  president's actions on human cloning

    Mr. Miller. What was the President's Executive Order, what 
did he do the other day?
    Dr. Varmus. The President did two things. First, he issued 
an executive order that would make it impermissible touse 
Federal funds for human cloning. Now, as you and I know, the NIH is 
forbidden to use Federal funds for research that leads to the creation 
of human embryos including research that might lead to human cloning. 
So we could not do any research in this area.
    But the President and his advisors felt it was appropriate 
to make the ban very clear, applying to all agencies, and 
applying to any circumstance of human cloning, research or not, 
to reassure the public. I think this was a fair thing to do.
    I don't believe the Federal Government is or would be 
likely to support human cloning through any vehicle other than 
our Department, but I think it was definitely a reasonable 
thing to do, to provide public confidence that the Government 
is holding things in abeyance until the National Bioethics 
Advisory Commission can have a full debate on the issues.
    The other thing that he did was to ask for a voluntary 
moratorium on human cloning and research related to or 
involving human cloning in the private sector. I believe that 
the important issue was, again, to reassure the public that the 
biotechnology industry is not busily working in these areas.
    In fact, as you have no doubt observed, the biotechnology 
industry was highly supportive of the President's action, 
because it provides them an opportunity to say publicly that 
they are not even interested in doing such research, that their 
concerns are elsewhere. I don't think they wanted to be tainted 
with any public perception that they approve human cloning.
    Mr. Miller. What input did you or Dr. Collins have in those 
decisions?
    Dr. Varmus. We were involved in the discussions about how 
they should be carried out. And as you know, I was with the 
President, as was Secretary Shalala and Harold Shapiro from the 
National Bioethics Advisory Commission and Jack Gibbons from 
the Office of Science and Technology.
    Mr. Miller. Were you called in after the decision was made?
    Dr. Varmus. We were consulted throughout the few days 
before.
    Mr. Miller. I saw in the Post this morning, a front page 
article, a news analysis article, that mentions this. But it 
mentions it from a political perspective, which raises the 
question that, and Dick Morris even makes a comment, in the 
article, that the President is trying to do little things to 
distract the media attention away from his other problems, and 
doing things like he did in the campaign about talking about 
school uniforms.
    And Dick Morris' quote in this article is, well, ``the 
headline in the article is, `President forbids human cloning,' 
rather than what took place at the White House in the Lincoln 
Bedroom.'' It bothers him that decisions are being made for 
political reasons like this rather than the well thought-out 
type of policy decisions. That's what the inference of that 
article was, and I just raise that question.
    Dr. Varmus. I think there's good reason not to go along 
with that. I think, first of all, that by making 
pronouncements, the President appears before the press and 
opens himself to questions, some of which were about his 
pronouncement, and some which were about the other policy 
matters that you mentioned. So I think if he wanted to remove 
himself----
    Mr. Miller. I don't mean to put you in the political 
predicament, it raises the question that we want to have good 
policy on these types of things.
    Dr. Varmus. The President has a serious interest in these 
issues. He is very concerned about the public reassurance and 
the opportunity for his Commission to debate these questions in 
an open forum without the threat of pending experiments that 
would be repugnant to the public.

                      professional judgment budget

    Mr. Porter. Dr. Katz, question number one----
    Dr. Katz. Let's see, where were we? [Laughter.]
    Mr. Porter. I figured I could just say question one and 
you'd know what I was talking about.
    Dr. Katz. I got it.
    Mr. Porter. Professional judgment budget, or----
    Dr. Katz. I got it. Well, of course we do fund the very 
best that we think will yield important information in all 
areas. And we're constantly reprioritizing in terms of funding 
the best. We have many exciting and outstanding research 
proposals that we cannot fund. And our professional judgment 
budget would get us to the NIH average in terms of the success 
rate, with an amount of $280 million, which reflects a 9 
percent increase in our budget.
    Mr. Porter. And that is what Dennis Williams knocked down? 
[Laughter.]
    Dr. Katz. No, I wouldn't say that. I would say that 
discussions go on frequently with Dr. Varmus in terms of 
discussing our budget, our needs, the areas of emphasis that he 
talked about in his opening statement, that all of the 
Institute directors are addressing. They are broad areas of 
emphasis in which the budget is organized.
    Mr. Porter. My real question is, what was submitted by NIH 
to the Department for your Institute? Do you know that?
    Dr. Katz. I don't.
    Dr. Varmus. There was no submission by Institute, just one 
overall number.
    Mr. Porter. Just one number for NIH.
    Dr. Varmus. Initially.

                          antibiotic treatment

    Mr. Porter. All right. You mentioned doxycycline. It is 
destructive of what tissue or cells?
    Dr. Katz. Doxycycline is an antibiotic. So it destroys 
bacteria. But many of these chemicals have other effects. And 
it was shown some years ago that doxycycline has an effect on 
inhibiting certain types of enzymes, which are called 
collagenases. And that's the reason for the interest in 
doxycycline in osteoarthritis. One of the pathways to 
destruction of cartilage is thought to be due to enzymatic 
degradation of the cartilage cells, and doxycycline is thought 
to block this process. And it's been shown to be effective in a 
form of osteoarthritis in dogs. As a consequence, there was a 
proposal sent to us--a research project grant--which received a 
very high priority score, and that's why we funded it.
    Mr. Porter. And that is going on right now?
    Dr. Katz. That is going on right now.
    Mr. Porter. Dr. Katz, you weren't here then, but 15 years 
ago, almost before this subcommittee, was a Dr. Brown of 
Virginia who was doing exactly that. I don't know if 
doxycycline was the antibiotic of choice, but he was providing 
treatment to his patients, and we had his patients in here to 
testify, telling us that he had miraculously cured them after 
years of suffering.
    Dr. Katz. I think that was a different form of arthritis.
    Mr. Porter. Different form?
    Dr. Katz. That was for rheumatoid arthritis. And the basis 
of that treatment, as I understand it, was because it was 
thought to be a disease in which bacteria or some type of 
organism which was sensitive to an antibiotic, was part of the 
causative agent. So it's a completely different form of 
arthritis. And in fact, the Institute was asked a few years ago 
to do a study using doxycycline in rheumatoid arthritis. And 
such studies are going on right now. I will report those 
results to you when they come out.
    In rheumatoid arthritis, there are two main studies. One is 
in North Carolina, done by Dr. St. Clair, and the other is done 
within the clinical research center at NIH.
    Mr. Porter. My recollection is that the issue revolving 
around those studies is the question of time. Because if I 
remember, Dr. Brown's patients and Dr. Brown, who testified one 
year before the subcommittee, this was a long-term kind of 
treatment that lasted four or five years. Is your clinical 
trial lasting that long a time?
    Dr. Katz. No. The study that's going on now, the IV study, 
is a double-blinded study that's going on for 12 week periods. 
But there was another study that was requested by the Congress 
about seven years ago. This was a multicenter study using 
antibiotics, again in rheumatoid arthritis, different disease 
than osteoarthritis, to test an antibiotic for rheumatoid 
arthritis. And this is what we call the MIRA study, that is, 
minocycline in rheumatoid arthritis. That was a multicenter 
study that's been completed. It showed a very marginal benefit 
of minocycline, long-term, in patients with rheumatoid 
arthritis.
    Mr. Porter. But now you're finding that the antibiotics may 
work very well in osteoarthritis?
    Dr. Katz. In osteoarthritis, in the dog model, they have 
been shown to be effective. And we have no clue as to whether 
it will be, but we thought it was a very good scientific 
opportunity to pursue, since it does affect so many people and 
there is a good basis for those studies.
    Mr. Porter. Antibiotics are being tested as a treatment for 
both osteoporosis and osteoarthritis. Is there a common 
mechanism at work? Is it thought the antibiotics somehow 
inhibit the substances that degrade both bone and cartilage?
    Dr. Katz. I'm not familiar with the antibiotic studies in 
osteoporosis.
    Mr. Porter. It's over in the Aging Institute, my staff 
tells me.
    Dr. Katz. There is a study that was just started in 
osteoporosis, because there was a preliminary finding that was 
thought to be beneficial in terms of building up bone. So they 
are pursuing that. And I can't tell you which antibiotic it is.

                              osteoporosis

    Mr. Porter. We've heard testimony about osteoporosis, 
largely in the context of it being a women's disease. Your 
justification indicates that men also suffer from osteoporosis, 
and that one-third of all men will be affected by the age of 
75.
    Given the focus on estrogen as a treatment for osteoporosis 
in women, will entirely different treatment regimens be needed 
to be developed for male patients, or can estrogen be used 
there, too, and if so, what are the side effects?
    Dr. Katz. We know that history tells us that estrogens have 
been used in men, in older men, for prostate cancer. This was 
years ago. And there were many side effects from the estrogens.
    What we've done with this, through the Federal Working 
Group on Bone Diseases, which includes many of our NIH 
Institutes as well as 10 other Federal agencies, is we have put 
out a program announcement to study osteoporosis in men, 
because they do represent 20 percent of people who are 
affected. Men are about a decade or a decade and a half behind 
women in terms of osteoporosis. And through studies like those 
I talked about with regard to the role of estrogen in blocking 
osteoclasts, or in causing osteoclast death, we're looking for 
other agents that may be used that can simulate those findings, 
that can be used in men without having the other side effects 
that one gets, the feminization, etc.
    Also, there are forms of estrogen now that are being 
developed that have specificity for certain types of tissue. In 
other words, as opposed to current estrogens, which have an 
effect on all tissues, there are estrogens that are being 
developed that will specifically bind to receptors in bone, for 
example, rather than in breast tissue. And that's the goal for 
the future, in terms of developing more specific therapies. 
They may be called estrogens now, in the future they may be 
called something else.
    Mr. Porter. Does Shannon Lucid, the space shuttle 
astronaut, provide any lessons for osteoporosis researchers as 
her accelerated bone loss in space is analyzed and treated?
    Dr. Katz. I think she represents what many of the 
astronauts have taught us in terms of bone, in terms of 
weightlessness and loss of gravity, and in terms of the 
importance of load on bone formation. We have had cooperation 
with NASA for a long time in terms of co-sponsoring studies 
that look at just this question of bone loss and 
weightlessness. There are many studies now that have shown that 
certain types of exercise are very helpful in terms of building 
the integrity of bone.
    And I believe----
    Mr. Porter. Even at an advanced age?
    Dr. Katz. Yes. And I believe that she, as a consequence of 
some of these studies, rigorously exercised while she was in 
space, using some of these load concepts that have been 
developed through NASA and through the NIAMS and through other 
Institutes' research in this area.
    Mr. Porter. Mr. Miller, I yield to you.
    Mr. Miller. No questions, Mr. Chairman.
    Mr. Porter. Mrs. Lowey.

                              osteoporosis

    Mrs. Lowey. Thank you, Mr. Chairman. And I thank you, Dr. 
Katz, for appearing before us.
    I'd like to follow up on the osteoporosis question. We're 
aware that, as has been discussed, that osteoporosis is the 
leading cause of bone fractures in older women and older people 
in general. And while hormone replacement therapies can help 
women to gain bone mass and thereby decrease their risk for 
fractures, there is evidence that for some women, estrogen 
supplements can unfortunately increase their risk for breast 
cancer.
    What has your Institute learned that would help women to 
prevent osteoporosis so they could avoid the difficult choice 
about whether or not to take estrogen supplements, at least 
until more evidence about the risks of estrogen are known and 
perhaps you could also discuss any work that's being done 
concerning estrogen replacement therapy.
    I think what we find too often is that there are a great 
many questions involved, and women are puzzled because of the 
inadequate research concerning estrogen replacement therapy. 
And if there's a history of breast cancer in their family, this 
is not the direction that most choose to pursue.
    Dr. Katz. You've gotten to the real issue of the concern 
with regard to estrogen and osteoporosis. But there are other 
means that women and men have to reverse susceptibility to 
osteoporotic fractures. A recent study reported from Dr. Recker 
and Dr. Haney from Creighton University in Nebraska showed that 
if one adheres to an adequate dosage of calcium in patients who 
have already had one fracture, once you have one vertebral 
fracture, you're very likely to get another one within a very 
short amount of time--a calcium dosage of 1,500 milligrams per 
day would prevent a second fracture in a significant number of 
them.
    So that's one issue that's obviously being looked at. 
Another issue was one that I addressed in my opening statement, 
which is the interesting and important findings that open up 
many scientific opportunities with regard to understanding how 
estrogens work. Because once one understands how they work, one 
can try to devise other chemicals that will do the same thing.
    Estrogens recently have been demonstrated to cause death of 
the cells that actually break down bone. One has a constant 
breakdown and buildup of bone. If you can kill off the cells 
that are breaking down the bone and continue building up the 
bones, you're not going to have as much osteoporosis as long as 
the integrity of the bone is still good.
    And what these scientists have found is that estrogen will 
kill off these osteoclasts, which are the bone degrading cells. 
This provides us with an opportunity to look for other 
chemicals that will interfere with the osteoclast formation and 
get the beneficial effect of blocking the degradation of bone 
while continuing to get the buildup.
    So there are estrogens that are actually being developed 
that have been reported to have a specific effect on bone as an 
end organ as opposed to breast tissue. So all estrogen 
receptors are not exactly the same.
    There was a very good review in the New York Times this 
week in the science section, showing what companies are 
actually trying to do in terms of looking specifically at end 
organ effects of estrogens.

                          stress and arthritis

    Mrs. Lowey. Thank you. In this month's publication of the 
Arthritis Foundation, there is an article about the role of 
stress in arthritis. It points out that while many sufferers of 
arthritis believe stress plays a key role in their disease, 
researchers have had a difficult time substantiating a link, 
because stress is a difficult thing to measure. If stress is 
something that people can control, or at least try to control.
    Dr. Katz, can you please comment on whether or not you 
think that more research should be done on the link between 
stress and arthritis, either with regard to preventing the 
disease or treating the symptoms?
    Dr. Katz. I would say there have been many studies that 
have tried to address the issue of stress. Often it's the 
control group that's the difficult group to really compare the 
tested group to. It is clear, though, in rheumatoid arthritis 
in particular, that there is a certain empowerment of patients 
if they take control of their disease. There are studies that 
we have supported through educational programs, particularly 
the ones at Stanford from Kate Lorig, that have shown that 
patients who take charge and become more involved in their 
disease--obviously you can't do this if you're depressed with 
stress, but you can in other circumstances--have a much better 
outlook and a much better prognosis in terms of dealing with 
their rheumatoid arthritis.
    So clearly, one can, in a positive way, say there is 
something that one can do about one's symptoms and dysfunction 
from arthritis by taking charge of it.
    Mrs. Lowey. You're talking about dealing with the symptoms?
    Dr. Katz. Right.
    Mrs. Lowey. You're not relating it to the actual----
    Dr. Katz. To the actual cause and effect. Right.
    Mrs. Lowey. I know there are people that have worked with 
hypnotherapy and other forms of stress reduction, because they 
feel its impact. But again, you're talking about the symptoms?
    Dr. Katz. Right.

                        gender and autoimmunity

    Mrs. Lowey. You're not talking about the actual illness.
    We know that women are more likely than men to develop 
lupus and other autoimmune diseases. In your budget 
justification, you note that your Institute joined with several 
other Institutes at NIH to issue a program announcement 
inviting applications for basic research on the ways in which 
gender influences the development of autoimmune disease.
    What is the status of this endeavor? Did you receive many 
applications? How much money will be allocated to this 
research, and when will you begin to have research findings?
    Dr. Katz. As a consequence of a conference that was 
sponsored by several groups at the NIH, including the NIAID, 
the Office of Research on Women's Health, the Office of 
Research on Minority Health and the NIAMS, there was a program 
announcement in May of 1996, for soliciting studies on gender 
and autoimmunity. So far, we have not gotten much in the way of 
response to that program announcement. But we look forward to 
it. As you know, a program announcement is in existence for 
quite some time, and to get the community interested in looking 
at that, sometimes it takes some time.
    Mrs. Lowey. Thank you, Dr. Katz.
    Dr. Katz. Thank you.
    Mrs. Lowey. Thank you, Mr. Chairman.

                            cartilage repair

    Mr. Porter. Thank you, Mrs. Lowey.
    Dr. Katz, last month research findings were reported from 
the Mayo Clinic of a technique called biological resurfacing 
that successfully restored joint cartilage damaged in injuries, 
thus delaying the need for joint replacement. How wide an 
applicability does this technique have?
    Dr. Katz. Those studies from the Mayo Clinic are supported 
by our Institute, and are really just starting. There are many 
studies that we are supporting that are addressing this 
question. Cartilage is a tissue that when it's destroyed, it's 
not replenished like some of the other tissues, like liver 
that's replenished, like skin that's replenished. Once the 
cartilage is gone, it's gone.
    So we are supporting many studies that are looking to 
replenish the cartilage. There is a study from San Diego by Dr. 
Coutts who is looking at rib perichondrium. These are rabbit 
studies, as are the Mayo Clinic studies. They're taking the 
very superficial parts of a rib, the chondrocites, which are 
part of the cartilage, and they are transplanting them into 
specific injuries that are made in rabbits in the joints.
    The same is being done by Dr. Driscoll, I believe it is, at 
the Mayo Clinic, who is looking at the bone periosteum, that is 
the most superficial layer of bone. He thinks these cells may 
be precursors to cartilage cells. But these types of studies 
are really in their early stages, and I would say that the 
reason we are supporting them is because they offer a high 
likelihood of success in terms of resurfacing of cartilage.

                breast implants and autoimmune diseases

    Mr. Porter. Dr. Katz, the debate about the dangers of 
breast implants has been heated. Women who feel they have been 
injured by the implants often cite symptoms that fall within 
the jurisdiction of your Institute, autoimmune diseases such as 
lupus and scleroderma. On the other hand, the scientific 
evidence on breast implants is sometimes derided as junk 
science.
    What does your review of the evidence lead you to believe 
about the health impacts of breast implants?
    Dr. Katz. Well, there are several studies that have 
addressed this head-on. And our conclusion from all these 
studies is that there is no causal relationship between 
implants and well-defined rheumatic disease, that is, 
rheumatoid arthritis, lupus erythematosus or scleroderma.
    Despite that, there is a lingering doubt as to whether 
there is an association between silicone breast implants and an 
atypical or an undifferentiated form of rheumatic disease. 
Because of our concern about this lingering doubt, we have 
organized a round table discussion on April 17th, which is 
going to be chaired and paneled by people who have had no 
particular stance one way or the other. They are going to hear 
from the community of scientists and clinicians about this 
undifferentiated rheumatic disease and help us determine if 
there is anything that we can do to further elucidate whether 
there is an association.
    So we are addressing that issue head-on--the lingering 
doubt of atypical, undifferentiated or ill-defined rheumatic 
disease and whether it can in fact be defined. We utilize 
people from our Advisory Council, Dr. Arend, for example; from 
our Advisory Council, and people from the community who are 
good scientists, who are good clinicians, who can assess 
information for us as a panel.

                           gulf war syndrome

    Mr. Porter. Dr. Katz, we've discussed with the 
Environmental Health Sciences Institute the general scientific 
evidence related to Gulf War Syndrome. Has your Institute done 
any work on the particular symptoms of joint stiffness and pain 
and skin rashes to determine whether they are caused by 
exposures in the Gulf War?
    Dr. Katz. We have not addressed any studies on the Gulf War 
syndrome specifically. But many of the symptoms that are 
defined in the Gulf War syndrome, that is, cognitive 
disabilities, specific types of muscle and joint pains, and 
skin rashes, are a constant concern to us, because these cover 
many of the symptoms that we are concerned with within the 
Institute.
    And there is a disease, for instance, fibromyalgia, which 
is a now well-defined disease that has many of the symptoms 
that relate to some of the symptoms of Gulf War syndrome. And I 
think that from our activities in fibromyalgia--for example, 
from our workshop, from the support of many studies in 
fibromyalgia, from our recently held conference that I talked 
about in my Congressional justification statement on the 
neuroscience and endocrinology of fibromyalgia syndrome--
something may be learned about some of these symptoms that are 
said to be related to the Gulf War syndrome.
    So the symptoms, we are addressing those symptoms.

                      depression and osteoporosis

    Mr. Porter. Representative Lowey raised the question of 
stress. I've been interested in the ways that stress and 
emotional states may affect physical health as well. But even I 
wouldn't have expected the research finding from the Mental 
Health Institute linking depression to a significantreduction 
in bone mass in women. The average age of the women in the study was 
41. But they had bone loss equal to that of a 70 year old.
    What are the scientific explanations for why depression 
might lead to bone loss?
    Dr. Katz. That's a very interesting question. I think even 
in that paper, there were some speculations, but there was no 
cause and effect relationship. That is, there are two findings 
that may be true, true and unrelated, or they may be true, true 
and related. If they are related, theoretically they could be 
due to some neuroendocrine problem, or they could be due to the 
fact that people are not taking care of themselves in terms of 
being depressed--not eating properly. But that would just be 
all speculation on my part.
    Mr. Porter. Are you doing any studies in this area?
    Dr. Katz. We are not.

                      central nervous system lupus

    Mr. Porter. Two-thirds of patients with lupus are now 
thought to suffer some sort of brain or behavioral problems as 
result of the disease, in addition to the skin and joint 
ailments we more commonly associate with lupus. How does this 
autoimmune disorder affect the brain, and do physicians know 
how to treat this aspect of the disease?
    Dr. Katz. That's a very important question. I think that 
central nervous system lupus has been known for quite some 
time. In fact, I should tell you that one of the first patients 
whom I ever saw in the clinic had lupus erythematosus, and she 
had central nervous system lupus with coma at times.
    The mechanism by which the brain is affected is not known. 
It's undoubtedly related to the inflammation that occurs 
elsewhere, because virtually every organ system is involved in 
lupus. Organs can be involved as a target of autoimmunity, in 
other words, the cells of the body are attacking itself; this 
could happen in the kidney, in the brain, in the lungs, etc.
    So the mechanism of injury is presumably a similar 
mechanism as is found in other organ systems. I know that the 
American College of Rheumatology has discussed with our program 
director convening a conference that will address how to 
diagnose CNS lupus more specifically, number one, and number 
two, about a year and a half ago, we co-sponsored a meeting of 
the New York Academy of Sciences that directly addressed 
central nervous system lupus to direct attention by 
investigators to this important area.

                 fibrodysplasia ossificans progressiva

    Mr. Porter. Dr. Katz, Science magazine reported last August 
on the identification of a signalling protein that erroneously 
signals the formation of bone, causing a rare disease which 
converts soft connective tissues into bone, fusing the skeleton 
and leading to complete immobilization. There is apparently 
hope that a therapy may some day be developed to block the 
production of this protein. Beyond the small population of 
people affected with this disease, could this finding have 
implications in the opposite direction for those facing 
deterioration of bone through osteoporosis or other diseases?
    Dr. Katz. I think that's a very good example of how 
studying a very, very rare disease, fibrodysplasia ossificans 
progressiva--is that okay? [Laughter.]
    It's a disease that is studied by Dr. Kaplan at the 
University of Pennsylvania; he has really been the champion of 
the small number of patients who have this disease. And much of 
his research is supported by our Institute. But all of his 
research for years has had a focus on these patients, although 
he has not been able to directly develop any sorts of 
mechanisms related to this disease.
    And it's because of his long-term interest in studying 
what's called the bone morphogenetic proteins, that is, 
proteins that help produce bone, that he realized that in these 
patients, wherever they have inflammation, wherever these 
lymphocytes go to an inflamed area, the lymphocytes start 
producing bone.
    So understanding the mechanism for these patients, that's 
number one important, number two important is the potential of 
interfering with these bone morphogenetic proteins that are 
produced by T cells in areas of inflammation for these 
patients. But then as you say, one would like to convert these 
findings to some way of building bone.
    We know that the immune system and the blood system have a 
lot to do with bone, in terms of the precursors of bone 
producing cells found in the bone marrow.
    And in this regard, our Institute is sponsoring a workshop 
this summer on bone and the hematopoietic and the immune 
systems, to look at these particular points of the interaction 
between T cells and other cells of the immune system and of the 
bone system, and of the bone marrow with bone.
    So Dr. Kaplan's discovery is a very important advance in a 
very rare disease. It could have wide application.

                         collaborative research

    Mr. Porter. Perhaps more than most, you seem to coordinate 
with other Institutes on a whole host of disease areas. Allergy 
for autoimmune diseases, Cancer for skin cancer, Aging for 
osteoporosis, NIDDK for estrogen replacement, for example. When 
grant applications are received in these disease areas, how do 
you decide which Institute will fund them?
    Dr. Katz. The application is sent to the Division of 
Research Grants, which has well-defined criteria as to which 
Institute has a primary and which Institute has a secondary or 
tertiary interest in that particular area. So for example, when 
it comes to bone formation, in terms of NIDDK and NIAMS, when 
it involves endocrine factors like parathyroid hormone, usually 
NIDDK is given a primary designation for that type of research.
    When it comes to estrogen, we are often given the primary, 
because that is our particular focus. There are many institutes 
that have an interest in bone--The Dental Institute, Child 
Health--for example, many Institutes have an interest. And 
there is a Division of Research Grants guideline which the 
primary reviewer looks at and then makes the designation. Our 
program people will then look at that designation, if there's 
some sort of a mistake or controversy, then it is discussed.
    To the investigator this process is transparent; the 
investigator really doesn't care who funds that application, as 
long as it's funded. So it does make it transparent to the 
investigator.
    Mr. Porter. How often do you co-fund projects with other 
Institutes and how much funding do they contribute to 
activities that are part of your Institute's mission?
    Dr. Katz. We do a lot of that. In the fiscal year 1996, 
there was almost $2.5 million co-funded. And in the same year, 
we received in reimbursements from various Institutes and 
various offices within the Office of the Director about $3.8 
million. And this type of activity goes on because ofthe 
interactions between program staff and various offices.
    So for example, the Office of Research on Minority Health, 
John Ruffin's office, or the Office of Research on Women's 
Health, Vivian Pinn's office, we have a lot of interaction with 
them. They don't have authority to directly pay applications. 
There are many applications that we receive, in terms of areas 
of research on women's health and on minority health that they 
are interested in and we are interested in, so they will co-
fund many of those applications.
    Our total co-funding for 1996 was over $6 million. And this 
is really how we can work together, number one, and also make 
the dollars go much farther.
    Mr. Porter. Dr. Katz, you have answered all of our 
questions very well and forthrightly. We appreciate your 
testimony this morning. We particularly appreciate the 
excellent job you are doing at your Institute. And thank you 
very much for your appearance here.
    Dr. Katz. Thank you very much.
    Mr. Porter. Thank you, sir.
    The subcommittee will stand in recess.
    [The following questions were submitted to be answered for 
the record.]

[Pages 1517 - 1572--The official Committee record contains additional material here.]

                               ----------

                                           Thursday, March 6, 1997.

                 NATIONAL CENTER FOR RESEARCH RESOURCES

                               WITNESSES

DR. JUDITH L. VAITUKAITIS, DIRECTOR
DR. LOUISE E. RAMM, DEPUTY DIRECTOR
DR. DOV JARON, ASSOCIATE DIRECTOR FOR BIOMEDICAL TECHNOLOGY
ANNE E. SUMMERS, BUDGET OFFICER
DR. HAROLD VARMUS, M.D., DIRECTOR, NIH
DENNIS P. WILLIAMS, DEPUTY ASSISTANT SECRETARY, BUDGET, DHHS

    Mr. Porter. The subcommittee will come to order.
    We are pleased to welcome Dr. Judith Vaitukaitis, Director 
of the National Center for Research Resources, and we apologize 
to you for all these votes, but there isn't much we can do 
about them.
    I am able to stay until 12:30, and we'll just do our best 
to get as far as we can.
    Dr. Vaitukaitis. Certainly.
    For the record, I will submit my opening statement----
    Mr. Porter. I think I would prefer hearing your oral 
summary, at least, if you would like to do that.

                       Introduction of Witnesses

    Dr. Vaitukaitis. Okay, fine.
    Before I do that, I would like to introduce Dr. Dov Jaron, 
farthest down to my left, who is the Associate Director for 
Biomedical Technology; to my immediate left is Anne Summers, 
our Budget Officer; on my immediate right is Dr. Louise Ramm, 
who is our Deputy Director; and, of course, Dr. Varmus, and Mr. 
Williams from the Department.

                           Opening Statement

    Mr. Chairman, it is a pleasure to appear before you today 
on behalf of the National Center for Research Resources in 
support of the fiscal year 1998 budget. NCRR has a unique 
responsibility for biomedical research infrastructure at the 
National Institutes of Health. That infrastructure can be 
compared to a great locomotive that transports passengers--in 
this case scientists, who explore disease and its remedies--
toward ever-changing destinations. Investigators depend on NCRR 
to create, develop, and provide the ``engine'' or 
infrastructure of modern science.
    In 1998, NCRR's programs will continue to foster 
development and access to critical research resources and tools 
ranging from those for clinical research, animals, 
repositories, and high-end biomedical technologies. In 
addition, NCRR will develop and continue an initiative that 
will focus on understanding the structure and function of the 
brain and its dynamic changes with time, the fourth dimension. 
That effort will lead to improved knowledge about 
neurodegenerative diseases, such as Parkinson's and 
Alzheimer's, as well as many others.
    Another initiative will focus on development of innovative 
software and techniques for use with high performance computers 
and telecommunications facilities to increase the number of 
biomedical technology resources and their applications that can 
be remotely accessed by investigators across the country over 
the next generation of the Internet. Magnetic resonance imaging 
resources and other imaging and modelling resources essential 
for structural biology are candidates for that kind of 
approach.
    In conjunction with the Regional Primate Research Centers, 
investigators will focus on the development of novelvaccines 
for AIDS. Studies that may pave the way for developing vaccines against 
HIV in humans were recently reported by scientists at the NCRR-
supported New England Regional Primate Research Center. Investigations 
with rhesus monkeys showed that vaccine protection against intravenous 
challenge with simian immunodeficiency virus, similar to its human 
counterpart, could be attained with live attenuated vaccine from which 
certain viral genes had been deleted. These and other related efforts 
will be extended to help identify an effective vaccine for HIV.
    There are several other priorities that are outlined in our 
justification and in our longer opening statement.
    Now, Mr. Chairman, the fiscal year 1998 President's budget 
request for NCRR is $333,868,000. I would be happy to answer 
any questions you may have.
    [The opening statement follows:]

[Pages 1575 - 1578--The official Committee record contains additional material here.]


                       use of animals in research

    Mr. Porter. Thank you, Dr. Vaitukaitis.
    Contrary to the expectations of several years ago, will the 
use of vertebrate animals in research stay constant, or 
increase, because of genome research with its emphasis on 
knockout mice?
    Dr. Vaitukaitis. The use of transgenic and knockout mice 
has increased markedly over the past several years with the 
advent of that technology. The number of animals being used in 
research, based on USDA data, has stayed relatively level or 
decreased somewhat. The mice that are being used are much more 
complex and much more costly to develop, and are used to 
address specific questions that could not be addressed with 
other forms of animal models. So with the mouse models and 
other invertebrate and vertebrate models, the total use of all 
animals in research will probably continue to decline somewhat. 
The use of primates in research has been declining for the past 
several years because of the marked cost of holding these 
animals for investigators in specialized facilities.

                        chimpanzees in research

    Mr. Porter. That's my next question. We have been 
approached by groups who have developed draft legislation which 
they believe will resolve the problem of the long-term care of 
research chimpanzees who are no longer being used in research, 
but who have a life span of as much as 50 years. We understand 
that the National Research Council will soon issue a report on 
the subject.
    Do you have some idea of what they will recommend? And when 
do you expect NIH to develop a response to the report?
    Dr. Vaitukaitis. To answer the last question first, we are 
expecting the report from the National Research Council later 
this month. I will have to take a look at the scope of that 
report before we can know the timeframe it would take to 
develop a response.
    Chimpanzees in research is a complex issue, because in the 
wild there are only about 125,000 to 150,000 chimps, and in the 
U.S. there are about 2,100 chimps; of those, 400 are in zoos, 
and the remainder are used for biomedical research. In 1975, 
the U.S. Government signed an international treaty prohibiting 
the importation of chimpanzees, so consequently, since 1976, 
there have been no imported chimps.
    When the AIDS epidemic--or pandemic--raised its head in the 
1980s, the National Academy of Sciences did a study looking at 
the resource needs for addressing that whole area of research, 
and one of the recommendations from the National Academy was to 
provide chimpanzees to investigators for research, noting that 
the number of chimpanzees available was restricted. 
Consequently, the Division of Research Resources, a predecessor 
organization of NCRR, was directed to start a chimpanzee 
breeding program. Currently we have 538 chimpanzees in that 
breeding program. When it was begun, the animal rights people 
were concerned that the animals could not reproduce in 
captivity, and that their life span would be shortened. 
However, they were wrong on both counts. In captivity the 
chimpanzees live longer, for over 50 years, and they reproduce 
so well that we are now actually giving them contraceptives so 
that they will not breed, to try to keep the population that we 
have in our chimpanzee program constant.
    The cost of supporting these animals averages about $20 per 
day, per diem costs, and we maintain this breeding colony in 
the southern part of the United States, where costs are more 
favorable for that activity. There have been about 115 
chimpanzees used for vaccine research over the last several 
years, and about 145 or 150 animals used for HIV research.
    Now, the ones that have been used for HIV research are 
actually being used again for other HIV-related activities; 
just because an animal has been infected with HIV does not 
necessarily mean that that animal is permanently retired from 
research.
    So we have to look at this precious pool of animals, and 
it's a conundrum in terms of what to do with it. That's why we 
sought the advice of the National Research Council on this very 
important issue.
    Mr. Porter. Does your daily cost of caring for research 
chimpanzees--does that compute to a lifetime cost of $300,000 
to $400,000, as we've been led to believe?
    Dr. Vaitukaitis. Per animal? No. It's roughly, in current 
dollars, about $20 per day.
    Mr. Porter. They live 50 years, though.
    Dr. Vaitukaitis. The animals aren't retired until they are 
probably--it would be variable--probably in their 20s and 30s. 
So it's the last 15 to 20 years of their life span that they 
would need to be supported.
    There is an arrangement with the Food and Drug 
Administration, the Centers for Disease Control, and the 
National Institute of Allergy and Infectious Diseases to 
provide what is termed ``lease fees'' or endowments for animals 
that are returned to the source for housing the chimpanzee. The 
current going price for that is about $55,000 per animal to 
assure the retirement of that animal.

                         chimpanzee retirement

    Mr. Porter. We understand that Jane Goodall is in town 
right now, and that there's a proposal that she has made to 
provide a kind of ``reserve'' for chimpanzees that are no 
longer used in research. Have you talked to her and do you know 
about this?
    Dr. Vaitukaitis. No, I have not recently talked to her, but 
I know of her interest in that. That is an issue that the 
National Research Council report will address.
    As I said, it's a conundrum in terms of what to do with 
these animals, since we'll never be able to get these animals 
again because they're limited in the wild. We can't import them 
from the wild. There is a limited resource in this country, and 
the chimpanzee has been an invaluable model for vaccine 
development against hepatitis. There may be another virus that 
is not currently evidenced, like HIV, that chimpanzees may be 
the ideal model for. So we have to figure out ways of making 
sure that we have access to those animals if we need them, but 
also to keep the cost down and support them in a way that would 
be most cost-effective.
    Mr. Porter. I guess there are many issues associated with 
this. For example, do you put chimpanzees that have been made 
HIV-positive back into the wild? What happens to that 
population? I can see a lot of very great difficulties in how 
you deal with these animals.
    Dr. Vaitukaitis. We don't think that the HIV-infected 
animals should be placed back in the wild. In fact, it's not 
clear that the animals, even those that are not HIV-infected, 
could be placed back in the wild, based on studies with other 
nonhuman primates.
    Mr. Porter. I would imagine there's an issue as to whether 
some of these chimpanzees that have been bred and never been in 
the wild, what effect that would have upon their existence.
    Dr. Vaitukaitis. Absolutely.
    Mr. Porter. Do NIH grants for researchers using chimpanzees 
include any component for care of the animalsonce the 
experiment ends?
    Dr. Vaitukaitis. I can't address that specifically. I know 
that for the animals used by intramural scientists, funds are 
provided for them through the Allergy Institute or the Cancer 
Institute, and I know that some of the other animals--about 
150--are endowed in this way, but some of these certainly have 
been used for extramural research purposes. The funding source 
does make provision for retiring the animal to New Mexico State 
University or the Coulston Foundation or the Southwest 
Foundation, or wherever the animal would be housed.
    Mr. Porter. But if there is an NIH grant to an academic 
medical center that involves the use of chimpanzees in their 
research, you don't have any responsibility for those animals 
at all? Or later?
    Dr. Vaitukaitis. We at NCRR do not.
    Mr. Porter. No? You would only have responsibility for 
those used intramurally?
    Dr. Vaitukaitis. Currently, in the breeding colonies that 
we have, we own none of those animals. However, we feel a moral 
obligation to help support those animals, unless the 
institutions that are hosting those colonies wish to assume 
that responsibility.
    This is an area where we need help through the National 
Research Council report.
    Mr. Porter. So there is no national repository of research 
chimpanzees where there is some clear policy affecting all of 
them?
    Dr. Vaitukaitis. That covers the entire group? No, because 
most of the animals are actually owned by the site where they 
are hosted, the universities, or by private companies.
    Mr. Porter. Exactly. So there is no national policy on what 
happens to the chimpanzees after they've finished their 
scientific role?
    Dr. Vaitukaitis. That's correct.
    Mr. Porter. Should there be?
    Dr. Vaitukaitis. There probably should be, to be certain 
that the animals are treated humanely for the remainder of 
their natural lives.

                         chimpanzee retirement

    Mr. Porter. Do you have any knowledge what some of the 
academic health centers or research centers do with animals 
like these after they have finished their scientific role?
    Dr. Vaitukaitis. They just maintain them as best they can. 
I know that some of them look to see if there are zoos nearby 
that would be willing to take them on, at least on an interim 
basis, to help alleviate some of the costs of maintaining these 
animals.
    Mr. Porter. Because, as you say, they probably have 20 to 
30 years of remaining life, and in some cases maybe even much 
longer, after the research role is completed, and that's both a 
huge cost and a huge responsibility, it seems to me.
    Dr. Vaitukaitis. That's absolutely true. Some of these 
animals can be reused for other kinds of research studies. Once 
they are HIV-infected, they can be used for other HIV studies, 
and the other animals could be used for linguistic studies, 
other vaccine studies, and other behavioral studies.
    Mr. Porter. Can I ask Dr. Varmus--Dr. Varmus, do you think 
there ought to be a national policy and something done to 
provide a way to take care of research chimpanzees?
    Dr. Varmus. We're hoping the NRC report will address that.
    Mr. Porter. Do you think they're looking to all the animals 
involved--in other words, those all around the country?
    Dr. Varmus. That's my assumption. The charge was fairly 
broad. We asked them to look at national policy regarding 
chimpanzees used for research.
    Mr. Porter. Now, how many of the entire population that 
you've described are considered surplus now? That is, their 
role has been fulfilled?
    Dr. Vaitukaitis. We technically don't consider any of them 
surplus----
    Mr. Porter. Well, that's probably a misuse of the word. I 
meant those whose scientific role has been fulfilled----
    Dr. Varmus. Retired.
    Mr. Porter [continuing]. And they are retired, yes.
    Dr. Vaitukaitis. All I can tell you is that there are about 
150 animals that have been returned to the source from which 
they were leased in the first place. But those animals can 
still be reused for other research, HIV research or some other 
related research. That would be out of a pool of roughly 1,700 
animals in the biomedical research arena.

                          ncrr strategic plan

    Mr. Porter. All right.
    You're beginning a process to update your 1994 strategic 
plan. If you are doing strategic plans every three years, does 
that indicate that the pace of change in your programs which 
provide research resources and technologies is so rapid that 
you need to rethink your approaches almost constantly?
    Dr. Vaitukaitis. Our strategic plan is really a living 
document. It has to evolve constantly. The strategic plan we 
published in 1994 was such that we have completed--have 
implemented, or are in the process of implementing--about 90 
percent of the recommendations within that plan. So it takes 
about a year and a half or two years to move forward, to update 
that plan, in concert with the research community. That's 
basically where we are at this point.

                      transgenic research animals

    Mr. Porter. A number of years ago, when the Jackson Lab in 
Maine burned, there was great concern that there would be an 
inadequate supply of specialized lab mice for NIH grantees. 
Since that time there has been an explosive growth in the 
development of even more specialized knockout mice, as we 
mentioned. Has the supply of all these specialized lab animals 
kept up with the demand?
    Dr. Vaitukaitis. The demand is increasing steeply. We have 
funded Jackson Labs as a shared resource to take on established 
knockouts and transgenics that then can be made available to 
the general biomedical research community. Through our 
construction program we have also provided them substantial 
levels of construction money to enhance their facilities. We 
have actually had to increase the level of support to Jackson 
Labs for this activity, over a very short period of time double 
it, and we seem to be holding at a reasonable level right now. 
But these technologies are very expensive, and investigators 
would prefer that a resource like the Jackson Labs handle the 
animals, validate them, and share them with other investigators 
around the country. This need is a continuing one, and as the 
techniques become even more sophisticated, better mouse and 
other models will be developed. There is also a need for other 
models that are larger animal models, other than just the mice.

                     euthanasia of research animals

    Mr. Porter. Is euthanasia of so-called ``surplus'' 
laboratory animals prohibited under animal use guidelines or 
Federal policy?
    Dr. Vaitukaitis. Euthanasia is permitted for terminal 
experiments and for animals that are in pain or in discomfort. 
Euthanasia of chimpanzees is something that we do not do 
because there are no guidelines for that. It's an endangered 
species, and it's a concern of both investigators, as well as 
animal rights individuals.

                   general clinical research centers

    Mr. Porter. Dr. Varmus' Advisory Panel on Clinical Research 
has made several recommendations about the NIH General Clinical 
Research Centers, which are administered by your center. They 
suggest that the NIH centers should be more broadly available 
to investigators supported by non-NIH funds. What is your 
reaction to this proposal?
    Dr. Vaitukaitis. This is actually an ongoing activity for 
investigators at the General Clinical Research Centers, or 
GCRCs. In 1990, the level of support to investigators using the 
centers was a little over a billion dollars. Of those funds, 72 
percent came from the NIH, and the other sources were about 5 
or 6 percent from other Federal agencies, and the remainder of 
the funds were from the private sector. Between that time and 
1995, in a little over a five-year period, the level of support 
to investigators has increased from $1.0 billion to $1.5 
billion, and the portion from NIH has stayed relatively the 
same, about 70 percent. But the increased funding to 
investigators using GCRCs from drug companies has almost 
doubled, from about 8 percent to almost 16 or 17 percent. There 
is also other funding from the private sector.
    It is the standard practice for investigators to get other 
sources of funding for pilot studies or other related 
activities, in addition to competitive funding from the 
National Institutes of Health. That is not a problem for the 
GCRCs; that's a standard operating procedure for them.
    Mr. Porter. The panel also recommended that General 
Clinical Research Centers should shift their orientation more 
heavily to outpatient care. I know that the centers have been 
moving in this direction the last several years. What share of 
their patient load is presently outpatient, and how much more 
will they be able to increase that proportion?
    Dr. Vaitukaitis. Outpatient-based research is the major 
form of research at GCRCs. In fiscal year 1995, for which we 
have complete data, there were 270,000 outpatient research 
visits as opposed to 82,400 inpatient research days. The rate 
of increase of the outpatient visits is almost at a 45 degree 
angle, and we suspect that when we get the reports for the last 
fiscal year, that those numbers will continue in that same 
direction. My guess would be that we will approach about 
290,000 to 300,000 outpatient research visits for 1996, and 
stay steady in terms of the number of inpatient research days.
    Mr. Porter. With the current pressures on clinical research 
in academic health centers, are you considering increasing the 
number of your General Clinical Research Centers to help 
support the clinical research enterprise?
    Dr. Vaitukaitis. We are receiving more applications from 
institutions that do not currently have GCRCs because of the 
impact of managed care and the cost of doing clinical research. 
We are trying to accommodate these institutions as best we can 
within the framework of what we have available.
    Mr. Porter. Do the General Clinical Research Centers enter 
into agreements with private industry to conduct clinical 
trials or test experimental surgical procedures?
    Dr. Vaitukaitis. Yes. We have a category of research in the 
GCRCs called ``Category D''--it happens to be D for drug 
company-related research. The drug company is responsible for 
paying the cost of doing that research, and there is an offset 
back to the GCRCs for hosting that research. The research must 
be done in such a way that it does not restrict the 
investigators reporting their findings through the scholarly 
process of reporting in peer review journals.
    Mr. Porter. And is this a mechanism that will be used more 
broadly to supplement the resources of the centers?
    Dr. Vaitukaitis. The Category D days, as well as the 
Category C days, in the outpatient units, have been the major 
source of third-party funding for GCRCs. In 1995 there was 
about $15 million in third-party offsets to operate the GCRCs 
and help them keep cost-effective. Of that $15 million, about 
$9 million was for Category C, or boarder, patients; $2 million 
was from Category B, or research patients who had to be 
hospitalized because of their underlying disease, and were also 
research patients; and about $4 million was for Category D 
patients. Category C and D patients are those that are helping 
offset the costs of operating the GCRCs, both on the inpatient 
and the outpatient sides.

                   extramural facilities construction

    Mr. Porter. Your budget requests $4 million for extramural 
facilities grants. Given the pending backlog of facilities 
requests and the small number that can likely be accommodated 
with this funding, would it be more cost-effective to allocate 
this funding to a program such as the Shared Instrumentation 
Program, which could help more institutions?
    Dr. Vaitukaitis. The research facility needs are 
considerable, and to shift that to Shared Instrumentation, I 
think--although $4 million is not that great a level, and it 
would make it easier to handle administratively, but 
programmatically, there is a huge need for construction out 
there. For instance, HBCUs have 40 percent of their research 
space whichis not acceptable for modern research. That's been 
an unmet need for some time, and those institutions are not covered, 
for the most part, by the Centers of Excellence setasides through the 
construction program.
    A recent report from the National Academy of Sciences has 
estimated that there is about $10 billion of research facility 
needs that has been pent up across biomedical research. For the 
first time in their tracking of that data there has been a 40 
percent decrease in research construction carried out by 
medical centers, and a 9 percent decrease across all academic 
institutions in the country.
    We are seeing that there is a need out there, but there are 
priorities that we have in putting the NIH budget together in 
terms of funding investigators through the research project 
grants. So it's a question of priority-setting at this point.
    Mr. Porter. What does the President's 1998 budget request 
for the facilities construction program operated by the 
National Science Foundation?
    Dr. Vaitukaitis. The comparable program of the National 
Science Foundation contains no funds in their request. There 
were none in 1997, and there was $50 million in 1996.

                          virtual laboratories

    Mr. Porter. You have funded some of the first work in 
virtual laboratories, that is, the sharing of sophisticated 
equipment like electron microscopes and MRI systems, over the 
Internet, with digital controls run through a personal 
computer. How widely used is this technology in biomedical 
research? Is it an eligible item for reimbursement under a 
regular grant application?
    Dr. Vaitukaitis. There is no charge to investigators for 
access over the Internet. This approach to creating virtual 
laboratories over the Internet is an evolving process. The 
current Internet has difficulty handling information exchange 
in real time. It really won't be until the next generation of 
Internet, which is 1,000 times faster, that we can really 
handle the large amount of information that would go over the 
Internet.
    This would create access for a wider array of investigators 
to high-end technologies over the Internet and provide online 
collaborations among individuals from different disciplines by 
using this kind of technology. It would be a very cost-
effective way to approach some aspects of research.
    Mr. Porter. So it's not today an eligible item for 
reimbursement?
    Dr. Vaitukaitis. That's correct.

                   coordination of imaging activities

    Mr. Porter. As we discussed with Dr. Varmus last week, some 
in the radiology community are interested in the creation of a 
separate institute at NIH for diagnostic radiology and imaging, 
to draw together these activities which are currently dispersed 
throughout the NIH. To what extent does your center already 
perform this coordinating role?
    Dr. Vaitukaitis. Our role at NIH is to develop high-end 
technologies, including those for imaging, which includes a 
whole host of technologies for whole animal, human organ, or 
molecular structure imaging. We coordinate with the other parts 
of NIH to determine the needs of their investigators who are 
funded predominantly through the research project grant 
mechanism.
    Some of the institutes have developed some very specific 
imaging technologies that are within the direct mission of 
their institute, but our role is to provide the research 
infrastructure, and hence our interaction with the other 
institutes is one of a collaborative approach in that we are 
trying to develop those technologies that investigators who are 
funded by the other institutes can gain access to.

                   regional primate research centers

    Mr. Porter. We understand that you have begun a major 
evaluation of the NIH-funded network of primate centers. Has 
the mission of these centers changed since the original 
facilities were funded in the 1960s? Are separate primate 
facilities still the most efficient way to conduct this type of 
animal research?
    Dr. Vaitukaitis. The seven regional primate centers are 
really a set of seven national laboratories that are unique. 
They would not be able to be reproduced anyplace else in this 
country, or anyplace else in this world, for that matter.
    As primate-based research has become more precious--there 
are fewer investigators doing it because they can't afford to 
do it within their own institutions--primate centers host 
probably a third of all biomedical research that relates to 
primate-based research in this country. We are looking at a way 
of more cost-effectively arranging how the primate centers 
operate in order to accommodate more investigators, if 
possible. The tension on these centers is that they can't 
accommodate many more investigators within their current 
configuration, and we're trying to see if there's a better way 
of doing it.
    Mr. Porter. Dr. Vaitukaitis, I think you've answered our 
questions. We have a few more for the record.
    We very much appreciate your answering the questions, the 
good testimony, and the fine job that you're doing. Thank you 
very much.
    Dr. Vaitukaitis. Thank you.
    Mr. Porter. The subcommittee will stand in recess until 
1:30 p.m.
    [The following questions were submitted to be answered for 
the record.]

[Pages 1587 - 1634--The official Committee record contains additional material here.]

                               ----------

                                           Thursday, March 6, 1997.

        NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

                               WITNESSES

DUANE ALEXANDER, M.D., DIRECTOR
DR. YVONNE T. MADDOX, DEPUTY DIRECTOR
DR. FLORENCE P. HASELTINE, DIRECTOR, CENTER FOR POPULATION RESEARCH
BENJAMIN E. FULTON, ASSOCIATE DIRECTOR FOR ADMINISTRATION
DONNA S. CASADY, ACTING BUDGET OFFICER
DR. HAROLD VARMUS, DIRECTOR, NATIONAL INSTITUTES OF HEALTH
DENNIS WILLIAMS, DEPUTY ASSISTANT SECRETARY, BUDGET, DEPARTMENT OF 
    HEALTH AND HUMAN SERVICES

    Mr. Porter. The subcommittee will come to order.
    We have now confirmed a new hearing date for the NIH groups 
that were originally scheduled to testify tomorrow morning, 
including the Office of AIDS Research, the Office of the 
Director and Buildings and Facilities. These will now be heard 
on Thursday, March 20, at 10:00 a.m.
    This afternoon we are pleased to welcome Dr. Duane 
Alexander, the Director of the National Institute of Child 
Health and Human Development. Dr. Alexander, it's good to see 
you.
    Dr. Alexander. Good to be here, Chairman Porter.

                       Introduction of Witnesses

    Mr. Porter. If you will introduce the people that you 
brought with you, and then proceed with your statement, please.
    Dr. Alexander. Thank you.
    Beginning on my left, I'd like to introduce Dr. Florence 
Haseltine, the Director of our Center for Population Research; 
Mr. Ben Fulton, our Executive Officer; Ms. Donna Casady, our 
Budget Officer. To my right, Dr. Yvonne Maddox, our Deputy 
Director. And you know Dr. Varmus and Mr. Williams.

                           Opening Statement

    Mr. Chairman, the NICHD is charged by the Congress to 
conduct research on maternal and child health, the population 
sciences and medical rehabilitation. Last year, during our 
appropriations hearings, I reported good news of research 
advances and the awarding of the Nobel prize to two of our 
long-time grantees. I'll be continuing many of those same 
themes this year, as these positive trends continue, including 
reduction in the Nation's infant mortality rate and high honors 
for NICHD-supported scientists.
    Following on the 4 percent decline in infant mortality in 
1994 that I reported last year, the trend continued with a 6 
percent decline from 1994 to 1995, and the preliminary data for 
1996 looks similarly encouraging. Since the NICHD was 
established in 1962, the U.S. infant mortality rate has 
declined by 70 percent. Most of this decline can be traced to 
NICHD research advances, particularly to improvements in 
preventing or treating respiratory distress syndrome and the 
Back to Sleep campaign.
    This campaign is based on NICHD research, and recommends 
that healthy infants be placed on their backs to sleep, to 
reduce the risk of sudden infant death syndrome, or SIDS. 
Stomach sleeping has changed from 80 percent of babies to 25 
percent of babies, and deaths due to SIDS have declined by 30 
percent in the last three years. Since the campaign, 1,600 
fewer babies annually die of SIDS.
    The introduction of surfactant treatment developed from 
NICHD and NHLBI research continues to reduce deaths from RDS. 
Still, nearly a thousand infants a year suffer from a breathing 
problem called hypoxic respiratory failure. A new therapy, 
using inhaled nitric oxide, has just been shown by NICHD 
research to rescue many of these infants, and avert the need 
for a costly surgical procedure used to oxygenate the infant's 
blood.
    A brief historical note dramatically illustrates the 
progress from NICHD research. In 1963, President Kennedy's 
infant son Patrick was born prematurely and died of respiratory 
distress syndrome. Despite all his advantages, his doctors and 
his parents could only watch helplessly as Patrick struggled to 
breathe, because we didn't know the cause of RDS, and there was 
no treatment.
    Now, with treatment with surfactant, new respirators, 
better isolettes and advanced intravenous fluid therapy, 
premature babies have a far better chance to live. When Patrick 
Kennedy was born, an infant with RDS at his weight and 
gestational age had a 95 percent chance of dying. Today, an 
infant at that weight and gestational age has a 95 percent 
chance of living.
    This has been a year of unprecedented acknowledgement of 
research supported by NICHD. It began with the award of the 
1995 Nobel prizes to Dr. Eric Wieschaus and Dr. Edward Lewis, 
whose basic research on birth defects had been funded by NICHD 
for decades. The awards continued last fall, when two NICHD 
intramural scientists, Dr. John Robbins and Dr. Rachel 
Schneerson, received the 1996 Albert Lasker Clinical Research 
Award for their landmark development of a conjugate vaccine for 
Hemophilus influenza type b, or Hib. The Lasker prizes are 
often referred to as the American Nobel prizes.
    For many years, the leading cause of acquired mental 
retardation in the United States was brain damage from 
meningitis due to Hib. The Hib conjugate vaccine reduced Hib 
meningitis from 20,000 cases a year to fewer than a hundred. 
This is one of the NIH's greatest contributions ever to public 
health.
    Completing the cycle of the world's leading scientific 
awards, Dr. Ryuzo Yanagimachi, an NICHD grantee for 29 years at 
the University of Hawaii, was awarded Japan's equivalent of the 
Nobel Prize, the 1996 International Prize for Biology.Dr. 
Yanagimachi's animal research has laid the foundation for much of 
today's human infertility treatments.
    Not all our research has been honored with such 
distinguished prizes, but much of it has already made a 
significant difference in peoples' lives. One dramatic 
achievement has been the development of an effective treatment 
for the inherited disease cystinosis. NICHD scientists in the 
NIH Clinical Center identified the basic defect in the disease, 
developed a drug to treat it, and tested it in a clinical 
trial. Prior to this treatment, affected children were severely 
stunted in growth, went blind from cystine crystals deposited 
in their eyes, lost their kidney function and died by age 10 
unless they received a kidney transplant. Today, with early 
diagnosis and drug treatment, the development and lives of 
these children are entirely normal.
    NICHD has led an expanded research program in autism. A 
research conference on autism was held in 1995, followed by a 
solicitation for research grant applications focused on 
neurobiology and genetics. Funding these applications this year 
will markedly expand autism research and bring new scientists 
into the field.
    Abnormalities of brain development can result in children 
having difficulties in learning. Almost half of all the 
students receiving special education in this country have 
learning disabilities. Screening procedures have been developed 
for preschool identification of risk for learning disabilities. 
Longitudinal studies using a new approach for children with 
these reading disabilities have been conducted in ordinary 
classrooms in several states. Approximately 97 percent of this 
group of high-risk children is now learning to read using these 
techniques.
    At any time, any of us can suffer an injury or an illness 
that changes our entire life. Christopher Reeve has turned his 
own tragedy into a remarkable stimulus for research. Thanks to 
NICHD research, a new generation of assistive technology is 
becoming available. Novel imaging techniques facilitate rapid 
fabrication of prosthetic and orthotic devices that are 
customized to fit individual users. An advanced portable oxygen 
system will help school children with breathing problems, and 
an electronically controlled knee-lock device will improve 
lower limb bracing to increase mobility.
    We study issues related not only to the individual but to 
families and populations as well. We lead a Government-wide 
effort to improve Federal statistics and research on 
fatherhood. Also, as many more women are joining the work 
force, the issue of child care is increasing in importance. 
Last year, the early results of the NICHD study of early child 
care showed that, in and of itself, child care by non-maternal 
figures does not adversely affect the mother-child 
relationship. This study continues to examine other important 
issues in the first seven years of life.
    A major study of adolescent health is concluding, and will 
soon be available to help understand the social changes and 
structures influencing teenagers and their needs.
    Mr. Chairman, the awards and achievements we report to you 
today represent part of the return on the long-term investment 
of the American people provided by the Congress which has made 
these lifesaving advances possible. The fiscal year 1998 
President's budget request for NICHD is $582,032,000, excluding 
AIDS. I will be pleased to answer any questions.
    [The prepared statement follows:]

[Pages 1639 - 1642--The official Committee record contains additional material here.]


                                 autism

    Mr. Porter. Dr. Alexander, we congratulate you and your 
Institute on these awards and recognitions. I think it's fair 
to say that this subcommittee believes that your reward ought 
to be more than a 2.5 percent increase. And your work is far 
more important and of greater priority in my mind, at least, 
than that figure would represent. We'll see if we can improve 
on that but, every year in appropriations, you start from 
ground zero and have to build the case.
    So we will have our work cut out for us in terms of 
addressing the priority that I think certainly most of the 
members of this subcommittee believe biomedical research to be 
for our country. And we hope that we can do better than the 
President has suggested. We'll have to wait and see.
    Dr. Alexander, autism is thought to affect 400,000 people 
in the United States, with a devastating emotional and 
financial impact. Is it fair to say that there has not been 
very substantial progress made in the biological understanding 
of autism in the past 15 years?
    Dr. Alexander. That's quite an accurate statement, Mr. 
Porter. Unfortunately for many years, the biological 
investigations of autism were back-burnered because of a belief 
that this was a psychogenic disorder caused by abnormal 
parental interactions with their children. As we have studied 
the condition more, we have come to realize that this is 
probably not the case, that this is probably a neurologically 
or even genetically based disorder, probably related to some 
abnormality of brain functioning, perhaps as a result of either 
a genetic disorder or some intra-uterine insult to the brain.
    Our efforts now are being directed to these particular 
aspects of the autism spectrum disorders. And in fact, we have 
just completed the competition under a request for grant 
applications for neurobiology and genetic studies of autism. 
These grants are being funded come April. We have received 
additional funds from Dr. Varmus to supplement the funds that 
the Institutes can put toward this area of research.
    And we believe that we have assembled a top group of autism 
researchers, as well as people in the neurosciences and 
genetics who have not worked in autism before. We believe that 
we stand poised to make major advances in our understanding of 
autism, and hope that we will be able to produce the kinds of 
results that we are anticipating in making real progress 
against this disorder.
    Mr. Porter. I think you've indicated this is possibly true, 
but is it likely that advances in autism through research will 
also help shed light on other illnesses like obsessive 
compulsive disorder, attention deficit disorder, and learning 
disabilities?
    Dr. Alexander. I think there's a high likelihood of that. 
Anything that we learn about brain functioning and abnormal 
behaviors, such as these disorders manifest, will help whether 
we're studying one or the other. There is carryover to the 
other condition. And I believe that the work we're going to be 
doing on autism will probably help us to understand these other 
disorders as well.

                             autism centers

    Mr. Porter. Do you think the field of autism research could 
benefit from a center based approach?
    Dr. Alexander. This has been something that we've 
discussed. I'm not sure that the field is ready for centers 
yet. The program project grants that we are going to be funding 
have many characteristics of centers. As these projects develop 
and function over the course of the next few years, we'll be 
able to assess whether they are functioning quite capably as 
program project grants, or whether there might be a need for a 
centers approach.
    Right now, it's the belief of myself and the other 
Institute directors involved in autism research that a centers 
based approach would be premature.

                     autism research investigators

    Mr. Porter. According to autism family support 
organizations, one of the biggest problems in the field is the 
small number of talented scientists who are actually working in 
it. Do you agree, and are you taking steps to encourage more 
scientists to enter the field of autism?
    Dr. Alexander. We are. This increase in funding in autism, 
particularly using the program project grants, willcertainly 
attract investigators to this field, both people who have not been 
working in autism before, who are experienced, as well as young 
investigators. There is ample room in these particular program project 
grants for young investigators to be brought on to work with people who 
are more established in the field and represent the new entry of people 
who will continue an interest in autism research.

                       learning disabled children

    Mr. Porter. Dr. Alexander, recent findings suggest that 
learning disabled children have trouble distinguishing between 
some spoken syllables, perhaps indicating that the auditory 
system is the focus of the defect, rather than the language 
centers of the brain. Does this mean that early training aimed 
at helping learning disabled children distinguish between 
sounds could prevent them from ever becoming impaired?
    Dr. Alexander. That's a very promising area of research 
that needs to be pursued. We're not sure yet whether this group 
of children who demonstrate deficits in the auditory system 
represents a sub-class of children with learning disabilities 
who demonstrate this overall problem with phonological 
processing, or whether it represents just a totally distinct 
group. We need to study this area further.
    The studies that we are doing, the studies that the 
Neurology Institute is doing, and the Deafness and 
Communication Disorders Institute is doing in these areas I 
think will help us to sort out whether these are clearly 
different categories of children who have different bases for 
their learning disability, or whether they are all part of the 
same kind of a continuum.
    We need to do more work that's going to pursue that. We 
will be aided in that work with some of the new sophisticated 
techniques of neuroimaging, and other methods that will help us 
to investigate this in a very clear way.
    Mr. Porter. How are you disseminating the results of these 
studies relating to learning disabled children?
    Dr. Alexander. We're working, both independently ourselves 
and producing information from the Institute for others to 
disseminate. Certainly, the work our investigators are doing is 
being published. Each year we are putting out a book about the 
year's progress in learning disabilities. And we have worked 
cooperatively with the Department of Education in producing a 
set of information called Learning to Read-Reading to Learn 
that is being disseminated widely by the Department of 
Education.
    We're also working actively with the learning disabilities 
associations, and there are several of these, to disseminate 
information to parent groups about the progress that's being 
made. Also, Dr. Reid Lyon, from our Learning Disabilities 
Research Program, has testified to the Congress, has testified 
before a number of State legislatures, and parent groups in 
States around the country about the results of this research on 
learning disabilities. And the word is getting out about the 
progress that's being made.
    We are also sponsoring with the Learning Disabilities 
Association a summit here in Washington in April, with the 
concluding event here on Capitol Hill, also in an effort to 
disseminate the word about research from this program.

                      sids back to sleep campaign

    Mr. Porter. Your Back to Sleep campaign, urging parents to 
place infants on their backs when sleeping to prevent SIDS, 
which you mentioned in your testimony, has been quite 
successful in reducing the number of SIDS deaths. What research 
strategies are you pursuing to address the remaining SIDS 
cases?
    Dr. Alexander. Well, we're not satisfied that we've done 
all we can do yet with just Back to Sleep. We're at the point 
now where about 25 percent of babies are still sleeping on 
their tummies. We are going to be intensifying the Back to 
Sleep campaign with the goal of achieving 90 to 95 percent back 
sleeping in infants. Because we believe that just with this 
measure, we probably can reduce SIDS by over 50 percent and not 
stop at 30 percent reduction where we are now.
    We're also not satisfied that we yet understand the basic 
underlying mechanism of SIDS. Our basic research has given us 
some tantalizing leads, some suggestions and clear indications, 
in fact, that there is a area of the brain stem, called the 
arcuate nucleus, that has a deficiency in neurotransmitter 
receptors in infants that die of SIDS, compared to infants who 
die of other causes.
    This could explain, in fact, why infants placed in the 
tummy sleeping position could bury their face in the covers and 
not detect that they are in fact suffocating, that their levels 
of oxygen are dropping and carbon dioxide are rising, and turn 
their head to the side to clear their airway. If they don't 
have those receptors there, they don't get the message. So we 
believe that this is an explanation for a substantial number of 
infants with SIDS.
    We are also conducting a study of home infant monitoring, 
the CHIME study, Collaborative Home Infant Monitoring 
Evaluation, looking at whether the latest generation of apnea 
monitors can in fact pick up preceding events or clues that a 
SIDS death is impending in time to arouse an infant, if parents 
are there and can respond to an alarm.
    Also, if in fact we are able to demonstrate that this 
defect in neurotransmitters is an underlying mechanism for 
SIDS, we will be looking for some markers of that defect, or 
some way to detect it, so that we could determine the infants 
in the population that are at the greatest risk of SIDS, and 
monitor them particularly intensively.

                      premature labor and delivery

    Mr. Porter. Premature labor and delivery are leading causes 
of infant mortality. What clinical trials are you currently 
pursuing in this area?
    Dr. Alexander. We're very excited about our prospects here, 
Mr. Porter. We have gotten some evidence from some basic 
studies as well as from some small, preliminary clinical 
trials, to suggest that a condition called bacterial vaginosis 
is associated with premature labor in a number of instances. 
And it could account for a substantial portion of the premature 
deliveries in this country, as well as account for the higher 
proportion of premature labor and delivery in the African-
American population.
    Studies identifying bacterial vaginosis either by a vaginal 
smear or using a new technique called detection of fetal 
fibronectin by a vaginal cervical swab give an indication of 
the presence of this condition, which increases the risk for 
premature labor and delivery.
    We now have major clinical trials underway looking at both 
these methods of detection, followed by initiation of treatment 
with antibiotics to try and eradicate the bacterial vaginosis 
infection to see whether eliminating that infection can in fact 
reduce the increased risk of premature labor and delivery. 
There is evidence from a small preliminary trial that this 
might be the case. We have now started definitive studies to 
provide clear indication of whether this will work. If it does, 
this should give us our first real handle on a means to detect 
and intervene to prevent premature labor and delivery.
    Mr. Porter. Thank you, Dr. Alexander.
    Mr. Hoyer.

                            early child care

    Mr. Hoyer. It's good to see Dr. Alexander, whom I get to 
see regularly at places around Maryland. He and his wife are 
neighbors, and we're glad to see him here.
    Early child care. A lot has happened in my life, some not 
so happy; but one happy thing, I had a new grandson on November 
18th. And one of the wrenching things that my 32 year old 
daughter is going through is that he's now three months old and 
he's starting child care and she's going back to work. This 
happens to hundreds of thousands of young people, so I'm very 
concerned about child care.
    I'd like to hear a little bit more about the studies that 
seem to show that there is not an adverse effect from non-
maternal care for a period of time during the day. Could you 
expand on that? It's obviously a very, very important issue for 
our country, as we see more and more women in the work force, 
welfare reform requiring work, all of that. This is a critical 
area of study.
    Dr. Alexander. You're right on target with the question and 
the concern, Mr. Hoyer, which is the reason that we initiated 
this study some years ago. At the present time, more than half 
the mothers of infants, children under a year of age, are in 
the work force. And those infants are being cared for either by 
a father, a grandparent, some other relative, a small group day 
care home, or a large day care situation. And parents are 
concerned about whether placing the infant in a child care 
situation is going to have a good, bad, or indifferent effect 
on that child's development, that child's relation with family, 
and the whole family's interaction with the child.
    Because of this very clear trend, back in 1988, we 
initiated this NICHD Study of Early Child Care, trying to get 
an answer to the questions that were really beguiling parents. 
Does early child care have a good, bad or indifferent influence 
on my child and the rest of my family. We started this study 
with a competition to select 10 sites around the country with 
top-notch investigators where we could accumulate 1,200 
families for a prospective study and evaluation of the impact 
of child care.
    Children have been picked up at birth and followed with 
intensive evaluation at several points in their lives. They are 
presently completing their four and a half year evaluations, 
and they will be continuing the study until age seven. We're 
currently trying to decide whether to extend that study any 
longer.
    The evaluations have been completed now with the data 
analysis through the 15 month evaluation, and we're starting on 
the 3 year data. The finding that I mentioned in my opening 
statement was one that came to the public last spring, and 
indicated an answer to the question most frequently asked, and 
the concern that had been raised: will placing my child in a 
day care situation have an adverse effect on my relationship 
with that child.
    And the study, based on the 15 month evaluation, gave a 
reassuring answer for parents. It showed that regardless of 
where that day care was being provided, whether it was the 
other parent, a relative, large or small day care setting, that 
there was not an adverse influence or a positive influence on 
the maternal-child relationship, that the child and mother did 
just fine, as long as there was not some other problem with the 
mother-child relationship in the home.
    So this data, I think, got wide publicity at the time and 
gave a lot of reassurance to parents who were in the same 
situation as your daughter. We are asking a lot of other 
questions; obviously the issue of maternal-child attachment is 
not the only one. What are the effects on social development, 
on language development, on cognitive development, on other 
forms of parent-child interaction? On the child's health?
    One thing we do know is that children in day care get more 
ear infections and other upper respiratory infections than 
children who are not. But they seem to do okay anyway.
    So the assessments of the data from this study continue. 
There will be about five more papers and public presentations 
released this spring. And data from this study are continuing 
to become available.
    As I say, we'll be following these kids through age seven, 
and we will be learning an awful lot about the day care 
situation. It is everybody's hope that all the data will be as 
reassuring as the initial findings that were released, but we 
don't know.
    Mr. Hoyer. Well, that is reassuring, and I'm going to get a 
copy of that study and send it down to Susan. She'll be glad to 
hear it.
    Dr. Alexander. We'll be glad to provide it.

                            learning to read

    Mr. Hoyer. She is a very conscientious parent, and very 
concerned about it.
    Let me ask you about another question that the Chairman 
talked a little bit about in the autism field; learning to 
read, how children learn to read, how that occurs. You 
indicated there was a relationship between you and the 
Department of Education on this issue, and you've disseminated 
certain materials. How particular have you gotten from your 
perspective in your Institute on the specific teaching 
techniques in terms of learning to read, phonics versus whole 
language, and that whole debate?
    Dr. Alexander. We've gotten very specific about that, Mr. 
Hoyer. Once we had identified some specific problems that 
characterized children having difficulties learning to read, it 
was our intent to look at interventions to see if we could 
overcome these difficulties. And we made a very specific point 
of testing these interventions in a school situation in a 
clinical trial type of methodology. So we developed ways to 
test, first of all, children, pre-school, for the presence of 
these particular difficulties we call phononemic awareness or 
phonological processing. And we're able to identify the 
children who are at highest risk of reading disability, based 
on this pre-school testing.
    In a number of States, in California, in Texas, in New York 
and Florida and several other places, we have now conducted 
interventions looking at a phonics-oriented type of approach, 
but a modification of the traditional phonics that's intended 
to teach the skills involved in decoding of words, using 
phonetic types of skills and approaches. With these techniques, 
we have demonstrated that these children are usually able to 
learn to read and come close to the rest of their peers by the 
end of the third grade in most instances.
    There is still a very small group, maybe 3 percent of this 
group, that in spite of this intervention don't make it. Their 
reading problem is probably based in a different way than the 
techniques that we're using are able to overcome. And we need 
to study that further.
    But the basic finding is that we can identify these kids 
before they start school. We can intervene with this phonics-
oriented approach in the regular classroom with training of the 
regular classroom teacher, and have these kids performing up to 
grade level in most instances by the end of second or third 
grade.
    We are now trying to look at variations on these teaching 
techniques, applying them in a wider variety of school 
settings. And we're also asking a slightly different question, 
that is, when a high proportion of the students in the school 
are likely to suffer learning disabilities that affect their 
reading skill, can you apply this kind of technique with 
everybody in the class, and not just a subgroup that's at high 
risk. Can you apply the same principles with the whole 
classroom and have this approach work and improve the reading 
skills of everybody and bring them, not just up to grade level, 
but in many instances above grade level.
    So that's the next step that we're going to be taking with 
this, as well as looking at the whole relationship of the 
modified phonics approach with integration of some forms of the 
whole language approach. And throughout this, we are in contact 
with the Department of Education. We are working with them, 
providing them with the results, and working with them to try 
to make sure that the appropriate information is passed on to 
teachers, to teacher training schools, and to boards of 
education.

                                web page

    Mr. Hoyer. In terms of that, I've been very interested, 
with the National Library of Medicine; a decade ago, I started 
talking about this. And I am essentially computer illiterate, 
as most of the people are in my generation who don't have to 
use a computer, and who unfortunately--or fortunately--have 
people working with them who are really very facile with the 
use of computers.
    But on this Web page, if the teacher in the classroom 
wanted to get that information on your Web page, is that 
available?
    Dr. Alexander. That's one of the things we're doing, yes.
    Mr. Hoyer. When you say one of the things we're doing, 
we're getting it on or it is on?
    Dr. Alexander. It is not on yet, but it will be.
    Mr. Hoyer. Okay. Because this is critically important to 
the classroom teacher, it seems to me, to have that information 
at their fingertips, where we spent a lot of money centralizing 
this information. Again, my daughters, I've got a 25 year old 
daughter that when something happens, I just ask her about it. 
I don't have to ask CRS about it any more, she sits down, 
accesses the internet, and she's got it for me in minutes, 
almost. It's incredible.
    It's just an unbelievable power that she has to access that 
information; that if the classroom teacher or the local 
practitioner in Timbuktu who's got a computer on his or her 
desk can access that information, it's going to make a 
revolutionary difference to be able to get what Alexander has 
at his or her desk anywhere in the world, essentially.

                                 asthma

    Last question, Mr. Chairman, I appreciate your tolerance. I 
have to leave, unfortunately, I have another hearing.
    I'm interested in asthma, and I was concerned about what is 
an alarming rise in childhood asthma. To what do we attribute 
that, and what are we doing?
    Dr. Alexander. We don't know just what the cause of the 
increase is. There are many different and often conflicting 
claims. The most frequent one that we hear is that it's related 
to increased air pollution, environmental air pollution. Others 
claim that there are other antigens in the home that are 
increasing, and that as we further close up our homes for 
insulating purposes that there's greater exposure to these.
    I don't think anyone knows for sure what the cause of 
increased asthma is. But it's very clear that this is the only 
condition that's increasing in children, and the only thing, 
other than AIDS, that's increasing deaths in kids.
    The primary responsibility for asthma research lies with 
the Heart, Lung and Blood Institute and the Allergy and 
Infectious Disease Institute. And they're making major efforts 
in this. And in fact, Dr. Varmus, with funds from the Pediatric 
Research Initiative, has targeted asthma in children as one of 
the three areas for focus for the use of these funds this year. 
So there will be an increased effort in that.
    Dr. Varmus. It's also highlighted in the areas of emphasis 
for 1998.
    Mr. Hoyer. Good. I appreciate that.
    Let me ask you something. You mentioned environmentally 
related issues. To what extent do we continue to look at the 
psychosomatic implications of asthma?
    Dr. Alexander. I think there is still interest in that. But 
I think that the trend of today is to look more at specific 
triggers, environmentally induced triggers of asthma, rather 
than so much a psychogenic component.
    Mr. Hoyer. Thank you.
    Mr. Chairman, thank you again for allowing me this time, 
and Doctor, thank you for what you did today and what you've 
been doing, and all your colleagues at NIH. The Chairman is 
absolutely correct, the more investment we make the better 
payoff for our people. Thank you.
    Dr. Alexander. Thank you, Mr. Hoyer.

                         protection from asthma

    Mr. Porter. Thanks, Mr. Hoyer.
    Let me follow up with two questions in this area, since 
we've opened it. We heard from Dr. Lenfant that, paradoxically, 
exposure to respiratory infections at a young age may offer a 
protective effect against asthma. And that asthma, the 
antibodies or whatever may be produced from those exposures are 
not as great today as they used to be in the past, and that 
therefore, children are more subject, and adults more subject, 
to this disease. Are you following this kind of research?
    Dr. Alexander. This has been a hypothesis that's been put 
forward with some supporting data from one study, the claim 
being that with vaccination, immunization, for example, we are 
less exposed to the antigens that the children used to be 
exposed to and actually get an illness. Whether or not there's 
any strong support for this hypothesis, I think, remains to be 
tested. This is one interesting idea that's been put forward. I 
think we'll see some more research on that. But I don't think 
we know enough yet to say that there's a very strong indication 
that that's the case.
    Mr. Porter. The EPA has recently promulgated new 
regulations on particulate matter that will affect cities all 
across the country. Were you consulted in regard to their 
action, because they've cited the increase in asthma as one of 
the reasons for this. Were you consulted with regard to these 
regulations?
    Dr. Alexander. My Institute was not. My suspicion is that 
the National Institute of Environmental Health Sciences 
probably was, and probably NHLBI and NIAID, who are the ones 
who have the major responsibility for research in children with 
asthma. And I know that one of the motivating factors in these 
regulations was the hope that by doing so, we would perhaps 
decrease the incidence of childhood asthma and the severity of 
it.
    Mr. Porter. Ms. DeLauro.

                      PREVENTING PROBLEM BEHAVIOR

    Ms. DeLauro. Thank you, Mr. Chairman.
    And thank you, Dr. Alexander, thanks for all the wonderful 
work that you all do here. If you don't mind, I'd like to just 
say hello to my pal, Dr. Haseltine. How are you?
    If you could, please, Doctor, profile for the committee 
your Institute's efforts on preventing problem behavior among 
middle school students. Tell me a little bit about what's 
planned in that area.
    Dr. Alexander. There are several separate efforts here. One 
of these, the local effort that is one of the most visible 
ones, is an effort from our Division of Epidemiology, 
Statistics and Prevention Research. It's involved in the public 
school system, the middle schools, in one of the Maryland 
counties, and involves development of baseline measures of 
behavior in middle school students, and then interventions 
targeted to reduce the likelihood and frequency of some of 
these problem behaviors.
    Currently, we've completed the baseline data gathering 
year, and are in the first year of implementation of some of 
the interventions in this school system where we are making 
interventions in some of the schools and not in some of the 
control schools, and measuring the differences in these target 
behaviors at the completion of the study.
    We are also supporting individual investigators in studies 
looking at middle school behavior in a number of areas. And 
then we have a number of studies, the largest being the 
adolescent health study, which is post-middle school, but some 
of the middle schools are in that, as well, a series of studies 
on minority youth health behaviors that are in eight different 
sites around the country that are targeting particularly high 
risk sexual behavior, as well as violence prone behavior.
    So there's a wide variety of studies that are addressing 
this issue. The most on-target of those is the one in the local 
school system.
    Ms. DeLauro. You talked about violence and substance abuse?
    Dr. Alexander. Substance abuse, yes.
    Ms. DeLauro. When you talk about interventions, tell me 
what you're thinking about.
    Dr. Alexander. There are a variety of these. Some are 
almost traditional educational interventions. Others are peer 
education types of interventions, where they will either be 
talked to by their own age peers or older age adolescents who 
come and talk in the schools about some of these health 
behaviors and problems.
    Others involve teaching approaches to conflict resolution, 
for example, for the violence prone behavior. So there's a wide 
variety of these. Some are targeting health behavior, 
nutrition, exercise, elimination of some health problem 
behaviors. Some also target smoking behavior, and a variety of 
others.

                         MIDDLE SCHOOL CHILDREN

    Ms. DeLauro. I'm interested because of what I have done as 
a start to this within the community that I represent, 
something called Kick Butts Connecticut campaign. It takes 
about 50 or 60 middle school kids, [and the schools have been 
enormously cooperative in allowing us to come in and talk to 
the kids have been] and shows videos and have material on 
smoking and its effect on youngsters, and what it means to 
smoke as an adult and so forth. We have, what I call, a little 
army of middle school kids who are going into the elementary 
schools. We have worked with the elementary schools to go in 
and do skits, ask their questions, role play to address this.
    We've also used some eighth graders to come in to talk with 
the middle school youngsters. We've just started this 
initiative, so I don't have any data or analysis. But we have 
at least interested a bunch of youngsters in getting engaged in 
being mentors and carrying this as a health message.
    I'm interested in what you're finding in terms of the local 
schools and some of these health related issues. Because I 
continue to believe that with kids, they can have a strong 
effect on each other.
    We've seen this with something we've got called an anti-
crime youth council. This council talks about crime and violent 
behavior. It's been in existence for about three years, with 
juniors and high school kids, who are again in the schools 
talking about how kids themselves can deal with the issue of 
crime and what their responsibilities are.
    Dr. Alexander. We're eager to get the results of this. As 
your experience was, ours here has been no difficulty getting 
into the schools. We were welcomed.
    The problem is, many places have done things like thisand 
variations on the theme. Very few of them have done it in a research 
context, or in a way that it can be evaluated. What we have attempted 
to do here has been to do this in a research context, where we 
collected baseline information before we went in with the intervention, 
tested different types of interventions, to address the same problem, 
and then followed up the students to see whether the interventions made 
any difference at all, and which of the interventions were the most 
effective.
    So we hope by approaching this in a research context we can 
gather information that will help many middle schools around 
the country to design programs that will take advantage of what 
we have learned here and apply them in a local way.
    You are absolutely right in terms of the timing here. This 
is the group where the health behaviors and social behaviors of 
the future are shaped. There are many disorders that we see in 
adulthood that can be avoided if we shape the health behaviors 
correctly in this age range, if we can avoid smoking, if we can 
avoid inappropriate sexual behavior, if we can avoid the 
violent behavior, if we can improve nutrition and dietary 
behavior. We can have an impact on a large number of diseases.
    So we hope that what we learn from these studies, done in a 
research context, can provide valuable information to many 
schools around the country that would do a similar thing.
    Ms. DeLauro. Your results, I think, are particularly 
critical for us. I for one would love to see them, because we 
can take the research and make the local application. And I 
believe that those of us who serve in public life can do this. 
We can work with our community. It's a way in which we can have 
a direct effect.
    We're trying this and trying to engage, the middle school 
kids. When these kids meet and come into training, I have also 
had an office filled with their parents who were there taking 
an interest in what the kids were doing. So you wind up dealing 
with both kids and parents.
    Dr. Alexander. We're also looking forward to the results 
and we'd be happy to share them with you.

  DRUG DOSAGES FOR CHILDREN AND PEDIATRIC PHARMACOLOGY RESEARCH UNITS

    Ms. DeLauro. Okay.
    Just one other question that has to do with children, I'm 
not sure that this is cause and effect, but we do have people 
being moved into managed care. More prescriptions for 
antibiotics that are going to replace doctors visits, etc. Then 
you've got prescription drugs dosages that have been tried out 
on adults but not kids. That could be harmful to kids. What is 
the Institute doing in terms of dealing with the proper usage, 
and dosages for drugs for children?
    Dr. Alexander. Well, Ms. DeLauro, you've put your finger on 
a very major problem in pediatrics. About 75 percent of all the 
drugs that are available by prescription have never been 
studied or tested in children. So they don't have a pediatric 
indication listed. And this is a problem. Because children 
react differently to drugs than adults do.
    We say oftentimes, a child is not a small adult. And the 
smaller a child is, the less they are like an adult. They 
metabolize drugs differently, absorb them differently, excrete 
them differently, and they stay around for different lengths of 
time. And a liquid formulation of a drug that's often necessary 
particularly for younger children may be quite different than a 
pill formulation of a drug.
    So drug companies are able to get drugs introduced to the 
market based on adult studies, and never do any studies on 
children. Those drugs are obviously of value for children, and 
pediatricians often wind up prescribing them, even though there 
is not a basis, a specific indication listed for them for 
children.
    We have tried several ways to get around this. One of our 
major responses has been to establish a network of pediatric 
pharmacology research units. There are seven sites around the 
country, awarded competitively as cooperative agreements, with 
the top researchers in pediatric pharmacology in the Nation, 
where we provide not only top notch capabilities for clinical 
trials and laboratory capabilities for doing a number of the 
analyses that are required, but also access to a patient 
population of children where there is experience in doing 
studies, experience in institutional review boards in reviewing 
applications to do this work, and experience in investigators, 
nurses, the whole team that's capable of doing high quality 
clinical trials in children.
    We don't fund a clinical trial. We fund some of the basic 
metabolic studies. But the clinical trials are funded by 
industry. We tried to take away from industry the capability of 
saying, well, it's too hard to do these studies, there's no 
patient population available, there's nobody experienced in 
doing these studies. It's there now. And we have publicized 
this widely to industry, and encouraged them to make use of 
this resource for doing drug studies in children.
    That's now taking off. We have a number of drugs now that 
have gotten pediatric indication labels because of studies that 
have been done in this network. We have a large number of drugs 
that are under study in the network now, and are in the process 
of getting pediatric indications. And we have hopes that this 
network is going to be able to provide an expanding resource 
and capability for pharmaceutical companies to do the drug 
testing in children that's necessary.
    The FDA has been very cooperative with us in this effort. 
They have prodded industry and encouraged them to get studies 
done in children very quickly, either concurrent with adult 
studies or not far behind. And we hope that this problem is on 
its way to resolution.
    Ms. DeLauro. Thank you very much, and thank you for your 
work. I appreciate it.
    Dr. Alexander. Thank you.
    Mr. Porter. Thank you, Ms. DeLauro.
    Mr. Wicker.

                            LEARNING TO READ

    Mr. Wicker. Thank you, Mr. Chairman.
    Dr. Alexander, I notice in your testimony you mentioned 
that your Institute's researchers have been using non-invasive 
neuroimaging methods to study brain systems that are involved 
in the ability to read.
    Dr. Alexander. Yes.
    Mr. Wicker. A recent article in the Chicago Tribune cites a 
quote from Reid Lyon, Research Director of your Institute,with 
respect to reading skills. And Mr. Lyon is quoted as saying, we know 
what to do, we have the information within our grasp. We just can't get 
the message across. That's what makes the issue so frustrating.
    I wonder if you could comment on that, and tell us what 
science has discovered that might provide us more effective 
tools.
    Dr. Alexander. We know what to do in a large number of 
children. We're learning what to do in many others. We have the 
ability to identify a substantial proportion of the children 
who are at risk for learning disabilities before they begin 
school. We know what to do to help a large proportion of those 
children to learn to read.
    We are in the process of learning how to do that in a more 
effective way, by testing variations on the theme, if you will, 
of the interventions that we have found to be effective, to see 
if there are ways that we might make those more effective for a 
larger percentage of children.
    There remains a group of children for whom these techniques 
don't always work. And those children certainly require 
additional study and evaluation. One of the things that we're 
doing involves this neuroimaging technique. It's called 
functional magnetic resonance imaging. And it's a non-invasive 
method of studying what's going on in the brain of children. 
Because it is non-invasive, doesn't involve x-rays, we're able 
to use it in normal children. And it's teaching us a lot about 
how the brain functions.
    The neuroimaging studies have identified differences in 
activation sites, differences in processing activities, of 
areas of the brain in children with learning disabilities 
compared to children without. One of the things that we're 
studying right now is if we apply these remedial techniques, 
does the picture of the neuroimaging change in these children? 
Will they become more like their normal reading contemporaries, 
and their functional neuroimaging picture?
    I don't think we're going to be at the point where 
neuroimaging is the diagnostic criterion for learning 
disabilities. We have paper and pencil tests that work much 
better and much less expensively for that than a neuroimaging 
test does. But they do help us to study the basic underlying 
neurological problems that may be at the core of problems with 
learning to read, and help us to understand that whole process.
    Mr. Wicker. Which children are candidates for these 
functional MRIs?
    Dr. Alexander. At the present time, these are just children 
who are participating in some specific research studies. There 
are sites that have a particular interest in the underlying 
brain mechanisms associated with learning disability, and also 
have at their institutions exceptionally good capability for 
doing these studies. These are not easy to do. It requires 
sophisticated equipment, techniques, and people to interpret 
the images that we get.
    So there are just a couple of sites around the country 
where we are funding these particular studies of functional 
neuromagnetic resonance imaging to try and assess the 
underlying brain function or dysfunction of children with 
reading disabilities.

                   children with reading disabilities

    Mr. Wicker. Based on what you know at this point, do you 
have an opinion about the advisability of using volunteers on 
children to assist children with reading disabilities as 
opposed to trained professional teachers?
    Dr. Alexander. I think children differ in what they're 
going to benefit from. All children can benefit from having a 
volunteer who reads with them, works with them in their early 
years of learning to read. A child with reading disability may 
not benefit from a volunteer who does not have some extra 
training above and beyond just reading a book to that child. A 
child with a reading disability may very much enjoy having a 
story read to them. But that may not have anything to do with 
improving their ability to read.
    If we want to try and improve the ability to read, one of 
the useful things is increasing the desire to learn to read, 
and the association with that volunteer reading the stories and 
books to them may increase that desire. But if we want to help 
overcome basic underlying problems of phonemic awareness and 
phonological processing and so forth, it's going to take 
probably more than just an untrained volunteer. It will take a 
teacher who is trained in the intervention techniques that have 
been shown effective in helping these children.
    Some of these techniques are not extremely difficult to 
teach a volunteer. And if there's a volunteer with an ongoing 
relationship with a child with a learning disability, that 
volunteer can learn from the trained teacher how to apply these 
techniques with that particular student, and be a substantial 
help to that child in amplifying what the teacher is able to do 
in a limited time they have to interact with the child in 
helping that child overcome the basic difficulty.
    These are not very difficult things to do. They can be 
taught to volunteers who can work with kids to help them.
    Mr. Wicker. Thank you, Mr. Chairman.
    Mr. Porter. Thank you, Mr. Wicker.
    Mrs. Lowey.

                          infertility research

    Mrs. Lowey. Thank you, Mr. Chairman. And welcome, I do 
apologize that I missed your presentation.
    With regard to infertility research, in your testimony, you 
did state that your Institute has completed several clinical 
studies on the causes of infertility. How close are these study 
results to commercial application, that is, to assisting 
couples seeking infertility treatment, and what is the process 
of taking these findings and making them useful to the public?
    Dr. Alexander. The two findings that I described in the 
opening statement have just been made, so they are very early. 
We now have to pursue what the underlying bases of these 
abnormalities are, and also determine whether or not there are 
hormonal interventions or some other interventions that can be 
made to overcome the specific difficulties. So there is a 
substantial amount of work yet before they are ready for broad 
clinical application.
    We would hope that we can understand very quickly the 
underlying pathology and develop interventions that will be 
ready for clinical trials fairly soon.

                           maternal mortality

    Mrs. Lowey. Thank you. We think of death due to childbirth 
as a thing of the past. Yet every day, two to three women die 
from pregnancy-related conditions. Many of these deaths can be 
prevented. I'm working on legislation to improve maternal 
health through strengthening our surveillance of pregnancy-
related mortality and morbidity data, increasing the use of 
folic acid to prevent birth defects, provide for better follow-
up care after the birth of a child, and improving the quality 
and use of ultrasound tests.
    Can you briefly comment on the research you aresupporting 
in the area of maternal health, and in particular, any research looking 
at maternal mortality? Following up on that, I met with some people 
from the CDC yesterday and one of the questions I asked them in 
response to questions that were asked of me was whether their research 
has led to any connection between infant defects, child defects, and 
drug use during teen years. Could you comment on that as well? We're 
talking about prevention, how do you prevent birth defects. It was 
brought to my attention, and this person, everything you read may not 
necessarily be valid. But was telling me about information they read 
that did make a connection.
    Dr. Alexander. OK. First with regard to maternal mortality. 
Decreasing maternal mortality has been one of the great public 
health triumphs of this century. At the beginning of this 
century, a woman who was pregnant faced a 1 percent chance of 
dying as a result of that pregnancy. Now, it's less than 1 in 
10,000. There's still over 300 women a year in this country 
that die from complications associated with pregnancy. And 
every one of those is too many. Pregnancy should be a condition 
which any woman can approach without any fear of death, 
certainly.
    The rarity of maternal mortality today makes it a difficult 
thing to study. One of the things that is associated with 
maternal mortality is infection. One of the hoped-for benefits 
of our bacterial vaginosis study, where we are looking at 
treating bacterial infections of the vagina and cervix during 
pregnancy with antibiotics as a means of reducing infant 
mortality due to premature labor, may in fact have as a side 
benefit that we will look at the potential of reducing maternal 
mortality associated with infection. That would be an outcome 
that we would hope we would see.
    Aside from that, the causes of maternal mortality are 
largely hemorrhage and some other complications that occur 
later, following delivery. As I say, the rarity of it is great, 
but it makes it a difficult topic for study.
    As far as birth defects in association with drug use during 
pregnancy are concerned----
    Mrs. Lowey. Not during pregnancy.
    Dr. Alexander. Before pregnancy.
    Mrs. Lowey. Right.

                       drug use before pregnancy

    Dr. Alexander. We do have a study that's going on looking 
at the complications, in fact, on the infant, of drug use 
during pregnancy. We don't have any studies at the present time 
looking at impact of prior drug use on birth defects in the 
infant. There was a flurry of interest maybe 15 years ago in 
association with some reports of chromosome breaks, in 
particular, being more frequent among teenagers who were using 
drugs, particularly marijuana and LSD.
    That research has not proven consistent in subsequent 
evaluations. I'm not sure what work the CDC has been doing that 
you discussed with them. I'm not familiar with that.
    Mrs. Lowey. None.
    Dr. Alexander. OK. That's a good reason not to be familiar 
with it. But we are not doing any work in that area at the 
present time.
    Mrs. Lowey. Is that because there is no one out there who 
thinks there's a connection, or you're focused on other things? 
It would seem to me, certainly we're aware of the tremendous 
difficulties that the crack babies have, so that the pregnant 
women who are on drugs and then leave us with thousands and 
thousands of crack babies, cause a tremendous impact on 
society, not to minimize the impact on them and their families. 
I just wondered, in pursuing this, is it because your 
hypothesis leads you or to the work done, that there is no 
connection?
    I would think that if there is any possible thesis that 
there may be a connection, after all, the eggs are there, are 
they the same eggs that are there during that time that the 
teenagers or older youngsters are experimenting, that we should 
be looking in that area, unless you're discounting it. So I'm 
puzzled by your response.
    Dr. Alexander. I think that the reason we're not now is 
that the work was done, like I say, 15 or so years ago. And the 
early suggestions and indications that there were problems with 
chromosome breaks and so forth did not pan out. And people who 
did follow up these adolescents with a history of drug abuse 
did not in fact find a higher incidence of birth defects in the 
offspring.
    The CDC has a very intensive birth defects monitoring 
program that they probably discussed with you that follows the 
incidence of about 25 or so birth defects around the country 
over time, and looks for any changes in incidence, and tries to 
track any fluctuations that they see to any causative event. 
And they have not seen any association from that study that I'm 
aware of with drug use or abuse in adolescents prior to 
pregnancy.
    We do have a maternal lifestyle study that's going on in 
our neonatal network that's a collaborative effort between us 
and the National Institute on Drug Abuse and the Administration 
on Children and Families. This has picked up a cohort of women 
screened from a total of 19,000 pregnant women, identified 
about 1,000 of those who did have a history of drug exposure 
during pregnancy, picked up their infants, who screened 
positive on meconium screening in the newborn period, went back 
and got very detailed drug abuse histories from the mothers, 
whose infants screened positive, and is following these 
infants, looking at their behavioral development in particular. 
This is being done at three of the sites in the neonatal 
network.
    We now have followed these infants to about three years of 
age, it's our intent to follow them at least through beginning 
of school, trying to look at just exactly what their cognitive 
and behavioral profile is, and associate that, if possible, 
with the maternal drug exposure history. It's very difficult to 
do this kind of research, because there is a lot of 
environmental influence on this that's very difficult to 
separate out from the actual influence of what happened as a 
consequence of the mother's drug abuse during pregnancy.
    This study gives us the best shot of anything that's ever 
been done of trying to make that distinction and try to 
separate out effects of drug use during pregnancy from the 
environmental situation in which that child is raised 
subsequently.

                     teenage drug use and pregnancy

    Mrs. Lowey. I think my time is up. So I'm to conclude that 
based upon all available evidence, whether it's crack cocaine, 
marijuana, heroin, used by a woman in her teenage years who 
then becomes pregnant and gives birth, there is no connection 
between that drug use and breakdown in cells, chromosomes or 
whatever?
    Dr. Alexander. This is not a subject that has been studied 
extensively. The limited studies that have been done, and they 
are probably too limited, have not to my knowledge given any 
clear evidence of an association with birth defects.
    Mrs. Lowey. Just to follow up, you're saying they're 
probably too limited.
    Dr. Alexander. Yes.
    Mrs. Lowey. So you would say----
    Dr. Alexander. I don't think we have a definitive answer to 
your question based on the work we've done.
    Mrs. Lowey. Has there been any effort to put some more 
money into that research? I just think that the tremendous 
problems of drug use, which seem to be on the increase again, 
permeating every part of our society, and again, this was 
brought to my attention, and I'd be most interested in 
continuing the dialogue with you.
    Dr. Alexander. That's not something that we have done, Mrs. 
Lowey. I think it's something that we ought to take a look at 
and try to get an assessment on how adequate the studies are 
that have been done, and make a determination in conjunction 
with our colleagues in the National Institute on Drug Abuse, in 
particular, and probably the CDC as well, as to whether this is 
an issue that ought to be reopened and reexamined.
    Mrs. Lowey. And I'd appreciate if you'd get back to me on 
that.
    Dr. Alexander. We'll do that. Thank you.
    Mrs. Lowey. Thank you.
    Mr. Porter. Thank you, Mrs. Lowey.
    Mrs. Northup.

                      phonics based reading system

    Mrs. Northup. Yes, thank you. I'd like to return to the 
question of learning disabilities and what sort of 
recommendations you make to the Department of Education. I 
noticed in your statement that you talked about a phonics based 
reading system being sort of the preferred, I suppose, in a 
remedial form for a child that has learning disabilities to 
learn to read. For example, a dyslexic child.
    Dr. Alexander. Based on our studies, it is the preferred 
initial one, but not the exclusive one. These kids who have 
this particular problem with phonological awareness and 
processing seem to learn better with a phonics based approach, 
not a strict, rigid phonics only approach, but a modification 
of the old phonics approach, where they are taught word 
recognition and basic reading with a phonics based approach 
initially.
    This seems then best followed along maybe by the second or 
third grade with introduction of the more whole language 
approach that's been used more recently in schools. But 
starting these kids with this particular disability with a 
whole language approach doesn't work. They do benefit from the 
whole language approach once they have mastered the basic 
skills of word recognition, decoding and reading.
    Mrs. Northup. And that's what your scientific 
investigations show?
    Dr. Alexander. That's where we are right now. We're not 
done.

                  children with learning disabilities

    Mrs. Northup. Well, there's considerable anecdotal evidence 
in schools that are strictly for children, for example with 
dyslexia, that their phonetic system does truly remedy that 
child's problems for years. If they go to these schools, local 
ones, for three to four years, and then transfer back into a 
mainstream situation, they'll do fine.
    I guess I have to ask you what sort of recommendations you 
make when 20 percent of the school population has that problem 
and there is literally, in our schools, no phonetic based 
system for children until they are accomplished readers. I have 
supported new efforts at better ways of engaging children in 
learning. But I do think we leave our children with learning 
disabilities behind when we do that.
    I just wondered if you'd comment on that first.
    Dr. Alexander. I think you're absolutely correct. And our 
data also show that if these kids are not identified early, if 
we wait until third grade or so to pick them up until they meet 
the technical criteria of a year or two years behind in reading 
before we can begin any remediation, it's too late. Seventy-
five percent of these kids who are not intervened with until 
third grade wind up never being able to read adequately by the 
time they're in high school. So early identification is 
important.
    We've also, I think, gotten very clear evidence that we 
have passed on to reading experts, to our colleagues in the 
Department of Education, to colleagues in States, that this 
population of children we can identify early on as at high risk 
for learning disability benefits most from a phonics based 
approach, and that they are not going to benefit from a whole 
language approach. If they are going to learn to read, they 
have to have this kind of an intervention and this kind of a 
teaching approach.
    Mrs. Northup. With that said, I have great experience with 
this issue myself, with children and the profound effect it has 
made on them to take them out of the public system and put them 
in three years of remediation. How can we continue spending 
money like we do to put children in a classroom that's totally 
based on whole language, which may be great, and I'm convinced 
in many cases it is, for children who are not learning 
disabled, and provide them totally mainstreamed in there with a 
little bit of a support system?
    When you're talking and saying that when you get to it if 
you try to remediate them at third grade or fourth grade it's 
too late, they're high risk and they almost never make up for 
the lack in that basic education skill.
    Dr. Alexander. Right.

                         intervention programs

    Mrs. Northup. Would you agree then that it's not enough to 
send a tutor in for an hour or two, but to put that child in an 
intensive remediation program that allows them to be re-
mainstreamed?
    Dr. Alexander. I think that our evidence indicates that you 
are absolutely correct, that this child does, in order to learn 
to read, has to have that kind of intensive intervention. I'm 
not sure that we know yet that that can't be done in a regular 
classroom. That's what we're still trying to learn. And in 
fact, the studies that we have done, in California and Texas 
and New York, have kept these kids in a regular classroom, 
provided the teacher with training skills in this intensive 
modified phonics approach for these kids, and have demonstrated 
this kind of an improvement with the kids in the regular 
classroom.
    Now, what we're trying to learn is, whether we can apply 
these kinds of techniques in the whole classroom, so that 
everybody is learning with the same kind of procedure, not just 
the kids who are identified as high risk for learning 
disabilities.
    Mrs. Northup. Well, let me just say, you raise some 
profound questions. And there are millions and billions being 
spent that do not reflect the science that you're talking 
about.
    Number one, I would like to see the studies that show a 
child that is mainstreamed in a whole language process that a 
little bit of support, either an aide in that classroom, that 
that remediates the child. I've seen no evidence of that.
    And number two, what you've just suggested is that maybe 
the whole class would learn better phonetically. There are 
whole States, including Kentucky, that have just gone in the 
direction of mandating, and I have to tell you I was part of 
that, mandating whole language for the school system, because 
we were convinced that it engaged all children.
    But if that leaves 20 percent of the population behind, 
that's a pretty startling fact, especially if what you tell me 
is that the older, the more traditional phonics based system 
would benefit all children. Here's a system that 20 percent 
lose out. I've seen no evidence, and I hope you'll provide me 
the studies that you say give evidence, that it's just as 
effective to try to have whole language classroom and one aide 
in there, for example, that provides a little bit of tutoring 
for kids that are learning disabled. That's entirely different 
than intensive remediation.
    And now we know from your studies that if this isn't 
accomplished by third or fourth grade, they're left behind 
forever. That's pretty powerful information and the education 
community really ought to know about that.
    Dr. Alexander. What we don't know, is if it is just as 
effective. One of the issues we are trying to address now is 
whether it is even more effective if the whole class is on a 
phonics oriented approach and the whole class benefits from 
that, rather than some kids one system, some another.

                          phonics based system

    Mrs. Northup. Key question. That's a key question. But in 
the meantime, we know that children that are learning disabled 
need a phonics based system. Are we experimenting on whether we 
can leave them in a whole language system and give them a 
little bit of tutoring?
    Dr. Alexander. Yes, we are trying to learn that, along with 
these others. And really as a product of what we have learned, 
other States have gone the opposite direction, States like 
California and Texas that have been on a whole language system 
are now mandating a phonics oriented approach. So the pendulum 
swings.
    Ms. DeLauro. Would the gentlelady yield?
    Mrs. Northup. Sure.
    Ms. DeLauro. Just to follow up, you're talking about third 
or fourth graders, but with the information you're now 
beginning to uncover, can we find out information about a child 
that's learning disabled from zero to three? How do we find 
this in the zero to three period? What then are the 
implications?
    What can be done to impact that at an earlier time, thereby 
avoiding the process that winds up compounding year after year 
after year and whether it's mediation, etc. How early we can 
uncover the problem and what are the implications?
    Dr. Alexander. That's a question that we don't have an 
answer for yet. We thought we were doing pretty good to pick up 
these kids at four or five. If we could pick them up sooner, it 
would be terrific. We don't have the capability of doing that.
    Mrs. Northup. Let me reclaim my time.
    Ms. DeLauro. Sure.
    Mrs. Northup. The fact is that these children learning in 
the newer phonetic ways is a very proscribed system of 
learning. It literally takes them from where their visual and 
hearing impairment begins to the point of where they are very 
accomplished readers. And there are whole schools that do this 
now. They have a 95 percent success rate. And they've been in 
existence long enough to prove that these kids graduate from 
colleges, and they are not impaired in the future. A few of 
them happen to be my children.
    In the meantime, we have parent after parent whose children 
go to the public school system who diagnose them as dyslexic, 
who then the school says, we're going to give them, we're going 
to mainstream them all day, every day, except for one hour on 
Monday, Wednesday and Friday, or we're going to put a tutor or 
whatever, and the child never gets out of the learning disabled 
class. Meanwhile, we are paying Federal funds for this child 
that's so diagnosed and never is remediated, when we know of a 
system that works.
    I think, I didn't realize until I listened to you and read 
your statement how clear your evidence is in this area and how 
abusive it is to those children who are in the public school 
system that refuses to accept your scientific information.
    Dr. Alexander. We're going to do the best we can, Mrs. 
Northup, to get that information out. I described earlier to 
Mr. Porter some of the efforts, and to Mr. Hoyer, some of the 
efforts we're making to do that. We will have a learning 
disability summit co-sponsored with the Learning Disabilities 
Association here in Washington in April, with the concluding 
day here on Capitol Hill. Efforts will be made at that time for 
some very broad dissemination to Congressional staff members.
    And also, this again will be a joint effort with the 
Department of Education. So we are trying to get information 
out that we have so far. We are trying to broaden the research 
base that we have to examine some additional questions about 
how best to serve these children, and hope that we can turn 
around a situation that we know now is intolerable.
    Mrs. Northup. Well, in the meantime, since we have a system 
that works that's not available in most school systems, 
intensive remediation based on phonics in first grade, maybe 
what we need is for children that are diagnosed to have a 
voucher so that they can go to these special programs for three 
years, and go to a school that has a 95 percent success rate, 
so that they get out of not having to be remediated the whole 
rest of their educational years.
    Mr. Porter. The gentlelady's time has expired. We do have 
Dr. Slavkin and the Dental Research Institute yet on our 
afternoon agenda. The gentleman from Mississippi has asked you 
to yield. Why don't you yield to the gentleman then we'll 
finish our discussion.
    Mrs. Northup. I would be happy to yield.
    Mr. Wicker. I really didn't take all my time. [Laughter.]

                                phonics

    Just a quick follow-up on that. Is phonics the answer for 
everybody? An administrator told me that there's a substantial 
population where phonics doesn't work at all.
    Dr. Alexander. That's why we need to be a bit careful about 
saying that this is the approach for everybody. There are some 
kids, the majority of kids, who learn fine with the whole 
language method. We don't know whether they wouldlearn equally 
as well if we had an all phonics method.
    Probably with this, as with most things, the truth is 
somewhere in between, that most kids probably learn best with 
an initial phonics approach, and then move better into a whole 
language approach, as they are ready and able to do so.
    We do need to do some additional studies to find out, just 
what is the best way to teach not just the LD kids, but the 
kids who are not LD as well, and how to accommodate the needs 
of a variety of kids in a regular classroom to the best extent 
that we can.

                         research on fatherhood

    Mr. Wicker. Thank you. And my last quick question concerns 
your Institute leading a Government-wide initiative to improve 
research on fatherhood and develop policies to assist and 
encourage men in their role as fathers. Other than the obvious, 
what are you accomplishing there?
    Dr. Alexander. This is a broad based kind of an approach. 
Part of it is trying to just improve the Federal statistics 
base. We have a lot of statistics and measures about mothers, 
about children, but not nearly as many about fathers. We need 
to get better information about fathers, their participation in 
raising children, how their work and family responsibilities 
are shared, just what they do in terms of their engagement with 
children these days. Their roles are changing, as is a mother's 
role.
    We're also trying to look at various influences on how a 
father is able to fulfill his role in the home. Jobs, 
joblessness, time, and a variety of other factors. So it's a 
very broad kind of an approach. This has been underway now for 
about a year and a half. There have been several conferences on 
this.
    There will be sort of a wrap-up conference held at the 
National Institutes of Health in two weeks. And this will bring 
together a number of the different efforts that have been going 
on in various agencies to both improve the statistics effort 
that the Federal Government is engaged in to gather information 
about fathers, and their participation in the family and work 
types of activities, as well as efforts to stimulate an 
increased amount of research on fathers and their role with 
children.
    Mr. Wicker. Thank you.
    Mr. Porter. Thank you, Mr. Wicker.
    Dr. Alexander, thank you for your very good testimony, and 
for the wonderful work that you do at your Institute, the 
honors that have been received by researchers, both within the 
Institute and funded by the Institute. It's very, very 
impressive to us. Obviously the recognition is well deserved, 
and we appreciate the fine work that you're doing there.
    Thank you very much.
    Dr. Alexander. Thank you, Mr. Porter. We appreciate your 
support.
    [The following questions were submitted to be answered for 
the record.]

[Pages 1665 - 1736--The official Committee record contains additional material here.]

                               ----------

                                           Thursday, March 6, 1997.

                 NATIONAL INSTITUTE OF DENTAL RESEARCH

                               WITNESSES

HAROLD C. SLAVKIN, DIRECTOR
DUSHANKA V. KLEINMAN, DEPUTY DIRECTOR
YVONNE H. DU BUY, EXECUTIVE OFFICER
EARLENE S. TAYLOR, BUDGET OFFICER
DR. HAROLD VARMUS, DIRECTOR, NIH
DENNIS WILLIAMS, DEPUTY ASSISTANT SECRETARY, BUDGET, DEPARTMENT OF 
    HEALTH AND HUMAN SERVICES

    Mr. Porter. The subcommittee will come to order.
    Next on our agenda is the National Institute of Dental 
Research. Dr. Slavkin, welcome. We're delighted to see you. 
We're sorry, we're a little late in getting started here. We 
had a very--obviously you heard the very spirited discussion we 
had at the end, there.
    Please introduce the people who are with you at the table 
and then proceed with your statement.

                       Introduction of Witnesses

    Dr. Slavkin. Thank you.
    To my left is Yvonne du Buy, the Executive Officer for the 
Institute; and then to her right is Earlene Taylor, our Budget 
Officer; our wonderful Deputy, Dushanka Kleinman; and of 
course, Dr. Varmus and Mr. Williams.

                           Opening Statement

    I'm celebrating my 20th month as part of Dr. Varmus' 
leadership team, and at the same time, I'm getting ready to 
celebrate a birthday that I would like to share with you, and 
that is the 50th birthday of the National Institute of Dental 
Research. On June 24th, 1948, the Dental Institute was created, 
at a time when life expectancy was about 62 years of age, when 
dental caries, tooth decay, was rampant in the United States, 
and when the typical adult could look forward to being 
edentulous by the 45th year of life.
    Some 50 years later, the United States is enjoying the 
finest oral health in the world, in no small measure because of 
the investment in the science of oral health. Children born 
today can pretty much take for granted fluoridated drinking 
water, fluoride in toothpaste, mouthwashes, dental sealants, 
panorex x-rays, all kinds of preventive measures that improve 
oral hygiene.
    The measurable outcome is that 90 percent of the adult 
population in this country still have their teeth at the time 
of death. That is a remarkable tribute to a relativelymodest 
investment in the National Institute of Dental Research. It's 
calculated that this investment is saving roughly $4 billion per year 
in the oral health bill of the United States.
    That is a wonderful yesterday. But as we take inventory of 
where we are today and look to the future, there are some 
terrific things going on. Last year when I had an opportunity 
to give my first show and tell, I was very excited about 
sharing with you an exciting paper that was published in Nature 
Genetics in which an overview was done showing that there were 
40 craniofacial syndromes in which the genes had been 
identified and had been mapped to particular chromosomes, and 
that a molecular understanding was evolving for diagnosis.
    That was in February of 1996. We now have identified and 
mapped over 100 such craniofacial syndromes. What I'd like to 
show you with these prompts is an example of two of them that 
are extremely interesting. This particular disorder, called 
anhydrotic ectodermal dysplasia, was first diagnosed by the 
famous Charles Darwin and written up in 1875. He had made a 
trip to India and identified four generations of males who were 
losing their hair, had no teeth, had no sweat glands, and 
presented with this unusual phenotype, ectodermal dysplasia--
EDA.
    Scientists supported by the NIDR as well as other 
colleagues around the world this year, in August of 1996, 
reported the EDA gene on the X chromosome, mapped it and found 
it to be a transmembrane receptor associated with epidermal 
tissues. This is leading to a standard diagnostic approach to 
this disease.
    Also, as you can see, these children are born without 
teeth. The NIDR took the leadership in developing implant 
technology to be able to create sort of miniature dentures that 
are fabricated through the life of these children until they 
reach maturity. These are individual children who have high 
self-esteem, can get through the socialization in the school 
setting and go on to become college graduates and do very, very 
nicely.
    The next example I want to highlight is a counter-intuitive 
discovery, primarily done by our colleagues at Johns Hopkins, 
at one of our centers for craniofacial anomalies led by a very 
outstanding geneticist, Mimi Jabs. This is an example in which 
one human gene, when there are multiple point mutations, a 
misspelling in one letter of the genetic code, gives rise to 
five different syndromes, all due to these mutations in a very 
particular region, a busy region in the molecule of fibroblast 
growth factor receptor type 2.
    This discovery is leading very quickly to new diagnostics, 
opening up a better understanding of normal development. These 
same observations are also relevant to other Institutes at the 
NIH and other colleagues.
    The last example is looking at this child with ectodermal 
dysplasia with no teeth, and the inability to have a dentition. 
An area has evolved over the last few years referred to as 
biomimetics, to mimic biology. That is, if one knows enough 
about the biology, then in theory, one could design and 
fabricate a biological solution to certain kinds of clinical 
problems.
    Here on your left is a typical example of growing cells in 
tissue culture in two dimensions where over time, they 
aggregate and make cartilage, which is stained in a bright blue 
color.
    Scientists have recently developed a strategy where you can 
take these same cells but grow them in a matrix and produce a 
three-dimensional form. In the lower right of the figure, you 
can see efforts to fabricate structures that have three-
dimensional forms--a biomimetic approach toward developing new 
joints, new synovial joints, new temporomandibular joints, new 
hip replacements, new cardiovascular valves.
    In this area, through the generous support of Dr. Varmus, 
and through collaboration with the Heart Institute, we're 
starting an initiative on new therapeutics, taking the basic 
biology and moving it towards the ultimate realization of 
having biological solutions to knee joints or hip replacements 
or tooth replacement or valves or any of those tissues which 
need to be repaired, regenerated or augmented.
    So that is a reflection of where we are at this point. And 
I just wanted to mention in closing that as a smaller 
Institute, our future, if you will, is through leveraging our 
resources with other partners to be able to pursue these kinds 
of problems. For example, I'm pleased to report that by 
collaborating and co-funding with the National Cancer 
Institute, we've now set up four centers of oral cancer in the 
country. By collaborating with the Burroughs-Wellcome 
Foundation, we've been able to set up a genome study of a yeast 
called candida albicans which is expressed in immunosuppressed 
individuals. We hope this effort will lead to new diagnostics 
and new therapeutics.
    In closing, Mr. Chairman, the fiscal year 1998 request for 
the National Institute of Dental Research is $191,081,000. I 
would be very happy to answer any of your questions.
    [The prepared statement follows:]

[Pages 1740 - 1747--The official Committee record contains additional material here.]


    Mr. Porter. Dr. Slavkin, thank you for your excellent 
statement, I might say without notes, except you had to read 
the final number. [Laughter.]
    Dr. Slavkin. That's the hard part.
    Mr. Porter. Well, that was a very impressive presentation, 
and we appreciate it very much.
    Dr. Slavkin. Thank you.

                            dental amalgams

    Mr. Porter. You're funding two clinical studies examining 
the health effects of mercury-containing dental amalgams in 
children. This has been a concern for some time. Do you expect 
these two studies to provide definitive information about the 
safety of amalgams?
    Dr. Slavkin. The short answer is, I hope so. A number of 
people over the last five or six years have looked at the 
clinical efficacy and the costs and benefits of dental 
amalgams. To date, we have no scientific evidence that says 
that dental amalgams are harmful.
    But we do have a very strong environmental concern to try 
not to contribute to putting mercury into the environment. 
We're supporting research to quickly come up with a non-mercury 
containing solution in the short term. We're doing two 
prospective randomized clinical trials, one taking place in 
Lisbon, and the other taking place in New York, in northern New 
York, near the University of Rochester.
    The effort is designed to look at, with modern assays, if 
there are immunological consequences, effects on antibiotic 
resistance, or is there anything that we can define as a 
negative consequence of dental amalgam alloys. Those studies 
are just beginning. They are supported for five years. We hope 
they will put closure on this issue.
    Meanwhile, and independently, we want to get away from 
mercury-containing dental restorative material being used on 
people in this country. And that is the tack that we're taking.
    Mr. Porter. Well, I think you answered this, but let me ask 
it anyway. Given that children today have so few cavities, have 
you had trouble finding a study population for your clinical 
trial?
    Dr. Slavkin. In this country, we seem to have at least two 
kinds of children. We have children and grandchildren, like my 
own, who have no evidence of dental caries. This is probably 
shared by many of us in the room today. But we have a number of 
children in this country, especially in the inner cities of 
this country, who, with limited access and with a number of 
issues associated with poverty and inappropriate nutrition, 
etc., do present rampant dental caries, and do need solutions 
to those problems.
    So, in almost every urban setting in this country, one can 
find appropriate populations to look at.
    Mr. Porter. Does the low incidence of caries mean that 
there is little commercial interest in developing alternative 
substances for fillings, should problems be found with the 
currently-used amalgams? In other words, if you found something 
new, would you get a commercial interest in it?
    Dr. Slavkin. Despite the remarkable progress that's been 
made from fluoridating drinking water and developing dental 
sealants and improving dental hygiene, even in that context, in 
the United States last year, 200 million fillings were placed. 
In part because of our cultural diversity, a number of people 
live in this country who were not necessarily brought up with 
fluoridated drinking water and fluoridated toothpaste.
    So as a consequence, the background noise, if you will, of 
this advance in technology, is still 200 million fillings were 
placed last year, of which about 70 million were dental 
amalgams.

                              biomimetics

    Mr. Porter. You are increasing your effort in biomimetics, 
the creation of replacement parts for body tissues and bones, 
which you discussed here. You indicate that it is a rapidly 
growing area in biotechnology with considerable private 
investment interest. If that is the case, what is the 
appropriate role for your Institute in developing these 
materials? What can you contribute that private industry 
cannot?
    Dr. Slavkin. In the hearings this year and last year, I 
think you've seen example after example where the NIH is 
perhaps at its best in doing fundamental basic scientific 
inquiry. We then move into translational research, where there 
are prototypes, before it goes to industry, before it goes to 
practicality, where expertise by NIH-supported scientists 
fulfills that requirement in this process of going from basic 
to translational to patient oriented to eventually the 
community.
    In this case, the opportunity is really focusing at that 
translational level; for example, to move the discoveries of 
extracellular matrix molecules and their different genes toward 
prototypes for the replacement of a cornea, replacement of the 
pancreas or salivary glands, or certain kinds of manipulations 
for cartilage, bone and ligaments. And there is a very exciting 
interest in the investigator-initiated research community to 
really pursue these and bring these ideas to fruition.

                           fluoridated water

    Mr. Porter. Thank you. We've heard for years of the 
benefits of fluoride in preventing dental caries. But 
apparently India is in the midst of a battle about whether 
toothpaste with fluoride should carry warning labels, because 
very high levels of fluoride occur naturally in the drinking 
water, to the point that millions of Indians have been crippled 
by fluorosis.
    Is this phenomenon of heavy fluoridation of water an 
aberration of nature that doesn't occur elsewhere in the world?
    Dr. Slavkin. It's a very good question, and the answer is 
no. The creative insight that really led to fluoridation was 
observed by an American dentist in Colorado, Frank McKay, who 
made the observation that children who lived in Colorado had 
something called ``Colorado Brown-Stained Teeth.'' These 
children were consuming water from the Colorado River, and in 
that community, there was no evidence of tooth decay. 
Scientists were able to make that leap and that association.
    That is the downside of fluoridation, that like everything 
there is a benefit and a risk. In levels of one part per 
million fluoride, the benefit is to profoundly reduce dental 
caries. If you have excess fluoride in the water supply, or in 
the food supply, then mottled enamel or fluorosis becomes 
evident. In those parts of the world that have that 
situation,they have either put it into the food supply in 
excess, or it's in the natural water in excess, so they have to 
be concerned, and act accordingly.
    Mr. Porter. So why would they want to put it in their 
toothpaste at all, if they have an excess already? Why do they 
need to?
    Dr. Slavkin. I have not been privileged to the discussions 
they're going through. I don't know.

                             tmd conference

    Mr. Porter. At last year's hearing, you were frank with us 
in saying that we don't know much about how to treat or even 
diagnose temporomandibular disorder, TMD. You held a technology 
assessment conference last May on TMD management. Did that 
conference produce any agreement about treatments, or at least 
promising research areas?
    Dr. Slavkin. It did an excellent job in identifying 
excellent research opportunities, specifically to focus on the 
etiology and pathogenesis of temporomandibular joint diseases 
and disorders. But it very strongly concluded that at this time 
in history, there is not a treatment that is being recommended.

                     oral complications of diabetes

    Mr. Porter. What studies are you supporting in the area of 
diagnosis, treatment and prevention of the oral complications 
of diabetes?
    Dr. Slavkin. Diabetes, as I'm sure you're aware, is an 
extreme challenge because of the oral manifestations, such as 
diabetic neuropathies, ulcerations that don't heal, teeth that 
become mobile, rampant yeast and bacterial infections, and 
activation of viruses. There's a whole field of problems. In 
particular, the Pima Indians in this country have been looked 
at, because they have the highest frequency of diabetes. They 
have been remarkably helpful in illuminating some of these 
kinds of problems.
    We have investigators both in our intramural research 
program and in our extramural research program who are looking 
at the genetics of diabetes, looking at ways of focusing on 
this balance between anabolic and catabolic degrading tissues 
processes. So it's an effort to understand the physiology and 
the cell biology between insulin and glucagon. We are pursuing 
that in terms of basic research and ways of making earlier 
diagnoses; we are interested in using saliva as a non-invasive 
tissue to be able to diagnose glucose levels and correlate them 
with serum levels to determine pre-diabetic conditions.
    We're also in the early talking stages of developing a 
relationship with the Juvenile Diabetes Foundation, based in 
New York, to see about co-funding opportunities. So we're very 
interested, and are supporting that work.

                          future expectations

    Mr. Porter. Dr. Slavkin, you mentioned that your Institute 
will be celebrating its 50th anniversary next year. With the 
pace of science and technology, perhaps it's unfair to ask, but 
could you hazard a guess as to the areas of accomplishment that 
are likely in dental research in the next 50 years?
    Dr. Slavkin. I hope there are. I guess it's easy to say 
because many of us won't be there to keep score. But the human 
genome project, of course, will be completed before 2005. A 
gene-based diagnosis for the viral infections and the bacterial 
infections and yeast infections, I believe, will be a given. 
Drugs will be designed based on the legacy of the genome study, 
so that there will be enormous specificity for analgesics for 
the management of chronic pain, for example. I think we'll 
understand bone formation and bone resorption, so that issues 
of osteoporosis affecting the craniofacial areas will be 
significantly advanced.
    But having sat through the previous interview with my 
colleague, Dr. Alexander, one of the areas that needs attention 
is birth defects and the issue of trying to make inroads in 
reducing the burden of birth defects. Currently, the numbers 
are 1 in 28 or 1 in 33 live births. That is just too high for a 
highly civilized country.
    So in that area, it really leaves the bench sciences, and 
it becomes public education and better communication and 
modifying human behavior, and a better understanding of 
prenatal care. Those areas, I suspect, will go much slower, 
because they're dealing with the philosophy of the human 
condition. And in those areas, we tend to progress very slowly.
    Mr. Porter. Thank you, Dr. Slavkin.
    Mrs. Lowey has asked to be taken out of order, because she 
has to catch a plane. So, Mrs. Lowey.

                    osteoporosis and oral bone loss

    Mrs. Lowey. I'll just ask two brief questions, and I thank 
you.
    I'm very interested in the connection between osteoporosis 
and oral bone loss, if there is. Are you continuing to pursue 
the relationship between osteoporosis and oral bone loss, and 
what do you feel are the potential benefits of this research to 
people who may be at risk for osteoporosis?
    Dr. Slavkin. As you probably heard earlier in the day from 
my colleague, Dr. Steve Katz from NIAMS, we and NIAMS and Aging 
and NIDDK co-support a number of activities and initiatives 
focusing on women's health as specifically related to 
osteoporosis. A data base has evolved that is very compelling 
that osteoporosis is a player in the resorption of bone in the 
oral cavity.
    But to define precisely under what conditions, with 
estrogen therapy and without estrogen therapy, we have studies 
that are currently in progress, one at the University of 
Alabama in Birmingham, with very high-resolution radiography, 
to precisely define changes in bone density, bone density mass, 
and to identify individuals who are truly at risk as opposed to 
sort of a background of osteoporosis that might be tolerable in 
some situations.
    The answers are not yet in. Those are still research areas 
in progress. We're all looking at understanding the basic 
principles of coupling between bone formation and bone 
resorption, identifying the cytokines, identifying what turns 
on osteoclasts, and also how to retain the bone matrix 
optimally throughout an extended life span. It's still very 
much basic research inquiry at this point.
    Mrs. Lowey. I thank you. Just among my colleagues, this 
recently has been the subject of conversation. There seems to 
be a good deal more work in osteoporosis generally, rather than 
any connection to bone loss. Is that because this is more 
recent research, and there really hasn't been much work on bone 
loss in the mouth?
    Dr. Slavkin. You touch upon a very profound issue.
    Mrs. Lowey. Frankly, I was surprised, as we were pursing 
this.
    Dr. Slavkin. Yes. All of us in the room who were 
undergraduates of some fine university, we recognized there 
were two cultures, the science versus the humanities. And in 
the research area, until recently, there was not as much 
crossover, cross-disciplinary, multi-disciplinary activity as 
there should be or could have been. I think you're 
experiencing, and we all are, much more collaboration. People 
are realizing that the problems of medical or dental 
orthopedics, and the orthopedic-related issues, have an 
enormous amount in common.
    So there's co-supporting, people are doing grants together, 
working in centers together, going through training programs 
together. And I think that's changing the scientific culture.

                            gender and pain

    Mrs. Lowey. Thank you. And lastly, I understand there have 
been some recent findings relating to gender and pain. Could 
you share some of these findings with us?
    Dr. Slavkin. It was an exciting observation that was 
published in November of last year in the periodical, Nature 
Medicine, by a group at U.C. San Francisco, John Levine and his 
colleagues. They were basically using a model of men versus 
women having wisdom teeth extracted, and looking at different 
kinds of analgesic drugs; specifically, they're called mu kappa 
opioid or kappa opioid analgesics.
    The surprise was that a particular regime of analgesic 
worked specifically well for females and not for men and vice 
versa. That opens up a very fresh opportunity to rethink the 
differences between men and women in terms of the reporting of 
pain, the tolerance of pain, the response to opiates, and the 
response to non-opiate analgesics. There are many scientists 
who have become very interested, both at the fundamental 
science point of view in terms of receptors and signalling 
processes, all the way to what could this mean clinically.
    Dr. Varmus last year gave a terrific lecture at the 
American Pain Society meetings which were held in Washington. 
He indicated that he was asking Zach Hall, Director of the 
Neurology and Stroke Institute, and myself to co-chair a trans-
NIH effort to bring everyone together who has a common interest 
in the management of chronic pain and the science of pain, to 
really see if we could coordinate internally what we're doing 
much more effectively, and then from that position of strength, 
do the same with other Federal agencies when appropriate.
    To get this started, we created a trans-NIH interest group 
which is now in place. We're planning a ``New Directions in 
Pain'' research conference which will be held at the NIH in 
November, I believe it's November 21st and 22nd, at the Natcher 
Building, which will focus on trying to get people who are not 
necessarily in the pain research field to move their expertise 
and their intellectual prowess to begin to think about these 
areas.
    We have gotten a buy-in from 21 of the Institutes and 
centers and offices at the NIH. I think there's a very terrific 
interest in trying to see if we can get this much better. This 
is a $100 billion a year industry, pain pills. This is 
impacting on basically four out of every five adults over 65, 
who suffer from some type of chronic pain. So it is, with 
changing demographics, a very significant problem. I think the 
NIH is trying to position itself to be even more effective.
    Mrs. Lowey. Thank you. And thank you, Mr. Chairman.
    Mr. Porter. Thank you, Mrs. Lowey.
    Before I call on Mr. Wicker, Dr. Slavkin, I have to leave 
at 3:30 and I'm going to ask Mrs. Northup to take the chair and 
finish the hearing. But let me say that you're doing a 
marvelous job as one of our newer directors. You're obviously 
very excited by the work that you find yourself in and the 
great progress that is being made, and we very much appreciate 
the fine job that you're doing.
    Dr. Slavkin. Thank you.
    Mr. Porter. Mr. Wicker.

                             tmj disorders

    Mr. Wicker. Thank you, Mr. Chairman.
    Let me just ask you to answer basically one question. If 
you would, elaborate on your answer to the Chairman about TMJ 
disorder. What do we know about the nature of this disease, and 
why did the panel come to the conclusion that it did?
    Dr. Slavkin. The temporomandibular joint is a synovial 
joint like the joints in our elbows or knees. But it's one of 
the busiest joints in the body, because it's essentially always 
moving.
    Mr. Wicker. Some more than others. [Laughter.]
    Dr. Slavkin. Yes. As we breathe and speak, etc. And as you 
might imagine, when you look at it clinically, there are 7 
million people who report temporomandibular joint dysfunction. 
Most of these people are women. Most of the women are of child 
bearing age. It is not clear how much of TMD is a problem of 
premature osteoarthritis, how much of it is a neuromuscular 
disorder, or how much of it might be transient or hormonal.
    Clinicians have taken on the problem basically from their 
specialty points of view. Some assumed that the surfaces of 
teeth were the variable and would try to adjust the surfaces of 
teeth. Others performed surgical removal of the joint and put 
in silastic implants, thinking that might be the solution to 
this problem. And others have used behavioral modifications, 
biofeedback therapies, and nutritional changes.
    The panel came together, looked at the information that was 
available, and concluded that without prospective, randomized 
clinical trials, the evidence that is available does not 
support any one of these approaches with clinical efficacy. The 
recommendation was, we need to get a handle on the etiology and 
pathogenesis of TMD. And TMD may turn out to be four or five 
disorders rather than a single disease or disorder. We put out 
an RFA, we got a good response, we have funded a number of 
grants, we've got people around the country beginning to work 
on this problem.
    We're hopeful that in the near future, we will know about 
the etiology and pathogenesis, and then there could be a 
rationale that's evidence-based for diagnosis and treatment.
    Mr. Wicker. Your grants that you funded, how are they 
progressing and are you expecting results from them?
    Dr. Slavkin. From the conference that was held, which was 
last April, to the funding of the grants which probably 
happened in September of 1996, we haven't gone far enough to 
get a progress report. There's a large scientific meeting 
that's coming up later this month in Orlando, where there will 
be 4,000 or 5,000 scientists who are interested in oral health. 
And within that mix, some of the preliminary studies on TMD 
will be reported. But it's still quite early.
    Mr. Wicker. Is TMJ the subject of discussion by your trans-
NIH pain research consortium?
    Dr. Slavkin. Yes.
    Mr. Wicker. Thank you.
    Mrs. Northup [assuming chair]. Mr. Hoyer.

                              fluoridation

    Mr. Hoyer. Dr. Slavkin, welcome.
    Dr. Slavkin. Thank you.
    Mr. Hoyer. I've had a great interest in the Dental 
Institute over the years. Dr. Loe, of course, an outstanding 
Scandinavian leader, and we Danes cared about that.
    And he pointed out, which you have also pointed out, I 
believe you used the $4 billion figure in your statement, in 
terms of the savings that have been effected by theinvestment 
of a relatively small amount of money, a relatively large payoff.
    I asked Dr. Lenfant a little earlier in the week about a 
similar analysis. It's more difficult, obviously, there, 
because it's not as discrete an analysis. Nevertheless, we 
obviously have gotten a real payoff for the investment that we 
made.
    In the course of your testimony you mentioned, and the 
Chairman was talking about the fluoridation, the Communist 
threat that was going to undermine the country, as you recall, 
it occurred to me--well, I have all these personal experiences 
and have no place to put them. [Laughter.]
    Up until 1989, I always lived in a city or a suburb, for my 
entire life. And as a result, I drank city water, through a 
pipe. Now I live in the country and I drink water from the 
ground, the aquifer. It occurred to me, and my wife had us get 
some bottled water as well, some spring water.
    Do either one of those have any fluoride in them of 
significant value to oral health? Or are we undermining the 
oral health of rural people? It just never occurred to me. But 
are rural people, other than getting Crest or whatever they 
get, they don't have fluoride in their water.
    Dr. Slavkin. Well, Mr. Hoyer, we typically don't provide 
the service of coming to peoples' homes and measuring the 
fluoride level, but in your case----
    [Laughter.]
    Mr. Hoyer. I can see it tomorrow in the Washington Post, 
Hoyer pressures NIH to test his fluoride. [Laughter.]
    Is there a difference in the oral health of rural children 
on non-city fluoridated water?
    Dr. Slavkin. It really depends, case by case. We have in 
the country perhaps 10,200 water supplies that are fluoridated 
at the level of one part per million. And there are a number of 
sources of water which already are fluoridated, where there is 
no need to add fluoride.
    And in the food supply, fluoride has been added to 
mouthwashes and some brands of commercially available bottled 
water that people use in their homes.
    Mr. Hoyer. That's my question. Commercially bottled water 
does add fluoride?
    Dr. Slavkin. I can't speak universally.
    Mr. Hoyer. Read the label, I understand.
    Dr. Slavkin. Right. But it is an element in the larger food 
supply, and because many people purchase food that comes in 
cans with fluoridated water, there is always the potential risk 
of having too much fluoride, vis-a-vis mottled enamel.
    Mr. Hoyer. I heard you say that. That was interesting. That 
was not the question I had, but I was interested, because it 
occurred to me that an awful lot of kids live in rural areas 
that don't have the city water.

                       diagnosis of cleft palate

    In any event, cleft palate, you've talked about a lot of 
this and I understand that was your first, I was a little late, 
I missed your first slide. In terms of cleft palate, can that 
be diagnosed in utero, and can it be affected, can we operate, 
can we do something to alleviate the condition in utero?
    Dr. Slavkin. Clefting occurs in approximately 1 in 500 live 
births; in utero, it can be diagnosed with ultrasound, 
noninvasively. But the formation of the face begins to happen 
at the 19th day of pregnancy, post-fertilization. So the face 
is forming usually before the woman knows that she's pregnant. 
The ultrasound diagnosis is made after these developmental 
processes have taken place.
    So the state of the art is really to have teams of people, 
pediatricians, plastic surgeons, various dental specialties, 
work together to address the special needs of a newborn child 
with surgical closure. We don't have a way in utero to correct 
this facial deformity at this time. The treatment that is 
currently available runs about $100,000 to $110,000 per child.
    And so looking at 1 in 500 live births per year, it's a 
little bit under $1 billion a year in costs, and the treatment 
extends from closure of the lip soon after birth to a series of 
reconstructions that often go well into the adolescent years. 
And clefting has speech and hearing consequences. So it really 
requires a costly team approach to habilitate these kids so 
they become productive and do very well.

                   medicare coverage for dental care

    Mr. Hoyer. Doctor, last question, I know Mrs. Northup has 
to leave--are we critical? Because I can stop if you need to 
get out. They don't want to leave just a Democrat in the room 
alone. [Laughter.]
    They're very nervous about that. Everybody can understand 
that concern, of course.
    Congressman Cardin and I, and perhaps others, I don't know 
how many co-sponsors we have, are about to put in a bill that 
will deal with Medicare covering certain instances of 
outpatient dental care. The premise being that the ounce of 
prevention of that dental care will save effectively 
substantial multiple dollars, because of the dental care that 
is issued.
    I'm not asking you a question about that, I don't know 
whether you were aware of that or whether my staff--you're 
shaking your head, you were aware of it. Okay, good.
    But I think that in an era where we're talking about 
prevention being cost-effective, Congressman Cardin and I, 
Congressman Cardin is of course on the Ways and Means Committee 
dealing with HCFA and dealing with the Medicare issue, believe 
that this could be a real savings for seniors to get outpatient 
dental care, if in fact it is related to certain specific areas 
where the lack of care will then lead to much greater costs.
    Again, that wasn't a question but I wanted you to be aware 
of it. I'm glad to hear you're aware of it, and we'll be 
following up with you.

                       dentist scientist program

    I said that was the last thing, but I know my good friend 
Nick Cavarocchi is in the back of the room here, who does a 
terrific job for health care generally. And I have been very 
interested, as you know, in the dental scholarship program and 
fellowship program. I frankly have not focused on what the 
status of that is. What is the status of that?
    Dr. Slavkin. At the moment, in that pipeline of the dental 
scientist fellows, they are being recruited for job positions 
two or three years before they're completing their training. 
The supply and demand issue is very skewed towards recruiting 
the DSA fellows into dental and medical schools.
    For many young people who are seeking that particular 
career path, and measuring the outcome in terms of getting a 
job and a very good job, they are very pleased. From our point 
of view, the DSA program is part of an agenda for training and 
then, in mid-career, retraining to keep people as current as 
possible with all of these scientific opportunities that you've 
been hearing about last week and this week.
    We're very proud of the DSA program, which was an idea that 
Harold Loe put forth a little over a decade ago. It's really 
been staffing a lot of dental schools around the country with a 
much higher caliber of faculty member. We're very proud of it.
    Mr. Hoyer. Congresswoman Northup, I will tell you, you 
heard that was Dr. Loe's idea. It was, but he made me think it 
was my idea. And we worked on it pretty hard together. 
[Laughter.]
    So it worked pretty well. And you will have that 
experience, sitting on this committee. A lot of people will be 
able to give you Northup ideas.
    Thank you very much.
    Mrs. Northup. Thank you, Congressman.
    I have one question in one area I'd like to ask you--
several questions. Before I start, I might point out to 
Congressman Hoyer just a little bit of anecdotal advice. If you 
start having dental problems after you've moved to the country, 
before you think about fluoride, I've noticed that age has 
something to do with that. [Laughter.]
    Mr. Hoyer. Boy, oh, boy. This is a rougher hearing than I 
thought it was going to be. I wouldn't know, but it's certainly 
something I'll watch out for. [Laughter.]

                      spit tobacco and oral cancer

    Mrs. Northup. Dr. Slavkin, I was surprised in your 
presentation there was nothing about snuff tobacco and the 
relationship between the use of snuff tobacco and cancer of the 
throat and mouth. Does that fall under your investigation?
    Dr. Slavkin. Yes. Briefly, one of the things we were very 
pleased to do in this current year was to fund four centers for 
oral cancer: one at the University of Alabama, a cooperative 
program between the University of Chicago and Northwestern, a 
center at U.C. San Francisco on the west coast, and M.D. 
Anderson with the University of Texas at Houston.
    Oral cancer is the life and death issue in oral health, 
with about 42,000 cases a year, about 9,000 deaths, unusually 
skewed towards African-American men who are 44 years of age or 
older, who have the highest prevalence. I think it's the fifth 
most common source of death of cancer in that particular 
community.
    And to address it, we absolutely are committed to a number 
of programs designed to convince young people that chewing 
tobacco is not the way to get better statistics in baseball. 
You can do it without that. We're finding young kids trying to 
emulate behavior, and thinking that spit tobacco is the linkage 
to catching and throwing and so forth.
    So we're working with organized baseball, we're working 
with NCI, we're working with the Oral Health Alliance. The spot 
announcements on television during the baseball series where 
the athlete looks into the camera and talks about a successful 
career without spit tobacco is part of this campaign.
    Kentucky and Tennessee are two specific areas with very 
high prevalence of oral cancer in relatively young people 
because of the preponderance of this habit. And we want to do 
something about that.
    Mrs. Northup. Well, I am aware of the problems in Kentucky 
and the rising use among the youth. And I hope that you will 
focus a lot of research on it, and point that in the direction 
of the education community, so that children become aware of 
it.
    Do you do studies about the amounts of fiberglass that 
exists in snuff?
    Dr. Slavkin. I can check. I am not familiar with fiberglass 
as a component of snuff.
    Mrs. Northup. I'm pretty sure I'm right, what my children 
tell me is that the difference between snuff and chewing 
tobacco is that there are the fine particles of fiberglass in 
the snuff that ever so slightly, almost undetectable, develop 
cuts in the gum so that the juice and the tobacco are 
immediately absorbed into the bloodstream, as opposed to 
chewing tobacco, which has an entirely different concept.
    Dr. Slavkin. We will definitely look into it. I wasn't 
aware of that.
    Mrs. Northup. Would you let my office know if you all have 
any evidence about that.
    Dr. Slavkin. Sure.
    Mrs. Northup. Actually, for several years, I have been 
under the impression that that was a very well recognized 
difference between those two products. So in fact, the research 
and the cause and effect and the immediacy of the problem would 
be different between the two products if that understanding is 
correct.
    Dr. Slavkin. Right.
    Mrs. Northup. Are you beginning the research on oral cancer 
in teens that comes as a result of the use, I'm talking about 
teens and early 20s, of snuff and its effects?
    Dr. Slavkin. Yes, I think there was, because of the 
profound changes in our culture, a bias, not based necessarily 
on science, that all cancer was a problem of more mature 
individuals. But it's been rediscovered that we must pay close 
attention to young children. And we're finding nine year olds 
and ten year olds using spit tobacco in baseball leagues around 
the country, in so-called well off socioeconomic communities as 
well as in have-not communities. We will pay attention to this.
    Mrs. Northup. Okay, Congresswoman Pelosi.
    Ms. Pelosi. Madam Chair, I'm sorry, but other 
responsibilities kept me from being here. I don't want to hold 
up, I just want to get the testimony and read through it.
    Mrs. Northup. Okay. That concludes our afternoon session. 
Thank you very much.
    Mr. Hoyer. Time to take a nap.
    Mrs. Northup. That age thing. [Laughter.]
    In closing, I'd also like to thank you, Dr. Varmus, for 
being here the last week and a half, and I thank your 
colleague. This has been very enlightening, very illuminating, 
very interesting. I think the entire subcommittee has very much 
appreciated your testimony and we look forward to continuing it 
March 18th.
    With that, I'll recess the committee until Tuesday at 10. 
Thank you very much.
    [The following questions were submitted to be answered for 
the record.]

[Pages 1759 - 1807--The official Committee record contains additional material here.]

                               ----------

                                           Tuesday, March 18, 1997.

                  NATIONAL INSTITUTE OF MENTAL HEALTH

                               WITNESSES

STEVEN E. HYMAN, M.D., DIRECTOR, NATIONAL INSTITUTE OF MENTAL HEALTH
RICHARD K. NAKAMURA, PH.D., ASSOCIATE DIRECTOR FOR SCIENCE POLICY, 
    NATIONAL INSTITUTE OF MENTAL HEALTH
WILLIAM T. FITZSIMMONS, EXECUTIVE OFFICER, NATIONAL INSTITUTE OF MENTAL 
    HEALTH
GEMMA M. WEIBLINGER, SPECIAL ASSISTANT TO THE DIRECTOR, NATIONAL 
    INSTITUTE OF MENTAL HEALTH
J. RICHARD PINE, BUDGET OFFICER, NATIONAL INSTITUTE OF MENTAL HEALTH
HAROLD VARMUS, M.D., DIRECTOR, NIH
DENNIS P. WILLIAMS, DEPUTY ASSISTANT SECRETARY, BUDGET, DHHS

    Mr. Porter. The subcommittee will come to order.
    We continue today with the hearings of the National 
Institutes of Health. This morning we are pleased to welcome 
Dr. Steven Hyman, the Director of the National Institute of 
Mental Health.
    Dr. Hyman, why don't you introduce the people at the table 
with you and then proceed with your statement.
    Dr. Hyman. Of course.

                       Introduction of Witnesses

    I have to my right Dr. Varmus, the NIH Director, and Mr. 
Dennis Williams from the Department.
    And from the National Institute of Mental Health, beginning 
on my left, Mr. William Fitzsimmons, Executive Officer; Mr. 
Richard Pine, the head of our Budget Office; Dr. Richard 
Nakamura, the head of our Policy Office. And this is Mrs. Gemma 
Weiblinger, who is our Legislative Liaison and my Special 
Assistant.

                           Opening Statement

    It's my pleasure to appear before you to discuss the 
research programs of the National Institute of Mental Health, 
programs dedicated to understanding the brain, its role in 
behavior, and what goes wrong in the brain to produce mental 
illness. More than 5 million Americans have schizophrenia, 
major depression, manic depressive illness, severe anxiety 
disorders, obsessive compulsive disorders, anorexia nervosa and 
other severely disabling mental disorders. Additional millions 
of Americans suffer other mental disorders that occur across 
the life span from autism in childhood to dementias frequently 
complicated by mood disorders and psychotic symptoms in the 
aged. All told, mental disorders cost the Nation more than $148 
billion each year.
    Throughout the world, moreover, the relative burden of 
mental disorders will increase as a cause of disability and 
death as medical science conquers infectious disease. Indeed, 
the World Health Organization has noted that without marked 
improvements in recognition and treatment in the next 30 years, 
and I call your attention to this table up on the easel, and 
you have a copy of this, major depression alone will rival 
chronic ischemic heart disease as the single leading cause of 
Disability Adjusted Life-Years lost worldwide. Thus it's clear 
from a public health point of view that mental health demands 
the best science that we can apply.
    [See table 1.]

[Page 1811--The official Committee record contains additional material here.]


    Fortunately, the opportunities for scientific progress have 
never been greater. We now recognize that mental illnesses are 
disorders of a specific organ, the brain, just as coronary 
artery disease is a disorder of a specific organ, the heart. 
Given the complexity of the brain, the task of understanding 
its function and dysfunction is formidable. But ultimately to 
make progress, we must understand mental disorders in terms of 
molecular and cellular processes in the brain, the assembly of 
neurons, that is the nerve cells into circuits, and the brain's 
interaction with the environment, including the broader context 
in which we all live.
    Examples of progress from the past year include 
identification of a protein marker on the surface of nerve 
cells that, early in brain development, may guide 
specificemerging cells to become part of the brain's limbic system, a 
set of structures that are involved in the control of motivation and 
emotion.
    In addition, observation through functional magnetic 
resonance imaging has permitted us to see alterations in brain 
circuitry during different processes of learning, that is, the 
experience of life literally changes brain function in a long-
lived way. In addition, for the first time, we've seen 
convincing evidence through neuroimaging of the circuits 
involving a structure called the amygdala, which are the cause 
of fear and almost certainly anxiety disorders in the human.
    With the tools of molecular genetics, a team has identified 
a gene which is likely to prove to be the ``master controller'' 
of our daily biological rhythms, including the sleep-wake 
cycle, which is markedly disregulated in mood disorders, and is 
also crucial to understanding a variety of human problems, 
ranging from insomnia to jet lag.
    Two teams together have markedly deepened our ability to 
add, alter or inactivate genes in the mouse, leading to what I 
think are remarkable discoveries on the molecular and cellular 
bases of memory of place in the rodent. But more importantly, 
providing novel methods of dissecting gene-brain behavior 
relationships.
    It is noteworthy that much of the science that will get us 
to the level of understanding that we need to deal with mental 
disorders is interdisciplinary, spanning the level from 
molecules to behavior and even more broadly, to social context. 
As we look to the coming year, we will continue to strengthen 
our efforts in fundamental molecular biology, in neuroscience, 
in basic behavioral science. We must also look to success in 
the realms of clinical and health services research. Thus we 
are engaged in a very thorough review of our approach to the 
complex human genetics of vulnerability to mental disorders. We 
are planning a renewal of our efforts in clinical trials and in 
the understanding of the effectiveness of new treatments in the 
complex settings provided us by the real world.
    I want to emphasize our commitment to children, in 
particular, our commitment to developmental brain research and 
clinical and services research focused on childhood and 
adolescent mental disorders. As many as 20 percent of young 
Americans between the ages of 7 and 14, approximately 10 
million children, have a mental disorder that is enough to 
compromise their ability to learn and to develop, for example, 
normal family and peer relationships. Our knowledge base in 
this area clearly is an area where we must focus.
    One example is a severe disorder of communication and 
behavior which is autism. Family and twin studies point to a 
genetic cause for autism, and NIMH researchers at three 
different locations are now studying families using a 
combination of strategies. And I think the likelihood of 
finding susceptibility genes in the coming years is high.
    I highlight the area of autism, though, also because it 
reminds me to point out that this is a new arena of cooperation 
among four NIH Institutes, each of which brings to bear 
valuable and different perspectives on the problem of autism. 
And the collaborative spirit at NIH, I think, makes all our 
work better.
    Let me conclude by looking forward in the clinical and 
services realms, since I highlighted in the beginning progress 
more in the basic science realms. In the coming year, as I 
noted, we'll see new initiatives in the genetics of 
vulnerability to mental disorders. We will push to develop 
novel programs to translate what we learn from basic brain and 
behavioral research to clinical applications, ranging from 
neuroimaging to therapeutics, and we will begin reforming our 
approach to clinical trials and adapting what we learn to the 
needs of people in the real world.
    An additional important task for mental health services 
research will be the study of the impact of managed-care on the 
mentally ill, a particularly vulnerable population.
    For the scientific activities that I have briefly 
highlighted here and for related programs, NIMH requests 
$629,739,000 for the fiscal year 1998.
    Thank you, Mr. Chairman, and I will be pleased to answer 
any questions.
    [The prepared statement follows:]

[Pages 1814 - 1817--The official Committee record contains additional material here.]


                        global burden of disease

    Mr. Porter. Thank you, Dr. Hyman.
    As you mentioned, the 1996 WHO study of the global burden 
of disease found that neuropsychiatric disorders are important 
to health status and economic productivity in developing as 
well as developed countries. To reiterate, the study predicted 
that major depression will be the second leading cause of 
disability worldwide in the year 2020. If these figures are at 
all accurate, are we likely to have the therapeutic tools to 
address disorders of this magnitude, and will developing 
countries be able to afford them?
    Dr. Hyman. That's a very important question. And of course, 
not much farther down the list would come other mental 
disorders, such as manic depressive illness and schizophrenia. 
And just to reiterate, the demographic trend you point out 
reflects partly the hope that we will be able to conquer the 
first three on this list, which are infectious diseases in the 
developing world. And I would also point out that the 
demographic trends which create the picture that is projected 
for 2020 already in many cases are in place in the developed 
world.
    In order to make an impact, we clearly need new therapeutic 
tools, in several regards. First, taking major depression as an 
example, we are fortunate to have medications, a combination of 
which can now treat depression in 80 to 90 percent of people. 
But given a disorder that is so common and so disabling, the 
fact that there are 10 to 20 percent of people who remain as 
yet fairly treatment resistant is a problem. In addition, we 
have not yet been able to fully address the issue of 
recurrences throughout life, and indeed, in many cases, the 
depression may become more treatment refractory over time. We 
need more research, therefore, in understanding the fundamental 
brain mechanisms that lead to depression in order to develop 
really novel medications that will supplement the armamentarium 
that we have.
    In addition, staying close at home here in the developed 
world, we have a major issue in terms of the recognition of 
major depression. It is unfortunately a fact, demonstrated by a 
great deal of research, that major depression is recognized 
only about 40 percent of the time in many clinical settings, 
and under-treated when it is recognized. So that in addition to 
providing new treatments, we also need an educational effort to 
overcome stigma, to overcome the unfortunate tendency not to 
see mental disorders as real brain diseases which are worth 
intervening in.
    Mr. Porter. And about the cost, if you have the therapies 
and you have the diagnosis made in developing countries, is the 
cost for these drugs high or low, and would they be affordable?
    Dr. Hyman. The cost of these drugs is certainly not cheap. 
But to give you an example, the most modern antidepressants 
that are widely used in the United States cost between $70 and 
$90 a month. And while this is a staggering cost for developing 
countries, there are first of all tradeoffs, in that, the use 
of these drugs will markedly enhance economic productivity. 
More than that, we hope that as new compounds become available, 
competition among various treatment modalities may indeed 
decrease the overall costs.
    Mr. Porter. I recall about 10 years ago discussing what the 
developing world could do about AIDS. And WHO told me that they 
had virtually, in most countries, for example, in sub-Sahara 
and Africa, they had no money to spend whatsoever on treatment, 
no money to spend to even help people as they were dying from 
the disease. And the only thing they could hope to do was spend 
a little bit of money on public education to try to prevent the 
disease from occurring in the first place. Seventy dollars a 
month would be--a dollar a year would be a lot.
    Dr. Hyman. I agree. One thing that is rather striking, 
however, if you look at this list, is that four of the five 
diseases are actually preventable, based on obvious behavioral 
maneuvers. And interestingly, that does not include unipolar 
major depression. But ischemic heart disease, cerebrovascular 
disease and chronic obstructive pulmonary disease, are 
projected to be such problems based on the growing epidemic of 
tobacco use in the developing world. And of course, road 
traffic accidents also have the potential for behavioral 
prevention.
    It is interesting, therefore, that one of the things 
implied by your questions is that hopefully we can, through 
research on risk for the etiology of major depression, 
schizophrenia and other mental disorders, eventually prevent 
their occurrence. But at the present time, there clearly are no 
known readily modifiable environmental risks.
    Mr. Porter. I hope that by the year 2020 we're sending them 
our pharmaceuticals to help them, rather than our cigarettes to 
kill them.
    Dr. Hyman. I agree.

  use, needs, outcomes and costs for child and adolescent populations

    Mr. Porter. You have temporarily halted a large research 
project on children's mental health services known as UNOCCAP 
because of concerns about the study design. I understand the 
project has a $45 million price tag. And it certainly seems 
prudent to review its design before going into the field. What 
are the major concerns about the UNOCCAP study? Could the study 
be modified to address these concerns without major delays, or 
would you have to initiate an entirely new project?
    Dr. Hyman. This is a very important question for our 
Institute. It is clear, first of all, that we have great needs 
in the area of child mental health, including understanding the 
epidemiology of mental disorders in children and also their 
service needs. Just a moment's reflection tells us that 
children are not just like little adults. And so the diagnosis 
of depression in a seven year old needs special modifications.
    We undertook as an Institute a number of years ago a very 
ambitious project to understand the epidemiology but also the 
service needs of children. In retrospect, a number of things 
happened. The proposed idea of this very big project was likely 
quite ambitious. In addition, and I want to be very clear to 
say ahead of time that I absolutely value health services 
research, but this was being planned during the time when NIMH 
was in transition because of the health services research 
setaside, and had to move from 9 to 15 percent of its budget 
over a small number of years toward health services research, 
which meant that there were not felt to be, by my predecessors, 
funds to do the epidemiology first and then the health services 
needs second. But rather, everything was combined into a rather 
large study.
    And then the world changed radically. Which is to say that 
with the failure of comprehensive health reform legislation, 
there were all kinds of changes in the service delivery system, 
as you know, with the growth of managed care. Taking these 
things into account, the UNOCCAP investigators made what was an 
attempt at an altered study design to meet these, to turn the 
shifting sands of health service delivery systems from a 
liability into an advantage. Unfortunately, with all of these 
changes, the structure that had been created by UNOCCAP and the 
ambition of the study made the overall structure unwieldy. 
Therefore, because of this change in design, I asked for a 
thorough scientific review. And I engaged our council in 
overseeing the results of that review.
    Both the review group and the council found that there were 
many valuable things that have come from UNOCCAP, including 
study instruments to be able to understand both childhood 
diagnoses across various ages, and also service needs. But they 
also found that the project was more ambitious than could be 
accomplished with the time allotted. Therefore, a 
recommendation has been made to focus on finishing the 
development of these very valuable instruments that will be 
used in a wide variety of children's studies, and to thoroughly 
validate them. I'm also concerned that these instruments be 
translated into Spanish and be culturally appropriate for use 
in a diversity of populations.
    We will appoint an oversight committee to see whether there 
is appropriate time and appropriate organization to move beyond 
this instrument development phase. I think if the study were to 
end with the instrument development phase, something extremely 
valuable will be learned. I do not want to use taxpayer money 
in a way that would not be well focused or serve the needs of 
children well. And if the oversight panel does not agree that 
the study should proceed beyond this stage, it won't.
    Mr. Porter. Is the oversight panel the subcommittee of your 
advisory council that you've asked to do a review?
    Dr. Hyman. No, I'm sorry. I should have clarified that. The 
National Advisory Mental Health Council working group asked 
actually for an expert scientific oversight panel to be 
appointed, literally to follow this collaborative agreement 
within the Institute. And we have already identified, not 
everyone has said yes yet, but five people to serve on that 
oversight panel. They will report to council and to me. And 
council and I have entered, I think, into a very constructive 
partnership on this.
    Mr. Porter. So the subcommittee has completed its work and 
recommended this oversight committee?
    Dr. Hyman. That is correct. They recommended that the study 
be limited in its scope at this point, that there be an 
oversight committee, and that anything beyond the initial 
validation of instruments be approved by the oversight 
committee.

              setaside for mental health services research

    Mr. Porter. The 15 percent requirement for mental health 
services research----
    Dr. Hyman. That is correct.
    Mr. Porter [continuing]. Staff tells me that that was part 
of the old ADAMHA statute.
    Dr. Hyman. That is correct.
    Mr. Porter. And was retained on its transfer to NIH. NIH is 
about to be reauthorized. Have you asked the authorizing 
committee to make any changes in that part of the law?
    Dr. Hyman. I have not had those conversations. Let me say 
that health services research, especially as we enter an era of 
managed care, is a very important area of research. And it's 
also a part of research that helps us translate clinical 
studies into understanding in the real world. My philosophy, 
however, is that specific setasides limit flexibility to pursue 
scientific opportunity. However, one of the accomplishments of 
the setaside, I think, was to develop a mature and vibrant 
health services research field, which should no longer need any 
special protection, but should be able to compete with the rest 
of the scientists applying in our portfolio.
    Mr. Porter. I have to say, and I want Dr. Varmus to know 
this as well, I've had some conversations with the Chairman of 
the authorizing committee in the House, Mr. Bilirakis of 
Florida, about directing NIH. It seems to me that if the 
appropriating committee attempts to do their very best not to 
politically direct research but the authorizing committee goes 
ahead and does it, you're bound to what they put into the law.
    So I think it's just as important that in the authorizing 
mode, that all of us send messages that the least amount of 
direction is the best, and the greatest amount of flexibility 
and decisions being made by science rather than politics are 
best for everyone. I've really been talking to Mr. Bilirakis 
about this and the importance of it. We'll see what happens.
    Dr. Varmus. We delivered some of those messages yesterday 
when Mr. Bilirakis and several of the other committee members 
visited NIH for several hours.
    Mr. Porter. Good.
    Ms. Pelosi.

                        needle exchange programs

    Ms. Pelosi. Thank you, Mr. Chairman.
    Dr. Hyman, thank you very much for your testimony and for 
your leadership at the National Institute of Mental Health.
    I was fascinated by ``clock'', as one who commutes on a 
regular basis to California I'll be very interested in 
following that jet lag and sleep, day-night aspects of your 
research.
    Again, I want to thank you for your leadership at NIMH. 
Your work is so important to so many families in America. Many 
people come to our offices to talk about health care reform, 
and say that they are locked into what they are doing because 
of a mental illness that their child or another family member 
may have. That's one aspect of it.
    Of course, the other aspect is what it means to that 
individual and what it means to the family. So for many 
reasons, personal, fiscal and otherwise, we all look to you and 
thank you for giving us hope. Your investment in brain research 
does just that. And, as you know, the disruption and lost 
productivity in our economy, is staggering.
    I also want to commend you and NIMH on your behavioral 
research and your leadership in convening the recent consensus 
conference on interventions to prevent HIV risk behaviors. This 
is a very important report and useful to us in Congress. I hope 
that we will pay attention to the science. And I want to ask 
you a question about that.
    Your outside experts cite an impressive body of evidence 
that needle exchange programs work. Studies show a reduction in 
risk behavior as high as 80 percent, with estimates of 30 
percent or greater for reduction in HIV infections. The 
secondary impact on reduction in women and children may be even 
greater than the 30 percent.
    I cite from your report that there are over 100 needle 
exchange programs in the United States, compared with more than 
2,000 in Australia, a country with less than 10 percent of the 
U.S. population. And the studies show a reduction in risk 
behavior as high as 80 percent, with an estimate of 30 percent 
or greater reduction of HIV in intravenous drug users.
    This is your report. You're familiar with it. I just want 
to call it to the committee's attention.
    It's my understanding that researchers now estimate that if 
Congress were to change our current policy and support needle 
exchange programs that an additional 5,150 to 11,000 plus cases 
of HIV infection could be avoided by the year 2000. Based on 
science, do you agree with the outside experts, Dr. Varmus and 
Dr. Leshner that Congress should lift the ban on Federal 
funding for needle exchange programs?
    Dr. Hyman. Yes, just one clarification. Of course, it's not 
my report because the consensus panel was picked independently 
of NIH. But we ensured through NIH that they had access to all 
the data, positive, negative and so on. I think that from a 
public health point of view, the data on needle exchange is 
particularly compelling, in no small part, because the sharing 
of needles is such an efficient way of transmitting the AIDS 
virus that we could rely not simply for these studies on self-
report of altered behavior, but one can actually see changes in 
sero-conversion to HIV.
    And I won't belabor what you've already read, but I think 
from a public health point of view----
    Ms. Pelosi. Please do.
    Dr. Hyman. Well, from a public health point of view, the 
data in favor of needle exchange is very strong, indeed.
    Ms. Pelosi. Thank you, Doctor. Dr. Varmus.
    Dr. Varmus. We continue to make a distinction, Ms. Pelosi, 
between the data on seroconversion, which is quite easy to 
obtain and to interpret, and the more ambiguous data on the 
incidence of drug use in needle exchange programs.

                  sexual abstinence in aids prevention

    Ms. Pelosi. Of course. Thank you for making that 
distinction, Dr. Varmus.
    As you know, in the welfare legislation, Congress provided 
$50 million, as some of us are just finding out, for programs 
for teaching adolescents abstinence from sexual behavior. This 
is far more money than we've been able to provide to CDC for 
programs that have been proven to work. While I support any 
programs to teach adolescents abstinence, I think we are 
delinquent if we don't teach abstinence ``plus.'' It is my 
understanding that this ``abstinence'' only approach is in 
direct conflict with science, since it ignores evidence that 
other programs would be more effective.
    What do we know about abstinence only education programs? 
Do you think this expenditure of $50 million could in fact 
increase the number of new HIV infections?
    Dr. Hyman. This is, of course, a very sensitive issue, 
because it treads not only on public health areas, but also on 
profoundly personal health values. Indeed, we have studied in 
as yet unpublished studies of abstinence-only education versus 
education which suggested abstinence but also emphasized safe 
sexual practices, should adolescents choose to engage in them 
despite admonitions to abstinence.
    What has been found is that abstinence-only programs do 
indeed delay the onset of sexual activity in adolescents, and 
tend to decrease the amount of sexual activity in those who 
have already begun. In several studies, however, the weakness 
in the abstinence-only approach--from a public health point of 
view--is that when adolescents then do become sexually active, 
they are not aware of practices of safe sexual behavior, and 
thereby may expose themselves to the risk of HIV.
    Ms. Pelosi. Well, as the mother of five, I know many 
parents in America, all, I could probably say, would be very 
concerned about this, and certainly would support the idea of 
abstinence. But I want to make a distinction, Mr. Chairman, 
between abstinence only and abstinence plus. It could be very 
effective as opposed to the disadvantage we're placing these 
young people when we know what the possibilities are.
    Dr. Hyman. I'm also the father of three young children and 
I have very similar kinds of concerns. And I think the really 
important issue is to recognize that there have been a lot of 
concerns that education about safe sexual practices would 
somehow increase the likelihood that children or adolescents 
would engage in sex, or engage in it earlier. And the kinds of 
programs that we are most interested in, recognize that there 
is a dual benefit in delaying the onset of sexual activity, and 
when sexual activity occurs for people to engage in practices 
that are not going to put at risk for HIV transmission.

                prevention of childhood mental disorders

    Ms. Pelosi. Thank you, Doctor.
    Our Chairman asked the question I was going to ask on 
children's mental health. I didn't know if you wanted to add 
anything about ways that we could prevent the onset of mental 
disorders in children.
    Dr. Hyman. This is a very vexed area. Indeed, I'm having a 
council-based review of our entire prevention portfolio. And 
let me say that given our current state of knowledge, the 
actual prevention of most cases of depression or manic 
depressive illness does not seem scientifically feasible.
    But there is an incredible public health need that is going 
unmet, which has to do with the identification of children at 
risk who are already showing symptoms of mental disorder early 
in life. The data suggest that these children are being 
recognized as having mental health problems very late. Often, 
kids get put in the wrong--I hate to use the term--but they're 
put in the wrong bin, they're called bad kids instead of kids 
who are in need of help.
    And one of my goals, indeed, one of the critical goals of 
the Institute, post UNOCCAP would be to provide the kind of 
epidemiologic and diagnostic information and also public 
education so that we recognize these children.
    But a second very important area is therapeutics. You might 
not be aware, and it's rather staggering, that there is only a 
single, well designed, federally-funded study at this point of 
the use of modern anti-depressants in adolescents. And we 
really need to do not only greater work in recognition but also 
in therapeutics for these children, so they can come to school 
ready to learn, and so they can form their normal relationships 
with peers and family. And I think it's really absolutely 
critical.

                    world-wide burden of depression

    Ms. Pelosi. Can I just ask one quick question, Mr. 
Chairman?
    On this chart, Dr. Hyman, why did you not include, when you 
put unipolar major depression, you didn't include bipolar.
    Dr. Hyman. To make this readable, I just gave you the top 
five causes. This is a chart that I did not prepare, but 
actually came from the World Bank. The World Bank and the World 
Health Organization were interested in basically what is the 
burden of disease. That is, not just mortality, but healthy 
days lost, that people are unable to function in normal life 
roles, including work.
    And it turns out that for the entire world, the left hand 
column represents the five main causes of Disability Adjusted 
Life-Years (DALY) loss currently, and the right column is their 
projection. Not far behind are manic depressive illness and 
schizophrenia. And the reason that these rank so high is 
because the onset of mental disorders tends to be early in 
life, and the course tends to be chronic or recurrent.
    So a disease like schizophrenia, tragically, will often 
strike just as someone is emerging into young adulthood and 
ready to become a contributing member of society. Then 
obviously, is unable to work.
    Ms. Pelosi. And AIDS is not on there because we're hopeful 
that----
    Dr. Hyman. AIDS is, I believe, expected to be the tenth 
leading cause by the year 2020.
    Ms. Pelosi. Of course, having more devastating effects in 
certain areas.
    Dr. Hyman. That's correct. This is divided over the entire 
globe.
    Ms. Pelosi. I appreciate it. Thank you very much, Dr. 
Hyman.
    Thank you, Mr. Chairman.
    Mr. Porter. Mr. Stokes.
    Mr. Stokes. Thank you, Mr. Chairman.
    Good morning, Dr. Hyman.
    Dr. Hyman. Good morning.

              minority investigators and research subjects

    Mr. Stokes. Dr. Hyman, one of my major concerns is that 
Federal agencies utilizing taxpayer funds reflect diversity in 
terms of the hiring practices at those agencies. Can you give 
me some idea of how diversified the upper echelons of your 
agency are?
    Dr. Hyman. Of our total staff, 20 percent are under-
represented minorities. At GS-14 and above, it is 12 percent 
[clerk's note: later corrected to ``8'']. But I have to tell 
you that diversity is very important, not only within our 
staff, but also among potential grantees.
    These difficult problems need every good mind we can 
possibly bring to bear on them. And we can't afford to lose 
anyone through failed educational opportunities. And I'm 
extremely proud of some of the programs NIMH has for getting 
college students, for example, who are minorities, involved in 
science and seeing them through.
    Mr. Stokes. Would you include in the record a staffing 
grade distribution table, both below and above GS-14?
    Dr. Hyman. I'd be delighted to.
    [The information follows:]

[Page 1826--The official Committee record contains additional material here.]


    Mr. Stokes. You mentioned grantees. And last year, when 
your Institute testified here, you indicated that you had taken 
part in an NIH-wide major initiative to track the enrollment of 
women and minorities over the course of funded grants. I 
understand that this initiative would allow the Institute to 
evaluate the success of its inclusion policy in achieving the 
Institute's goals. What are the findings of that effort?
    Dr. Hyman. I believe I'm going to have to provide those 
findings for the record.
    Mr. Stokes. All right.
    [The information follows:]

         initiative to track enrollment of women and minorities

    The NIH-wide initiative to track the enrollment of women 
and minorities over the course of funded grants is an ongoing 
activity for which data is still being gathered. For this 
reason the findings of this effort are not yet available. NIMH 
can report the following: 1) More than 88% of applications 
involving human subjects were found to meet the inclusion 
requirements as submitted (see table below). 2) Review 
procedures are in place to identify applications that do not 
meet the inclusion requirements. 3) Applications found to be 
unacceptable with regard to inclusion receive an administrative 
code of ``U'' that results in a bar-to-funding. 4) Applicants, 
whose grants would otherwise be approved for payment, may 
submit additional information to meet the inclusion 
requirement. After receipt of this additional information, 
these grants are submitted to the NIMH Associate Director for 
Special Populations for final determination that the inclusion 
requirement has been met. Approval at this level results in 
removal of the bar and subsequently to funding of the award.

    LEVEL OF COMPLIANCE WITH INCLUSION POLICY IN NEW EXTRAMURAL GRANT   
         APPLICATIONS AS ASSESSED DURING SCIENTIFIC PEER REVIEW         
------------------------------------------------------------------------
                                              Council assignment \1\    
                                         -------------------------------
                                               1/95            5/95     
------------------------------------------------------------------------
Total number of applications reviewed...           1,973           1,989
Number of applications with human                                       
 subjects...............................           1,261           1,182
Number (percent) of applications that                                   
 met the inclusion requirements as                                      
 submitted..............................    1,161(92.1%)    1,050(88.8%)
Number (percent) of applications with                                   
 unacceptable gender inclusion (Code G--                                
 H).....................................       53(4.20%)       41(3.47%)
Number (percent) of applications with                                   
 unacceptable minority inclusion (Code                                  
 M--U)..................................       79(6.26%)       59(4.99%)
Total number (percent) unacceptable \2\.       34(2.70%)       30(2.54%)
------------------------------------------------------------------------
\1\ These council dates were for the first councils that received       
  applications after the implementation date for the 1994 Guidelines.   
\2\ Some applications had deficiencies in both gender and minority      
  inclusion.                                                            

    Mr. Stokes. I understand that NIMH supports minority 
research centers.
    Dr. Hyman. That's correct.
    Mr. Stokes. The centers are confirming cultural differences 
in the expression of disease symptoms. As one would expect, 
such differences if not adequately taken into consideration can 
result in misdiagnosis and inappropriate treatment. What are 
some of the most significant findings of this research? Tell us 
how the results of the research are being incorporated into 
your basic and clinical research initiatives.
    Dr. Hyman. That's true. I think it is very important to 
recognize that the incidence of major mental disorders is often 
quite uniform across different populations worldwide, but that 
the expression of symptoms may differ. For example, to take the 
simplest example, there may be cultural taboos about admitting 
to depression which may be stronger or weaker in different 
populations. People may focus more on psychological symptoms in 
one population, and on somatic symptoms in another population.
    In order to take this into account, let me return to the 
instruments that are being developed for the UNOCCAP study. We 
are involved in and going to have, for example, Spanish 
language versions of these instruments, but not one Spanish 
language version, but rather a version that would be culturally 
sensitive. You can imagine that if an interviewer goes into a 
family and starts asking a list of diagnostic questions, those 
questions really have to be attuned to things that the family 
will find understandable and important to respond to.
    This is a major investment for the Institute.
    Mr. Stokes. Doctor, I understand the Institute is 
sponsoring studies of ethnically defined populations as they 
respond to psychoactive drugs, is that correct?
    Dr. Hyman. This is correct. Once, again, there may be 
differences in different populations in the metabolism of drugs 
and in the way the body handles them.
    Mr. Stokes. Tell us why this type of research is important, 
and what your findings have been.
    Dr. Hyman. One interesting finding recently was to actually 
look at African-Americans and their metabolic ``handling'' of 
lithium. And it turns out that lithium, which is still the 
standard treatment for manic depressive illness, is 
compartmentalized differently between red blood cells and the 
serum, that is the free component of lithium, in a way that 
might make African-Americans more sensitive to the side effects 
of lithium. This kind of information is really critical if we 
are going to have broadly useful therapeutics for a wide 
variety of medications. And I believe that not enough attention 
has been paid to this kind of diversity.

                brain as the touchstone of nimh research

    Mr. Stokes. Dr. Hyman, one of the areas of your budget 
submission, the biology of the brain, is one of your 
majoremphasis areas. Tell us what is your Institute's role in the 
initiative and how is the initiative expected to further expedite 
advances in mental health treatment, prevention and early diagnosis?
    Dr. Hyman. That's a tall order. Because in many ways, that 
relates to the entire mission of our Institute.
    In essence, it's clear that serious mental disorders are 
disorders of the brain that evolve through the workings of 
genes together with the environment. We are obviously 
collaborating with the nine other NIH Institutes that have a 
large amount of brain research in their budgets, sometimes on 
specific programs, and sharing information.
    But for us, we recognize that new treatments, the eventual 
identification of preventable environmental second hits that 
interact with genes and a whole variety of other interventions 
are going to require that we understand the genes which confer 
vulnerability to mental disorders, how they work in the brain, 
how they're modified by environmental factors, and what 
molecules and cells in the brain might be targets for novel 
therapies.
    Let me give you just one example to make this concrete. We 
have discovered, as a community, that there are certain 
circuits in the brain, especially involving something called 
the amygdala, which are involved in fear. Normally, fear is a 
very important adaptive response. Without fear, people might do 
all kinds of things to get themselves into trouble.
    However, this very same circuitry, when it malfunctions, 
can give rise to a variety of severe anxiety disorders, 
including panic disorder and post-traumatic stress disorder. 
We're beginning to understand in detail, in animal models, 
exactly how--not to be too dramatic--but exactly how these 
circuits can be usurped, or hijacked, in mental illness. And 
we're beginning to take those animal models to the human level, 
using functional neuroimaging.
    Now, the opportunity in understanding these circuits, we 
can now say, okay, this is a part of the brain that gets sick 
in these anxiety disorders, and what are the critical molecular 
targets in these brains that can be used as targets for 
therapeutics? What kind of behavioral or psychotherapeutic 
interactions might reverse some of these changes, and how might 
we follow them in humans with neuroimaging?
    In essence, the basic biology of brain disease forms the 
fundamental groundwork for our understanding of mental illness 
and for the production of new treatments.

                 RESEARCH NEEDED ON CHILDHOOD DISORDERS

    Mr. Stokes. Let me mention another area. Earlier on, you 
mentioned mental illness in children.
    Dr. Hyman. Yes.
    Mr. Stokes. I would imagine that this would be an area of 
great interest to many parents throughout the country. I think 
it would be helpful if you were to tell us firstly to what 
extent mental illness in children constitutes a major problem; 
and secondly, whether you have developed some type of a profile 
of these children. How can parents, at an early stage, 
ascertain whether or not a child fits a certain profile?
    Dr. Hyman. Mr. Stokes, I have to say with some concern that 
we do not have the information that parents and schools need in 
order to know what problems children are facing. And part of 
this is the difficulty of recognizing symptoms as they are 
reflected through the changing developmental profile of 
children. That is, someone who gets depressed at seven might 
look different from eight and from nine. One of the things that 
we have to do is to take the basic behavioral science, for 
example, that we support, and bring it out of the laboratory 
more effectively, and into the arena of the real world, where 
we can develop the kinds of usable symptom checklists and 
interviews which would allow us to identify children who are 
having problems with mental disorders.
    And in addition, one of the goals for use of the UNOCCAP 
instrument that I described to Mr. Porter, is the ability then 
to take that kind of information and gain the appropriate 
epidemiologic information. I have to tell you that we are 
starting, again, from a really deficient knowledge base, and 
this is going to be one of the major goals for me at NIMH, to 
make sure that we have this information for children.
    I should tell you, although it's slightly off the point of 
your question, but I find it heartening that there's been a lot 
of interest in this from other agencies. Secretary Shalala 
asked us to brief her on Attention-deficit/Hyperactivity 
Disorder several weeks ago. And we've had several very 
productive meetings, including some planned collaborations with 
ACYF, especially with respect to using Head Start sites 
potentially as an arena in which to start to look at some of 
these problems.
    Mr. Stokes. Then, from what you are saying to us, this is 
an area in which we obviously have yet a long way to go.
    Dr. Hyman. Yes, we do. I agree.
    Mr. Stokes. Do I still have additional time, Mr. Chairman?
    Mr. Porter. You have 30 seconds.
    Mr. Stokes. I doubt if I can pose another question in that 
time. Thank you.
    Mr. Porter. Thank you, Mr. Stokes.
    Mr. Miller.
    Mr. Miller. You seem a little more comfortable in that 
position than you did a year ago.
    Dr. Hyman. Yes, that was with two weeks experience.

                          SOCIAL WORK RESEARCH

    Mr. Miller. Glad to have you.
    Two different lines of questioning. One is, I see in your 
budget a social work area, would you explain to me what you're 
doing in the social work area and what these centers are, and 
are they locked into funding for a long time, and why they're 
in your area?
    Dr. Hyman. These centers were really requested in 
Congressional language. And the logic of these centers is that 
social workers are often on the front lines of making actually 
very important decisions about the future of children and 
families and the disposition of children, and also on the front 
lines in treating a lot of mental illness. And the concern of 
the Congress in writing this language was that there were not 
adequate research traditions in social work and that evidence-
based science within social work would help social workers make 
better and more informed decisions and be better able to use 
the science of mental health in their daily activities.
    Mr. Miller. How much money are we talking about?
    Dr. Hyman. We have, I think, five centers, it's just under 
$3 million.
    Mr. Miller. And you fund these centers through an annual 
grant?
    Dr. Hyman. They get a grant. The center grants are 
generally for five years.
    Now, the total number of centers in the Institute is 
capped, that's NIH policy and it's my policy, at 50 centers 
total. So this then would be a percentage of our total research 
centers.
    Mr. Miller. My daughter is getting a Masters in Social 
Work. I'm just surprised to see it's in your area.
    Dr. Hyman. We do end up spanning from molecules to society. 
Why this research is actually in NIMH rather than another 
agency is an issue that Congress helped us decide. [Laughter.]
    But wherever it is, I think it's very important that social 
workers have evidence based information. I think that's really 
critical.

                    TRAINING OF MINORITY RESEARCHERS

    Mr. Miller. I agree with the idea of the need for them, 
where it really fits in.
    Let me just get clarification on this whole issue of 
diversity, and discuss it within your Institute. Both 
intramural and extramural research, aside from knowing a 
specific minority type of study, but does that come into play? 
Because this is peer review. And so is there any weighing, if 
it's a minority, does that have any----
    Dr. Hyman. What we basically, I think this is true across 
NIH, that what we're interested in is scientific excellence. 
We're also interested, however, in bringing every talented 
American who is interested in science sort of up to a level 
where they can compete in peer review. So we have a number of 
programs, the Career Opportunities in Research--COR--program 
for college students, for example, and minority supplements to 
grants, which are not costly but, I think, represent important 
manpower development programs.
    When it comes to standard research grants, all decisions 
are made on scientific and technical merit and on the mission-
specific priorities of the Institute.
    Mr. Miller. So the main area of minority support is really 
at the beginning research level?
    Dr. Hyman. That's targeted, yes, it is really to bring 
under-represented minorities in a full-blooded way into this 
research enterprise.
    Mr. Miller. Thank you, Mr. Chairman.
    Mr. Porter. Thank you, Mr. Miller.
    Mrs. Lowey.

                      NEW DRUGS FOR SCHIZOPHRENIA

    Mrs. Lowey. Thank you, Mr. Chairman. And welcome, Dr. 
Hyman.
    I believe that one of the most important contributions that 
biomedical research has made towards elevating human suffering 
is the development of drugs for the treatment of mental 
illness. And I understand that a second generation of anti-
psychotic drugs are being developed for schizophrenia. I also 
understand that new anticonvulsant drugs are available for 
manic depressive illness.
    Can you describe to us how these new medications are more 
beneficial in treating these illnesses?
    Dr. Hyman. Yes. There's a very good, and I'll keep it 
brief, but a very good story about anti-psychotic drugs, which 
is, it began with a serendipity, which was the discovery of a 
drug called Clozaril. Clozapine is the chemical name. This drug 
has been known for a long time. It was not widely used, because 
1 percent of people who take it develop a life--threatening 
blood disorder.
    And yet there was something about it. It didn't cause some 
of the same terrible side effects in the motor system and 
emotional withdrawal of the standard anti-psychotic drugs. And 
so, despite the risk of the blood disorder, clinical trials, in 
which NIMH played a key role, showed that Clozaril had unique 
ability to treat people with schizophrenia and no liability of 
causing these terrible extra-pyramidal, or motor side effects.
    This discovery absolutely reinvigorated drug discovery in 
anti-psychotics, both in federally-funded laboratories and also 
in the pharmaceutical industry. And what we're seeing with 
drugs like risperidone, olanzapine, sertindole--are basically 
the children of clozaril, that is, attempts to make medications 
which will have the beneficial therapeutic effects of clozaril, 
but without the risk of this blood disorder, without other 
problems with Clozaril, such as a risk of causing seizures.
    And frankly, all of these drugs will have their place in 
treating people with schizophrenia and other psychotic 
disorders. We, as an Institute, now need to do the kinds of 
studies that I think the Federal Government is best at, which 
are studies which will help clinicians and families know which 
of these drugs will be most useful first, and in what setting.
    At the same time, however, we can't be satisfied, because 
all of these drugs, as good as they are, simply palliate, but 
do not cure, schizophrenia. And it's only by really struggling 
more with the genetics and the fundamental neurobiology that we 
will have more fully adequate treatments in the future.

                 TRANSLATION OF RESEARCH INTO TREATMENT

    Mrs. Lowey. I thank you. At your last advisory council 
meeting, you proposed the creation of a working group to 
oversee the translation of treatment discoveries to the actual 
care of patients. I happen to believe this is extremely 
important, particularly given the pace of change in research on 
major mental illness.
    Can you share with us how your research might more quickly 
or more effectively be made available to medical providers?
    Dr. Hyman. There are two major areas that have come to 
myattention. The first is actually in our centers program that Mr. 
Miller had asked about. I would like to encourage some proportion of 
our centers to be centers where basic scientists and clinical 
researchers might come together. So that I don't tell you too many 
different stories, let's just stick with this idea of fear and the 
amygdala. We already have one center, in fact, actually two centers, 
where attempts are being made to translate this knowledge about 
circuitry involved in fear and anxiety disorders into treatment by 
bringing together basic scientists who work on animals with clinical 
researchers who use neuroimaging and also, in one case, with treatment 
researchers.
    This is the kind of model where we can, in essence, ask 
basic scientists and clinical researchers who speak 
fundamentally different languages to work together over the 
long term so that they really understand each others' problems.
    The second area where I think some subset of our scientists 
can engage in translational research is in our intramural 
program. The scope of the intramural program and its size, 
along with the question which I have been asking myself, which 
is, what is the justification for an intramural program, what 
unique advantages does it have, well, one of them is that this 
critical mass can allow some subset of our scientists to 
engage, again, in sustained dialogue, sharing information that 
will bring clinical knowledge to basic scientists and speed the 
progress from basic science to clinical applications.
    I have to say, I'm always concerned, however, that we don't 
ask a lot of people to become either fish or fowl. It's got to 
be really only a subset of outstanding scientists who are 
involved in making these translations. Because so much progress 
really is made within disciplines, by pushing molecular 
biology, by pushing neurobiology, for example.
    Mrs. Lowey. Lastly, and it's really related, I have become 
very concerned recently because of some experiences I've 
witnessed, concerning the treatment of mental illness by HMOs. 
I'd like to ask you generally the positive and negative impacts 
thus far.
    But my concerns are the following. Because time in treating 
patients is such a factor, have you seen a rush towards 
treating the patient with medication, which indeed may be 
appropriate, however, not giving the appropriate psychotherapy 
and the time that the patient needs? In fact, I have become 
aware in discussions more recently that there has been a 
movement in psychotherapy towards psychotherapies that may not 
be the same for everybody.
    Dr. Hyman. That is correct.
    Mrs. Lowey. Whereas there used to be the usual, the 
procedure, and they are trying to direct it, especially with 
seniors, where seniors are being moved into HMOs, for some 
seniors, the medication may have such extraordinary side 
effects. And if there isn't the appropriate therapy with it, I 
am concerned about the treatment. This is a long question.
    Dr. Hyman. You're absolutely correct about psychotherapy. 
In the old days, it is true that often the approach was, here's 
the treatment, now what's the problem. But indeed, as we've 
become extremely sophisticated about particular diagnoses, 
about different age groups, we recognize that for many 
disorders, a combination of medications and targeted focused 
psychotherapies are often the most successful treatment.
    A good example might come from panic disorder, where 
someone will have spontaneous, overwhelming panic attacks which 
will lead them, over time, to constrict their lives because 
they are afraid to have a panic attack in some place where they 
might not be able to escape. They associate these terrible 
symptoms with places that they've been. Medications, for 
example, may abolish panic attacks. But someone might remain 
housebound without cognitive behavioral psychotherapy, which 
may very well be quite short lived, but is absolutely 
important.
    And so guidelines for treatment that are appropriate, 
whether in a fee-for-service or managed-care setting, really 
ought to look at the whole package of treatments that are 
necessary for a good health outcome.
    Now, the managed-care situation is complex. On the one 
hand, by keeping costs down, managed care could make mental 
health treatment available for all Americans. And as you know, 
we've been engaged in the last year in this parity debate and 
the Domenici-Wellstone amendment made the first early steps 
toward parity. The major concern being, just as I've told you 
how common mental disorders are, that treatment would break the 
bank.
    Well, by controlling costs, managed care makes parity not 
only feasible but, in our analysis, quite affordable. And above 
all, the doctrine of medical necessity that exists within 
managed care means that we are encouraged to tell the 
difference between someone who is sick, someone who has panic 
disorder, schizophrenia, manic depressive illness, versus 
someone who is less sick, and make those kinds of triages, so 
that the fear that there were millions of people on waiting 
lists for psychoanalysis would not literally break the bank.
    Now, the downside, however, is that in our zeal to cut 
costs, we may also cut recognition and treatment. I think one 
of the goals as a Nation, as we face managed care in general, 
is to ensure that managed care involves the management of 
quality, to make sure there are appropriate guidelines and 
implementation of guidelines, and not simply the management of 
cost.
    Because I agree with you, if somebody comes into their 
primary care practitioner and the primary care practitioner is 
doing a very good job, but has only a very short time to 
interact with the patient, and has to ask a whole list of 
questions, it will be difficult to elicit information about 
mental illness. These are often very personal matters, the 
patient might be unfortunately ashamed. And you can't just have 
a list, you know, headaches, blurry vision, are you depressed, 
are you an alcoholic, any stomach aches, that's not going to be 
effective.
    And I think we have to keep our eye on that.
    Mrs. Lowey. I believe my time is up, Mr. Chairman, and I 
thank you.
    I do hope we can continue this dialogue. Because I'm very 
concerned that it is easier to give a person Prozac, for 
example, or another drug, and say, well, it's going to take six 
weeks to kick in, and in the meantime, this young person is 
really finding their lives grossly interrupted at that time.
    Dr. Hyman. What we need are health outcomes, what we need 
to do is have a report card based on actual health outcomes and 
not on simple process variables that don't necessarily tell us 
whether the patients are doing well.
    Mrs. Lowey. Thank you. This is a longer conversation, but I 
appreciate your indulgence, Mr. Chairman. And thank you, Dr. 
Hyman.
    Mr. Porter. Thank you, Mrs. Lowey.
    Ms. DeLauro.
    Ms. DeLauro. Good to see you, Dr. Hyman.
    Dr. Hyman. Good to see you again.

                treatment of mental illness in children

    Ms. DeLauro. Let me just follow up a bit with what my 
colleague Mrs. Lowey was talking about. First, let me just 
applaud you in terms of your commitment to clinical research. I 
guess it's page 4 of the testimony that says ``To be sure that 
we capitalize fully on these priorities, the NIMH attaches high 
priority to research to translate basic findings into the realm 
of clinical investigation and application.'' We really do 
applaud that effort.
    I too have this real concern and particularly I want to 
talk about children. You and I have talked about this. Children 
are being treated for mental health disorders with medication 
rather than with therapy. Yet clinical trials for medication 
such as Prozac have not been done on children. Drugs that are 
highly effective for adults may be harmful, even deadly, if 
they're given to children. But we just don't know, because 
children have not been included in clinical trials.
    What is it that we can do to make sure that the dosages of 
drugs for children to treat mental health are of help to them 
and don't wind up harming them?
    Dr. Hyman. We need to know many things. First of all, we 
should always recall that having an untreated or under-treated 
mental disorder is not where we want to be. We want to find the 
most effective treatments so that children can learn and 
children can develop normally. And one of the really chilling 
facts of epidemiology is that we're recognizing that the age of 
onset of depression, for example, is getting younger and 
younger in all western countries. We really need, for example, 
to be able to grapple with this.
    So what we need to do is expand trials of drug efficacy. 
First of all, ask the question, does the drug actually work in 
children. And what are the tradeoffs in terms of toxicity.
    We have a small number of studies of adults, and none in 
children, of the long-term effects of drugs such as anti-
depressants. Now, again, I want to balance this by saying, 
there is no, there is little doubt that untreated depression 
and all of its psychosocial sequelae are a bad thing for a 
developing brain. But at the same time, we have got to know 
what the long term treatment with anti-depressants does to the 
developing brain.
    We've gotten a bit of good news in the past year, which is 
that women who, because they had such severe depression, had to 
remain on anti-depressants during pregnancy, and who have taken 
the modern serotonin reuptake inhibitor anti-depressants have 
given birth to children who seem, as we begin to follow them, 
healthy and without any developmental abnormality. But we 
mustn't lose our vigilance.
    So we need trials of efficacy, we need longer term trials. 
And we need, in order to do this, to work closely with FDA and 
other agencies to ensure that a whole therapeutic armamentarium 
is available for children.
    Ms. DeLauro. We agree that it needs to be done. How are we 
implementing what we know needs to get done here?
    Dr. Hyman. We have actually, in collaboration with the 
National Institute of Child Health and Development, attached 
pediatric psychopharmacology research centers onto a number of 
their existing pediatric pharmacologic research centers. In 
addition, we are going to try to, through program announcements 
and conferences, interest the field, many of whom have worked 
on adults, to get involved in these issues of children, and 
certainly, in developing part of our 1998 budget with Dr. 
Varmus, this was one of our major areas of emphasis.
    Ms. DeLauro. To include children?
    Dr. Hyman. To include children, yes.
    Ms. DeLauro. Here we are talking about mental illness. But 
this is true of children across the board. And I would be very, 
very interested in what you are doing in terms of putting 
children----
    Dr. Varmus. We recently had a workshop on inclusion of 
children in trials throughout the NIH. It was hosted by the 
National Institute of Child Health and Human Development. But 
we'd be happy to provide you with some information from that 
workshop.
    Ms. DeLauro. I would like to see that. Because I think it's 
important what you do, and I also think it's important to deal 
with this issue on the local levels as well--what the doctors 
are doing or not doing, and that they are the beneficiaries of 
this information, or to try to call some attention to this area 
in an effort to help you, but also to help youngsters in this 
process.
    [The information follows:]

[Pages 1837 - 1839--The official Committee record contains additional material here.]


    Mr. Porter. Will the gentlelady yield for just a moment? I 
want to catch Mrs. Lowey before she leaves, and say to members 
of the subcommittee, who have expressed some frustration with 
our schedule, that I feel the same frustration. I have just 
signed off on a revision of the schedule for next year that 
will spread the hearings out a little bit more and allow us to 
spend more time with the institutes and with other agencies and 
departments under our jurisdiction.
    I might say that we are attempting toward the end of our 
hearing schedule this year, to bring back certain of the 
Institutes that we felt didn't get enough time. And I also just 
looked at the schedule for next year, which suggested we have 
Mental Health and Aging in the same morning time frame and 
said, ``no, no, let's spread them out.'' Because we feel we're 
shortchanging members and Institutes both in having them so 
compacted.
    I thank the gentlelady.
    Mrs. Lowey. And I thank you. And I do apologize, but as the 
Chairman knows, I wish I could spend some more time. Thank you 
very much.

                  brain development and mental illness

    Ms. DeLauro. Thanks, Mr. Chairman. It really is unfortunate 
that we don't have the time, but it's truly difficult to be in 
three places at one time. I don't have to tell you that. But we 
don't need to give short shrift to anyof the Institutes here. 
Because we're very much interested in the work.
    Again, let me just follow up on this children's piece. If 
you covered this before I came in, I apologize. It is about the 
issue of mental illness in youngsters. And much of what we know 
about mental illness comes from the study of adults and these 
circumstances. How are we working at looking at mental health 
in children and how children are diagnosed with mental health 
illness? And if you can make a connection for me, if you will, 
I mean, we are doing all of this work on the study of the 
brain, or the development, and so forth, and how is that all 
being tied in to where we're, so we can see these things 
earlier than they normally manifest themselves?
    Dr. Hyman. What you're asking is actually very 
sophisticated, and it points to the fact that so much of this 
science has to be interdisciplinary. One of the most exciting 
conferences that I have attended is a conference that was put 
on by our basic neuroscience division on brain plasticity in 
early development. And it brought together a wide variety of 
scientists, developmental neurobiologists, molecular 
geneticists, ranging to people who studied the Romanian 
orphans, to people who study the effects of stress on the 
brain, and people interested in compensatory education.
    And we recognized with great humility the difficulty of 
bringing all of this information together, but also the 
necessity of starting in a serious way to do this if we are 
going to derive the information that's very important.
    So for example, in the mental health arena, we have to 
discover the genes that create vulnerability to mental 
disorders, not only because these are potential targets of 
treatment, not only to make a diagnosis, but also because these 
genes, which create vulnerability and not the certainty of 
illness, will permit us to be able to identify what else in 
development might occur that would be a potentially modifiable 
environmental second hit, turning vulnerability into disorder. 
All of these things will require concerted effort on many 
fronts in the Institute.
    And then I think bringing people together periodically to 
recognize where we are and how we have to set priorities in 
order to make progress.
    Ms. DeLauro. How far along do you think we are in terms of 
how much we know about mental illness in children, and how 
children are diagnosed with mental illness, in your 
professional judgment?
    Dr. Hyman. In my professional judgment, it is very early, 
it is to my mind a national emergency that compared with what 
we know about adults, what we know about children does not 
serve children, their development, our educational system, or 
our work force very well at all.
    Ms. DeLauro. Until we're able to grasp that, I mean, we 
have pieces surrounding the process, a Yale child study is 
trying to deal with the effect of violence in kids. And that's 
in the realm. But until we get some move along, I noted your 
words here, it's a national emergency, we need to move on a 
national emergency that's dealing with youngsters, because 
there's a whole lot of things that get triggered.
    Dr. Hyman. It is, but nature has given us a very hard 
problem. The building of the brain, which is the most complex 
structure in the known universe, with all due respect to the 
other institutes----
    [Laughter.]
    Dr. Hyman [continuing]. Is something that is going to 
require an immense and thoughtful effort. And there's a lot of 
smoke, frankly. We go between, ``it's all genes'', and ``it's 
all environment'', and really digging in and making those 
connections is going to require a long-term investment in the 
fundamental science of development and plasticity.
    But the point you're raising, which is so important, is 
that it cannot be narrow. We have to understand everything from 
genes to the broad social context if we're to understand how 
the brain is built and how people become who they are.
    Ms. DeLauro. Thank you.
    And thank you, Mr. Chairman.
    Mr. Porter. Thank you, Ms. DeLauro.
    Before I call on Mr. Wicker, I want to explain one other 
thing. The Chair has been proceeding under these principles, 
and will continue to do so. Those members who are here at the 
time the subcommittee is called to order will be part of the 
initial group and in the question period, we will then start 
with my questions followed by a minority member, then a 
majority member, then a minority member and the like, for those 
who are here at the time we are called to order.
    For those who come later, we will simply put them into the 
order of their arrival and call on them in the order of their 
arrival. And I've also said, and have been following a third 
rule, that we will give special treatment for ranking members 
who request it, so that they can come and go and get back to 
their other subcommittees if their duties require them to do 
so.
    I also would say to members that we have been allowing ten 
minutes for questioning. Today we expected there would only be 
a few members here, because we don't have votes until 5:00 
o'clock, but suddenly there were six or seven. And that's what 
sometimes causes us to go over.
    So perhaps the Chair will adjust the time for questioning 
downward as the necessity may appear, so that we can give a 
fair amount of time to each of the Institutes or agencies 
before us for that day.
    Mr. Wicker.
    Mr. Wicker. Well, where does that leave me, Mr. Chairman? 
[Laughter.]
    Mr. Porter. You're known as one of our most patient 
members. [Laughter.]
    Mr. Wicker. I think the Chair may have been suggesting that 
I was the last member of the subcommittee to arrive.
    Mr. Porter. I would suggest your arriving right at the 
beginning, then you know where you are. [Laughter.]

       relationship of mental illness to other physical illnesses

    Mr. Wicker. By now Dr. Varmus and the members of the 
subcommittee have heard me mention several times that my home 
State of Mississippi has one of the highest rates of death due 
to heart disease in the Nation. I mention it again today in the 
context of the National Institute of Mental Health, because I 
understand that there is some new research concerning a 
connection between depression and heart disease. The 
information I have says that depression perhaps carries as 
grave a risk of heart disease as elevated levels of 
cholesterol.
    I wonder if you could elaborate on this research, how 
significant a connection do you think there is, and where is 
this research leading as a practical matter?
    Dr. Hyman. That's a good question, Mr. Wicker. And indeed, 
Mississippi being a rural State, our research suggests that 
citizens are less likely to seek treatment fordepression, both 
because of the lack of services, but also because of often rural 
traditions of self-sufficiency, and stigma, and shame. So sometimes 
it's a compounded problem in some of our States.
    There has been very suggestive data for years about the 
association between coronary artery disease and depression. The 
problem with most previous studies is it could not sort out the 
cause and the effect. It was certainly known that people who 
had had myocardial infarctions were depressed at very, very 
high rates. And indeed, they were often untreated using the 
very poor logic of, well, if you had had a heart attack, 
wouldn't you be depressed. And the answer may truly be yes, but 
in fact, all the data suggests that people do much better, and 
indeed mortality is lower, if you aggressively treat the 
depression.
    Now, the new piece of data which is important actually 
comes from an epidemiologic study initiated by NIMH a few years 
ago, just simply to look at the incidence of different mental 
disorders. But because we had this population, it was possible 
to follow them prospectively. And therefore, everyone with 
depression could be followed, and one could look at the 
incidence of heart disease in these people who entered knowing 
they were depressed but not having heart disease.
    And it was found that in people who had a history of major 
depression, there was a four-fold increased risk of heart 
disease.
    Now, there were some technical flaws in the study. So it 
needs replication. But there are some very interesting facts 
here that can be sorted out. One possibility is that people who 
are depressed are less likely to adhere to medical regimens 
such as taking their anti-hypertensives or exercise or weight 
loss. One factor that was ruled out, however, was smoking. That 
is, the investigators corrected for smoking. So that's not the 
villain in this piece.
    But the other possibility is that the brain disease of 
depression activates a whole variety of hormonal responses in 
the body, including the elaboration of stress hormones like 
cortisol, which affect metabolism and might actually produce 
atherosclerosis. Many people with depression are often agitated 
and have higher levels of norepinephrine and epinephrine 
circulating, which might contribute to hypertension.
    Therefore, the disease of depression may be an independent 
risk factor. What we need to know is, first of all, can this be 
replicated prospectively? Second of all, and most importantly, 
and the Heart Institute is already involved in something like 
this, can we intervene? That is, can aggressive treatment of 
depression actually prevent heart disease, or for people who 
have had heart attacks, can it decrease mortality? And I'm very 
optimistic about the possibility of doing those studies and 
getting valuable results.
    I would only add that with that information, then, we will 
have to redouble our efforts to get primary care physicians and 
physicians in all States and settings to recognize and 
intervene in depression.
    Mr. Wicker. Who's carrying on this study?
    Dr. Hyman. The National Heart, Lung, and Blood Institute is 
proposing a study of intervention right now. We are still 
following this sample. The investigator who published the most 
recent prospective data is William Eaton, who's at Johns 
Hopkins.

                  circadian rhythms and mental illness

    Mr. Wicker. Okay. Well, that's very encouraging.
    Tell me what we're doing in the area of research into the 
relationship between altering sleep patterns and manic 
depression.
    Dr. Hyman. That's a very interesting and important area. 
But lacking a good animal model of manic depressive illness, we 
have had to do all of this research on human subjects, and 
therefore, in a non-invasive way. But it is clear that altered 
sleep, one clear public health factor is that altered sleep 
patterns, like shift work, should be avoided by people with 
manic depressive illness, that changes in their daily schedule 
may actually initiate episodes of mania.
    In addition, there are some very tantalizing findings that 
sleep deprivation actually elevates mood. There are other 
findings that have to do with people who don't have manic 
depressive illness, but there are clear mood changes depending 
on the time of day. And I know sort of at 3:00 or 4:00 in the 
afternoon, except for my self-prescribed mega-dose caffeine 
therapy, I would often start drooping and have some mood 
changes.
    We're really beginning to get a handle on this. For this 
reason, I think it's so exciting that we have almost in hand 
the first, the key switches in the hypothalamus, which may be 
controlling our internal clocks, and which may give us better 
tools to see what's happening, both in people with manic 
depressive illness, but also in the rest of them.
    Mr. Wicker. What do you have almost in hand?
    Dr. Hyman. A gene--I'm sorry, I mentioned it in my opening 
statement. An NIMH-funded researcher, Joseph Takahashi, at 
Northwestern University, has over many years narrowed in on a 
gene that seemed to be the master controller of our normal, 
free-running daily periods. That is, what gives us our own 
internal 24 hour cycles.
    And this is going to lead, I think, to very important 
information about understanding our circadian rhythms and what 
goes wrong. I mean, it's important, such genes were actually 
known, but they were known in the invertebrates. There were two 
genes, ``per'' and ``timeless'', that were known in flies, for 
example. But this is the first mammalian gene. And it looks to 
be the key controller of our 24 hour cycles.

                            eating disorders

    Mr. Wicker. Okay. One more question. On the first page of 
your testimony you mention a number of disorders, including 
anorexia nervosa. I'd be curious to know what we've been able 
to accomplish there, but also, if you could, give me a little 
of the history of this disorder.
    Dr. Hyman. One fact is that from everything we can tell, 
all eating disorders are increasing in incidence. But this is 
especially true, not of anorexia nervosa, but of bulimia. And 
basically, what one has, and this is a particular scourge among 
high school and college age women. What one has is basically 
youngsters learning from each other about weight loss 
techniques and binging and purging.
    Then what happens in vulnerable people is they find they 
can't stop, that this takes on a life of its own. And part of 
this increased incidence really is real, that is, probably 
there was not this kind of incidence of eating disorders 40 
years ago. The question is, would these women have been 
perfectly well 40 years ago?
    Here the evidence is rather complex. We find eating 
disorders often in the same families that have depression and 
substance abuse. So one possibility is that this is a 
manifestation of some underlying problem that might have 
alsomanifested itself as depression and then indeed, many women with 
bulimia also have depression.
    Now, there's good news about bulimia, and then I'll get 
back to anorexia nervosa, which is that we've made a lot of 
progress in treatment. The combination of modern serotonin 
reuptake inhibitor anti-depressants, the Prozac-like drugs, 
that hide those, plus behavioral psychotherapies, really have a 
marked effect on improving the symptoms and course of bulimia.
    Anorexia nervosa, I'm sorry to report, remains a difficult 
to treat and refractory disorder. Fortunately, it is relatively 
uncommon, but common enough, depending on the severity, 
affecting between half of 1 percent to perhaps 2 percent of 
women at some level of severity. But at its highest level----
    Mr. Wicker. Almost entirely women?
    Dr. Hyman. Almost entirely women. More than ten to one 
women.
    And there's still perhaps a 10 percent mortality. This is a 
very severe disorder.
    Medications that we have provide modest benefits. But 
there's no medication that is really profoundly successful in a 
large number of women. The mainstay of treatment is still 
cognitive and behavioral therapies, including such common 
sensical things as, you have to achieve a certain weight in 
order to partake in desired activities. But we have a long way 
to go in anorexia nervosa.
    Mr. Wicker. Thank you very much.
    Mr. Porter. Thank you, Mr. Wicker.
    Dr. Hyman, we have many, many more questions. This is very 
frustrating not to have sufficient time, and we will simply 
have to put them in the record in order to give at least some 
time to Dr. Hodes.
    I might say that what I have planned to do is to add on at 
the end of our hearing schedule the three Institutes that 
previously we felt we didn't have enough time with. And I'm 
going to ask each member of the subcommittee if they will 
submit to me an indication of any other Institutes that they 
would like to invite back as well.
    Then on another day, we will also have before us for the 
information of the subcommittee members and Dr. Varmus, NCI, 
NIDDK, NHLBI, OAR and if we can, Dr. Varmus, yourself, for a 
panel on the priorities of funding by disease, an issue that 
has been raised so often by so many members that I think we 
ought to spend some time and really address that.
    The three Institutes that we have now that were not given 
sufficient time are NCI, NHGRI and NIAID. And there may be 
more.
    So thank you very much, Dr. Hyman, for the fine job you're 
doing. We'll have to put our questions in the record.
    You may be invited back, and thanks for your good statement 
and answers to the questions that were posed.
    Dr. Hyman. Thank you very much.
    Mr. Porter. Thank you, sir.
    We'll stand in brief recess.
    [The following questions were submitted to be answered for 
the record.]

[Pages 1846 - 1913--The official Committee record contains additional material here.]

                               ----------

                                           Tuesday, March 18, 1997.

                      NATIONAL INSTITUTE ON AGING

                               WITNESSES

RICHARD J. HODES, M.D., DIRECTOR, NIA
TERRIE WETLE, PH.D., DEPUTY DIRECTOR, NIA
COLLEEN F. BARROS, EXECUTIVE OFFICER, NIA
KARYN S. ROSS, FINANCIAL MANAGER, NIA
HAROLD VARMUS, M.D., DIRECTOR, NIH
DENNIS P. WILLIAMS, DEPUTY ASSISTANT SECRETARY, BUDGET, DEPARTMENT OF 
    HEALTH AND HUMAN SERVICES
RUTH KIRSCHSTEIN, M.D., DEPUTY DIRECTOR, NIH

                       Introduction of Witnesses

    Mr. Porter. The subcommittee will come to order.
    I apologize for the time constraints that we've found 
ourselves under. You may well be invited back.
    Dr. Hodes, I have to leave at 12:00 o'clock, because I have 
a speech to make out at American University over the noon hour. 
And I have asked Mr. Miller if he could take the Chair at that 
time and finish up the hearing.
    So I hope that you have time to stay a little bit longer if 
necessary.
    Dr. Hodes. Certainly.
    Mr. Porter. Thank you, sir. Would you introduce the people 
you have brought with you and then proceed with your statement.

                           Opening Statement

    Dr. Hodes. I think Mr. Williams from the Department and Dr. 
Varmus have already been introduced.
    To my left, Karyn Ross, who's the Financial Manager for the 
Institute; Dr. Terrie Wetle, the Deputy Director; and Colleen 
Barros, the Executive Officer of the Institute.
    The National Institute on Aging supports research on the 
basic aging process as well as research on a variety of age-
related diseases and conditions, including Alzheimer's disease, 
cancer, cardiovascular disease and osteoporosis. The overriding 
goal of all this research is to improve the quality of life for 
older Americans and their families.

                          alzheimer's disease

    The NIA leads a national effort in research on Alzheimer's 
disease, a devastating disease which as you know affects 
approximately 4 million Americans at present, taking an 
enormous toll on the patients, their families, caregivers, and 
the public. Some of the recent discoveries in Alzheimer's 
disease and the pace of the discovery are typified in the first 
poster, illustrating some of the findings of underlying genetic 
relationships to Alzheimer's in the period from 1990 through 
the present.
    [See figure 1.]

[Page 1917--The official Committee record contains additional material here.]


    There have been descriptions now of three genes on 
chromosomes 21, 14 and 1, which are responsible for the 
familial form of Alzheimer's disease, often of early onset, 
affecting individuals as early as their 30s, 40s and 50s. The 
fourth factor, ApoE, a gene on chromosome 19, is associated as 
a risk factor for the more common form of later onset 
Alzheimer's disease.
    This genetic information has already been translated into a 
number of steps toward application. It has been shown over the 
past year, for example, that combinations of modern techniques 
of brain imaging, together with genetic analysis, have 
suggested the ability to diagnose abnormalities in brain 
function as many as 20 years before the appearance of symptoms, 
providing an opportunity to identify disease early, and an 
opportunity to intervene before irreparable damage has been 
done to the brain.
    In addition to these diagnostic issues, we've moved a step 
toward understanding risk factors for Alzheimer's disease. 
Among the risk factors identified are age and genetics. We've 
also uncovered over the past year or two more dramatic 
information about possible protective factors.
    [See figure 2.]

[Page 1919--The official Committee record contains additional material here.]


    There's been a good deal of scientific as well as press 
interest in the role of estrogens resulting from recent 
demonstrations that women who have a history of estrogen use 
have dramatically lower incidence of Alzheimer's than those who 
have never used estrogens.
    In the area of anti-inflammatory agents, a great deal of 
basic research has suggested that there might be a role 
forinflammation and immune response in the pathology of Alzheimer's 
disease. And in fact, there has been a good deal of attention paid to 
the finding that individuals who have a history of using anti-
inflammatory agents for diseases such as arthritis have dramatically 
lower incidence, once again, of Alzheimer's disease.
    In both of these cases, the epidemiologic and basic science 
imperatives now converge on the need for direct clinical 
testing. And in the areas both of estrogen use and anti-
inflammatory agents, there are in fact clinical trials 
underway.
    In the area of anti-oxidants, there's been a good deal of 
basic science showing that oxidative damage appears to be a 
candidate for a part of the mechanism involved in death of 
neuronal cells. And here once again, trials testing the effect 
of antioxidants on the progression of Alzheimer's disease are 
in progress. And in fact, as early as next month, we expect 
publication of one study which will again emphasize yet another 
area for hope in the treatment of this disease.

                            biology of aging

    The basic research supported by the Aging Institute and 
across NIH tends to find underlying biological processes which 
are critical to many of the problems and processes of aging. 
Over this past year, there's been discovery of a number of 
genes in lower organisms which, when expressed in altered 
forms, are capable of extending both the health and life span 
of organisms several fold, providing interesting opportunities 
for translation into areas of understanding and intervention 
relevant to humans.
    Interventions such as caloric restriction provide another 
interesting phase of scientific advance. Studies showing that 
restricting animals calorically by 30 percent while maintaining 
nutrition has dramatic outcomes in reducing incidence of 
diseases such as cancer, and in fact of prolonging life span by 
35 percent and more. Once again, these studies will be the 
basis for determining whether there are interventions 
appropriate for human use.
    The issue of translation of discoveries such as this into 
practice and application is, as for all Institutes at NIH, a 
high priority. Cardiovascular disease, for example, remains the 
major cause of death among older Americans, accounting for 
nearly 50 percent of deaths of Americans 65 and older.
    In the past year, there's been identification of stiffening 
of large and medium size arteries as a potential risk factor 
for serious cardiovascular events. Taking advantage of 
information such as this, intervention studies have been 
carried out with efforts using, in one case recently reported, 
a diuretic based anti-hypertensive therapy to reduce 
hypertension association risk with the finding that five years 
of such treatment has lowered the risk of serious 
cardiovascular consequences by 34 percent. In fact, that risk 
reduction in absolute terms was nearly double for diabetics 
than for non-diabetics.

                          demography of aging

    Overall, all of these issues take on an imperative with the 
change in demography of the American, in fact, the world, 
population. The demographic predictions for the population of 
the world in the next 50 years are summarized or illustrated in 
this format. What you can see in 1950 and in 1995, the near-
present, is a very familiar sort of pyramid, in which, in lower 
ages at the bottom, there are the greatest numbers of people 
living, with a very rapid decrease toward small numbers living 
to advanced age.
    [See figure 3.]

[Page 1922--The official Committee record contains additional material here.]


    A dramatic change in that is expected, as you can see 
illustrated here, for the year 2050, with what is called a 
squaring of that curve, a great increase in the number of 
people at advanced ages, and a great increase in the ratio of 
older to younger individuals, making more imperative our 
efforts to find solutions to the problems of disability and 
poor health in older people.
    The next poster illustrates some of the good news that has 
again been published of late, with a good deal of attention 
even in today's press, from a study that will be appearing in 
the proceedings of the National Academy of Science. This study 
has followed participants in the National Long Term Care Survey 
from 1982 through the present.
    [See figure 4.]

[Page 1924--The official Committee record contains additional material here.]


    What you can see graphed here in the upper line in red is 
the number of individuals over 65 in the United States who were 
expected to be disabled if the rates of disability reported in 
1982 had not changed. The lower line in blue illustrates the 
actual observed numbers of Americans with disability observed 
in 1982 through 1994.
    The difference between that predicted by unchanged rates 
from 1982 and those which reflected decreased rates of 
disability observed over these years amounts to 1.2 million 
fewer Americans disabled in 1994 than would have been predicted 
if those rates had not changed.
    Our challenge and the opportunity for the years to come is 
to sustain and in fact to accelerate these changes based on 
increased understanding of the mechanisms which underlie the 
cause of disability, and the discovery of ways to intervene to 
alter those risk factors.
    Mr. Chairman, thank you for the opportunity to discuss 
these issues with you. The fiscal year 1998 budget request for 
the National Institute on Aging is $495,202,000, and I welcome 
an opportunity to answer any questions you might have.
    [The prepared statement follows:]

[Pages 1926 - 1932--The official Committee record contains additional material here.]


                          disability research

    Mr. Porter. Thank you, Dr. Hodes.
    We note that you gave your entire testimony without a 
single note, not even a heading or anything like it, which is 
very, very impressive.
    Let me ask regarding this chart, since you've got a rising 
population above 65 but declining rates of disability, are the 
absolute numbers more or less remaining constant?
    Dr. Hodes. You can see, or almost see on the scale in that 
lower curve that the absolute numbers of disabled Americans 
increased from 6.4 million in 1982 to 7.1 million in 1994. From 
1989 to 1994, it's a very small slope, an increase from 7.0 to 
7.1 million.
    It has been projected, and of course, projections become 
more speculative than recorded fact, that what amounts here to 
a 1.2 or 1.3 percent decrease in the rate of disability per 
year over this time period would need to be increased to 
approximately 1.5 percent to produce a straight line projected 
into years to come.
    Mr. Porter. Reading today's Washington Post and the article 
that resulted from the release, have researchers put forward 
any predictions about the longer term savings in Medicare, if 
the trend continues? In other words, they've mentioned 
substantial savings in one year. What would it amount to into 
the future? Can we balance the budget on this?
    Dr. Hodes. These areas remain certainly far too speculative 
for me to engage and involve a good number of factors, other 
than projections of disability. It needs to be emphasized how 
complex such a projection is. That is, there are enormous 
savings presumably associated with decreases in disability, 
since disabled persons cost the health care system far more 
than non-disabled persons.
    There also are costs to the research and the interventions 
which are responsible for those changes. Certainly those 
involved in policy and those involved in balancing the budget 
and Medicare finances are highly concerned with these issues. 
Our efforts in terms of generating research such as this are to 
provide such policy makers with the information which is vital 
to their projections.
    Mr. Porter. Can I ask you about the release itself? Was the 
release done by NIA or was it done by Duke University?
    Dr. Hodes. There were separate releases from NIA and from 
Duke, which is fairly typical of the way a lot of such 
discoveries are handled. The institution that funds the 
research is always welcome and most often will issue its own 
press release. In selected instances, NIA and NIH will 
supplement, complement or cooperate in those releases. In this 
case there were two.
    Mr. Porter. And was the timing----
    Dr. Hodes. Dr. Varmus reminds me that journals, such as 
PNAS, will often also highlight specific articles and issue 
their own releases. So it's not uncommon for there to be 
multiple releases.
    Mr. Porter. I'm very happy that the release was made and 
these questions are not at all critical. But was the timing of 
the release, did it have anything to do with the timing of your 
testimony today?
    Dr. Hodes. If so, it was orchestrated by powers far beyond 
our own. It's of interest that the release for the publication 
in PNAS was initially scheduled for the day before the original 
date of scheduling for our Institute's testimony. 
Coincidentally, when you altered our schedule, the article's 
publication was delayed, and so it appeared one day before our 
current hearings. None of this had anything to do with our 
intervention, to our knowledge.
    Mr. Porter. I think that's, whatever caused this timing, I 
believe that the good news has to come out and be highlighted 
more than the bad news. This is obviously very, very good news 
and something that has captured the press's attention and I 
think will also capture the public's attention. And it's 
something that I want to very much encourage.
    Dr. Varmus. I'd like to emphasize, though, we don't really 
know the explanation for the decreased disability rates. While 
we think that medical research plays some role, there are many 
other factors alluded to in Dr. Manton's paper that really 
contribute, and the relative contributions made by the various 
components have yet to be sorted out.
    Mr. Porter. It's funny, you anticipated my next question 
perfectly.
    Dr. Hodes. I would add only that the sorting out of those 
causes is in fact a very high priority in the research that 
will be forthcoming based upon this finding.

                          alzheimer's disease

    Mr. Porter. Well, it certainly got Senator Kennedy 
interested in more money for research. And I think that's all 
to the good.
    The news about decreasing disability rates in the aging 
population is welcome. But is there any similar news with 
regard to Alzheimer's disease? Will the increasing numbers of 
older Americans afflicted with Alzheimer's swamp whatever 
beneficial impact lower disability rates may have on health 
care expenditures and the quality of life? You partially 
answered this in your opening remarks.
    Dr. Hodes. But it's a very important question. The 
incidence of Alzheimer's disease as noted is very highly age 
related. In the age range from 65 to 74, the prevalence of 
Alzheimer's is about 3 percent. By the time it reaches the age 
group 85 and over, it's been estimated to be as high as 47 
percent, that is, nearly half the people 85 and over. The 
extrapolation of these demographic projections for an increase 
in the age 85 and over population in the United States over the 
decades to come, would indeed have staggering consequences if 
there is not an increased ability to delay, prevent, or treat 
Alzheimer's disease.
    And that is a part of the underlying urgency behind that 
effort. I think there is reason for optimism. There are 
candidates for effective treatments. There are candidates based 
on our increased understanding of the basic biology of the 
disease. But the urgency is clear.

                          demographic research

    Mr. Porter. Dr. Hodes, some researchers believe that there 
is a practical limit to age span of about 85 years, while 
others think typical life spans could extend into the upper 
90s. Average life span obviously has major implications for the 
depletion of the Social Security and Medicare trust funds, 
independent of the health status of the population. Is there 
anything in demographic research to provide counsel to the 
Social Security actuaries or are findings on life span too 
uncertain at present?
    Dr. Hodes. Clearly, the research area of demography has a 
great deal to offer to the policy makers in particular. 
However, in precise answer to your question, the recent 
publication summarizing efforts at projecting average life 
expectancy in the American population over decades to come is 
most notable for the very wide confidence limits. So wide, that 
the implications for, for example, the expenditures in Medicare 
and Medicaid leave enormous ranges of uncertainty. And I think 
one has to concede at times that some of these projections are 
simply beyond the level of current science to be carried out 
with fine limits of discrimination.
    So just as you alluded to in your suspicions, the 
projections by various equally skilled and expert investigators 
and agencies are extremely diverse, reflecting uncertainty in 
those estimates.

                          alzheimer's disease

    Mr. Porter. Another study reported last week suggested that 
small, silent strokes may cause much of the memory loss and 
dementia associated with Alzheimer's disease, and that symptoms 
of Alzheimer's can be prevented by preventing strokes. How 
should we interpret this finding, that the dementia that is 
thought to be linked with Alzheimer's is really a consequence 
of small strokes instead? And this particular study was done 
with female subjects. Do you expect the results also to be 
confirmed in male subjects?
    Dr. Hodes. This was an extremely interesting study that was 
carried out on a population of nuns, the School Sisters of 
Notre Dame, a population that has been highly committed to the 
study who have been followed over years with very detailed 
analyses of cognitive function and with a commitment to autopsy 
or post-mortem examination of brains. And the finding, as you 
note, reported last week, was that there was a dramatic effect 
of clinically undetectable but pathologically detected strokes 
which influenced the amount of clinical dementia, of memory 
loss, that occurred in individuals with Alzheimer's.
    In fact, the findings of the study showed that these 
strokes had an effect on cognitive function only in individuals 
who also had Alzheimer's disease; that is, the population of 
nuns who did not have pathologic findings of Alzheimer's did 
not have any changes in cognitive function as a result of the 
stroke. So that in this population, for the kind of microscopic 
strokes being detected, it appeared that it was not a confusion 
of diagnoses, but an effect on the symptoms of Alzheimer's 
disease of concomitant cerebrovascular disease and stroke.
    The implication is, of course, that even with the diagnosis 
of Alzheimer's, and even apart from efforts to directly 
intervene to treat the causes of Alzheimer's itself, there may 
be room for preventing some of the clinical manifestations of 
Alzheimer's by preventing strokes, by treating hypertension, 
for example, in those populations at risk.
    Mr. Porter. Thank you, Dr. Hodes.
    Ms. DeLauro.

                            quality of life

    Ms. DeLauro. I want to follow up on the question that the 
Chairman was asking with regard to the article in the 
Washington Post. That research often, may succeed in reducing 
Medicare and Medicaid costs, I think it's fair to say that 
experience to date has been that while research improves the 
quality of life and life spans, oftentimes new tests and 
treatments have generally increased rather than decreased 
medical spending.
    I just wanted to ask what's different about this research 
that's going to lead us to expect cost reductions.
    Dr. Hodes. I think it's an important and very complex 
question, to which there is not a simple answer. Indeed, there 
are some interventions which have enormously positive outcomes 
on the quality of life, on health and on life expectancy which 
may be costly.
    There are also, I must hasten to add, others which are not. 
Last year, for example, I had the opportunity to present to the 
Committee an example that resulted from several studies carried 
out by investigators at Yale who were studying interventions 
for falls, in those individuals at highest risk for falls. And 
in that study investigators discovered multifaceted 
interventions which were capable of reducing by 44 percent the 
incidence of falls in a group at high risk.
    There was a subsequent follow-up to that study which 
analyzed the costs, including the costs of carrying out the 
study and of the intervention itself. That case concluded that 
there was a net savings, even with those factors accounted for, 
in the range of $3,000 per patient per year, and a net decrease 
in all medical costs as a result of that intervention.
    Clearly, our highest priority is to find interventions that 
will improve the quality of life and avoid disability and 
disease. But not to be disregarded is our commitment and 
responsibility to attempt to identify those which will also be 
cost effective and cost saving.
    Ms. DeLauro. Well, I applaud the interventions and where 
they can lead. But I think in some instances we've looked at 
where we have increased health care costs for a variety of 
reasons. I'm hopeful that that doesn't have to be the case, and 
that we can in fact, with what you and others are doing, to 
bring those costs down. That's where people can take advantage 
of what the discoveries are.
    Dr. Hodes. I apologize for borrowing perhaps an over-used 
example, but one highlighted frequently was the case of polio, 
and the high cost of technology for iron lungs, a technology 
that was not definitive, the comparison of course being the 
discovery of the cause of that disease and the ability to 
immunize in a highly cost-effective way. And that is certainly 
a model to which we aspire for most of those problems which we 
confront at present.

                            embryo research

    Ms. DeLauro. This subcommittee has debated the ethical and 
scientific pros and cons of embryo research in each of the last 
two years. And I anticipate that we will have that debate and 
discussion again. I understand that this research may hold 
particular promise in the treatment of Alzheimer's and in 
Parkinson's disease.
    What has been the impact on your research of a complete ban 
on federally-sponsored research in the use of human embryos?
    Dr. Hodes. I think that ban has had very little effect on 
the research areas supported by our Institute. In the areas you 
mentioned, such as Parkinson's, I think there, and again this 
has been largely conducted through collaboration, most of the 
funding is conducted through the Neurology Institute, and 
sources of tissues and cells other than those restricted by the 
ban have allowed research to progress. I think it has not been 
a great cost to the research conducted by the Aging Institute.

                              osteoporosis

    Ms. DeLauro. Osteoporosis, as you know is a serious problem 
on the elderly, particularly women. My understanding is that 
it's likely to become a more serious problem, as today's young 
people are not eating enough calcium, or taking in enough 
calcium. Bones stop being able to absorb calcium by age 22.
    What research on improved osteoporosis treatments is 
currently underway and how promising are the findings?
    Dr. Hodes. Well, there are a number of promising 
interventions that have pointed out the efficacy, as you are 
probably aware, of increased dietary calcium, of adequate 
vitamin intake to support both absorption and use of that 
calcium, and the role of estrogen and estrogen replacement 
therapy.
    One recent study just initiated by the Aging Institute is 
attempting to capitalize on preliminary findings in an animal 
model which is showing that a unique approach to treating 
osteoporosis with a drug called minocycline that's related to 
tetracycline, may provide an additional effect to the drugs 
currently in use, most of which prevent resorption. Minocycline 
has shown promise in animal experiments of allowing the actual 
addition of bone and increased bone strength, in addition to 
reducing the amount of bone loss that often occurs with aging 
and after estrogen withdrawal, for example.
    Therefore I think in summary it's fair to say that we are 
looking at the level of clinical trials of many of the more 
established treatments, and in small scale clinical 
interventions, we are trying to take advantage of basic science 
research which identifies innovative metabolic approaches to 
altering the balance of calcium deposition in bone.
    Ms. DeLauro. Thank you.
    Thank you, Mr. Chairman.

                          health care savings

    Mr. Miller [assuming chair]. Let me follow up with a couple 
of questions that had been asked earlier, and that is, this 
Duke study about understanding why we're going to save money. I 
remember we were saying if you encourage people to smoke more, 
they'll die earlier, we'll save money on health care. That's 
obviously a ridiculous statement. With people living longer, 
we're going to spend more money on their total health care.
    So how do we save money, just do the arithmetic?
    Dr. Hodes. Again, excuse me for emphasizing that our 
primary goal, of course, is the maintenance of quality of life 
and life without disability. And the concern you mentioned 
comes next. But it is nevertheless an important one. There are 
a number of facts that I think surprise individuals at times. 
There is no doubt that the longer one lives, the longer one is 
going to need care, including medical care.
    However, the costs of medical care later in life actually 
decrease substantially as age proceeds. So the medical care in 
the final year of life, for example, is much less costly for 
individuals 90 years old than for 80 or 70 or 60, 
whichindicates that the prolongation of life does not necessarily mean 
the extension of high costs to the degree that one might deduce unaware 
of those figures.
    Mr. Miller. We're all affected by our own personal stories, 
and I lost my father-in-law three years ago at age 91, my 
mother-in-law two years ago at age 87, and my mother's 87 and 
in a nursing home. When you see the quality of life being so 
poor, and you start wondering, will I see my mother again on 
Monday. And she's got a tube in the stomach, she's just going 
on, it's not a great quality of life.
    I think she knows me when I visit her, at least I have a 
feeling she does. She's been like this for a year. Her whole 
body's wearing out. There's no real diagnosis as such. It's 
just old age.
    And as Mr. Porter asked, that's the question, how long 
before, does old age overcome the diagnosis of a specific 
disease, not necessarily Alzheimer's, she's not swallowing, 
that's the reason she had the tube put in. At what stage does, 
how long can you prolong?
    Dr. Hodes. The answer to how long we can prolong life is of 
course not precisely known. I fully sympathize, I think all of 
us have the same very emotional experiences with loved ones, 
with family, and the difficulties people incur with aging. Our 
goal is clearly not, as a result of research, to extend life at 
any cost and at any quality. It really is to try to extend life 
of high quality.
    What is reassuring about studies such as this, showing 
decreased disability, is as noted in the article, for example, 
is that the gain is high even for those people of the greatest 
disability. That is, we're not only decreasing disability for 
people at the margin, while people at an extreme of disability 
go unimproved; rather the statistics show that there has been a 
real improvement in the quality of life measured by decreased 
disability even in the most disabled population, and even in 
the oldest of the most disabled population.
    And I think that's clearly what we all aspire to, not just 
allowing people to live some months or years longer, but 
finding a way to do that, such that the most disabling and 
distressing and anguishing of diseases are reduced and improve 
the quality of life.
    Mr. Miller. The percentage of people in institutions, 
nursing homes or other institutions, has that been declining or 
does it depend on the statistical measure you use?
    Dr. Hodes. Yes. There has in fact been a decrease in the 
numbers of people institutionalized below those expected from 
previous rates. Some of it may be accounted for by the decrease 
in disability shown here. Other components of it appear to be 
accounted for by changes in decisions about 
institutionalization.
    This also, of course, clearly relates to quality of life. 
For many individuals, if there's a way to provide the 
infrastructure, the research, the mechanism, to allow people to 
cope in a home setting, or non-institutionalized setting, that 
is likely to result in a higher quality of life for families 
and individuals. That as well as the decrease in disability 
itself are likely contributors to the decrease in 
institutionalization over the expected levels in recent years.
    Mr. Miller. My Congressional district in Florida has more 
senior citizens than any Congressional district in the United 
States. So I've got my area, Sarasota, Bradenton, has lots of 
retirees. So it's an area of great interest.
    But it's also different because people that move to Florida 
have broken their ties to the north. And there's a higher rate 
of institutionalization in Minnesota, for example, than in 
Florida, because people move into mobile home parks and take 
care of each other.
    Dr. Hodes. I think you're right, that social and family 
settings have a great deal to do with these outcomes.

                          falls in the elderly

    Mr. Miller. Last year, I remember when we were talking with 
the CDC during their appropriations hearing, they were talking 
about doing research on falls in the elderly. And I was 
intrigued by why they were doing it. Do you do that type of 
study?
    Dr. Hodes. Yes. I mentioned briefly some of the research 
conducted on falls, which is still ongoing, is attempting to 
first identify the causes of falls in older people. That 
research was highly successful as reflected by the fact that 
the next stage, designing interventions based on the 
identification of risk factors, has shown in clinical settings 
the ability to decrease falls nearly half in individuals at 
high risk. And to do so with interventions that are highly 
cost-effective.
    I think the CDC becomes involved in monitoring the 
incidence of this disability, or the causes of disability in 
the population, and being potentially a source for monitoring 
any changes in clinical outcomes, which might occur as a result 
of widespread application of the kinds of clinical 
interventions that have been identified by ongoing research.
    Mr. Miller. By monitoring, you mean more of a statistical 
measuring?
    Dr. Hodes. Yes.
    Mr. Miller. Because I got the impression it was actually 
the research on how to prevent falls, and they were talking 
about using inflatable devices around elderly people for 
falling. I was just curious why they were doing that research 
and, not that you oppose that research, it seems more logical 
to be in your realm.
    Dr. Hodes. Yes. Research such as the specific one that you 
mentioned, the use of padded devices to try to prevent 
fractures at the time of falls, is supported by NIH and by NIA 
specifically. Once again, as to the degree that those 
interventions are used in more widespread fashion across the 
population, a monitoring of their effectiveness might be a part 
of surveillance by CDC.
    Ms. Kirschstein. Mr. Miller, the CDC has a Congressional 
mandate to study injury prevention.
    Mr. Miller. Right, it's in the injury area.
    Ms. Kirschstein. Yes.
    Mr. Miller. And we're hearing this in another area, why is 
CDC doing it, before they were talking about social work in 
mental health, and I don't object to what they're doing, it's 
just, wait a minute, we're having another area doing the same 
thing, and is there an overlap and duplication. It seems like 
it's more logical under your area of research than CDC.
    But that's how they're justifying their program. I don't 
mean to put you on the spot in that.
    Thank you very much.
    Mr. Wicker.

                            prostate cancer

    Mr. Wicker. Thank you, Mr. Chairman.
    First of all, tell me about this new blood test on prostate 
cancer that could let us know earlier about a possible 
diagnosis.
    Dr. Hodes. That's an extremely interesting story. It was 
reported some years ago, on the basis of research carried out 
within the intramural program actually at the National 
Institute on Aging, that sequential measurements of prostate-
specific antigen over time could allow diagnosis of prostate 
cancer several years before it was otherwise identifiable.
    More recently, a new finding, published and publicized in 
January, indicated the use of a new test, devised 
collaboratively again, through the intramural program of the 
Institute on Aging, together with investigators at Johns 
Hopkins, that looked at compartments of the PSA or prostate-
specific antigen. In fact, it looked at ratios of free to total 
and reported that using this measurement, it was possible to 
identify prostate cancer up to 10 years before diagnosis.
    Now, all of this is in the context of a fair controversy 
about the role for diagnosing prostate cancer early. Prostate 
cancer can be aggressive and it can be less aggressive. And in 
some individuals, its progress is sufficiently slow that it's 
actually an issue of current medical debate whether it is 
justified to intervene surgically since at an extreme, the 
clinical course might be so slow as to never cause a clinical 
problem.
    What is going to be published this month in fact, and has 
just passed its embargo, so I'm comfortable being able to speak 
about it, is a further elaboration on the study that I think 
you were referring to in which it is reported most promisingly 
that use of the ratio of free to total PSA not only allows 
prediction of prostate cancer, but as reported by these 
investigators, allows a distinction between what are likely to 
be aggressive and non-aggressive cases of prostate cancer.
    It's one finding published in a journal which will await 
repetition and replication. But if true, it would, I think, be 
enormously important in decision making on how one uses the 
diagnostic criteria to make therapeutic decisions. If the more 
aggressive cases could be identified as those which would most 
benefit from intervention such as surgery, while cases less 
likely to be aggressive could be spared the morbidity of that 
treatment, this would indeed be an important advance.
    Mr. Wicker. You alluded to a recent controversy. And that 
surrounds even whether the test should be given at certain 
ages, is that correct?
    Dr. Hodes. I think that's correct. And it derives from the 
controversy of what one should do with the finding. The 
argument would follow that if indeed a positive finding on this 
test, meaning a likely diagnosis of prostate cancer, had no 
clear therapeutic implications, because one simply didn't know 
whether to treat or not, some would argue it's questionable 
whether the test should even be done. That's clearly a complex 
question, and there is not a unanimous opinion. But I think 
that's the essence of the current controversy.

                   alzheimer's disease and ibuprofen

    Mr. Wicker. But it is interesting that a scientist would 
suggest that we could know too much too early. It strikes me, 
as a layman, as being quite interesting.
    Well, let's see. You mentioned on Alzheimer's disease a 
cooperative study about prevention and treatment, and you 
mentioned a bunch of combinations, selegilene, vitamin E, 
prednisone, estrogen therapy perhaps. What are we learning 
about the relationship between Alzheimer's and ibuprofen? Where 
does that come in?
    Dr. Hodes. On the basis of suggestions that anti-
inflammatory agents might have a protective role on development 
of Alzheimer's, a study was carried out in the Baltimore 
Longitudinal Study on Aging, part of the intramural program of 
the NIA.
    In this study, there were individuals who were followed 
with examinations every two years for extended periods of time, 
up to decades. It was possible to do a retrospective analysis 
looking at the history of people over 15 years and ask whether 
they did or did not have a history of use of anti-
inflammatories, ibuprofen being one of them. And asking in turn 
whether there was a relationship between this history and the 
likelihood or risk of developing Alzheimer's disease.
    And it was found that individuals who had taken ibuprofen 
had approximately 50 percent the likelihood of developing 
Alzheimer's as those who did not. Even more striking for those 
who had been taking ibuprofen for two years or more, there was 
a 60 percent reduction in the likelihood of developing 
Alzheimer's. I have to emphasize that this is an observational 
study.
    It is strongly suggestive, but will not take the place of a 
direct treatment study in which individuals are for example, 
randomized in such a way that they are taking a pill and are 
unaware whether that pill is ibuprofen or a drug or a placebo 
which is being compared.
    That is the form of study which is most able to, with 
certainty, predict the utility of the therapeutic intervention. 
And it is likely now, based on the study that I mentioned and 
that you asked about, that such intervention studies will be 
proposed and supported in the very near future.
    Mr. Wicker. How far away is your agency from issuing a 
report saying, it's a good idea to take some of these drugs?
    Dr. Hodes. The time frame for a study, a demonstrated 
efficacy, is of course dependent upon the disease. In the case 
of Alzheimer's disease, which is a slowly but unfortunately 
progressively debilitating disease, there is a period of 
follow-up likely to be in the range of a minimum of two years 
that one will have to observe to see if a population is altered 
in the course of its disease.
    If one is looking to prevent disease, and if one begins 
with a population that doesn't have Alzheimer's and waits for a 
number of those, even if one selects a high-risk population, to 
develop disease, to see whether treatment A or treatment B 
makes a difference, one is likely to be talking about follow-
ups of at least five years and perhaps more. That is, for a 
study initiated today, even if all the patients immediately 
began taking the drugs of comparison today, there is likely to 
be a lag of this many years before, with certainty, a 
recommendation could be made.
    Now, some of the studies that I've mentioned to you, one 
involving prednisone and one involving estrogen, are underway, 
and the results of those studies are likely to be reported 
within the next one to two years. The more extensive, larger 
studies based on some of these new candidates will have a lag 
time that is therefore proportionately longer.
    Mr. Wicker. Are these studies with prednisone and estrogen 
among so-called high-risk populations?
    Dr. Hodes. The ongoing studies at present for estrogen and 
with prednisone are in individuals who already have a diagnosis 
of Alzheimer's disease. These studies are looking to see 
whether the progression of disease is altered or slowed by 
treatment.
    The second generation of studies, that of actual prevention 
by finding people at a high risk for disease although they have 
no disease, is the generation of studies that we are just 
embarking on now. The candidates for such interventions will 
frequently come from the first set of studies.
    So when one has a drug which seems to slow the progression 
of disease, a natural next generation of study will be to say 
if that intervention is moved to an earlier point in time, when 
detectable clinical damage has not occurred, to ask whether 
that same intervention will actually prevent the development of 
disease which is of course the most hoped-for objective of such 
intervention.
    Mr. Wicker. Who are high-risk people?
    Dr. Hodes. The most clear-cut answer for high risk, as I've 
indicated, is, for example, if one chooses a population that's 
at age 85. I've also mentioned some of the genetic risk 
factors. One could pick individuals with a given Apo-E type, 
which I must add is not a guarantee or an absolute predictor of 
disease, to identify an even higher risk population.
    I'd mentioned that modern techniques of brain imaging can 
identify abnormalities in individuals years before the 
detection of symptoms. The screening of individuals by such a 
technique in principle, though an expensive approach, could 
identify individuals at high risk to develop clinical disease, 
though not having the disease at present.
    Currently, investigators are looking individually and in 
combination at such identifiers as age, genetic risk factors, 
brain imaging techniques, which collectively may be able to 
identify populations at a high risk which would be appropriate 
candidates for intervention.

                            genetic research

    Mr. Wicker. And finally, let me just ask you what the 
Institute is doing with regard to attacking age-related 
diseases by manipulating or mutating genes? And I wonder if you 
could comment on some of the ethical questions which might 
arise in that connection.
    Dr. Hodes. Well, the approach to manipulating genes is 
being carried out extensively in animal models. In a number of 
them, mutations are identifiable which will have substantial 
effects on life span prolongation and on health span 
prolongation.
    Our principal goal in these studies is to identify biologic 
processes altered by the genetic manipulations which will give 
clues to interventions in humans that will not necessarily 
necessitate genetic interventions. The genetic interventions, 
as has been often discussed, carry scientific, medical and 
ethical complications that in the near future are probably 
going to be prohibitive.
    But that doesn't diminish the value of using genetic 
studies in animal models to pinpoint the biologic processes, 
the biochemistry that may be modifiable by other than genetic 
manipulation in humans, and therefore, the genetic studies may 
be quite valid and important in suggesting interventions 
appropriate to humans.
    Mr. Wicker. I don't understand what you mean. What would be 
an example of that?
    Dr. Hodes. Well, an example would be taking a gene from one 
of the familial forms of Alzheimer's disease, a mutation 
associated with Alzheimer's, and introducing that into a mouse, 
as has been done over the last year or two, making a transgenic 
mouse that expresses an abnormal human gene associated in 
certain families with early onset Alzheimer's.
    It's been observed that such animals develop lesions in the 
brain that look like Alzheimer's, and as they grow older, in 
the case of mice, this means by nine months of age or older, 
they develop abnormalities in learning that appear to be at 
least broadly defined analogous to what one sees in 
Alzheimer's.
    Now that one has gone this far, finding out the error in a 
gene, one can in an animal model look for ways to reverse it. 
For example, introducing an enzyme that will do the job that 
the mutated gene product in the affected patients can't do, 
thus eliminating the toxic material that might play a role in 
Alzheimer's disease.
    Mr. Wicker. Thank you.

                             long-term care

    Mrs. Northup [assuming chair]. Thank you.
    Doctor, I have just a couple of questions. Have you all 
done any research that looks at nursing facilities and the 
possibility that they have individualized, or whether or not 
they do have individualized or intensive therapies? Considering 
as you look at the aging process there are a number of 
different reasons and ways people wind up in nursing homes, how 
intensive or individualized are the therapies and how much 
difference does that make?
    Dr. Hodes. It's a very important question that is being 
pursued by an active research program supported by the Aging 
Institute. There is a serious look at so-called special care 
units, for example, which may be tailored to the special needs 
of individuals with dementia, or individuals with HIVinfection 
in another domain. The interest and importance here is both to find out 
how these special care units address the special needs of the 
individuals in those units and how in turn that impacts on the function 
of the remaining patients in a nursing facility.
    So, for example, the questions being asked at present, are 
how special care units are defined across the country, how many 
of them there are, and then to look, most importantly, at 
practices and how those practices affect the quality of life of 
patients, of family and of staff, which ultimately will be of 
importance as well. And there appear to be suggestions in at 
least some of these studies that there are advantages to 
individuals, again to cite the example of dementia, for care in 
a special care unit.
    And there are also secondary gains to the patients in the 
rest of the institution who are better cared for when their 
standard can be separated and distinguished from the standards 
that need to be applied to those in special care units.
    Mrs. Northup. But that's not widespread today, I suppose, 
that there are those opportunities for families who have a 
parent, for example.
    Dr. Hodes. The numbers, in fact, are increasing 
significantly and quite rapidly over time. And a part of the 
intent of the studies is to monitor these changes as they 
occur.
    So I think you're correct that this is still at an early 
stage. But it is a practice which is expanding quite rapidly.

                           predictive testing

    Mrs. Northup. One other question, and actually, you may 
have touched on this, I had to step out for just a minute. What 
are the dangers and what do you do about it, and I know that 
Alzheimer's is not the only area where we're beginning to be 
able to do predictive testing. You do a test on me and you tell 
me, hey, you are high risk for Alzheimer's. We obviously know 
there are the financial questions. What does that do to my 
insurance?
    But what are we doing in terms of the emotional and 
psychological effect of that sort of predictive testing, 
especially because that clearly has to forerun any sort of 
therapy to try to offset that?
    Dr. Hodes. You've asked an enormously important question, 
and you've touched on some of the important considerations, 
those related to health insurance, the finances, and in 
addition perhaps the most central one, the emotional impact. In 
the case of Alzheimer's disease, the circumstances are 
particularly complex.
    For a small proportion of the cases, the so-called familial 
Alzheimer's disease, for which at least three genes have been 
identified, the diagnosis in that genotype, of identifying an 
altered gene, has a very high, nearly 100 percent, predictive 
value that that individual will develop Alzheimer's. In that 
sense, it's equivalent to cystic fibrosis or some of the other 
defined genetic diseases.
    That needs to be separated, and I think it is not so well 
separated in the minds of, unfortunately, all of the public 
from the cases--where probably 95 percent of Alzheimer's at 
present, where, although we may be aware of a risk factor such 
as Apo-E 4, this by no means predicts disease with certainty. 
So we have an added level of complexity in having to interpret 
for individuals what the outcomes of these tests might be.
    This is all superimposed on a situation in which at present 
there are no definitive or preventive interventions. All of the 
circumstances will hopefully of course be altered in the future 
if or as we develop interventions.
    In the meantime, recommendations of panels which we ask to 
revisit this repeatedly, panels consisting of scientists, and 
of ethicists as well, have been to suggest that genetic testing 
for Alzheimer's be carried out only in either experimental 
settings where communications or results may be anonymous, that 
is, individuals may not know the results of their tests, or 
carried out as an adjunct, in individuals that already have the 
diagnosis of dementia.
    And here, I have to say there's a difference of opinion 
among experts, both ethicists and scientists, who would allow 
in that situation the possibility that if you have a diagnosis 
of dementia, the question of whether it is Alzheimer's or not 
might be assisted by the use of this genetic test, in 
association with other tests, there is discussion of whether 
that is an appropriate means.
    But there is widespread agreement that genetic testing at a 
population level to find out whether you've got a higher or 
lesser predisposition based on genetic statistical assessment 
at this point is simply unwarranted and rather unanimous 
recommendations are against such testing at present.
    Mrs. Northup. Thank you, Doctor, and members of the panel.
    We are recessed until 2:00 o'clock today.
    [The following questions were submitted to be answered for 
the record.]

[Pages 1946 - 2000--The official Committee record contains additional material here.]

                               ----------

                                           Tuesday, March 18, 1997.

        NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

                               WITNESSES

DR. ZACH W. HALL, PH.D., DIRECTOR
DR. AUDREY S. PENN, M.D., DEPUTY DIRECTOR
RICHARD L. SHERBERT, JR., EXECUTIVE OFFICER
ANDREW C. BALDUS, BUDGET OFFICER
DR. HAROLD VARMUS, M.D., DIRECTOR, NIH
DENNIS P. WILLIAMS, DEPUTY ASSISTANT SECRETARY, BUDGET, DHHS

    Mr. Porter. The subcommittee will come to order.
    Let me apologize to you for the delay. I was out at 
American University making a speech on human rights in Hong 
Kong. I apologize. There just aren't enough hours in the day 
some days.
    This afternoon we're pleased to welcome Doctor Zach Hall, 
the Director of the National Institute of Neurological 
Disorders and Stroke. Before you give your testimony, would you 
introduce the people whom you've brought with you, and then 
please proceed with your statement.

                       Introduction of Witnesses

    Dr. Hall. Yes. This is Dr. Audrey Penn, on my right, who is 
the Deputy Director of our Institute, on my far left is Mr. 
Richard Sherbert, who is the Executive Officer of our 
Institute, Mr. Andy Baldus, who is the Budget Officer for the 
Institute, and we have at the end of the table Mr. Williams 
from the Department, and Dr. Varmus, whom I assume is a fixture 
at this table.

                           Opening Statement

    Mr. Chairman, thank you for the opportunity to appear 
before this committee. These appearances are a real pleasure 
for me because we are in an era of unprecedented progress in 
research on the brain and its diseases, and I appreciate the 
opportunity to share with you some of the important advances of 
the last year. As you may know, this is Brain Awareness Week. I 
was, this morning, at a symposium at the NIH that is being held 
in connection with Brain Awareness Week and heard several 
exciting talks on recent progress in Alzheimer's disease and in 
epilepsy. This afternoon there will be talks on addiction, on 
development of the brain, on mental illness, and on learning 
and memory.
    The symposium, which is reporting the latest findings from 
some of our most distinguished and promising scientists, is 
sponsored by 12 Institutes at the NIH working together to 
promote and support research on the brain. We work together in 
a number of areas of mutual interest that include Alzheimer's 
disease, sleep, pain research, autism, and neurological aspects 
of AIDS.
    Our own Institute, the National Institute of Neurological 
Disorders and Stroke has responsibility for more than 600 
neurological disorders. These include a number of well-known 
disorders that affect millions of Americans--stroke, 
Alzheimer's disease, epilepsy--as well as a number of less 
well-known diseases and disorders that affect maybe a few 
hundred people. These include such things as ataxia-
telangiectasia, Friedreich's ataxia, and Batten disease--
diseases which, although they affect only a few people, are 
nevertheless devastating to those who have them and to their 
families.
    Our research brings new hope to those suffering from 
neurological disorders. As you know, in the past we've had 
little to offer those suffering from brain disease. When I was 
in medical school and first became interested in neurological 
disease, I was told by my advisors that if I was interested in 
the intellectual challenge of diagnosis, I should go into 
neurology, but that if I wanted to make people well, I should 
find something else. Fortunately, that chilling judgment is 
changing as we understand more and as we begin to find new 
treatments.
    Today, I want to tell you about our progress in three 
important disease areas: stroke, Parkinson's disease and 
developmental disorders.
    Stroke is a major health problem in the United States; 
500,000 Americans have a stroke each year, of whom 
approximately one-third die. The total number of those who have 
suffered a stroke in our society is currently estimated to be 4 
million people. Many of these have significant disabilities and 
must receive care. The estimated cost to the Nation is $40 
billion per year for stroke.
    Last year at this time I reported to you that the NINDS, 
working with investigators and hospitals and medical 
institutions across the country and with the private sector, 
had organized a clinical trial showing the first effective 
treatment for stroke. The trial found that prompt 
administration of a so-called clot-buster--tPA--to those with 
the most common form of stroke gave a 30 percent increase in 
the chance for full recovery.
    One might think that such a dramatic result would lead 
immediately to widespread use of this treatment across the 
country. But, in fact, there is a fundamental problem. 
Treatment with tPA is most effective when it is given within 
three hours after the symptoms first appear. Beyond that time, 
there is an increased risk to the patient which, at least with 
present information, makes its use unacceptable.
    In order to get people to the hospital and give them tPA 
within three hours stroke must be treated as an emergency. 
Since there has been previously no effective treatment for 
stroke, this requires a massive change in attitude on the part 
of patients and their families, on the part of physicians, on 
the part of emergency room personnel, and on the part of 
hospitals.
    Last December, our Institute convened a major symposium 
that brought together all of those concerned with acute care 
for stroke--doctors, nurses, paramedics, as well as hospital 
and patient representatives. The purpose of the symposium was 
to provide guidelines for health care providers implementing 
acute stroke therapy in a variety of medical settings across 
the country, from small rural hospitals, to suburban hospitals, 
to large urban hospitals, to those in academic medical centers, 
each with different problems. Our Institute continues to take a 
leading role in coordinatingpatient and professional 
organizations in the vast educational effort that will be required to 
realize the benefit of this important research.
    Let me make another point about these findings. We hear 
much these days about the high cost of modern technology in 
medicine. tPA, in fact, is one of the products of modern 
technology, since it is made by recombinant DNA technology, and 
its use adds to the immediate cost of stroke treatment. And 
yet, this investment pays off. A recent follow-up study on the 
patients in the NINDS clinical trial showed that tPA use 
results in dramatic long-term savings. Those treated with tPA 
stay in the hospital for a shorter period of time, and more are 
discharged to their own homes rather than going to nursing 
homes or to rehabilitation centers. When this is extrapolated 
to make an estimate, the best figures are that tPA use will 
save $4 to $5 million for every 1,000 patients treated. So not 
only does its use then bring significant health benefit to the 
patient, but also results in a substantial cost-saving.
    Let me now turn to Parkinson's disease, where we have 
dramatic recent progress of another kind to report. In 1995 our 
Institute and three others sponsored a workshop whose purpose 
was to identify new directions of research for this terrible 
disease. A major conclusion of that workshop was that 
Parkinson's disease was likely to have a larger genetic 
component than had been appreciated. In response to that 
suggestion and insight, NINDS initiated a collaborative project 
with the National Human Genome Research Institute and with a 
group of extramural researchers. Within a year after that 
project was initiated, we had important and dramatic results to 
report.
    In an issue of the journal, Science, published last 
November, we reported that in a single large family Parkinson's 
disease was found to result from an alteration in a small 
region of chromosome 4. Research continues with the effort to 
identify the gene involved and to determine if it is important 
in other families. But the significance of this is that one of 
the major tools of modern biomedical research, molecular 
genetics, can now be brought to bear on the problems of 
Parkinson's disease. We hope that identification of the gene 
involved, even if it doesn't affect a large number of patients, 
may offer us key insights into understanding why nerve cells 
die in Parkinson's disease, a question about which we presently 
have really no idea.
    Let me finally turn to developmental disorders of the 
brain. As you know, over the last several years, scientists 
have made tremendous progress in identifying genes for a number 
of developmental disorders, including spinal cerebellar 
ataxias, ataxia-telangiectasia, Batten disease, and others. 
You're familiar with many of these findings, as I and my 
colleagues have reported them to you year after year. These 
disorders make it very clear that genetic factors play a 
critical role in brain development.
    But I'd like to make the opposite point today, and to 
emphasize the critical role of experience in brain development. 
Much recent research emphasizes what we already intuitively 
know; that is, we are not simply the product of our genes, but 
that our early experience shapes in important ways how our 
brains become wired up and how we use them. We have become 
increasingly aware that even our adult brains have a surprising 
capacity for reorganization. This was illustrated in a very 
dramatic way by a recent research finding in our Institute that 
showed that when blind people read braille, they use a part of 
the cerebral cortex, in the back, that normally responds only 
to visual stimuli and not at all to touch. So this part of the 
cortex then has been at least functionally rewired to be used 
in the service of braille reading.
    The capacity for functional reorganization, as we know, is 
particularly well developed in children. A dramatic 
illustration of this is the astonishing recovery of children 
who have had large parts of their brain removed for intractable 
epilepsy. One would predict in many cases devastating 
consequences, but they show, again, a remarkable ability to 
reorganize and use the parts of the brain that they have 
remaining for their normal learning and development and to 
carry out functional tasks.
    Research at our Institute and others is revealing more 
about how early experience shapes the normal brain. We are also 
learning that in some cases the developing brain establishes 
maladaptive patterns of learning that lead, or can lead, to 
learning disabilities in children. Our Institute recently 
sponsored, in collaboration with the Office of Rare Disease 
Research, a workshop on neuroplasticity in rare developmental 
disorders. One of the things we heard at that workshop was that 
many of the children that have ``learning disabilities'' are 
perfectly capable of learning, and that by altering their 
experience in controlled ways we can help them achieve 
significantly improved performance. The conceptual basis for 
this discovery, which is now being explored clinically, grew 
out of fundamental research on the ability of the cortex to 
reorganize following a section of the nerves in animals.
    This combination of basic and clinical research is what 
makes brain research in this era such an exciting one and gives 
it such promise for future progress.
    Mr. Chairman, the funding year 1998 budget request for 
NINDS is $722,712,000. I am pleased to answer any questions 
that you might have.
    [The prepared statement follows:]

[Pages 2005 - 2009--The official Committee record contains additional material here.]


                           diseases of aging

    Mr. Porter. Thank you, Doctor Hall.
    I have a question for Doctor Varmus, and I think I know the 
answer but I want to make sure. We just had the National 
Institute on Aging here and Doctor Hodes and we talked about 
stroke, Alzheimer's and Parkinson's. Does NIA have the lead on 
any disease, or are those always in other Institutes and NIA 
simply relates them to aging?
    Dr. Varmus. There is coordination of Alzheimer's research, 
but the National Institute on Aging has the lead for 
Alzheimer's.
    Mr. Porter. Say again.
    Dr. Varmus. The National Institute on Aging has the lead 
for Alzheimer's.
    Mr. Porter. Okay.
    Dr. Hall. I should say also several other Institutes do 
carry out research in Alzheimer's disease. Our own particular 
portfolio is very biologically based. One of the important 
things that Richard Hodes did, actually, was to establish a 
working group on Alzheimer's among those Institutes that are 
concerned with it. The directors have gotten involved in this 
as well, and we have met several times. It has been extremely 
useful in exchanging expertise and being sure that our 
portfolios are well-coordinated. We often have overlapping 
interest and the current mood, I would say, among those 
Institutes is that that's perfectly all right and that we will 
cooperate in those areas where we do have overlapping interest. 
We also have, each of us, areas in which we are distinctively 
interested.

                      administering tpa for stroke

    Mr. Porter. Absolutely. I understood that. I just wondered 
whether NIA had the lead or whether you had the lead.
    Is it possible to administer tPA on site or in the 
ambulance, or do you have to administer it in the hospital?
    Dr. Hall. Let me address that, because that's a very 
important question. tPA, as you know, is a clot-buster, so 
while it breaks up clots, it also makes coagulation more 
difficult. There are two kinds of stroke--ischemic strokes and 
hemorrhagic strokes. Let me simply remind you that stroke 
results from an interruption in the blood supply to the brain. 
That can come about in two ways. If you block the arteries or 
some part of the circulation in the brain, you get what's 
called ischemic stroke; if small blood vessels break, then you 
get a hemorrhage and that also effectively stops the 
circulation in that area and the cells are without oxygen and 
without nutrient.
    tPA has the capacity to benefit and to help those with 
ischemic stroke, but it is dangerous for those with hemorrhagic 
stroke and you certainly do not want to give it to those 
patients. About 80 percent of stroke patients have ischemic 
stroke, and that is the most important thing to be found out. 
You do that with a CT scanner. So any hospital that has a CT 
scanner can give acute stroke treatment.But it would be very 
dangerous to give tPA in the absence of knowing whether it is ischemic 
or hemorrhagic.
    And so part of marshalling the efforts to bring about acute 
stroke treatment involves the mechanics of getting somebody to 
the hospital, first of all making sure that they do have the 
symptoms for stroke, because many patients report or think 
they're having a stroke and it turns out after a few questions 
you find out quickly that they do not, so that first screen is 
done, and then arrangements are made to get a CT scan very 
quickly. In large crowded hospitals, that means they go to the 
head of the line, and there's a protocol for that. There also 
has to be an arrangement that once the scan is obtained it 
needs to be read immediately, and that often is a time block by 
the time you can find somebody who has the time and can drop 
what they're doing to read it, and so you have to have an 
emergency protocol for that. And then also the pharmacist needs 
to be alerted in advance so that the tPA is there ready to be 
given when it's decided that it is appropriate. So all of these 
things have to be coordinated to get the tPA to the patient 
within that three hour time window. Of course, the worst thing 
of all would be to give a patient with hemorrhagic stroke a 
tPA. And so for that reason, everything waits on the CT scan.

                        future of brain research

    Mr. Porter. At a FASEB conference last week, Doctor Arthur 
Kornberg of Stanford predicted that ``following the decade of 
the 1990s in which science has been dominated by gene hunters, 
the next decade will be ruled by head hunters who study the 
functions of the brain.'' Do you share the view that brain 
research will be the next science frontier conquered?
    Dr. Hall. Without doubt. I'm actually pleased to hear 
Doctor Kornberg say that. I did my post-doctoral fellowship 
years ago in his department at Stanford. I had at that time 
already committed to the nervous system, and maybe, I'd like to 
think, perhaps some of my enthusiasm rubbed off on him. But, at 
any rate, I very much agree with that. There are several 
reasons for saying that.
    I think one of them is that the brain is the most complex 
organ that we have. It's the highest product of human 
evolution, if you will. It is incredibly complicated. When I 
began my career there were many who thought it was too 
complicated to get serious answers; you could not do 
experiments that gave you hard answers if you worked on the 
brain. And as the methodology has developed and as techniques 
have improved, I think what has now happened is that our tools 
and our technology are now up to working on these very 
complicated problems. And that is reflected I think, by the 
flood of people who are now coming into brain research.
    One of those tools certainly is genetics. It is estimated 
that a third of all genetic diseases have neurological 
consequences. Of the large number of diseases that I mentioned 
for which our Institute is responsible, a significant number of 
those are genetic diseases. And by identifying the gene, one 
gets a powerful clue to what may be going on with the disease. 
We've seen this in ALS with the identification of a superoxide 
dismutase, the enzyme responsible for at least a portion of 
those with familial ALS. It gives us an important clue that 
oxidative reactions are probably important in the 
neuropathology of the neurons that die in ALS.
    Imaging is another important tool that has really 
revolutionized what we do. It gives us literally a new view of 
the brain. The fact that one can look at the human brain in a 
non-invasive way is truly remarkable. As you know from some of 
the testimony by my colleagues, one can see the effects of 
drugs on the brain in this way; one can even ask people to 
think of particular things and see what areas of the brain 
light up. So many of the most subtle and complex things that 
the brain does, things that involve intention, or things that 
involve, even in a recent study, one's gut feelings about 
something, now can be addressed in a biological sense. One can 
actually ask what parts of the brain are involved in making 
these decisions, are there cells that we can find that are 
actually responsible for carrying out these tasks.
    So in that sense, we are able to address more and more 
complex problems. I think the future is bright and important 
for brain research.

                         ninds budget increase

    Mr. Porter. My next question begins with the words ``in the 
aftermath of Christopher Reeves' spinal cord injury.'' But 
before I ask that, there was a great deal made at the time of 
the injury to Christopher Reeves, a public figure, an actor and 
entertainer, and he even appeared at the Democratic National 
Convention to talk about the importance of spinal cord injury 
research. Your budget has a 3 percent increase in it. Do you 
think that reflects the priority that we ought to have for 
spinal cord injuries and other neurological disorders?
    Dr. Hall. Maybe we should check afterwards on the budget 
figures. Those are not the figures I have, but I may be wrong 
about that.
    Mr. Porter. No, I'm talking about overall increase for your 
Institute.
    Dr. Hall. Oh, sorry, for our Institute. I thought you meant 
for spinal cord.
    Mr. Porter. No, I only have it by Institute. But we can ask 
that, too. [Laughter.]
    Dr. Hall. That's fine. I think we have a number of 
opportunities in research on diseases of the brain. I would be 
happy to talk to you about the particular opportunities in 
spinal cord research which are important. But in many, many 
areas we have opportunities to make important advances. The 
rate at which those advances are made depends on our budget. 
I'm here to defend the President's budget, the 2.5 percent 
increase, or approximately that, and we are pleased with that 
increase. We would, of course, do more----
    Mr. Porter. Why are you pleased with that increase?
    Dr. Hall. Well, I'm pleased that it's not a decrease in 
these Washington days.

                      spinal cord injury research

    Mr. Porter. Let's talk about spinal cord injury research.
    Dr. Hall. Let's do. [Laughter.]
    Mr. Porter. What's the baseline level of effort in spinal 
cord injury research, and how much of an increase did you make 
in that in 1996 and what do you project for 1997?
    Dr. Hall. Yes. Our figures for 1996 were approximately $47 
million, and our estimated figure for 1997 is approximately $50 
million. And it was those that I was looking at when I spoke 
before.
    [Clerk's note.--Later provided, ``the 1995 baseline was $39 
million.'']
    Spinal cord injury presents a tremendous problem for us in 
that it seems like almost an impossible task. There are 
literally millions of nerve fibers that go out from the brain 
to connect with the circuits in the spinal cordthat control the 
muscles that allow us to move and that convey our sensations from our 
body back to the brain where they can be used. In spinal cord injury, 
these connections are damaged or in some cases broken. And the idea of 
trying to attempt that rewiring seems almost a Herculean task.
    But we are helped by the fact that even a small amount of 
regrowth and regeneration can often restore significant 
function. And for those who have spinal cord injury, even a 
small restoration of function can mean an important improvement 
in the quality of life. The ability, for example, simply to 
grasp a glass or grasp a pen or to use one's hands and fingers, 
even if not doing fine movements, can add immeasurably to what 
one is able to do and to one's independence.
    We are finding that there are ways in which we can improve 
that regeneration. We just heard on Monday at the NIH a 
visiting scientist from Switzerland who has found that the 
white matter, the myelin that coats our nerves, actually 
contains a substance that inhibits nerve growth. And the 
purpose of this normally is to, we think, confine the growth in 
the nervous system to those areas in which it is important for 
adaptation. If you remove that inhibition in his case, he's 
done it experimentally with antibodies, but there are other 
ways to do this--then one can obtain much more regeneration, 
and often in an appropriate way so that one can get partial 
restoration of function, more than one would have believed. And 
in experiments done in collaboration with scientists in the 
United States, there has really been some remarkable progress 
made in showing functional restoration.
    The other half of it is we are finding more and more about 
those molecules that can stimulate regrowth. These are growth 
factors. They occur in minute amounts. We know some of them, we 
don't know all of them. There's been a great deal of active 
research recently in trying to identify them. I think last year 
at this time I spoke about the identification of one, a factor 
called netrin that had been hypothesized for years but has 
finally been identified. And so, in a sense, with this 
combination of an attractant and removing the inhibitor, taking 
off the brake and putting on the gas, if you will, it is 
possible to get some regrowth.
    There are a number of other problems that we're interested 
in and making progress on. One of the things that happens when 
you damage a piece of nerve cord is that the glia that are 
responsible for making the wrapping of the long fibers, that 
essentially insulate the fibers that run up and down the cord, 
die. Recent research shows that some of those die in a delayed 
fashion as a result of a process called apoptosis; that is, 
they in essence commit suicide. We are very interested in 
understanding the factors that regulate this suicide program in 
those cells with the idea that if they can be saved, then they 
can help remyelinate the regenerating cord after that.
    So in spite of the fact that this is a tremendous problem, 
we are making some limited progress. I don't think anybody 
thinks it will be easy. And we are unlikely to be able to 
completely regenerate a cord within any time span that we see. 
But the important point is that we don't necessarily have to do 
that. And so we are continuing this research.
    The other area that we have been investigating are acute 
treatments that limit the damage after injury. Our trial 
several years ago on the use of methylprednisolone, for 
example, has been responsible for limiting the injury to a 
large number of patients in this area.
    So we see a number of opportunities. As you may know, our 
Institute allocates its funds through the competitive peer 
review process and, by long-standing agreement with our 
Advisory Council, the first 80 percent of our funds is spent 
strictly according to priority reflecting scientific excellence 
and opportunity. So we are pleased to see that this area is 
developing and that grants in this area are developing as well.
    Mr. Porter. Can you say that again, the first 80 percent of 
your funds are?
    Dr. Hall. Yes. The first 80 percent of our funds are given, 
by agreement with our Council, strictly according to the 
percentile score as judged by----
    Mr. Porter. What about the other 20 percent?
    Dr. Hall. The other 20 percent we can award out of order, 
and we do that on the basis of several criteria which include 
so-called creativity/originality, applications that perhaps 
didn't score as high as they might but that have unusually 
creative aspects to them that would bring something genuinely 
new to a field; areas of particular interest that we think 
might have been overlooked or are particularly promising; we 
look to support young investigators, and we also in some cases 
have an ongoing established group that has been active, we 
expect them to continue to be productive, but for one reason or 
another they've fallen below the line, and we feel there may be 
an investment to be lost, sometimes it's animals or sometimes 
it's personnel, if they were to have a lapse in funding.
    Mr. Porter. Looking at spinal cord injury, whether it's 
before or after Christopher Reeve was injured, research in this 
area is just as important in any case.
    Dr. Hall. Yes.
    Mr. Porter. But the President of the United States seemed 
to respond to that particular injury and the public interest in 
spinal cord injury after Christopher Reeve was injured. How do 
you respond to the commitments the President has made in these 
areas and still adhere to your principles of not earmarking 
funds for particular diseases?
    Dr. Hall. Do you want to answer that? Doctor Varmus----
    Dr. Varmus. The two of us worked together in an attempt to 
stimulate the field. Doctor Hall arranged a workshop that made 
it clear that we have special interest in this area, and that 
did bring a lot of people together and stimulated grant 
applications that met the review criteria. Do you want to speak 
specifically about the grants that have been supported?
    Dr. Hall. Sure. Yes, we've supported a number of grants 
that look at the factors that influence cell death in these 
spinal cord----
    Mr. Porter. Let me interrupt you, Dr. Hall. I understand, 
but did that have anything to do with Christopher Reeve being 
injured or the President's commitments?
    Dr. Hall. Yes.
    Mr. Porter. It did?
    Dr. Hall. Yes, it did.
    Mr. Porter. Would you have done this anyway, or did you 
only do this because the President indicated this was something 
he wanted to talk about?
    Dr. Varmus. It was a combination. I think it was a 
fortunate collision of an interest in doing something in 
response to public interest in this condition, but there have 
been a series of developments in the study of nerve regrowth--
particularly the study in the rat model that Dr. Hall 
mentioned--has provoked a great deal of interest in the 
opportunities for regeneration of nerves in the spinal cord, in 
particular.
    Some of the money that was used for meeting the President's 
commitment was from my Director's Discretionary Fund, and some 
was generated by the use of my 1 percent transfer authority. So 
a number of things were cobbled together to meet the 
President's commitment.
    Mr. Porter. Again, I don't at all question the importance 
of spinal cord injury research, but I think that political 
earmarking for diseases is reprehensible whether it's done by 
the Congress or by the Administration. It seems to me that 
we've got to be very careful that we aren't responding to the 
particular topical events of the news, but rather are seeking 
the best science.
    You're telling me you're seeking the best science, and 
that's certainly good enough for me, but, on the other hand, I 
worry that we could get to a position where we will be 
directing most of what you do because Members of Congress are 
interested or the President is interested. That's not what we 
ought to be about, it seems to me. We talked about this a great 
deal. I just wanted to see what your answer would be in respect 
to this particular circumstance.
    The Department of Defense and the VA are both major players 
in spinal cord injury research as well, are they not?
    Dr. Hall. Yes.
    Mr. Porter. Who is doing the largest amount of research in 
this area?
    Dr. Hall. I don't have the figures for spending in those 
areas. We could certainly get them for you. I do know that when 
we gave our workshop we certainly let representatives of those 
organizations know and they were in attendance. But I don't 
have the figures.
    Mr. Porter. Can you provide those for the record, Doctor 
Hall?
    Dr. Hall. We can provide them.
    [The information follows:]

                                              SPINAL CORD RESEARCH                                              
----------------------------------------------------------------------------------------------------------------
                                                                                    Fiscal Year                 
                             Agency                              -----------------------------------------------
                                                                    1995 actual     1996 actual    1997 estimate
----------------------------------------------------------------------------------------------------------------
Department of Defense...........................................     $12,000,000      $4,200,000      $5,850,000
Veterans Affairs................................................       6,000,000       6,500,000       7,200,000
----------------------------------------------------------------------------------------------------------------


    Mr. Porter. As you indicated, another approach to spinal 
cord injury was tested last year when researchers formed 
bridges across severed spinal cords in rats with multiple fine 
nerves. In conjunction with growth factor, the procedure 
allowed certain limited recovery of function. In the short 
term, do these reconstructive therapies hold greater promise 
than studying cellular processes?
    Dr. Hall. Well, those procedures arise, in part, from the 
study of cellular processes. It is actually precisely that 
study that I was referring to before, because one of the key 
features in that study was to provide bridges across the cord, 
the brain is on my left, you have the spinal cord here, you 
have an injury, and what you want to do is then make bridges 
from this side to the other. The point was to lead those 
bridges into the gray matter and to avoid the white matter. 
That was done for the specific reason that cellular work had 
led to the realization that there was an inhibitor substance in 
white matter that would prevent regeneration. And so the 
combination of having bridges that would be hospitable for 
growth, providing an extrinsic growth factor, and avoiding the 
white matter in the construction of these were all key 
features. So it's not an either/or situation. Those arise out 
of, those represent the application of insights that have come 
from cellular and molecular work to this complex clinical 
situation, if you will, involving an animal.
    I think the conditions under which those were done, very 
carefully controlled for the purposes of the experiment, of 
course there was a nice clean break made and so forth, are 
rarely the conditions that you see in spinal cord injury in the 
clinic. So they cannot be simply transported wholesale from the 
experimental situation to the real life situation. But by 
telling us what factors are important and by validating, if you 
will, these insights from cellular and molecular studies at the 
tissue level, these then provide the basis for future study and 
I think are an important foundation for research that is now 
going on.
    An important aspect of those experiments, I might add, was 
showing not only did you get fibers growing across, but you 
also got functional recovery. And this ties into the point I 
was making before that sometimes only small amounts of regrowth 
are sufficient to give you a surprising amount of functional 
recovery. And extensions of those experiments, some of which I 
heard about earlier this week, as I mentioned to you, indicated 
that the regenerating axons don't simply regenerate randomly, 
but appear to regenerate in an appropriate way to reestablish 
control of the brain over these spinal cord circuits that are 
local circuits that remain intact.

                    genetics of parkinson's disease

    Mr. Porter. As you mentioned, last fall researchers 
identified a specific genetic region in a large Parkinson's 
prone family in Southern Italy that seems to be linked to the 
disease. This upset the conventional wisdom that Parkinson's 
was not genetically linked. Do you think this finding will 
prove to be an important clue to Parkinson's, or is the disease 
likely to have multiple causal factors including those which 
are environmental?
    Dr. Hall. Our suspicion is that the disease arises through 
some combination of genetic and environmental factors. And for 
many years, much of the interest in the field focused on 
environmental possibilities in part because of a discovery 
which you may have heard of made on the West Coast some years 
ago in which a number of young people were found to have 
essentially a very severe form of Parkinson's disease that was 
traced to their use of a drug that was contaminated by a 
substance that actually destroyed the same cells that die in 
Parkinson's disease. This was carried out by researchers in 
California and at the NIH. One of the consequences of that was 
to increase interest in the possibility that there might be 
some environmental toxin that was acting in the same way as 
this drug contaminant did.
    So there have been a number of studies that have looked for 
such an environmental influence. So far nothing has been 
identified that acts in such an effective way. It is known that 
in certain cases after a viral infection, on occasion there has 
been the development of Parkinson's symptoms. So it can be 
influenced by external events.
    But people had really sort of overlooked the genetic angle, 
or many people had. What we found at the meeting was that there 
were large families who had many patients in them with 
Parkinson's disease and in which it appeared to be inherited in 
a very clear-cut fashion. And so we, as I said in my opening 
statement, put together this collaboration and we have worked 
with the Human Genome Institute which has really provided the 
very latest in gene hunting technology to pursue this. So in 
this large family it is very clear that a defect or an 
alteration in a single gene causes Parkinson's disease. And I 
might add, this is perfectly typical Parkinson's disease as far 
as we know. There might be a slightly earlier age of onset, but 
it appears indistinguishable from any classical Parkinson's 
disease.
    The question is, first of all, will this particular gene 
prove to be important in other families even though it may not 
exert as strong an influence, perhaps because the mutation is 
different or something of that sort. We now have the tools to 
begin to ask that question. And then the other point is that 
even if this gene turns out to be important in the most extreme 
case only for this family, our hope is that it will provide 
this important clue to what's going on. We simply do not know 
why cells die in Parkinson's disease. Wehave a number of 
clinical trials, these are all aimed at trying to replace the cells 
that have died, but the cells continue to die. It is a progressive 
disease, as you know, and we simply don't know why.
    Huntington's disease, Alzheimer's disease, ALS, Parkinson's 
disease, all are neurodegenerative diseases in which cells die 
for unknown reasons. In each case, a specific population of 
cells is involved, and in each of those cases these are adult 
onset diseases, these are cases in which people function 
perfectly well for many years and then something happens and 
these cells die. We think there may be links between those. We 
are very interested in perhaps looking at using what's been 
found with one disease to try to understand another. The 
powerful tool that has been missing so far in Parkinson's has 
been molecular genetics and we now think that tool is at hand.

                           targeted research

    Mr. Porter. I want to go back to what I said earlier about 
the President's commitments on spinal cord injury research. I 
don't mean to suggest that there's anything wrong with the 
President being very interested in this and promoting and 
encouraging NIH to work harder in this area. I also will 
suggest that many Members of Congress do exactly the same 
thing. The fact that Silvio Conte and George O'Brien both had 
prostate cancer certainly led to a greater concern about that 
disease I think in NIH. We have members all the time that 
express concern about diseases. We wrote into the report last 
year an urging that you pursue research on therapeutic 
approaches to Parkinson's disease, and I think you might have 
just answered that question of what you've done.
    But, again, there's nothing wrong to have that concern. My 
worry is that we begin to have all of science politically 
directed, that's what worries me. I'm sure it worries you also.
    What share of your research portfolio would you categorize 
as basic research that cannot appropriately be designated as 
targeting one disease or another?
    Dr. Hall. Those judgments are somewhat arbitrary, as you 
know, but our guess is somewhere between 60 and 65 percent of 
our research is directed at fundamental mechanisms that may be 
applicable to a variety of diseases but are not targeted to a 
specific disease.
    Mr. Porter. And Doctor Varmus, would Neurology's percentage 
of research that is basic mirror that for NIH as whole? Is that 
about where everyone is?
    Dr. Varmus. It's difficult to say, Mr. Porter. I think one 
of the things that makes this a hard question to answer is that 
a lot of research can be construed as being focused on one 
disorder but is clearly applicable to others. That's a little 
different from the question you asked, but it's something, I'd 
have to consider in answering your question.

                 neurodengenerative disease initiative

    Mr. Porter. Your Institute has been involved in the 
neurodegenerative diseases initiative funded for the past two 
years through the Office of the Director. Can you give us your 
impressions of how well this mechanism of centralized funding 
has worked?
    Dr. Hall. Let me ask, I'm not sure. There are two things. 
One is, we have the Biology of Brain Disorder Initiative which 
is part of each year's budget. We also have through the Office 
of the Director a group of us have funded research on 
neurodegenerative diseases, and perhaps it is that you're 
asking about.
    Let me tell you what we did, and we will do something like 
that again this year I think, and that is that a group of 
directors of the Institutes who are concerned with 
neurodegenerative diseases met, we then asked for applications 
for those Institutes that had projects that were in this area 
that were deserving of funding, we actually extended that 
beyond the small group to any Institute who had a project in 
this area that they wished to be considered. We then actually 
invited Dr. Varmus to sit with us if he would and look over 
these various applications, and then we discussed their 
excellence, importance, interest, and on that basis recommended 
funding for the various Institutes. So it was, in essence, a 
mini competition, if you will, in that area.
    Mr. Porter. The 1998 budget for the Office of the Director 
does not include funding for the neurodegenerative diseases 
initiative and, instead, indicates that the research projects 
funded will be supported by the individual participating 
Institutes. What projects from the initiative will be supported 
from your 1998 budget and at what funding level?
    Dr. Hall. From the 1998 budget, we don't know. Our sense 
would be to take those deserving applications in 1998 that were 
not going to be funded by our own funds and then apply them to 
the neurodegenerative initiative in the same competitive way. 
So in that sense, I can't tell you that we are pre-planning 
what those particular funds might be. That is, we will look at 
the applications that come in. We have not gone to the 
community, if you will, and said we want applications in this 
area because they're going to be used in the neurodegenerative 
disease area.
    Dr. Varmus. We could provide on estimate of the continuing 
cost from the 1996-97 awards.
    Dr. Hall. Yes, that's true. We have made awards in the past 
that will continue, and so we will fund those.
    Mr. Porter. Maybe you can provide those figures.
    Dr. Hall. We'll be happy to provide those figures.
    [The information follows:]

         funding for the neurodegenerative diseases initiative

    In FY 1996 an additional $3.5 million of NINDS 
neurodegeneratie research was supported with funds from the NIH 
Director's Discretionary Fund and the NIH Director's use of the 
one percent transfer authority. The commitments from these 
awards will be supported by the NINDS and total $3.6 million 
for FY 1998.
    In a similar manner, FY 1998 commitments for research 
projects funded by the NIH Office of the Director in FY 1997 
will be supported by the institute that has responsibility for 
administering the project. Funding to meet these commitments in 
FY 1998 is estimated to be around $8 million, based on the FY 
1997 appropriation.

    Dr. Hall. We have not actually made the 1997 awards yet, so 
in that sense we will do that this year. A little bit later in 
the year when we've had a significant number of applications 
come in, we will sit down and we'll say what promising things 
we were unable to fund this year in this area. We will do the 
same again next year.
    Mr. Porter. And then those will be funded out of your 
Institute's funds? Because the Office of the Director doesn't 
have any budget for that, correct?
    Dr. Hall. We have in some cases matched those funds.
    Dr. Varmus. Remember, Mr. Porter, that in general when 
we've initiated new projects either through a specific earmark 
for the Office of the Director or through the use of the 1 
percent transfer authority, we pay the initial year's support 
with that money from the Office of the Director, then the 
Institutes have picked up the outyear costs.

                          estrogen and stroke

    Mr. Porter. Throughout our hearings we have talked a great 
deal about the benefits and hazards of estrogen use. Your 
budget justification mentions yet another possible use of 
estrogen to prevent strokes in post-menopausal women. What 
properties of estrogen might be expected to have a protective 
effect against stroke?
    Dr. Hall. You're quite correct. We have a large clinical 
trial that will look at the effects of estrogen in post-
menopausal women. We're very interested in that trial. We 
expect it to report in 1998 if all goes well and we will see 
what happens. The gender difference in stroke is interesting. 
Women, on an age-adjusted basis, have a slightly lower risk for 
stroke than men, but because women in general live longer and 
because the risk for stroke is age-related, more women than men 
end up being affected by a stroke particularly in later years. 
So this leads to the suggestion that there is maybe some 
beneficial effect in terms of a hormonal effect that might be 
responsible for the gender difference. So we hope that this 
trial will provide some support for that.

                possible therapeutic effects of nicotine

    Mr. Porter. For many years there has been evidence that 
smokers seem to have a reduced risk of developing Parkinson's 
disease. Nicotine has also been suggested as a potential 
treatment for Alzheimer's disease. Now that nicotine has become 
available in numerous non-tobacco forms without the risks of 
smoking, do you think the evidence is suggestive enough to 
support research into the possible therapeutic effects of 
nicotine?
    Dr. Hall. Yes. We, in fact, do support an interesting 
project on the therapeutic effects of nicotine. There was an 
article in the New York Times in which I stated incorrectly 
that we were not supporting such a project, but I found out 
later that we were. It's an interesting one, and that is for 
patients with Tourette's Syndrome in which there are so-called 
tics in which people make sudden unexpected movements or 
sometimes say things that they cannot control, then 
haloperidol, which is an antipsychotic agent, given in low 
doses has proven to be useful for these patients. The side-
effects of that are ameliorated by nicotine.
    But it has been very difficult to get the patients. These 
trials have been carried out on adolescents, and nicotine, if 
given orally, is very bitter and they tend not to take it. So 
what's been developed now is a skin patch whereby the nicotine 
actually is absorbed through the skin. That is in trial. We're 
very interested in the possibility that will be beneficial. 
Certainly anything that would help these young people, we would 
be very interested in.
    Mr. Porter. But that's not having a therapeutic effect, 
that's offsetting side-effects from the drug itself, right?
    Dr. Hall. Yes, it is. Yes. That's correct.
    Mr. Porter. Are there any possible therapeutic effects of 
nicotine itself?
    Dr. Hall. There is an old observation that smokers, as you 
mentioned, do not get Parkinson's disease. And within the last 
year, there has been some experimental support at the cellular 
basis for that. I think whether one would use nicotine and how 
it might be used in that context is at present only 
speculative. My guess is it will not be a key agent. And we 
don't have any plans at present to pursue that. So with the 
exception of the Tourette's case, we are not actively pursuing 
any case with nicotine.

                  prion hypothesis and mad cow disease

    Mr. Porter. In January, Science magazine published a study 
questioning the leading hypothesis about the cause of Mad Cow 
disease. Abnormal forms of proteins called prions have been 
thought to cause Mad Cow disease although no infectious disease 
has ever been shown to be caused by proteins. Do you think the 
new Science study is persuasive enough to send researchers and 
funding agencies in new directions looking for the cause of Mad 
Cow disease?
    Dr. Hall. This is a long-standing question. At its core is 
a scientifically very important idea, and that is, infectious 
agents replicate so that if we are infected with a virus, the 
virus divides to produce more viruses, and that's how the 
infection is spread within the body and spread from person-to-
person. We know that viruses and bacteria replicate through 
their DNA by dividing and splitting.
    The question of the prion diseases, which were originally 
called ``slow viruses,'' was a very perplexing one. Research at 
our Institute originally showed that some of the neurological 
diseases, specifically kuru and later Creutzfeld-Jakob disease 
and others, were actually caused by an infectious agent. That 
is, you could take brain material from someone who had kuru and 
give it to an animal and the animal would develop symptoms. 
This is the same thing that happens in Mad Cow disease, that it 
is transmitted.
    Now the question is, what is the transmissible agent? There 
have been literally decades of research that have gone into 
that question. I think it's fair to say that most people 
believe now that it is a protein, although the issue is not 
settled beyond doubt. The current hypothesis that is being most 
actively investigated is that the protein goes in and it is in 
an altered conformation that makes it infectious, and that when 
it goes into the body, it then induces in some catalytic manner 
the normal protein of the body to take on this altered 
conformation. And in that sense, the altered protein replicates 
itself even though there is no nucleic acid involved. And then 
that altered protein is transmitted to the next animal, and so 
on.
    The study that appeared in Science reported that in some 
animals, and not all, by the way, but in some animals that had 
the symptoms of these diseases, they were unable to detect 
these altered proteins. Whether that is a fundamental 
observation or a detection problem, we are not yet sure. I 
think that is the real question, as to whether or not they are 
there and simply not detected, or whether in fact, as some 
people believe, there is another infectious agent and that this 
change in the protein simply allows the infectious agent to 
come in and do its work.
    So research in this area will continue. We actually support 
people on both sides of that dispute, some who believe that it 
is the protein and others who are less sure. It is from a 
biological point of view a fascinating point, it is even a 
revolutionary idea. And as you know also, it has had tremendous 
economic-social consequences through the spread of Mad Cow 
disease in Britain.
    Mr. Porter. Thank you, Dr. Hall.
    Ms. Pelosi.
    Ms. Pelosi. Thank you, Mr. Chairman. Dr. Hall, Dr. Varmus, 
everyone, welcome. Thank you, Dr. Hall, for your testimony and 
for your good work at your Institute. Once again, Mr. Chairman, 
may I express my pride in a leader from the University of 
California-San Francisco making such a wonderful contribution 
to science under Dr. Varmus' leadership.
    This committee, I just love it, it's such a wonderful place 
to serve because of all the good testimony we receive, and 
under the leadership of our Chairman, the good work that the 
committee is able to accomplish. I don't know what is sadder, 
the days when people come in and they're talking about diseases 
that effect large numbers of people in the population, like 
cancer or AIDS, or the days when people come in and it's a 
small population, a small universe that is affected because you 
know it is going to be very difficult to build the public 
support. Dr. Varmus would not want that to happen in any event, 
that we would be sticking with our basic biomedical research--
but, in any event, that enough attention is paid in one way or 
another to some of the rare diseases that we see families have.
    I want to just ask about a couple of those.
    Dr. Hall. Please do.

                     amyotrophic lateral sclerosis

    Ms. Pelosi. In our report language last year, we talked 
about Lou Gehrig's disease and the need to sustain the momentum 
of current research. The committee encourages you to enhance 
your support of brain research relevant to ALS.
    Forgive me, Mr. Chairman, if that's already been addressed.
    Dr. Hall. ALS is a very active area of research right now, 
one that we're particularly interested in. I actually had used 
it earlier this afternoon as an example of a disease in which 
we have been able to make progress through insights in 
molecular genetics. About 10 percent of patients with ALS have 
a familial form of the disease, which means they inherit an 
alteration in their DNA which causes them to get it. In some of 
those cases, a portion of those cases have been shown to be due 
to alterations in a specific gene that encoded, in fact, an 
enzyme that was very familiar to us, an enzyme called 
superoxide dismutase. Basic science had studied that enzyme for 
years and it was one of those cases where clinical 
investigation suddenly is able to plug into a vast body of 
knowledge that was there waiting for it.
    The discovery that this enzyme was the problem led to the 
idea that there must be something wrong with the disposal or 
the generation of very dangerous compounds or class of 
compounds in ourselves called ``free radicals'' which are very 
reactive and which can do damage. These are generated as a by-
product of energy metabolism and the cells have a special 
machinery to dispose of these.
    Further research has indicated that it is not the absence 
of the enzyme that causes problems, but it appears that the 
altered enzyme actually itself is a pernicious agent and that 
it does bad things to the cell. We don't yet know what that is, 
but we think the enzyme, because of the alteration, doesn't get 
rid of these free radicals in the way it should but actually 
generates a particularly dangerous class of those free radicals 
and that they attack the cell.
    What's happened then is one has been able to take this 
altered gene that was responsible for ALS in these families, 
put it into mice, and now we are studying in mice what happens, 
what the pathological process is, how it is that these mice 
develop motor symptoms, which they do. It is a relatively good 
model for the disease. We hope that this will also be a place 
where one can investigate potential therapies. I think you'll 
hear later this afternoon from Dr. Cassman about some basic 
research that has gone on involving some of the pathological 
processes in these cells that occur during ALS.
    So this is an active area. In fact, I hope to be able to 
attend a workshop later this spring in Boston on motor neurons 
and ALS. We're very interested.

                         human embryo research

    Ms. Pelosi. Thank you, Dr. Hall. I'm going to skip a couple 
of diseases and go to another question in the interest of time. 
We've had quite a lively debate in our subcommittee and in the 
full committee about human embryo research. I was interested in 
what you had to say here about Parkinson's disease in your 
testimony. And I wondered if the actions taken by our 
committee, and therefore the Congress, on the restrictions on 
human embryo research have had an impact on your work?
    Dr. Hall. No. The work that you refer to that we support 
concerns experiments in which aborted fetuses have extracted 
from them the cells that make the chemical that's missing in 
Parkinson's disease, dopamine. These cells then are put into 
adult brains of people with Parkinson's disease. We are now 
carrying out two clinical trials to see if this treatment is 
effective. Because these are not human embryos that were 
created, these are aborted fetuses and they don't come under 
the human embryo research bans. So this work is not prohibited.
    Let me just say that no one believes that in ten years from 
now this will be the way we will treat Parkinson's patients. 
The reason that we're doing this is that there is a strong 
feeling that it may be more effective to give dopamine, the 
missing compound, by cellular secretion than by giving L-dopa, 
a precursor which people take and which has to enter the brain 
and get converted and so forth. L-dopa, as you may know, is not 
in the end a definitive therapy for Parkinson's disease. People 
develop side-effects, it becomes ineffective. And so the idea 
is that maybe if it were given in a more natural way it might 
be effective. The only cells that we know that one can put in 
the brain and have function in this way right now are cells 
from these young nervous systems. If those experiments are 
successful, then we will proceed to devise engineered cells 
that will do this in a different way. This will not in any 
long-term or large sense be the source of cells that will be 
used for therapy.
    Ms. Pelosi. That's interesting. I was also interested in 
terms of the in vitro fertilization, the debate that we had 
about the remains or the----
    Dr. Hall. Our Institute is not involved in that at all.

                      spinal cord injury research

    Ms. Pelosi. Okay. I thank you. Spinal cord injury, if I may 
just quickly, Mr. Chairman. Is there reason to be hopeful that 
with all the advances in science and technology that--well, 
could you address that, please?
    Dr. Hall. Yes, indeed. There is. We have made much progress 
in understanding the factors that make nerve cells regenerate 
and grow axons, the long extensions that they have. And we now 
know factors that positively stimulate them to grow and we also 
know that the nervous system has factors in it that prevent 
their growth. It actually has been a long-standing mystery or 
one of those well known puzzles that if you cut nerves in the 
peripheral nervous system, that is the nerves that run down 
your arm, they will regenerate. But if you cut nerves in the 
central nervous system, they don't. One of the reasons they 
don't is because there are substances that prevent this in the 
central nervous system. Presumably these are there to prevent 
aberrant connections being made in adults.
    We are finding ways of blocking that inhibition, if you 
will. And so there are some initial, very promising studies 
suggesting that you can increase the growth of nerves in spinal 
cord-injured animals and that this increase results in 
functional recovery. So we are very heartened by that and very 
eager to explore that further.
    Ms. Pelosi. When you say cut cells one place and another 
and compare the impact, when you bruise the spinal cord, is 
that the equivalent of cutting cells or is that something else?
    Dr. Hall. Yes. Well, several things happen in spinal cord 
injury. In fact, most spinal cord injuries are not clean cuts 
but are cases in which the vertebra are broken and actually 
compress the axons. So there's damage on several levels. The 
axons that run down the cord are sometimes damaged as if they 
had been cut. There is also edema, that is swelling of the 
cord, and the cells that are responsible for making the 
insulation around the axons die, we are now finding out, 
sometimes with a delay. We are trying to explore ways in which 
that cell death can be prevented.
    So it is not simply the physical separation of the cells, 
but a lot of the trauma has to do with increased pressure, 
edema, there is often an inflammatory reaction, and all of 
these factors contribute to spinal cord injury. So it is really 
a very complex sort of injury. It is not something as simple as 
a clean cut would imply.
    Ms. Pelosi. I appreciate your elaboration. I was encouraged 
by what your statement said on the subject and by your 
testimony.
    Dr. Hall. Absolutely.
    Ms. Pelosi. Thank you very much, Dr. Hall.
    Thank you, Mr. Chairman.
    Mr. Porter. Thank you, Ms. Pelosi.
    Thank you, Dr. Hall. You did an excellent job of 
testifying, except for the answer to my question as to why you 
don't want more money. [Laughter.]
    Mr. Porter. We very much appreciate the fine job you're 
doing at your Institute. Thank you for your appearance here 
today.
    Dr. Hall. Thank you very much, Mr. Chairman.
    Mr. Porter. We will stand in recess briefly.
    [The following questions were submitted to be answered for 
the record.]

[Pages 2026 - 2093--The official Committee record contains additional material here.]

                               ----------

                                           Tuesday, March 18, 1997.

             NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

                               WITNESSES

DR. MARVIN CASSMAN, PH.D., DIRECTOR
MARTHA PINE, EXECUTIVE OFFICER
DR. W. SUE SHAFER, PH.D., ASSOCIATE DIRECTOR FOR EXTRAMURAL ACTIVITIES
G. EARL HODGKINS, FINANCIAL MANAGEMENT OFFICER
DR. HAROLD VARMUS, M.D., DIRECTOR, NIH
DENNIS P. WILLIAMS, DEPUTY ASSISTANT SECRETARY, BUDGET, DHHS

    Mr. Porter. The subcommittee will come to order.
    We are now pleased to welcome Dr. Marvin Cassman, the 
official Director of the National Institute of General Medical 
Sciences. Congratulations, Dr. Cassman, on your becoming a full 
director rather than just an acting director. Congratulations 
also on your Institute having, together with the OAR transfer, 
passed the $1 billion mark in budgeting.
    Why don't you introduce the people at the table with you 
and then proceed with your statement.

                       Introduction of Witnesses

    Dr. Cassman. Thank you, Mr. Porter. I'm pleased to be here 
officially. On my far left is Mr. Earl Hodgkins, who is our 
Financial Management Officer, on my immediate left is Ms. 
Martha Pine, the Executive Officer of the Institute, and Dr. 
Sue Shafer, on my right, the Associate Director for Extramural 
Activities.
    I'm very pleased to be here and to present to you the 
programs of the National Institute of General Medical Sciences.

                           Opening Statement

    Today, I would like to highlight several recent discoveries 
that have emerged from NIGMS-supported basic research. This is 
something we do every year, of course, but this year I 
particularly want to use these highlights to illustrate that 
important discoveries do not occur in a vacuum, but build on a 
large body of previous work. This is another aspect of what Dr. 
Varmus in his opening remarks called ``culminations and 
inspirations.'' These breakthroughs are the culmination of 
decades of research representing the inspirations of many 
investigators. Isaac Newton said that the reason he could see 
so far was because he stood on the shoulders of giants. The 
reason that these exciting new discoveries are emerging is 
because they have been built on the efforts of a community of 
scientists. It is one of the goals of the NIGMS to ensure the 
continuing productivity of this basic research community.
    One of the benefits of the NIGMS' long-term support of 
basic research is that major discoveries can emerge in 
unexpected places. The breakdown of materials in the cell was 
for many years considered to be an essential process but, until 
recently, it was not viewed as very interesting or even very 
complicated. After all, waste removal has never had much 
appeal. But it turns out that both in our external environment 
and in our internal environment, in the cell, the process of 
removing unwanted or obstructive material is complex, highly 
regulated, and of central importance in our lives. There are 
indications that the failure of cells and tissues to properly 
dispose of molecular waste may be a factor in some diseases, 
including one which was just mentioned, ALS, Lou Gehrig's 
disease.
    On the poster to my left, you see a pathway that begins 
when a cell is stressed. One consequence of stress on cells, 
not necessarily human stress, is that proteins unfold from 
their highly ordered structure and lose their ability to 
function. In some circumstances this is irreversible and the 
molecule has to be disposed of. This is done by tagging it with 
another molecule called ubiquitin, that's the left-hand branch 
of that pathway, which signals to the cell that the protein's 
time is up.
    [See figure 1.]

[Page 2097--The official Committee record contains additional material here.]


    Ubiquitin was discovered more than 20 years ago and it was 
found to be ubiquitous in almost all cells and organisms; 
hence, its name. It was given the name of ubiquitin because 
nobody really knew what it did. It took quite a long time of 
patient investigation, much of it by NIGMS-supported 
investigators, to understand that its primary function was in 
this removal of proteins that have become damaged in some way.
    Recently, the ubiquitin story has taken an interesting 
turn. We now know that in addition to waste disposal, the 
selective and irreversible destruction of proteins by their 
coupling to ubiquitin also provides a means of regulating 
cellular processes. For example, perhaps the most significant 
new advance in understanding how cell division is controlled 
comes from the discovery this year by an NIGMS-supported 
investigator of a large cellular particle which contributes to 
the regulation of the cell cycle of growth and division through 
targeting specific cell cycle proteins for destruction by 
coupling them to ubiquitin.
    Understanding how this activity fits into the complex 
process of cell division is likely to provide further insights 
into the behavior of the cell cycle in normal and aberrant 
cells. It also demonstrates that the protein degradation system 
is being used by the cell not only to eliminate proteins that 
are damaged or no longer needed, but in the regulation of 
cellular processes as well. As one NIGMS investigator stated in 
a recent publication, ``Protein degradation represents a 
chapter of cellular regulation that is just beginning to be 
written.'' And all this from two decades of investigation of an 
initially unknown compound.
    On the right side of the poster you see a second possible 
response to stress in the unfolding of proteins, the refolding 
into an active form assisted by a compound called a chaperonin. 
Now, how proteins fold into their three dimensional active 
forms is one of the central questions of biology and it is one 
that's been studied for many years. But all along a key tenet 
that everyone has basically agreed on is that proteins don't 
need any help to fold, all the information is contained in the 
chemical structure of the protein itself. So it was a totally 
surprising and completely unexpected discovery that in the cell 
there exists this class of compounds which have been named 
chaperoninsthat help proteins fold. Obviously, once again, the 
name chaperonins are by analogy to the chaperones who once accompanied 
and protected young ladies.
    Apparently at least some proteins need a helping hand, or 
maybe a helping molecule, to achieve their mature folded form. 
The utility of chaperonins in the cell's economy and the way 
they function have been vigorously addressed by several NIGMS-
supported researchers, one of whom has determined the structure 
of a chaperonin in great detail. I wanted to show you this 
because it is beautiful, apart from anything else. You're 
looking at a chaperonin from the top down. It is a ring made up 
of seven separate and different subunits. There are actually 
two of these rings stacked one on the other. You can't see the 
second one, of course, because it is hidden below. The ring 
forms this doughnut-shaped cavity and in the cavity the 
unfolded protein sits and is shielded as it folds.
    [See figure 2.]

[Page 2099--The official Committee record contains additional material here.]


    This structure will help in understanding the mechanism of 
proper folding in the cell and may give clues to dealing with a 
number of diseases. Failures in correct folding of proteins 
have been implicated in retinitis pigmentosa, Tay-Sachs 
disease, and cystic fibrosis. This fundamental discovery will 
affect all of them and probably many more. Understanding the 
rules that predict correct folding, as well as the process by 
which it occurs, may help clarify the basis of these and other 
diseases.
    I should point out that the problem of how proteins fold is 
a very difficult one to solve. A variety of approaches to 
understanding this process have been supported by NIGMS for 
many years, even when progress appeared painfully slow. In 
recent years, the pace has picked up dramatically and major 
advances have been made, in part, due to a continuing 
investment in this field over a long period of time.
    The step-by-step progress of science also yields tools that 
can be of enormous importance both to industry and in the basic 
research laboratory. I've given several examples of these in my 
written statement, but I'll focus only on one, and that's on 
the next poster which shows the developments in the production 
of transgenic, or knock-out, mice--mice which have had genes 
introduced or removed. Two NIGMS investigators have been 
largely responsible for the development of this approach, and 
it's been based on the underlying basic research which is 
listed on the left-hand side of this poster. The highlights in 
gold are those areas in which NIGMS investigators have had 
major involvement.
    [See figure 3.]

[Page 2101--The official Committee record contains additional material here.]


    As you can see, many of the fundamental advances that 
resulted in the generation of transgenic mice have emerged from 
NIGMS-supported research. Now if you look on the right-hand 
side, you will see the mouse models that have been developed so 
far. Two of them are highlighted because two of them have been 
developed by NIGMS researchers, the mice that have the cystic 
fibrosis gene and one in which high blood pressure is being 
examined. But as you will see, most of the other mouse models 
are being supported by other NIH Institutes, as is quite 
reasonable because they are being used for the specific 
purposes of understanding the diseases that those Institutes 
are targeted toward.
    All of these discoveries build upon and were supported by 
many outstanding investigators whose individual contributions 
make up the body of science. It sometimes appears that progress 
moves seamlessly, without a hitch, because discoveries appear 
with such frequency. However, investigators sometimes stall in 
their efforts, and in order to ensure that temporary 
difficulties do not permanently cripple an otherwise productive 
laboratory, and to maintain momentum in the field, we have 
instituted a bridge funding mechanism for investigators whose 
applications fall just beyond our payline. This is intended to 
benefit the investigators by allowing them time to maintain 
their progress; to benefit the Government by ensuring that an 
investment in individuals and research is not lost; and to 
benefit science generally by maintaining the scope and breadth 
of effort that ultimately yield the discoveries that transform 
our world.
    Two other major areas of NIGMS support are training 
andprograms designed to increase the number of under-represented 
minorities in the biomedical sciences. I've discussed these programs 
previously before this committee. I'll leave the detailed remarks for 
my written testimony. Rather, I would like to conclude by looking at 
these programs through the lens of history.
    The seminal document in the development of the modern 
research effort in the United States is generally agreed to be 
Vannevar Bush's 1945 report called ``Science: The Endless 
Frontier.'' This is a document more often cited than read, 
which is a pity because it still has a great deal to tell us. 
At one point, Bush quotes from an advisory committee, which 
said the following: ``We think we probably would not, even if 
we were all-wise and all-knowing, write you a plan whereby you 
would be assured of scientific leadership at one stroke * * *. 
We think it is much the best plan, in this constitutional 
Republic, that opportunity be held out to all kinds and 
conditions of men whereby they can better themselves. This is 
the American way, this is the way the United States has become 
what it is. We think it is very important that circumstances be 
such that there be no ceilings, other than ability itself, to 
intellectual ambition.''
    This sentiment is applicable to all of our programs, but in 
particular it reflects the purposes of the Minority 
Opportunities in Research program, which is to ensure that 
under-represented minorities have an opportunity to achieve the 
scientific leadership of which Vannevar Bush wrote.
    Mr. Chairman, the fiscal year 1998 budget for the National 
Institute of General Medical Sciences is $992,032,000. I would 
be pleased to answer any questions that you may have.
    [The prepared statement follows:]

[Pages 2104 - 2107--The official Committee record contains additional material here.]


                         goals of the director

    Mr. Porter. Thank you. It is $1,020,000,000 with the OAR 
transfer.
    Dr. Cassman. With the OAR transfer, absolutely. Yes.
    Mr. Porter. Dr. Cassman, now that the ``acting'' has been 
removed from in front of your title, you get the vision 
question. Now that you've ascended to the top position, what 
goals have you set for the Institute during your tenure, and 
what steps are you taking to achieve them?
    Dr. Cassman. I think that not a unique, but a major 
responsibility of the NIGMS is to ensure the continuing 
productivity of basic research in the biomedical sciences. That 
means balancing a lot of different demands on the system. It 
means ensuring that established investigators with ongoing 
active programs are not disrupted in their research efforts and 
maintain the ability to continue to be productive. That has to 
be balanced against the needs of new investigators, and the 
needs of the scientific community and of the country to have 
new investigators come into the research system. It means 
making sure that areas that are dynamic and evolving continue 
to get the resources that they need but without starving the 
new opportunities that continually emerge. We look for new 
opportunities, for new ideas. We try to facilitate the 
development of the basic research effort, and we try to balance 
all of the needs that our community and that the broader 
research enterprise in the United States faces.
    One of the major things of course that we do is interact 
with the extramural community, with our scientists, and with 
our advisors, to get continued input into where science is 
moving and to make sure that our portfolio is balanced in such 
a way that all of the needs are addressed, not always met in 
full, of course.

              research in chemistry and physical sciences

    Mr. Porter. Dr. Varmus has often noted that biomedical 
research depends upon other disciplines--physics, chemistry, 
mathematics, and computer science, for example--to thrive. Does 
NIGMS support the lion's share of research in these other 
disciplines at NIH?
    Dr. Cassman. Certainly in chemistry, I don't think there's 
any doubt of that. Physics, probably. Physics has an input in a 
variety of different ways, including instrument development 
which occurs in many parts of NIH. Mathematics is an area where 
I think we need to have more involvement. In fact, we have been 
having discussions recently with individuals who have an 
interest in applying mathematical approaches to biological 
systems. I don't really believe that we are encouraging 
mathematicians to be as involved as they can and should be.

                            interim funding

    Mr. Porter. As you mentioned, you've instituted a program 
to provide interim funding to some unfunded competing 
continuation grants. Applications that fall within 10percentile 
points of the payline are eligible and will receive a third of the 
grant's total cost. When will these researchers apply again for full 
award? What success rate do you expect them to have?
    Dr. Cassman. Those are interesting questions. The award is 
made for only one year. So we expect them to apply within that 
one year period so that there will be no hiatus in funding. In 
the past, the success rate of this group of investigators has 
been somewhere between 55 and 65 percent.
    I would hope that the resources that we are providing 
through the interim funding will make them more successful, not 
necessarily in the immediate future, because this is really to 
tide them over, but to ensure that there is no break in the 
progress of their research, so that when they come in in the 
future they will be more successful than perhaps they have been 
in the past. That's one of the things we're going to follow to 
see whether this program in fact has been useful.
    Mr. Porter. How much funding do you allocate to these 
interim grants?
    Dr. Cassman. It will be about $3.5 million.
    Mr. Porter. Do any other Institutes operate similar 
programs?
    Dr. Cassman. Other Institutes are approaching the issue in 
other ways. I don't believe that there are any others that are 
doing bridge funding in this form.
    Mr. Porter. Your program has been criticized by some in the 
university community because it caps indirect costs at 25 
percent. How have you responded to these concerns?
    Dr. Cassman. This was never intended to be a program 
through which we could provide full support, we just don't have 
the resources, for either the investigator or the institution. 
It is an interim funding mechanism; it is not a full-funding 
mechanism, it's a partial funding mechanism. I feel that it's 
appropriate that we share the burden of supporting these 
investigators for this one year period where we are providing 
the one-third support in direct cost.
    Mr. Porter. I'm not sure that fully answers what I've 
asked. Obviously, there are institutions that have indirect 
costs that are far higher, correct?
    Dr. Cassman. The indirect cost rate is lower than the full 
negotiated level. That's, first of all, consistent with other 
programs at NIH, such as the Shannon Awards, which are interim 
funding programs, and it is simply a reflection of the fact 
that this program only provides partial funding either through 
direct costs or indirect costs. I have no theoretical objection 
to giving full cost to both in terms of direct and indirect, 
but we don't have the resources for it.

                           high risk research

    Mr. Porter. Your budget justification mentions plans to 
support innovative high risk research through two year pilot 
grants. You had previously tried another approach to supporting 
higher risk research. What are you hoping to achieve, and why 
did your first program not meet this objective?
    Dr. Cassman. In the first program, we were looking at 
applications that came in just through the normal route, and 
looking at applications that did not fall within our normal 
payline, in fact, in some cases fell far beyond it, and where 
the reviewers would say things such as, ``This is a terrific 
idea but--but there's not enough preliminary information'', 
``but we're not convinced the investigator can do it''--or 
because there was a lot of controversy. There really weren't a 
lot to select from. People do not send in applications that 
they don't think will be funded.
    So what we're doing in this new program is more proactive. 
We're soliciting applications that we hope will be somewhat 
controversial, that have substantial experimental risks but 
promise substantial benefits.

                           new investigators

    Mr. Porter. You also mention efforts to support adequate 
numbers of new investigators. Are you creating a new research 
mechanism to address this need?
    Dr. Cassman. No. No, we're not. Since 1992, we've given 
specific advantage to investigators who have no other source of 
support, and in particular new investigators. We're continuing 
to do this. I urge the staff to look carefully at new 
investigators coming in within 10 percentile points of our 
payline, and even a bit further. I'm also co-chair of a 
committee looking at the means that NIH uses to bring new 
people into the system and the mechanisms that we use, and to 
determine whether those mechanisms have been successful, 
whether they're doing what we hope they will do.

                     stimulation of research fields

    Mr. Porter. You intend to assess your grant portfolio to 
identify gaps in research coverage. If you find areas that are 
not being adequately addressed, what steps will you take to 
increase research in those areas?
    Dr. Cassman. What we normally do is we get advice, as I 
said earlier, from members of the extramural community, and 
from our advisory council. We usually hold at least a workshop 
to determine what kind of approach is appropriate, and then we 
put out a specific request for applications in that area.

               employment prospects for research trainees

    Mr. Porter. We continue to hear reports of considerable 
anxiety and stress in the biomedical community about job 
prospects, of positions having hundreds of applicants, and of 
young scientists moving from one post-doc to another rather 
than being able to secure a permanent job. At Dr. Varmus' 
December advisory council meeting, at least two members 
indicated concerns about this and felt the council should take 
a more active role in assessing the problem. They also 
questioned whether the periodic workforce studies by the 
National Academy of Sciences provided useful information.
    First, Dr. Cassman, can you give us your personal 
assessment of the situation? And then, Dr. Varmus, can you tell 
us how you plan to follow up on the suggestions of the members 
at your advisory council?
    Dr. Cassman. There's certainly some pressure on the 
workforce. I don't think there's any doubt of it. How much is 
not yet clear. Unemployment, as measured by the various indices 
that the American Chemical Society, for example, or the 
Federation of Societies for Experimental Biology use when 
they're looking at this, have not, until very recently, shown a 
significant increase in unemployment. Nevertheless, I do feel 
that the opportunities are fewer now than they certainly were 
during a period of high growth. But it's difficult to be able 
to project that very easily.
    The main point to remember is that all of our training 
programs train for eight to ten years in the future, and that 
we as a Nation, maybe anybody actually, are pretty bad at 
predicting things that far out. Attempts to estimate supply and 
demand in the past have been dreadful and have usually failed 
miserably. I don't think we can make our adjustments now on the 
basis of the fluctuations in the current situation. I think it 
has to be left to the individuals who have an interest in 
pursuing an area of excitement and great promise, and where 
those individuals, I really do believe, will find jobsthat are 
quite appropriate to their interest.
    Dr. Varmus, you have to give your half of this.
    Dr. Varmus. I'll be brief, Mr. Porter. Basically, the next 
meeting of my advisory committee will be devoted, at least in 
part, to this issue. Many of the members were unacquainted with 
the National Academy of Sciences study that is done every three 
or four years. We will have them read that report, and we'll 
provide them with data that Dr. Cassman and Dr. Ellie 
Ehrenfeld, Director of the Division of Research Grants, have 
been putting together with respect to the state of young 
investigators.
    We want to distinguish very clearly between the problems in 
obtaining grants on early applications and the problems of 
finding jobs. We also distinguish between the difficulty in 
obtaining jobs in a very restricted academic market and the 
other opportunities for using an advanced degree in science to 
work in industry, Government, or other sectors of our economy.

                scientists employed as temporary workers

    Mr. Porter. The Washington Post carried a story recently 
describing the increased use of highly trained temporary 
employees in scientific labs. Is this principally an issue for 
private industry, or is it becoming more common in university 
labs as well?
    Dr. Cassman. As far as I know, it is really an industrial 
issue. I'm not aware of temporary employees of the kind that 
was described in the article, which I did read, being involved 
in academic institutions at all.

             research training collaborations with industry

    Mr. Porter. Bruce Alberts, the head of the National Academy 
of Sciences, proposed last week at an AEI-Brookings conference 
that new hybrid models should be developed for students to 
blend the university research setting and the biotech company 
so that young scientists would have models other than the 
traditional tenure track as a career route. Are the NIH 
research training programs flexible enough to support training 
in settings like these should they be developed?
    Dr. Cassman. Absolutely. In fact, they already do. We have 
specifically at NIGMS a biotechnology training program that 
requires some involvement or some interaction with industry, 
frequently an internship and in other instances collaborative 
research, a variety of different ways. But in addition, our 
other training programs frequently have interactions both on 
the research level and on the teaching level with neighboring 
biotechnology companies. So I think this is not an uncommon 
phenomena even now.

                    rationale for stipend increases

    Mr. Porter. NIH has increased 1997 training stipends for 
pre-doctoral students and those in their first and second years 
of post-doctoral training. The President's budget proposes 
another stipend increase for the first two post-doctoral years 
for fiscal year 1998. What guiding principle is NIH using in 
these stipend decisions? Are you trying to achieve parity with 
other Federal training programs?
    Dr. Cassman. Would you like to respond?
    Dr. Varmus. It's difficult for us to achieve parity with 
all the programs. But we recognize that we have not been 
providing cost-of-living increases to our trainees, so they've 
fallen farther behind. Therefore, we have made a decision as a 
group, at a meeting of the Institute directors, to increase the 
level of support.
    Mr. Porter. Stipends for post-doctoral fellows beyond their 
first two years of training have remained unchanged since 1991.
    Dr. Varmus. They were relatively high, however, compared to 
the first two years. We tried to get the first two years up to 
what amounted to a fairer relationship to the more advanced 
years.

        evaluations of national research service award training

    Mr. Porter. Your advisory council last September heard the 
preliminary results of an ongoing evaluation of the National 
Research Service Award training programs. What are the major 
findings of the study to date?
    Dr. Cassman. That's an analysis that is being conducted of 
all of the NRSA programs at central NIH. I don't believe it is 
completed yet, although I understand that early this summer at 
least a preliminary version of the report should be available.
    Mr. Porter. Can you share that with us when you get it?
    Dr. Cassman. Oh, yes. Of course.

                compliance with nrsa payback requirement

    Mr. Porter. Your Institute is responsible for monitoring 
compliance with the payback requirements for research training 
grants. In general, what kind of track record do trainees have 
in fulfilling their research payback requirement?
    Dr. Cassman. Very high. It's difficult, I can't give you a 
good number, but I'm pretty sure it's under 1 percent where 
we've had problems with compliance.

                   medical scientist training program

    Mr. Porter. Do you intend to increase your emphasis on the 
Medical Scientists Training Program which supports joint Ph.D.-
M.D. trainees in order to ease the difficulties clinical 
researchers are facing in the new health care environment?
    Dr. Cassman. Our training programs have stayed essentially 
constant in numbers. The increases have been primarily through 
stipend increases and occasionally to compensate for 
inflationary increases in tuition payments. We don't really 
have any plans at this point to differentially increase the 
MSTP program. It would mean taking away resources from the 
other graduate training programs and those are the programs 
which support MSTP because the MSTP trainees do their research 
in the graduate programs.
    Dr. Varmus. I would add, Mr. Porter, that it isn't 
necessarily the case that M.D.-Ph.D. awards lead to greater 
protection for clinical investigators, because an awful lot of 
our M.D.-Ph.D. graduates end up doing basic research that's not 
clinical in nature.
    Mr. Porter. Well, that's my next question. What information 
do you have on the career outcomes of researchers who have 
completed the Medical Scientists Training Program?
    Dr. Cassman. We're doing a study now. I hope within the 
next year it will be complete, and we can report on exactly 
that, on the career outcomes. There have been previous analyses 
of these but none very recently. The last one I believe was in 
1984.
    We do know something about the career progression but it is 
more anecdotal than it is concrete. They tend to be among the 
best students at any institution. They do extremely well when 
they get out. They have a very good record of getting research 
grant support. Many of them are in clinical departments even 
though, as Dr. Varmus pointed out, they may be doing basic 
research, which I think is very appropriate because one of the 
intents of the program was to bridge basic and clinical and 
their presence helps in that bridging. I can give you more 
details I hope next year at the hearing.

             research areas pursued by young investigators

    Mr. Porter. What can NIH do to avoid imbalance in the 
research areas chosen by young investigators; that is, toomany 
students targeting one trendy field and ignoring other important areas. 
Can the research training program be managed to address this problem?
    Dr. Cassman. Well, we ask our training program directors to 
give us their best--their best students, their best faculty, 
their best programs. Beyond that, we try not to direct them. 
The programs that we have are all multi-disciplinary to begin 
with; they are not very highly targeted in some very narrow 
specific research area. And, in fact, we're hoping to broaden 
them even further. So I don't think that there is a lot that we 
can do, and perhaps not a lot that we should do, about that. It 
is still really up to the student to make that decision and 
they'll go where the exciting work is being done, no question 
about that.
    Mr. Porter. Dr. Varmus, do you want to add to that?
    Dr. Varmus. I do think this is an important question, Mr. 
Porter. We haven't talked all that much about this as an 
institution. But I think an argument can be made for trying to 
generate programs that would allow post-doctoral fellows, 
especially those of great excellence, to work independently 
within an existing laboratory for one or two years. The 
difficulty, as I'm sure you know, is that people who are good 
tend to train in labs that are very productive, often working 
in the most exciting areas. They develop research programs in 
those areas and then, when it's time for them to seek a job and 
apply for a grant, they naturally have to undertake their 
activities in that area. They are never given an opportunity to 
develop something novel in an atmosphere in which they have 
some protection.
    So I would like at some point to develop with a program 
that would allow us to diversify the scientific community a 
little more dramatically than we have been able to.

        training programs of the howard hughes medical institute

    Mr. Porter. The Howard Hughes Medical Institute supports 
almost $90 million in science education activities annually, 
from elementary to post-graduate. Do any of the Howard Hughes 
post-graduate programs target the same research trainee 
population as NIH programs, particularly in the minority area?
    Dr. Cassman. Actually, the Howard Hughes programs, the 
post-doctoral programs are quite limited. The only one that I 
am aware of is to M.D.s who have had at least two years of 
clinical experience. So it is essentially a reentry program 
almost. Beyond that, I don't believe they really target 
anything else, certainly nothing that's in the area that we 
deal with.

               percentage of ph.d.s awarded to minorities

    Mr. Porter. Have there been any encouraging recent trends 
in the percentage of Ph.D.s in the life sciences awarded to 
minority students?
    Dr. Cassman. The numbers are still very low. The last 
number that I'm aware of, which is based on 1994 data, shows 
that it is maybe just about 5 percent of the total.
    [Clerk's note.--Later corrected to ``6 percent''.]
    There is some indication that the bachelor's degree 
production in the life sciences may be picking up, and of 
course that's a necessary prerequisite. But right at the 
moment, it's still very poor.
    Mr. Porter. I might say we're also concerned about this in 
the education area, because the percentage of minority students 
getting advanced degrees is going down and that's of great 
concern.
    Dr. Cassman. Yes, the numbers are difficult to interpret.
    Mr. Porter. What share of these minority Ph.D. students 
graduate from minority institutions compared to so-called 
majority schools?
    Dr. Cassman. That data is usually reported by the 
Department of Education and the National Science Foundation in 
different publications they have. The only minority schools 
that they identify are the HBCUs, the Historically Black 
Colleges and Universities. There are other definitions--
Hispanic, for example. The University of Texas at El Paso has 
something like a 65 percent Hispanic population and could be 
considered a minority school, but it is not measured that way 
in their evaluation. So if you look at the HBCUs, on the order 
of 12 percent of the African-American Ph.D. degrees in the life 
sciences come from HBCUs. That's really the only number that I 
have available for minority institutions.
    [Clerk's note.--Later corrected to ``10 percent''.]

                gender differences in response to trauma

    Mr. Porter. One of the researchers you support has found 
that more males than females die after a traumatic injury, and 
that those males who survive are often more sick. Sex hormone 
levels are thought to be an explanation for this result. How 
might hormone levels modify response to trauma? And what 
implication could this have for the treatment of injury?
    Dr. Cassman. It's another example of the intrinsic 
superiority of the female. [Laughter.]
    Dr. Cassman. What happens is that after trauma there is 
frequently hemorrhagic shock; there's a loss of blood. One of 
the things that happens as a result of that is a reduction in 
the immune response. So people with hemorrhagic shock tend to 
be more prone to infections and, particularly in that kind of 
debilitated condition, therefore are more prone to die from 
infections.
    But this doesn't appear to be as true for females as for 
males. The answer appears to be not that females have something 
that the males don't have, but rather vice versa. The 
testosterone levels in the blood apparently in some way 
predispose men to this ultimate reduction in immune 
responsiveness. There have been some studies recently showing 
that anti-testosterone inhibitors provided for a short period 
of time help in reversing this effect in males. That's still 
underway in the preliminary studies.
    Mr. Porter. Dr. Cassman, you have answered all of my 
questions. I don't even have any for the record. We thank you 
for your good statement and your very direct answers. We're 
delighted that you are now complete and no longer acting. And 
we're delighted that a Chicago boy and a University of Chicago 
boy made good. [Laughter.]
    Dr. Cassman. Well, thank you, Mr. Porter. I appreciate 
that.
    Mr. Porter. The subcommittee will stand in recess until 
10:00 a.m. tomorrow.
    [The following questions were submitted to be answered for 
the record.]

[Pages 2116 - 2153--The official Committee record contains additional material here.]

                               ----------

                                          Thursday, March 20, 1997.

                        OFFICE OF AIDS RESEARCH

                               WITNESSES

WILLIAM E. PAUL, M.D., DIRECTOR
WENDY WERTHEIMER, SENIOR ADVISOR
DONNA ADDERLY, SENIOR BUDGET ANALYST, OFFICE OF FINANCIAL MANAGEMENT
HAROLD VARMUS, M.D., DIRECTOR, NATIONAL INSTITUTES OF HEALTH
DENNIS P. WILLIAMS, DEPUTY ASSISTANT SECRETARY, BUDGET, DHHS

                       Introduction of Witnesses

    Mr. Porter. The subcommittee will come to order.
    We continue today with hearings on the National Institutes 
of Health, and we are pleased to welcome Dr. William Paul, 
Director of the Office of AIDS Research. Dr. Paul, if you would 
introduce the people with you, and then please proceed with 
your statement.
    Dr. Paul. Thank you, Mr. Porter. I am delighted to have the 
opportunity to appear before you.
    I would like to introduce my colleagues. They are Ms. Wendy 
Wertheimer, who is a Senior Advisor at the Office of AIDS 
Research; Ms. Donna Adderly, a Senior Budget Analyst in the 
Office of Financial Management; and, of course, I don't need to 
introduce Dr. Varmus and Mr. Williams, but I will formally do 
that.

                           Opening Statement

    Mr. Chairman, this has been a year of progress and promise 
in AIDS research, a year clearly demonstrating the dividends 
made possible by our national investment in biomedical science. 
So striking was this progress that Science Magazine named the 
``New Weapons Against HIV'' as the breakthrough of the year, 
and Time Magazine named Dr. David Ho, an NIH-supported 
investigator and a member of our Advisory Council, as its Man 
of the Year.
    We can take collective pride in the dramatic changes that 
have occurred just since our hearings last year. Protease 
inhibitors, a new class of drugs, used in combination with 
other antiretroviral therapies, have been shown to dramatically 
diminish the amount of HIV in the blood of an infected 
individual. Receptors for molecules called chemokines have been 
identified as critical co-factors for HIV infection, providing 
us with an entirely new set of targets for anti-HIV therapies 
and new approaches for vaccine development.
    These critical advances have brought a sense of hope and 
renewed vigor to the AIDS research community and to our 
patients. But it is essential to point out that the news, while 
good, cannot lead to complacency. The covers of many magazines 
may fantasize about the ``end of AIDS,'' but, Mr. Chairman, the 
end of this pandemic is not yet in sight.
    The new drugs, while promising, are not a panacea. We do 
not know how long the benefits will last. It is far from clear 
whether immune function of treated individuals can be restored 
without additional intervention. There are many for whom the 
new drug regimens have not been effective or for whom the side-
effects are not tolerable. Because of their expense, these 
drugs are not affordable or accessible to many who need them.
    Furthermore, the sobering fact is that we have made little 
progress against the devastating spread of the epidemic around 
the globe. AIDS is the number one cause of death among young 
adults in the United States. Rates of increases in AIDS cases 
in the U.S. are greatest for women, for adolescents, for 
persons infected through heterosexual contact, for minorities, 
and for injecting drug users. Worldwide, more than 29 million 
people have been infected with HIV, with more than 3 million 
new infections in just the past year. The great majority of 
these infections occur in the poorest parts of the world, in 
countries without the resources or the health care systems to 
benefit from the new anti-HIV drugs.
    AIDS has brought about a significant decline in overall 
life expectancy in many African countries, threatening the 
economies of these already-poor nations, and robbing them of 
their workforce. A safe and an effective AIDS vaccine is an 
urgent global public health imperative. Without a vaccine, AIDS 
will soon overtake tuberculosis as the leading infectious cause 
of death in the world.
    Three years ago, the prospects in AIDS research appeared 
dim. The pipeline of new potential drugs or vaccines seemed 
empty. The OAR convened a small group of eminent scientists at 
the Stone House on the NIH campus, a meeting which has proven 
to be pivotal for AIDS research. We asked the group to help us 
identify the critical gaps in our knowledge about AIDS and to 
suggest what steps could be taken to open up new scientific 
opportunities and move the scientific frontier forward.
    The late Dr. Bernard Fields stated his firm conviction that 
further advances against the virus would require that NIH shift 
its priorities and its resources to bring about a rededication 
to building the knowledge base about HIV and how it causes 
disease. Without this knowledge, he argued, the pipeline would 
remain empty.
    In every budget year since then we have increased the 
proportion of funding for research on basic aspects of HIV, on 
the immune system, and on the mechanisms of disease, and we 
have placed a greater emphasis on investigator-initiated 
science. Between fiscal year 1994 and this budgetary request 
for fiscal year 1998, we will have increased the number of 
research grants by approximately 50 percent. This has 
encouraged innovation from a wider group of investigators.
    Another important initiative emerged from the Stone House 
meeting. Dr. Phillip Sharp, a Nobel Laureate, stated that to 
plot a course for the future, we needed to understand all of 
the facets of the existing AIDS research program. He suggested 
that OAR undertake a critical evaluation of the entire program 
to ensure that the most promising areas of science were being 
supported, the most critical scientific questions were being 
asked, and the most effective use being made of Federal AIDS 
research resources.
    As you know, that discussion led to a review of 
unprecedented scope across all the NIH Institutes and Centers, 
led by Dr. Arnold Levine of Princeton University. The report, 
commonly called the Levine Report, provides guidance to the NIH 
for strengthening our AIDS research programs. This report is 
not sitting on a shelf, gathering dust; its recommendations 
helped frame the OAR's finaldistribution of the fiscal year 
1997 appropriation, and are reflected throughout our fiscal year 1998 
research plan and budget request.
    I would like to update you about the implementation of some 
of these recommendations.
    The report recognized that only a truly effective 
preventive vaccine can limit and eventually eliminate the 
threat of AIDS. The reviewers placed a high priority on the 
need to restructure and reinvigorate the AIDS vaccine program, 
with leadership and guidance from eminent non-Government 
scientists.
    The NIH has taken important steps to carry out this 
critical recommendation. Nobel Laureate Dr. David Baltimore has 
been recruited to lead this effort, and he has gathered a group 
of outstanding scientists to serve with him. Their charge is to 
energize the development of new strategies that will lead to 
the discovery and development of a safe and effective AIDS 
vaccine.
    To facilitate this effort, the OAR has made a major 
financial investment in AIDS vaccine research. The fiscal year 
1998 budget request represents a 33.6 percent increase for 
vaccine research in the two-year period since fiscal year 1996, 
a sign of our commitment to this effort.
    The President also highlighted the importance of vaccine 
research in his State of the Union address.
    Some have argued that a protective anti-HIV vaccine is 
simply not possible. As an immunologist, I believe there is 
persuasive evidence that a protective immune response can be 
induced, and that an effective vaccine is possible. I also 
believe that the Government has a unique role and obligation to 
support the basic research needed for the development of a 
successful vaccine.
    The Levine Report also urged NIH to develop a Prevention 
Science Agenda, combining research on behavioral interventions 
with biomedical interventions such as topical microbicides, 
female-controlled barriers, methods to prevent mother-to-child 
transmission, and prevention and treatment of sexually-
transmitted diseases. The OAR has convened a group of experts 
to assist us in identifying the most promising areas for 
additional investment.
    With these actions, we believe that the necessary balance 
has been struck between research to develop treatments for 
those who are infected, and to develop vaccines and other 
prevention methods for those who are at risk. This is a 
delicate balance and one that will almost certainly shift as 
science progresses.
    Thus the fiscal year 1998 budget for AIDS research has been 
crafted to reflect the recommendations of the Levine Report and 
the broad consensus on the current scientific opportunities, 
including a rededication to understanding the basic biology of 
the virus and how it causes disease; a stronger vaccine 
research and development effort; increased research on human 
immunology; an emphasis on prevention science research; and a 
vigorous therapeutic program with an efficient clinical trials 
system in which there is increased participation of women and 
minorities.
    Mr. Chairman, we are reaping the rewards of years of work 
by dedicated scientists. Those who met at the Stone House 
helped us set a new course for AIDS research. We have gained 
new knowledge of the basic biology of HIV and developed new 
targets for therapies and vaccine development.
    The science of AIDS is moving forward and opening whole new 
areas of research that can advance the treatment and prevention 
not only of AIDS, but of other diseases as well.
    The Office of AIDS Research requests a consolidated 
appropriation of $1,540,765,000 for NIH AIDS research. The 
budget authorities provided to the OAR, allowing us to make 
resources available where the greatest opportunities lie, are 
even more critical today, as these opportunities constantly 
change.
    We are grateful to the committee for your continued support 
for AIDS research and providing us the flexibility critical to 
meeting the enormous scientific challenges posed by HIV.
    I will be pleased to answer any of your questions.
    [The prepared statement follows:]

[Pages 2159 - 2162--The official Committee record contains additional material here.]


    Mr. Porter. Dr. Paul, thank you for that wonderful 
statement. Let me say that the progress that has been made in 
AIDS research makes one's heart leap for joy, and yet you warn 
us, very properly, that we're only making substantial progress 
and the end is not yet in sight, and we certainly need to 
assure that you have the resources that you and your 
investigators need to continue the fine work that you have 
done. So we very much appreciate your leadership and all the 
progress that is being made, and we obviously want to provide 
you with the resources that you need to continue doing the fine 
job that's being done.
    I might add that I don't think the President is giving you 
enough, but you knew that already. [Laughter.]

                            aids statistics

    Let me ask some questions.
    Perhaps because of the relative newness of the AIDS 
epidemic, the number of cases is usually described in 
cumulative rather than in annual terms. Can you give us an idea 
of the number of new AIDS cases and AIDS deaths in the United 
States on an annual basis over the past few years?
    Dr. Paul. Yes. For the last year for which we have complete 
numbers, the number of new diagnoses is slightly in excess of 
70,000--I believe approximately 71,000. The number of deaths--
again, in the last year for which we have complete data--was 
approximately 50,000. There does appear, however,in the last 
six months to have been a trend towards a diminution in the death rate. 
CDC's numbers suggest that death rates are now falling, possibly by as 
much as 10 to 13 percent, although we will have to see that on an 
annualized basis.
    Mr. Porter. Were they rising in previous years, previous to 
this?
    Dr. Paul. Yes. The death rates--deaths have been rising 
from in the mid-40,000 range to 50,000 in the last year. I 
believe that would be the 1995 to 1996 year. And as I say, in 
the first six months of the most recent year that we have data 
for, the CDC indicates that the death rates are now beginning 
to diminish.

             demographic groups with increasing aids cases

    Mr. Porter. In which demographic groups is the annual 
number of new cases continuing to increase?
    Dr. Paul. Yes. Well, we are certainly seeing increases, of 
course, quite substantially, among women. Tragically, the 
numbers continue to increase and the proportional burden of 
this disease on members of minority populations are continuing 
to rise. As I indicated earlier, the number of new cases also 
amongst injecting drug users is increasing, and we are seeing a 
greater degree of transmission through heterosexual means.

      prospects for international availability of an aids vaccine

    Mr. Porter. The international picture of HIV infection is 
terribly bleak, as you said in your statement. Even if the 
unimaginable occurred and a promising vaccine candidate was 
identified tomorrow, how many years would it take for the 
vaccine to pass through testing and approval before reaching 
the international organizations that would sponsor its 
distribution?
    Dr. Paul. The general process through which trials are 
conducted, in which we do initial safety trials, is the so-
called Phase I, and then, following the model that is used in 
drugs, we do trials that establish that the vaccine actually 
induces an immune response, which is the equivalent of Phase II 
trials. And then, finally, conducting efficacy trials. This is 
a period which probably cannot be accomplished in much less 
than four to five years. That would probably be, I would have 
to say, the lower limit of the time required, and that's 
probably if everything is working perfectly. Unfortunately in 
this business there are almost invariably needs for adjustments 
that have to be made.
    So were we to have in our hands tomorrow something which 
eventually proved to be an efficacious vaccine, I would guess--
if I said five years, that would probably be a very optimistic 
statement. But we would obviously want to push the pace of this 
as rapidly as we could.

                projected aids deaths without a vaccine

    Mr. Porter. Assuming current demographic trends in looking 
worldwide, how many people would die before the vaccine became 
available to them?
    Dr. Paul. Well, as I said earlier, the rates of new 
infections for the last year or two have been in the range of 3 
million per year. The actual number of AIDS cases worldwide now 
is probably in the order of over 8 million. We have 29 million 
infections, and the reason for that discrepancy, of course, is 
that the epidemic is gathering force, so that many of those 
infected have not yet progressed to the point that they can be 
diagnosed as AIDS.
    Almost invariably, we will see the great burden occur 
several years out. But for every year that we don't have an 
effective vaccine, we can anticipate three to four million--and 
in the outyears, more--new infections.
    So to answer your question appropriately, I would say that 
failing good treatments, with the concept that every infected 
person in poor parts of the world will eventually succumb to 
this disease, each passing year is a minimum of 3 million in 
new deaths.
    Dr. Varmus. Just adding something, Mr. Porter, although 
vaccines are traditionally thought of as being preventive, 
there is the possibility of having vaccines that act in a 
therapeutic manner, and that would obviously affect the 
outcome.

              benefits of aids research to other diseases

    Mr. Porter. As you know, the committee is often drawn into 
the debate about whether an inappropriate share of NIH funding 
is devoted to AIDS research. Your budget justification 
described quite powerfully how advances in AIDS research have 
had an important impact in other disease areas. I wonder if you 
would highlight these examples today.
    Dr. Paul. Well, I would like to make several comments on 
that point. I think it is not fully appreciated what a 
remarkable accomplishment the antiretroviral therapy has been, 
not only because it has such a powerful impact on patients 
living with AIDS, but it really represents the first time there 
has been a concerted and rational effort to develop drugs to 
treat viral diseases. Until now we have had some drugs that can 
treat viruses, in various limited circumstances. Almost 
invariably, their ability to do so has been discovered in a--I 
would say, in a serendipitous manner.
    By contrast here, scientists have shown that if you take 
the virus apart piece by piece and examine how it works--with 
the aid, of course, and participation of the pharmaceutical 
industry--drugs can be made to treat virus diseases. That's an 
entirely paradigm-shifting concept. We have relied in the past 
on preventing virus diseases and treating bacterial diseases. I 
believe that this approach will herald an era when we will have 
the ability to undertake true treatments of viral diseases.
    So I believe this is, in a sense, a path-breaking concept 
which is largely due to the investment the Nation has made in 
HIV research.
    In addition, there has been an enormous increase in our 
attention to human immunology, to fundamental immunology. The 
advances in this area have enormous impact for a wide range of 
disorders, for virtually all of our autoimmune diseases, which 
include, of course, multiple sclerosis, rheumatoid arthritis, 
systemic lupus erythematosus, juvenile--so-called Type 1--
diabetes. The range of disorders which are actually caused by 
disrupted immune responses is quite staggering.
    So I believe that the scientific advances that have been 
made by my colleagues working in this area--and by my 
colleagues, of course, I mean the whole of the enterprise, 
which is a very considerable one--have very great implications 
for the health of the Nation and the world.

            flexibility for oar to change icd distributions

    Mr. Porter. Dr. Paul, I don't want to belabor a dispute of 
sorts that I believe has been resolved, but in last year's 
debate about the consolidated appropriation for AIDS funding 
one of the arguments raised was that because of changing 
circumstances, like the publication of the Levine Report, it 
was important to have flexibility to change the distribution of 
AIDS funding among Institutes. Yet from 1996 to 1997, the 
actual changes you made in the percentage of NIH AIDS funds 
allocated to each Institute were very, very small. In 
retrospect, was this argument just not relevant?
    Dr. Paul. Well, let me say, Mr. Porter, I believe that the 
consolidated appropriation has been a very effective tool for 
responding to these changes. I must also say that the 
authorities that the committee has given to the NIH for this 
purpose have worked rather well within the last year or two, 
and I might say that I believe in large measure that has been 
because we have been fortunate to have a set of personalities 
in the NIH Director and the directors of the key Institutes 
that work very effectively with our office, so that problems 
that might have occurred are just not issues.
    With regard, however, to your general point about the 
distribution of resources, I don't think it is entirely fair to 
say that we haven't really made changes amongst the Institutes. 
Indeed, if you will look in our proposal for fiscal year 1998 
you will discern that the distribution isn't even. There are 
one or two Institutes that get quite substantial increases; 
there are a few Institutes that are actually receiving less in 
the way of proposed appropriations than in past years.
    We believe that these changes reflect the imperatives of 
the Levine Report, the need to increase investment in vaccine 
research, in human immunology, in prevention sciences. That 
logically drives the budget in certain directions.

                      total aids research funding

    Mr. Porter. Well, again, we want to give you all the 
flexibility you need to do your work, obviously, and we would 
intend to do that this year as we have previously.
    Do you expect to change your estimate of the total amount 
of NIH funding targeted to AIDS research during 1997?
    Dr. Paul. Well, of course, that's an issue that would be 
decided, in association with my colleague on the right--that's 
a decision that impacts not only AIDS research, but non-AIDS 
research.
    But my personal view is that the current practice in which 
the AIDS research dollars are increasing, in concert with the 
total NIH appropriation, is a wise one. It must be recalled 
that we are now in a position in which the advances made in 
AIDS research have an impact on science in general; but of 
course, and it must be said very clearly, the great advances 
that we are seeing in all aspects of science supported by the 
NIH budget have enormous significance for AIDS research. And I 
don't believe that we can imagine the two out of step with one 
another.
    So I feel very comfortable about the proposal that we are 
putting forward for increases of a comparable magnitude.
    Dr. Varmus. I should also say that this is in accordance 
with the recommendations of the Levine Report, which argued 
that the amount of the budget that is allocated to AIDS 
research is appropriate and the issue is reallocation within 
that amount.
    Mr. Porter. It's going to be necessary to stand in recess 
because there is a vote on the floor, so the subcommittee will 
stand in recess until I return.
    [Recess.]
    Mr. Porter. The subcommittee will come to order.
    Dr. Paul, I apologize. I not only had to vote, but I had to 
answer press inquiries about your testimony. [Laughter.]

                    three percent transfer authority

    Mr. Porter. Dr. Paul, do you and Dr. Varmus intend to use 
the 3 percent transfer authority we have provided in the 1997 
bill to move AIDS funding between Institutes?
    Dr. Paul. Mr. Porter, we regard the transfer authority as a 
very valuable tool, but we also recognize that the Institutes 
need to plan ahead, and that moving resources in the middle of 
the year can be very disruptive to them. So we have taken the 
position that that transfer authority should be reserved for 
really special situations, particularly situations which our 
own discretionary fund cannot meet.
    So we regard it as an important authority, but one that we 
don't want to use simply for the sake of utilizing it. It ought 
to be reserved for very special events.
    So the answer is, I do not see today the need to utilize it 
in fiscal year 1997, but of course, some event could occur that 
might change that judgment.
    Dr. Varmus. Well, Mr. Porter, we did use my 1 percent 
transfer authority last year to shift some money to the AIDS 
domain, before the 3 percent authority was established.

             aids research proportion of total nih request

    Mr. Porter. Dr. Varmus, did the proportion of the fiscal 
year 1998 NIH budget request allocated for AIDS research change 
at all as it went through the Department and through OMB?
    Dr. Varmus. Not as a proportion of the total.
    Mr. Porter. How did it change?
    Dr. Varmus. It only changed because the total value for NIH 
changed.
    Mr. Porter. I see, like everything else changed?
    Dr. Varmus. That's correct.
    Mr. Porter. All right.
    Mr. Miller.
    Mr. Miller. No questions.
    Mr. Porter. Mr. Stokes.

                 status of minority and women's health

    Mr. Stokes. Thank you, Mr. Chairman.
    Good morning, Dr. Varmus and Dr. Paul.
    Dr. Varmus, as the hearings have progressed, I have on 
several occasions, as you know, inquired of various Institute 
heads regarding the status of minority health in our country 
today. Let me now ask you, as Director of the National 
Institutes of Health, what is the status of minority health in 
America?
    Dr. Varmus. As you know, it is----
    Mr. Stokes. And let me include women also. So my question 
becomes what is the status of minority and women's health.
    Dr. Varmus. Well, that makes it a larger question, because 
the health problems are different.
    Mr. Stokes. Yes, they are.
    Dr. Varmus. It is difficult to encapsulate all the possible 
answers here in a short time.
    In general, the health of minorities is less robust than 
that of the majority population. That is particularly true in 
the roughly seven areas that we and you have identified--
cancer, violence, drug abuse, hepatitis and other liver 
diseases, and AIDS. Dr. Paul just recently reviewed the data 
that shows that minorities bear a disproportionate effect of 
HIV; 60 percent of the burden is on the minority community, 
which is about 22 percent of the population.
    Part of that discrepancy can be attributed to differences 
in socioeconomic status and health care, but other components 
are attributable to genetic differences and cultural 
differences, and other issues that we're trying to understand.

                   role of the office of the director

    Mr. Stokes. In terms of minority health, the Office of the 
Director has a special role, would you agree?
    Dr. Varmus. We have a leadership role, and we have a role 
that is intended to promote efforts by the Institutes to 
support research that leads to the betterment of minority 
health, and to develop the capacity of minority scientists to 
contribute to the improvement of minority health.
    Mr. Stokes. In your opinion are you making any progress in 
terms of that responsibility?
    Dr. Varmus. We are in some ways. But in some ways it has 
been disappointing to me because, as you know, I would like to 
see parity of health for all people in this country.
    Mr. Stokes. I know.
    Dr. Varmus. We have, of course, continued to provide 
support for a variety of training programs. In general, the 
number of minority Ph.D.s has not changed very much over the 
years. But we have achieved an increase in the number of 
minority students at medical schools and, as a result, 
increased the number of minority M.D.s.
    I have noticed that we have seen an increased number of 
research project grants going to minority applicants, nearly a 
doubling since I became NIH Director. I am pleased by that. The 
number is still low in proportion to the minority population, 
but it is increasing with respect to the number of minority 
scientists.
    We have a very large investment in research that affects 
minority health. It is always very difficult to decide where 
the boundaries are, since many of our very large investments in 
cancer and hypertension and heart disease and diabetes and many 
other areas affect all populations. But when we try to look at 
those grant proposals that specifically target minority 
populations one way or another, we have well over $1 billion 
invested in those areas.

                 minorities on research training grants

    Mr. Stokes. I understand that the National Institutes of 
Health has a requirement that underrepresented minorities be 
recruited onto regular research training grants. Is that 
correct?
    Dr. Varmus. Yes.
    Mr. Stokes. Okay. How does NIH enforce this requirement? 
Are you seeing any positive results in the numbers of 
minorities participating in these programs?
    Dr. Varmus. I have to get those numbers for you for the 
record.
    [The information follows:]

      Number of Minorities Recruited Into Regular Research Grants

    To comply with federal mandates, all questions related to 
race and gender are identified as optional on all NIH research 
grant applications. Although statistics vary from year to year, 
and across Institutes and Centers, a significant number of 
grant applicants, 25 percent in FY 1994, choose not to identify 
their race and/or gender. Since there is no way to predict 
accurately the race and/or gender composition of these 
applicants NIH is unable to identify accurately the number of 
applications submitted by minorities and women or the number of 
awards made to minorities and women. This information available 
is summarized in the tables below:

                                   GROWTH IN NUMBER OF RESEARCH PROJECT GRANTS                                  
                                                  [Fiscal year]                                                 
----------------------------------------------------------------------------------------------------------------
                                                     1992         1993         1994         1995         1996   
----------------------------------------------------------------------------------------------------------------
Total RPGs.....................................       24,033       23,952       24,964       24,899       25,519
Percent increase...............................                      -0.3          4.2         -0.3          2.5
RPGs to African-Americans and Hispanics........          769          847        1,153        1,256        1,698
Percent increase...............................                      10.1         36.1          8.9         35.2
----------------------------------------------------------------------------------------------------------------


                                     GROWTH IN RESEARCH PROJECT GRANT AWARDS                                    
                                                  [Fiscal year]                                                 
                                             [Dollars in thousands]                                             
----------------------------------------------------------------------------------------------------------------
                                                     1992         1993         1994         1995         1996   
----------------------------------------------------------------------------------------------------------------
Total RPGs.....................................   $5,459,375   $5,657,630   $5,981,328   $6,194,524   $6,612,358
Percent increase...............................                       3.6          5.7          3.6          6.7
RPGs to African-Americans and Hispanics........      158,161      192,523      261,467      284,375      421,721
Percent increase...............................                      21.7         35.8          8.8         48.3
----------------------------------------------------------------------------------------------------------------


    We do ask, whenever the training programs are recompeted, 
that the directors of those programs provide us with 
information about recruitment of minorities into those 
programs.
    Mr. Stokes. Okay.
    Dr. Varmus. And I know that some programs have been 
penalized as a result of their failure to mount an active 
minority recruitment process.
    We also have to take into consideration not just the 
success of the minority recruitment effort, but also the 
efforts that are made. And when good faith efforts are made, we 
do allow some leniency, but we do require a good faith effort 
and evidence that the training program is seeking, particularly 
from minority schools and other places where minority 
candidates are likely to be, an effort to recruit those 
students into the programs.
    Mr. Stokes. Please feel free to expand upon your response 
in the record.
    Dr. Varmus. Absolutely.
    [The information follows:]

        Efforts To Recruit Minorities Into NIH Training Programs

    As part of the Minority Health Initiative (MHI), the NIH 
through the Office of Research on Minority Health (ORMH) 
focuses on the recruitment and retention of minorities in a 
wide array of biomedical research and health professions. In 
recognition of the underrepresentation of minorities in 
biomedical research, a systematic approach has been taken 
ranging from support of students at the precollege and 
undergraduate levels, through graduate/post doctoral and 
faculty training. ORMH collaborates with the National Science 
Foundation to support science and mathematics educational 
programs at the kindergarten level through grade 12, including 
classroom and laboratory research experiences for student 
participants, teacher training and standards-based curricula. 
Community-based outreach activities to encourage minority 
students to pursue biomedical careers are also conducted in 
collaboration with the HHS Office of Minority Health. At the 
same time, NIH continues to support the Minority Access to 
Research Careers (MARC) and the Minority Biomedical Research 
Support (MBRS) programs--two primary undergraduate research 
training programs. The Minority High School Research 
Apprenticeship Program is continuing. ORMH funds a relatively 
new program called ``Bridges to the Future'' which encourages 
students at key transitional points in their education to 
continue for their bachelor's degree--if they started a two 
year college--at partner colleges and to continue to work 
toward the Ph.D. degree--if they attend terminal master's 
degree institutions--at a partner university. Also, the ORMH 
supports pre-existing NIH minority training and educational 
programs, international research training programs through the 
Fogarty International Center, as well as research supplements, 
for undergraduate students. A new program co-sponsored by the 
ORMH and the National Institute of Neurological Diseases and 
Stroke (NINDS) has established a graduate/post doctoral 
neuroscience program at Morehouse Medical School. Further, the 
NIH continues to fund clinical associates programs and career 
development opportunities for minority faculty development. In 
the intramural program of NIH, a loan repayment program for 
young clinical researchers is aimed primarily at disadvantaged 
students. As with the health research agenda, the assessment/
evaluation underway by the ORMH will review these training 
initiatives to ensure that they are operating as they are 
intended.

                      aids in minority populations

    Mr. Stokes. Dr. Paul, you may have already covered this 
because Dr. Varmus sort of indicated that prior to my coming in 
you had some comments relative to AIDS in minorities.
    I happen to sit on the International Advisory Committee on 
AIDS up at Harvard University. As you may know, this past 
October they had a council meeting where leaders from 
throughout the country were called there to Harvard to talk 
about the whole problem related to AIDS. I have just recently 
come from another meeting up there.
    Obviously, the minority community now has had an expansive 
growth in terms of AIDS. Is that correct?
    Dr. Paul. Tragically, it is correct.
    Mr. Stokes. Can you tell us what that situation is?
    Dr. Paul. Well, in terms of numbers, in the last year for 
which we have complete numbers, the new diagnoses, roughly 60 
percent of those were amongst our minority community; and over 
the life of the epidemic, that number is in excess of 50 
percent. So minority populations make up a disproportionate 
share of those infected and, unfortunately, a growing share. 
There are so many bad things about this epidemic, but this is 
one that I have always personally regarded as one of those 
especially tragic aspects of the character of the epidemic.

                  aids research addressing minorities

    Mr. Stokes. Dr. Paul, how does your budget address this 
particular situation?
    Dr. Paul. Well, in several ways. Firstly, of course, we 
have taken very seriously the notion that we need to be certain 
that members of minority groups and women are adequately 
represented amongst our clinical trials and our natural history 
studies, because it is only through that process that we can be 
certain that the therapies that are developed and the 
understanding of the disease will reflect the particular 
characteristics of the disease in these populations.
    In our large clinical trials programs, minorities are 
represented in roughly the proportion in which they are 
represented amongst those who are affected by the disease.
    We have certain natural history studies, particularly those 
targeted at understanding the disease in women and the issue of 
perinatal transmission, in which minority participation is 
actually in excess of 80 percent, so that we will be gathering 
information which we believe has great impact on the disease in 
minorities.
    Further, I should say--and this is on a more worldwide 
scale--that the growing emphasis is on the need to find 
preventive measures, and particularly a vaccine. While of 
course it would benefit all who are at risk of the disease, 
since so much of that risk throughout this world occurs in the 
poorest parts of this world, I believe that were we to be 
successful in developing a vaccine--as I very much hope we will 
and have a degree of confidence that we will--that we will have 
great impact on individuals within the U.S. minority 
population.

       reluctance of minorities to participate in clinical trials

    Mr. Stokes. Let me ask you this. I recently had a 
conversation with a New York Times reporter who was writing an 
article about the fact that the Tuskegee syphilis study has had 
a negative impact upon the African American community, in that 
the community is very reluctant to subject itself to clinical 
trials.
    Are you aware of this, and can you comment on that for us?
    Dr. Paul. Well, it is certainly known that there is, in 
many of our minority populations, a substantial suspicion. We 
feel it is fundamentally unfounded, but we also understand the 
basis of that suspicion regarding the motives of those who are 
conducting trials.
    Now, we have, as part of our research enterprise, 
particularly in the behavioral aspects of that, efforts 
underway to determine mechanisms that are most effective in 
dealing with access to care, access to trials, and the 
institution of appropriate preventive measures amongst various 
populations that are culturally sensitive, because we recognize 
that different groups have different needs. Indeed, I would 
have to say, particularly in the prevention arena, there has 
been a growing recognition that one size does not fit all, that 
we need programs that are tailored to particular cultural 
groups, particular racial groups, if we're going to really have 
impact, and that is, I would say, a growing aspect of the way 
those studies are being conducted.
    Mr. Stokes. Thank you, Dr. Paul.
    Thank you, Dr. Varmus.
    Thank you, Mr. Chairman.
    Mr. Porter. Thank you, Mr. Stokes.
    Mr. Wicker.
    Mr. Wicker. I will pass, Mr. Chairman. Thank you.

                aids research proportion of nih funding

    Mr. Porter. Dr. Varmus, to confirm what you said earlier, 
if the committee is able to provide an increase larger than the 
2.6 percent for NIH for 1998, will you continue to allocate the 
overall NIH percent of increase to AIDS research funding? In 
other words, if we are able to go to 3 percent, would then the 
funding for OAR be 3 percent also?
    Dr. Varmus. That is correct.

               proportional increases for nih institutes

    Mr. Porter. And is that the same for all Institutes? We 
would simply move up in percentage terms?
    Dr. Varmus. Well, we would do some negotiation, but in 
general, yes.
    The reason I hesitated slightly is that my objective in 
proposing increases is to be sure that we can capitalize on a 
number of proposals within the areas of NIH emphasis that I 
have outlined for you before. Many of the proposals that the 
Institute Directors made to me were not proposed for funding 
within the 2.6 percent budget. If a larger budget is available, 
I would like to be able to work with committee staff to try to 
develop a budget that allows us to take advantage of the many 
specific opportunities that Institute Directors have 
identified.
    Mr. Porter. Speaking for myself, you simply have to tell us 
what allocations you want to make, and we will attempt--we 
will, as far as I'm concerned--we will simply reflect your 
priorities.
    Dr. Varmus. Needless to say, I appreciate that.

                    prevention science working group

    Mr. Porter. Dr. Paul, as you mentioned, one of the areas 
emphasized by the Levine panel was the need for enhanced 
research into AIDS prevention strategies. Has the prevention 
science panel headed by Dr. James Curran made its 
recommendations?
    Dr. Paul. Dr. Curran, as you know, is leading this panel 
that consists of some 10 members, derived from institutions 
outside NIH. They have made an initial set of recommendations. 
We had set aside a pool of resources that the Institutes could 
have access to this year in an effort to sort of ``jump start'' 
this prevention science process. They have made recommendations 
for the use of these resources; indeed, the Institutes are 
aware of them, and have responded to them with a large series 
of proposals. Indeed, we are going to make the distribution 
very shortly.
    Amongst the areas they have indicated would be studied, are 
behavioral studies in particular, revolving around the new 
therapies for HIV, how we can improve adherence to these 
difficult therapeutic regimens, dealing with the issues of HIV 
transmission by individuals under therapy. So that's one area 
they have focused on that is particularly important. They also 
stressed issues regarding maternal-to-fetal transmission, and 
particularly the behavioral and the non-vaccine biomedical 
prevention areas.
    A further area that they particularly focused on was 
research on injecting drug users, with particular emphasis on 
mechanisms to foster getting them into drug treatment so that 
techniques could be used to diminish the burden of injecting 
drug use as an approach, of course, to diminishing the risk 
that would adhere to those who are such users.
    But beyond that, we look to this group over the next 
several years to be providing a changing agenda that the 
Institutes can use in crafting their plans for the future. So 
they have an immediate task, which they've done, and a longer-
term task, which they are in the process of carrying out.

                 the new generation of aids researchers

    Mr. Porter. Last June, an article in Science Magazine 
suggested that a new generation of AIDS researchers appeared to 
be overtaking the pioneer AIDS researchers, although theynoted 
exceptions like Dr. Fauci, who ranks as a powerhouse in both groups. 
[Laughter.]
    Do you think this characterization of a changing guard is 
correct? And do you feel the new group of researchers is more 
collegial and less competitive, as the Science article asserts? 
[Laughter.]
    Dr. Paul Well, I like to look at it somewhat differently. I 
think there was a core of truth in the article, in the sense 
that there has been developed in AIDS research a young group of 
outstanding scientists, largely as a result of the Nation's 
investment in this field. First-rate scientists have grown up 
in this field and are doing terrific work.
    On the other hand, the ``old guard,'' as we put it, is not 
so very old----
    [Laughter.]
    Dr. Paul [continuing]. And they are holding their own very 
well.
    So I like to think of it as having an expanded population 
of first-rate scientists, doing outstanding work. Inevitably, 
fields change and mature and develop; we see now a very good 
spirit of cooperation and collegiality among scientists. There 
always are controversies, but I think it reflects not so much 
the personalities as the maturation of the scientific field.
    Mr. Porter. The media loves to look at the controversies.
    I have other questions, and I assume other members do, for 
the record, which we would ask you to answer for the record for 
us. Again I want to say what a wonderful job you are doing, and 
the progress is simply the most heartwarming thing that we 
hear. We want to do everything we can to help you continue that 
progress.
    Dr. Paul. Thank you, Mr. Porter.
    Mr. Porter. Thank you, Dr. Paul.
    (The following questions were submitted to be answered for 
the record.]

[Pages 2174 - 2248--The official Committee record contains additional material here.]

                               ----------

                                          Thursday, March 20, 1997.

  OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH BUILDINGS AND 
                               FACILITIES

                               WITNESSES

RUTH L. KIRSCHSTEIN, M.D., DEPUTY DIRECTOR
ANTHONY ITTEILAG, DEPUTY DIRECTOR FOR MANAGEMENT
HAROLD VARMUS, M.D., DIRECTOR
STEVEN C. BENOWITZ, EXECUTIVE OFFICER
STEPHEN A. FICCA, DIRECTOR, OFFICE OF RESEARCH SERVICES
DENNIS P. WILLIAMS, DEPUTY ASSISTANT SECRETARY, BUDGET, DHHS

    Mr. Porter. The subcommittee will come to order.
    Next we are pleased to welcome Dr. Ruth Kirschstein, the 
Deputy Director of NIH, to testify on the Office of the 
Director; and Dr. Harold Varmus, to testify on buildings and 
facilities.
    Dr. Varmus. I am going to begin, Mr. Porter.
    First of all, let me just say that in view of the limited 
time available, Dr. Kirschstein and I are going to make very 
brief remarks to cover these two topics and leave as much time 
as possible for the questioning.

                       Introduction of Witnesses

    I am accompanied here today, in addition to Dr. 
Kirschstein, whom you know well as our Deputy Director, by Mr. 
Steve Benowitz, who is the Executive Officer of the Office of 
the Director, Mr. Tony Itteilag, who is the Deputy Director for 
Management, and by Mr. Steve Ficca, who is the Director of the 
Office of Research Services.

                           Opening Statement

    The function of the Office of the Director is to provide 
leadership for the entire NIH and coordination among its 
components. The budget request for the OD this year, provided 
in your summary, is $234,247,000, excluding AIDS.
    There are four general domains of our activity in the 
Office of the Director: first, to provide management services 
for the intramural research program, the extramural research 
program, and the general administrative functions of the NIH. 
In those domains we have continued emphasis on our streamlining 
proposals, reinvention proposals that the Administration has 
fostered, including electronic grant submissions and electronic 
reporting of inventions and many other such streamlining 
activities.
    We also are moving ahead, as I described in my opening 
statement a couple of weeks ago, in improving our information 
technology and in the recruitment of a central information 
officer, and we are also trying, through our administrative 
functions, to help control research management and support 
spending, as directed by this committee, and we are carrying 
out a study which you have requested and that we talked about 
very, very briefly at the time of my initial statement here.
    In the policy domain, we have a variety of activities that 
range from technology transfer to science education to ethical 
and economic issues that affect the NIH, and we coordinate 
reports on a wide variety of topics we've discussed here 
before, ranging from AIDS to clinical research, gene therapy, 
recent reviews of the Institute directors, and many other 
topics.
    Program coordination in certain areas, particularly those 
that have been Congressionally mandated as requiring special 
offices for coordination, is carried out by a series of offices 
that Dr. Kirschstein will review in just a moment, and we have 
the function in our office of overseeing buildings and 
facilities--I'll come back to that after Dr. Kirschstein has 
spoken.
    Before I turn the microphone over to her let me make two 
points about overriding issues that affect our function in the 
Office of the Director.
    First, we are trying to make the Office of the Director 
into a unit that serves the Institutes, Centers, and Divisions 
in the most effective possible way. We are trying to foster 
cooperation and unity of purpose among the Institutes. If there 
is any legacy that I would like to leave the NIH, it is the 
legacy that the NIH is one large agency in which there are many 
autonomous parts, and that those parts work collegially 
together, though maintaining an appropriate level of autonomy 
for the Institutes and Centers while encouraging a sense of 
unit, of purpose. That is an important component of what we're 
trying to do.
    This direction is symbolized by our annual retreat that we 
talked about before. We discuss matters as trivial as the use 
of the NIH logo in all communications of research findings by 
different Institutes, and a variety of coordinated activities 
that range from research topics we've discussed here to 
competitive service centers that provide administrative 
activities.
    The second general point I would like to make concerns 
budget formulation within the President's budget. The Office of 
the Director shows a decline in our budget request, and that's 
true for a number of reasons. We show little or no growth in 
most of our offices because we are trying to protect our budget 
priority, which is research carried out by research project 
grants. We are not requesting any new research earmarks, 
including those that were provided in our 1997 appropriation 
bill. We are trying to restrict our research management and 
service monies, as we have agreed to with this committee in the 
past. And we rationalize the restrained growth of program 
offices by recognizing that research is done by the Institutes 
and Centers; the program offices are there to stimulate 
research in those targeted areas, to coordinate that research 
and to inform the public. These functions have largely been 
established, and these offices have a very small commitment 
base because of very small continuation costs. They are not, 
for the most part, funding the bulk of the research.
    I would like to extend this discussion of the program 
offices by turning the microphone over to Dr. Kirschstein.

                   Opening Statement--Dr. Kirschstein

    Dr. Kirschstein. Thank you, Dr. Varmus.
    Mr. Chairman, members of the committee, as Dr. Varmus said, 
cooperation over trans-NIH activities occurs through the 
special programs and the special program offices which were 
developed and have been established to improve the health of 
women, minorities, and the medically underserved, to support 
research in the social and behavioral sciences, and to 
encourage research in prevention and in rare diseases, dietary 
supplements, and alternative and complementary medicine.
    The Office of Research on Women's Health serves as the 
focal point for research related to health and disease in 
women, for policies regarding the inclusion of women and 
minorities in research studies, and for activities to assure 
that all NIH research studies include women and minorities as 
subjects, and to continue programs to increase the number of 
women in biomedical research careers.
    The Office of Research on Minority Health and the Minority 
Health Initiative provide continued funding to improve the 
health of and address the highest priority health needs of 
minority populations, as well as to improve the preparation of 
minority scientists for careers in biomedical sciences.
    Behavioral patterns and social status are risk factors in 
an array of diseases, and it is the role of the Office of 
Behavioral and Social Sciences Research to encourage such 
studies. This includes a trans-NIH initiative for research in 
the four leading health risk factors in the United States: 
physical inactivity, smoking, diet, and alcohol abuse.
    The maintenance of health and the prevention of disease are 
critical to the length and quality of life, and that is the job 
of the Office of Disease Prevention, through a number of 
subunits within it. One of the major ones, in which this 
committee has had great interest, is the Women's Health 
Initiative, which is a $628 million, 15-year project involving 
more than 164,000 women, aged 50 to 79. It is to study 
strategies for preventing heart disease, breast and colorectal 
cancer, and osteoporosis in older women. The 1998 budget 
request for that office is $54.7 million, and that's a decrease 
from last year's level, but it's a decrease which was based on 
plans because the recruitment phase of the study will be 
completed in May, 1998, and then the study will go on at a 
decreasing rate as data are accumulated and are analyzed. The 
initiative, therefore, is on target as far as budget and 
schedule.
    One of the important things that is of great interest, I 
think, is that we expect to reach the goal of 20 percent of the 
participants of the study to be minority women, and this is 
probably the largest number of minority women ever studied in a 
research setting in the United States.
    As interest in alternative medicine increases, the NIH has 
research in that area with the Office of Alternative Medicine, 
which was established to investigate and validate therapies 
which are outside the general stream of therapy, and to 
recommend research programs to test fully the most promising of 
these practices. These are in areas of cancer, drug addiction, 
asthma, and the study of pain; and in addition, in fiscal year 
1998, we plan to make an award, after peer review of 
applications, to a yet-to-be-selected, Congressionally-mandated 
chiropractic center to foster chiropractic-related research.
    We have an Office of Rare Diseases which provides 
information on rare diseases and conditions. These are diseases 
which have a prevalence of less than 200,000 cases a year, and 
the office is very important in linking researchers interested 
in those diseases with families across the country that have 
such diseases within their families.
    The Office of Dietary Supplements was the most recently 
established office, in 1996, to support research related to the 
role of dietary supplements in maintaining health and disease. 
It is conducting a study to determine what types of information 
are needed to respond to the public's questions regarding 
dietary supplements.
    The one other program I would like to mention is through 
the Office of Intramural Research, which coordinates the loan 
repayment program at NIH and will initiate a new clinical 
research loan repayment program to repay the educational loans 
of people who go into clinical investigation. We are 
particularly interested, again, in attempting to increase the 
number of minority physicians and scientists who go into 
clinical investigation.
    With that, I think we will stop so that you will have as 
much time as you need for questions.
    [The prepared statement follows:]

[Pages 2253 - 2256--The official Committee record contains additional material here.]


                        buildings and facilities

    Dr. Varmus. Let me just finish briefly, Mr. Porter, with a 
brief presentation on buildings and facilities.
    We are requesting $190 million this year for buildings and 
facilities. The major request is for continuation of the 
financing of the Mark O. Hatfield Clinical Research Center, for 
which you appropriated $90 million last year.
    Let me give you a very brief status report on that project. 
At last year's appropriations hearings we told you that we had 
hired a distinguished West Coast architect, Zimmer Gunse & 
Frasca Partnership, to carry out the design. We have since 
hired a construction manager, McCarthy Brothers from St. Louis. 
The negotiations with those entities are carried out through 
our contract manager, Boston Properties, and administered 
through the GSA.
    We expect design development to reach the 50 percent 
completion point in March of 1998. We will have a 
groundbreaking ceremony, we believe, this fall, with official 
excavation of the building site to occur next summer. We expect 
occupancy at the end of 2001.
    Other items in the B&F request are mainly renovations and 
to upgrade our utilities infrastructure and modernize our 
buildings, many of these projects reflecting a legacy of 
infrastructural neglect over the years. About half of our 
buildings are over 35 years old. Those items are catalogued in 
the submission and I don't think I'll go through them in 
detail.
    I will note that Building 50, for which we have received 
complete appropriations in 1997, will soon start construction 
and we expect to occupy that new, consolidated laboratory 
facility in the year 2000.
    Now we would like to open the floor for questions on all 
the topics that we have addressed. Thank you.
    [The prepared statement follows:]

[Pages 2258 - 2261--The official Committee record contains additional material here.]


                         radiology and imaging

    Mr. Porter. Thank you, Dr. Varmus and Dr. Kirschstein.
    I have a couple of unrelated questions I would like to ask. 
I believe you answered this in our earlier hearings, Dr. 
Varmus, but what view do you have on creating a separate NIH 
Institute for Radiology?
    Dr. Varmus. Mr. Porter, radiology and other imaging 
modalities are incredibly important and have attracted a great 
deal of attention, both in our intramural and extramural 
research programs. We have, through the Office of Intramural 
Research, carried out a study of our intramural radiographic 
and imaging facilities and personnel, and are trying to 
coordinate that very carefully.
    My personal belief--and very strong belief--is that 
radiology and imaging are fundamental to the activities of 
many--perhaps most--of our Institutes, that to put those 
activities into a single Institute would not serve science and 
would create additional administrative costs that I would not 
endorse.
    Mr. Porter. I knew that was your answer. [Laughter.]

                               cholestin

    But I've been asked about it recently. I imagine that when 
we have an Office of Chiropractic Research, or an Office of 
Dietary Supplements, that radiologists feel short-changed that 
they don't have something specific for themselves. It's simply 
human nature. Thank you for that answer.
    This question is probably an FDA question, but I'm very 
curious about this. Have you ever heard of a product called 
Cholestin?
    Dr. Varmus. I heard about it roughly 15 minutes ago. 
[Laughter.]
    A series of calls back to the campus have failed to produce 
the information that you request.
    Mr. Porter. Well, I wonder, because this was advertised in 
a national news magazine, and it makes health claims. It says, 
``In fact, Cholestin's exclusive all-natural ingredients have 
been clinically proven to lower cholesterol levels an average 
of 25 to 40 points in just eight weeks.''
    That would be, it would seem to me, a violation of the law 
unless they actually can substantiate the health claim. It is 
obviously sold over the counter.
    Dr. Varmus. By tomorrow we will have----
    Mr. Porter. Yes. I am very curious as to how they can do 
this----
    Dr. Varmus. We will see.

                      crc advanced appropriations

    Mr. Porter [continuing]. Because it is making remarkable 
health claims that, it seems to me, must be unsubstantiated.
    Your budget requests $90 million for the next fiscal year 
for the second installment of the clinical center construction, 
but it also requests advance funding for 1999 and 2000----
    Dr. Varmus. That's correct.

                           crc cost estimates

    Mr. Porter [continuing]. For the remaining costs of the 
project. Why should the committee provide the entire cost of 
the construction now without access to the more accurate cost 
estimates being developed?
    Dr. Varmus. Well, this is a recommendation from OMB, with 
the intention of ensuring that the monies necessary for 
completing the project will be available. Now, as you point out 
quite correctly, we will not have an absolutely accurate cost 
assessment until sometime further along in the process of 
design development.
    I have provided for the committee members some current 
pictures of what we believe the general design of the building 
will look like, but obviously these are preliminary sketches. 
They need to be revised in accord with budget estimates. As you 
know, our initial projection for the cost of the clinical 
research center we thought to be programmatically appropriate 
was around $380 million. That estimate was revised down, in 
consultation with OMB, to $330 million for the entire project, 
and we're working within that number to try to develop an 
architectural plan.
    [Clerk's note.--Later corrected to ``333''.]
    We believe that we can work within that plan, and we will 
be reporting back to the committee about the correspondence 
between design requirements and cost estimates.
    Mr. Porter. Well, somehow I doubt that this subcommittee or 
our counterparts in the Senate are going to allow a half-
completed building out on your campus, so I think----
    Dr. Varmus. That is our hope. [Laughter.]
    Mr. Porter. As we discussed last year, precise cost 
estimates for construction of the clinical center will not be 
available until the detailed design and space programming are 
completed. What instructions have you given the planners in 
developing cost estimates? Have you directed them to fit the 
project within the OMB estimate of the $310 million remaining, 
or have you asked them to develop an accurate cost estimate 
regardless of whether it turns out to be above or below the 
$310 million figure?
    Dr. Varmus. Well, in a sense, both. My intention is to 
develop a plan that will be within the $333 million--the $310 
million remaining--for the project. We have to take into 
consideration what the bed needs and laboratory needsare going 
to be. The guidance at the moment is to give us the best plan they can 
within the recommended budgetary amount, and if we encounter a 
discrepancy between programmatic needs and what can be constructed, we 
will face that at that point.

                     renovation of clinical center

    Mr. Porter. We are frequently asked what NIH will do with 
the existing clinical center building, once some of the 
functions are moved to the new facility. Understanding that it 
may be difficult to have a firm strategy for a period five to 
ten years from now, what longer-term plans do you have for the 
original building? Is it most likely that the space would be 
used for labs?
    Dr. Varmus. Yes. The proposal--of course, it is not a 
detailed one as yet--is to use as much of the space as possible 
for offices and laboratories. There will be requirements for 
continual renovation because that building, as you know, has 
inadequate facilities infrastructure, and we will need to 
improve the utilities there. We estimate it may cost us $20 
million to $30 million a year over a time period of 10 to 15 
years to bring that building completely into conformance with 
modern design stipulations. But we expect that most of the 
building will be used, even as the new building is completed. 
But there will be parts of it that will be undergoing 
renovation in a multi-phase process.
    Mr. Porter. And did you say you had cost estimates for 
renovation?
    Dr. Varmus. Not precise ones, no. But we think--Mr. Ficca 
may want to correct me on this--the estimates that we've looked 
at suggest that if we plan to phase the renovation over 10 to 
15 years, we may have costs of around $20 million to $30 
million a year.

                       administrative cost study

    Mr. Porter. Now, you mentioned the administrative cost 
study that you are conducting, at my suggestion. I am 
encouraged by your serious efforts so far to make the study 
comprehensive and wide-ranging, and we are pleased that you 
were able to persuade Jack Mahoney to head up this effort.
    Can you tell us more about how you are structuring the 
study? Have you yet selected a contractor?
    Dr. Varmus. We are in the process of doing the contractor 
selection. We had six candidates; we have looked at their 
credentials very carefully and they have been interviewed, and 
we hope to be able to announce a decision very, very shortly.
    Mr. Porter. There are many administrative cost centers you 
could target in your study. What areas have you selected as 
first tier issues to be examined, and why?
    Dr. Varmus. Well, we attempted to identify areas in which 
we felt we could have a major impact. The first tier of areas 
to be targeted are buildings and facilities functions, equal 
opportunity functions, finance, logistics, mail and printing 
services, personnel and human resources, procurement, safety 
and security, and space and facility management.
    Mr. Porter. That sounds like everything.
    Dr. Varmus. It's not everything. [Laughter.]
    If you want to hear the second tier, I can give you that. 
There's a lot left. [Laughter.]
    But we chose areas where we thought there might be 
administrative overlap, there might be opportunity for 
reduction in costs, where we thought we might be able to 
develop centralized services, based on past experience in 
trying to generate some competitive service centers.
    But I think these are the areas where we can get our 
greatest gains, and we will of course keep you informed as we 
move along with them.

                 unified information technology system

    Mr. Porter. We understand that you are attempting to 
integrate all the computer systems on the NIH campus into a 
unified information technology system, and that you are 
recruiting a chief information officer. What does this project 
entail in terms of staffing and expenditures?
    Dr. Varmus. I may have to have someone else help me with 
the cost for staffing and expenditures, but let me explain that 
over the last several years, as computers have become much more 
important in the daily lives of everybody at NIH, whether 
researchers or administrators, we have had a ``tower of Babel'' 
on campus with respect to efforts to develop optimal 
information systems. At one recent count there were 37 
committees working on information technology development in a 
manner that was not completely cohesive.
    At our recent Institute Directors' retreat, there was a 
community-wide resolve to put an end to this Babel and to 
coordinate our information technology development in a way that 
would produce euphony. The result was putting together a 
committee that didn't cost us anything--just NIH employees who 
worked diligently and brought a report to me within about six 
weeks, that outlined a strategy for normalizing an information 
system that would allow free communication between Institutes, 
that would protect the privacy of information, and that would 
allow what we call ``interoperability,'' even though the 
hardware might be different in different Institutes.
    We have also resolved to hire a chief information officer, 
as you noted. That will cost us some money, obviously. There 
will be a need to have a highly-trained and well-experienced 
person come to the NIH to coordinate our information services. 
He or she will need an office and a few people. We believe, 
however, that given the importance of information services to 
everyone at NIH, that this will produce savings. I don't know 
if anyone on my staff is willing to estimate what the savings 
would be, but I believe that there is little doubt that an 
investment in our information technology is going to have major 
dividends. We already know from the activities that Wendy 
Baldwin has carried out in the Office of Extramural Research 
that we can make tremendous improvements in, for example, grant 
submission, invention reporting, and many other activities 
through an improvement in our computer technology.
    Mr. Porter. Mr. Itteilag is shaking his head no, he doesn't 
want to make a cost savings estimate. [Laughter.]
    Mr. Porter. We will bring this up next year and see where 
we are.
    Mr. Miller.
    Mr. Miller. I think----
    Mr. Porter. You're going to yield to Mr. Wicker?
    Mr. Miller. I'll come back.
    Mr. Porter. And go to the end of the line?
    Mr. Miller. Trade places.
    Mr. Porter. Yes, you may. You yield to Mr. Wicker.

                     office of alternative medicine

    Mr. Wicker. Well, I appreciate, Mr. Chairman, your allowing 
me to go out of line.
    I just want to ask a few questions about this Office 
ofAlternative Medicine. How long has the office been established?
    Dr. Kirschstein. The office was established in 1992, I 
believe. It was not completely functioning in 1993 when Dr. 
Varmus and I came, and it really began in earnest, if you will, 
somewhat later.
    Mr. Wicker. In 1994?
    Dr. Kirschstein. In 1994.

                           herbal medications

    Mr. Wicker. Well, I noticed that you are planning to look 
into herbal medications. What is the difference between herbal 
medications and the practice of pharmacognosy which, as you 
know, is using natural products to develop prescription drugs? 
And will this Office of Alternative Medicine be considering 
pharmacognosy as it considers herbal medications?
    Dr. Kirschstein. I believe it will. I would like to ask the 
director of the office to give you a more specific answer, 
unless Dr. Varmus would do that.
    Dr. Varmus. This office, of course, is coordinating 
research that is carried out by the Institutes. It doesn't have 
grant authority of its own. We would welcome at the NIH 
applications to study any herbal medications that are thought 
to have efficacy. One of the ways in which such medicines might 
be studied would be to use traditional chemical methods to try 
to identify the pharmacologically-active compounds in an herbal 
preparation. Classically, this has been the way many 
medications--digitalis, taxol, quinine, and many others--have 
been identified, and then further improved through 
pharmaceutical chemistry to make better medications.
    Mr. Wicker. So the office itself will not contract for the 
research? The office will coordinate with various----
    Dr. Varmus. It would encourage Institutes to take an 
interest in areas that are brought to the attention of the 
office.
    Mr. Wicker. And will the various Institutes, do you think, 
be contracting with universities?
    Dr. Varmus. Well, not necessarily contracting with, but 
inviting applications from.

                     office of dietary supplements

    Mr. Wicker. Inviting applications from universities to 
participate in this research.
    All right. I notice that you mentioned the Office of 
Dietary Supplements. I guess that means vitamins, is that 
right?
    Dr. Varmus. Vitamins and other things.
    Dr. Kirschstein. Vitamins and other additions to the diet. 
That office was established in 1996 by Congressional mandate, 
and has been actively developing a data base regarding the 
various dietary supplements. Vitamins are a very important part 
of that, and probably one of the major parts.

                       medical nutrition therapy

    Mr. Wicker. Well, I don't know if this question deals with 
the Office of Dietary Supplements or the Office of Alternative 
Medicine, but is the NIH coordinating any research concerning 
the area of medical nutrition therapy, which I think is a term 
of art? And I might add that Representative Nancy Johnson, I 
understand, has a bill to allow Medicare to cover medical 
nutrition therapy.
    And I would ask further, before I allow you to comment on 
all of this, the Lewin Group apparently has commissioned a 
study which was released only recently, and it estimates that 
medical nutrition therapy would save $11 million in the year 
2001, and increase up to a savings of $65 million in the year 
2004.
    So I just ask you what you are doing, if anything, with 
regard to medical nutrition therapy, and if you are aware of 
any study by the Lewin Group about this treatment.
    Dr. Varmus. I am not aware of the Lewin study. We do have 
an Office of Nutrition that exists within the NIDDK that works 
closely with the Office of Dietary Supplements. I don't know 
what medical nutrition therapy is explicitly, but I'd be happy 
to provide that information for the record and find out whether 
either of the two offices are doing anything explicitly on that 
topic.
    [The information follows:]

                       Medical Nutrition Therapy

    Medical nutrition therapy refers to specific services 
provided by dietitians and health care providers. In the 
Medical Nutrition Therapy Act of 1995 (H.R. 2247) this therapy 
is covered under part B of the medicare program and defined as 
services provided by registered dietitians and nutrition 
professionals only when referred by a physician. This bill 
defines medical nutrition therapy services as: ``nutrition 
diagnostic, therapy and counseling service which are furnished 
by or under the supervision of a registered dietitian or 
nutrition professional who is legally authorized to furnish 
such services under the state law of the state in which 
services are furnished, as would otherwise be covered if 
furnished by a physician or as an incident to a physicians' 
professional services.''
    The Lewin report to which this reference is made has not 
yet been released (the report will be titled ``The Cost of 
Covering Medical Nutrition Therapy under Medicare: 1998 through 
2004''). This report was commissioned by the American Dietetic 
Association with The Lewin Group. The report presents the 
results of an econometric study of covering medical nutrition 
therapy as a Part B benefit of the Medicare program. The study 
included 16,000 Medicare patients with diabetes, and 38,000 
with cardiovascular disease who participate in the Group Health 
Cooperative of Puget Sound. This ground health plan has 
provided coverage for medical nutrition therapy through visits 
with registered dietitians for over six years. Most health care 
programs do not include this benefit.
    The preliminary results without a narrative interpretation 
have been orally presented to the American Dietetic Association 
(ADA) by the contractor (The Lewin Group). The ADA has in turn 
shared their interpretation of these results with members of 
Congress because the data appear in part to support their 
contention that extension of Medicare coverage to include 
medical nutrition therapy would reduce health care costs. The 
inclusion of this benefit would provide coverage for dietetics 
services.

                    NIDDK Medical Nutrition Research

    The NIH Revitalization Act of 1993 identified the National 
Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) 
as the lead institute for coordinating trans-NIH nutrition 
research. The Division of Nutrition Research Coordination 
(DNRC), which was transferred from the Office of the Director, 
NIH, to the NIDDK synthesizes and leads the trans-NIH focus for 
nutrition.
    NIDDK supports major clinical trials and basic research 
studies to investigate both the role of diet and specific 
nutrients in prevention and treatment of disease, and the 
specific role of nutrients and other dietary components in the 
development of disease. An example of a major recent research 
effort is the trans-NIH Bionutrition Initiative. The Initiative 
is supporting research on the defective mechanisms as well as 
the normal processes involved in the direct roles of specific 
nutrients on cellular, genetic, and metabolic processes, and 
potential clinical applications.
    Recently completed major clinical trials, such as the 
Diabetes Control Complications Trial (DCCT) and the 
Modification of Diet in Renal Disease (MDRD) Study, both 
contained important dietary components. The DCCT examined 
whether intensive treatment with the goal of maintaining normal 
blood glucose levels could decrease the risk of diabetes 
complications. A diet and exercise plan was a component of the 
DCCT. The results indicate that intensive control of blood 
sugar levels effectively delays the onset and slows the 
advancement of diabetic eye disease, foot disease, and nerve 
damage in patients with insulin dependent diabetes mellitus. 
The MDRD tested whether low protein diets and rigorous blood 
pressure control could slow or prevent the development of 
various kidney diseases. Study results indicate that below-
normal blood pressure levels have a favorable impact on 
deteriorating kidney function, particularly in patients with 
proteinuria. The associated effect of protein restriction is 
less potent than blood pressure reduction.
    In June 1996, the NIDDK launched the Diabetes Prevention 
Program (DPP) clinical trial. This major trial will explore the 
feasibility of preventing or delaying the onset of noninsulin-
dependent or adult onset diabetes. The DPP will identify 
volunteers with impaired glucose tolerance (IGT) levels between 
100 and 139. An ``intensive lifestyle'' intervention, which 
consists of a diet and exercise program designed to help 
volunteers achieve and maintain a seven percent weight loss, is 
one of four treatment regimens that are being studied. This 
six-year study is recruiting individuals who are at high risk 
of developing diabetes, including African Americans, Hispanic 
Americans, American Indians, Asian Americans, and Pacific 
Islanders. NIDDK will receive additional support from the 
National Institute of Child Health and Human Development 
(NICHD), the National Institute on Aging (NIA) and the NIH 
Office of Minority Health.
    In addition to these clinical investigations, basic 
research on nutrient metabolism, the relative proportion of 
proteins, fats, and carbohydrates in the diet, and on energy 
metabolism serves as the foundation for the design of medical 
nutrition therapy and dietary guidance provided to both 
patients and the public. Across the NIH, similar research 
serves as a foundation for nutritional recommendations in areas 
of relevant illnesses, such as cancer and cardiovascular 
disease.

    Mr. Wicker. All right. Well, I would be very interested in 
your following up with my office on it.
    Dr. Varmus. As a matter of interest, was the savings 
millions or billions?
    Mr. Wicker. I have ``millions'' here. But as the late 
Everett Dirksen said, it all eventually adds up to real money. 
[Laughter.]
    So I thank you, Mr. Chairman, for allowing me to go out of 
order on this.
    Mr. Porter. Thank you, Mr. Wicker.
    Mr. Stokes.

                          ORWH's budget level

    Mr. Stokes. Thank you, Mr. Chairman.
    Dr. Varmus, Dr. Kirschstein, what is your current budget 
for the Office of Research on Women's Health?
    Dr. Varmus. The amount in 1997 is $17,241,000.
    Mr. Stokes. Can you give us some idea of what your plans 
are for future appropriation requests for this office?
    Dr. Varmus. That's the 1997 estimate. The President's 
budget for that office is $17,423,000.
    Mr. Stokes. Okay. Is there an increase there?
    Dr. Varmus. Yes. As I mentioned in my opening remarks, this 
office, like all the offices, is receiving a very small 
increase in the President's budget request to preserve as much 
money as possible for the highest priorities, the grants that 
would serve all these areas.
    Mr. Stokes. This office has an important role on research 
on women's health and has responsibility for collaborating with 
the Institutes and Centers of the NIH in promoting research on 
women's health. How high a priority does the Office of the 
Director give to this particular function?
    Dr. Varmus. We give it a high priority. I emphasize again, 
Mr. Stokes, as I've said before, that it seems to me that the 
important functions here are coordinating and instruction and 
the provision of supplementary money to encourage the 
Institutes to make the major investments in these areas, and I 
believe that the important thing for us to do in tight 
budgetary times is to continue to provide the Institutes with 
the funds required to support research projects, which will be 
encouraged even by slightly smaller amounts. I think the number 
of supplements and co-funding enterprises carried out by the 
office is actually more important than the actual dollar value 
that is in each of the supplements.

             national agenda on research on women's health

    Mr. Stokes. I note, Dr. Varmus, that the Office of Research 
on Women's Health is in the process of updating the National 
Agenda on Research in Women's Health. How is that office 
reaching out to ensure that issues of minority populations are 
incorporated into the development of the newAgenda on Research 
on Women's Health?
    Dr. Varmus. I think Dr. Kirschstein would like to answer 
that.
    Mr. Stokes. Dr. Kirschstein?
    Dr. Kirschstein. That office has been very active in that 
regard. As you know, Mr. Stokes, Dr. Vivian Pinn is the 
director of that office. She has been long active not only in 
women's health areas, but in minority health areas as well.
    Mr. Stokes. She is a very distinguished lady.
    Dr. Kirschstein. Yes.
    In order to update the original agenda, which was set some 
years ago at a conference in Hunt Valley which I had the honor 
to chair, Dr. Pinn and her staff are doing several conferences 
around the country which will reach out to people interested in 
women's health and the health of women in all groups, majority 
women, African American women, Hispanic women, American Indian 
women, in order to see what the gaps still are, and then we 
will update their agenda.

                      women in biomedical careers

    Mr. Stokes. Dr. Kirschstein, part of the mandate of the 
Office of Research on Women's Health is to enhance women in 
biomedical careers. What efforts are underway to increase 
minority scientists as investigators in women's health 
research?
    Dr. Kirschstein. One of the things we have found, and I 
know Dr. Pinn has found as well, is that very often, when one 
provides small incentives in terms of small amounts of money 
for studies in women's health or in the health of minorities, 
the individuals who are particularly interested in carrying out 
those projects are women or minority scientists themselves. Dr. 
Pinn's efforts, through the Office of Research on Women's 
Health, are to encourage women scientists who have been out of 
the workforce for some time because of family responsibilities, 
to reenter careers and to develop fellowships to provide them 
with the updating necessary. Also, encouraging young women--
minority women in particular--to enter science, is going to and 
will continue to, in one way or another, pay off in that 
regard.

                         marc and mbrs programs

    Mr. Stokes. OK.
    Earlier in your testimony today you mentioned the MARC and 
MBRS programs.
    Dr. Kirschstein. Not particularly here, but I love to talk 
about those programs all the time, Mr. Stokes.
    Mr. Stokes. I know you do, and you've had that 
responsibility for a number of years. I know that's a program 
that you have your heart in, and I appreciate that.
    Over the years the Committee has advocated increased 
funding on behalf of many of the NIH minority programs, but 
specifically the MARC and the MBRS programs. Can you clarify 
for me whether this Committee directed any increase through the 
Office of the Director for any expansion in these efforts?
    Dr. Kirschstein. I don't think the Office of the Director 
provided specific increases to those programs. Dr. Marvin 
Cassman was testifying just two days ago and did mention those 
programs. He has worked diligently, along with the Director of 
Minority Opportunities for Research Programs--the More 
Program--who has the responsibility for MARC and MBRS, to 
increase those programs, and particularly to increase the 
effectiveness of those programs. They have worked very hard to 
have the students in those programs enter biomedical sciences.
    One of the things that has clearly happened is something 
Dr. Varmus mentioned previously, which is that there has been a 
real increase through the efforts of MARC and MBRS, for 
minority students to enter medical careers. It has been, as you 
know, more difficult to persuade them--with, perhaps, good 
reason--to enter into fields that are not so medically driven. 
On the other hand there is an increase, therefore, in 
medically-trained minority investigators whom, we hope, will be 
moving into clinical research.
    Dr. Varmus. I might just add that Dr. Ruffin, who as you 
know is the head of our Office of Research on Minority Health, 
has been aggressive and imaginative in establishing a number of 
other minority training programs, including the Bridges to the 
Future Program and other undergraduate training programs that 
are funded through other minority research initiatives.

                       minority funding increases

    Mr. Stokes. I was about to move into that area, Dr. Varmus, 
because, as you know, I have a keen interest in the viability 
of the NIH Minority Health Initiative and the Office of 
Minority Health.
    How does the recommended increases for these programs 
compare to the overall increase in the NIH budget?
    Dr. Varmus. It is lower, and it is lower for the reasons 
that I outlined before. These are programs which provide 
supplements and encouragement to programs and grants that are 
run by the Institutes. My primary concern, in this fiscal 
situation that we're in of a fairly modest increase for NIH as 
a whole, is to preserve the ability of the Institutes and 
Centers to be able to make new grants.
    I believe, in consultation with Dr. Ruffin, that the office 
can continue to provide that stimulation of interest in these 
programs without an appreciable increase in the financing of 
the initiative.
    Mr. Stokes. Well, let me ask you this. When these two 
important programs were established and funded by this 
Subcommittee, it was contemplated that these resources and 
program activities would be utilized as an opportunity to sort 
of ``prime the pump'' at the other NIH institutes. The goal was 
to improve their overall effort to solving problems associated 
with the health status disparity that exists in the Nation 
among minorities when compared to non-minorities.
    I am concerned that, instead, these funds have become the 
primary source of NIH funds dedicated to research on minority 
health. Is that correct?
    Dr. Varmus. That isn't so, Mr. Stokes.
    Mr. Stokes. It's not so?
    Dr. Varmus. No, it's not so.
    Mr. Stokes. Then, what is the situation?
    Dr. Varmus. I believe the office is still serving the 
``pump-priming'' function. There have been very appreciable 
increases, well ahead of the overall increases for NIH, in 
previous years. The amount of money that NIH spends on minority 
health, as I explained, is a number that is open to 
definitional issues, but a conservative estimate is well over a 
billion dollars, roughly $1.2 billion. And, of course, the 
Minority Health Initiative is, in total, I think, about $61 
million.
    So the office is serving the priming function that you 
described, and I think it is doing so very well.

                    funding for minority researchers

    Mr. Stokes. An article appeared in the Chronicle of Higher 
Education pointing out that a relatively minor amount of NIH's 
budget is awarded to minority researchers. Has that situation 
improved any?
    Dr. Varmus. Yes, it has, Mr. Stokes. That article appeared, 
I believe, in 1992 or 1993----
    Mr. Stokes. It appeared in 1993, actually.
    Dr. Varmus [continuing]. And reflected numbers from 1991.
    Mr. Stokes. That is right.
    Dr. Varmus. And all is not as well as you and I would like 
it to be, but I recently found some figures that I think will 
provide encouragement to you as they do to me, suggesting that 
since I came to NIH in 1993, the number of research project 
grants awarded to African Americans and Hispanics has doubled 
from roughly 850 to roughly 1,700. Now, that is probably an 
underestimate, because not all applicants for our grants self-
declare their racial identity; but nevertheless, while the 
number is proportionately lower than the number of 
underrepresented minorities in the research population by about 
two-to three-fold, it still augurs well for the future and I 
believe it does reflect a number of things, including the 
effect of our training programs, our interest in trying to 
promote minority health, and the technical workshops we have 
provided for a number of institutions to try to improve the 
ability of minority applicants to compete successfully for our 
grants.
    Mr. Stokes. Mr. Chairman, how much time do I have 
remaining?
    Mr. Porter. Your time has expired, I am sorry to say.
    Mr. Stokes. All right. Thank you, Mr. Chairman.
    Mr. Porter. Thank you, Mr. Stokes.
    Mr. Miller.

                        minority research grants

    Mr. Miller. Mr. Chairman, I have a couple questions to 
follow up on what Mr. Stokes asked about minorities.
    For grants, if you are a minority, does that give you an 
advantage in receiving a grant?
    Dr. Varmus. No.
    Mr. Miller. How are you able to double the number of grants 
to minorities?
    Dr. Varmus. I think by improving the quality of 
applications that come from minority investigators, and 
training more effective minority investigators, and by 
providing them with better facilities.

                            minority funding

    Mr. Miller. You say that of your budget, $1.2 billion can 
be identified as minority----
    Dr. Varmus. No, no. We have identified roughly $1.2 billion 
as research that pertains to minority health; that is, it 
addresses issues that are special concerns.
    As I explained to Mr. Stokes a little earlier, this is a 
difficult problem definitionally because one could argue that 
since diabetes affects minority populations more profoundly 
than it does majority populations by some modest measure, that 
any research on diabetes is working to the benefit of minority 
health. So what we try to do is identify within that portfolio 
those projects which are specifically targeting problems that 
especially affect minority populations or use minority 
populations in greater numbers in clinical trials, or look, for 
example, at the pattern of diabetes pathogenesis among the Pima 
Indians, and therefore it can be categorized as a minority 
effort.
    Mr. Miller. Do you have a report that summarizes how that 
$1.2 billion--I missed the session; you did have one 
presentation that included minority issues earlier, last month. 
But where did you get the $1.2 billion? Do you have a report 
that reflects that and shows how that was derived?
    Dr. Varmus. Yes, I believe we do. The number comes, of 
course, from the various ways in which we catalog all of our 
research. But we certainly can provide for you the information 
that you require about how those numbers are developed and what 
they represent.
    [The information follows:]

[Page 2273--The official Committee record contains additional material here.]


                                 quotas

    Mr. Miller. You do not use quotas in biomedical research?
    Dr. Varmus. We do not.

                 undergraduate and secondary education

    Mr. Miller. What do you do in the area of undergraduate and 
even secondary education? Do you get involved in that?
    Dr. Varmus. Yes, we do. In fact, Dr. Kirschstein is 
involved in some of these----
    Mr. Miller. Not just minorities, but in all areas?
    Dr. Varmus. In all areas. We do that through a variety of 
mechanisms, some being the kinds of minority training programs 
that have already been mentioned briefly, and Dr. Kirschstein 
might elaborate on them, but also through our Office of Science 
Education, which is providing outreach to many schools in this 
area--and of course, many of those schools do have very large 
minority populations. Secretary Shalala and I were just this 
week, for example, at Eastern High School, where they have an 
academy that is sponsored by the Department of Health and Human 
Services, and we were there promoting the interest of those 
young people in science in a school that is almost entirely 
African American. So there are many ways in which we do 
outreach. We could very easily provide you with a list of those 
activities.
    Mr. Miller. There is another vote coming, so let me just 
proceed. Maybe you can get me that information.
    [The information follows:]

[Pages 2275 - 2288--The official Committee record contains additional material here.]


                      nih organizational structure

    Mr. Miller. In sitting through the presentations, not only 
today but all the time, I see--I haven't heard from the 
Pentagon recently, but they're very big with acronyms, and I 
see you are, too----[Laughter.]
    Mr. Miller [continuing]. But I think I counted 12 new ones 
here.
    Mr. Porter talked about the administrative study. The 
question I have is, the Office of Science Policy or the Office 
Intramural Research or the Office of Dietary Supplements--you 
never close those down, I'm sure. Mr. Porter asked the question 
in the area of imaging; you're not going to create one. In the 
area of AIDS, you did not create a new Institute, because five 
years from today or ten years from today it may be a very 
different situation.
    Basically, you can never shut one down. I mean, I'm a 
business school professor; the number of people that have to 
report to you probably violates all organizational management 
charts. I would hate to see your organizational chart right 
now.
    Dr. Varmus. Oh, I don't think it's all that bad. 
[Laughter.]
    Mr. Miller. Well, how many Institutes are there? There are 
17 or 18 Institutes?
    Dr. Varmus. Well, 22.
    Mr. Miller. And then all of the offices.
    Dr. Varmus. Institutes and Centers. It depends on what you 
call them.
    Mr. Miller. Okay.
    Dr. Varmus. And then there are some Divisions that are 
independent, as well.
    Mr. Miller. Is this administrative study going to be 
looking at any consolidation? At some stage--what was the one 
that was mentioned a few minutes ago that the Congress asked 
you to create, the Office of Alternative Medicine?
    Dr. Kirschstein. And Dietary Supplements.
    Mr. Miller. Dietary Supplements. That was a mandate?
    Dr. Kirschstein. Yes.
    Mr. Miller. I'm not saying that that shouldn't be 
investigated or studied or such, but I get concerned that 
you're getting an organizational structure that----
    Dr. Varmus. Some of this, you recognize, is at the 
directive of Congress.
    Mr. Miller. But there are some things where you need to 
take an overview and say, ``Wait a minute; are we getting 
ourselves just added and added and added, organizations and 
offices and Institutes?'' Is this administrative study going to 
look at that at all? Or is it too sensitive politically?
    Dr. Varmus. Well, you should recognize that not all these 
offices are, in fact, reporting directly to me. Some of them 
have been located within Institutes; some of them have been 
located within larger offices, such as the Office of Disease 
Prevention. So we have tried to impose some order on the system 
so that those of us who are at the upper echelons are not 
overloaded by people reporting to us.
    Mr. Miller. Have there been any studies about the overall 
organization of NIH to consider that factor? How many more 
offices were just created? Two in the last Legislature?
    Dr. Varmus. Well, I don't think it's appropriate for us to 
ask our consultants to tell us whether or not Congressionally 
mandated or authorized institutions should be continued. We are 
asking them to look at lines of reporting and to look at the 
overall administrative structure. But the emphasis has been on 
functions which we believe might be consolidated and 
streamlined, fundamentally in response to the concern of the 
committee, as expressed by Mr. Porter, that we have as few 
full-time employees and as few dollars as possible allocated to 
these functions that could be considered ancillary to research, 
and not research itself.

                        plans for new institutes

    Mr. Miller. Do you have any plans for any new Institutes? 
Are any being discussed?
    Dr. Varmus. I do not. [Laughter.]
    Mr. Miller. I guess the one on the Human Genome Project was 
the last one that became an Institute.
    Dr. Varmus. That's correct. That, of course, was an 
existing Center which changed in name but not appreciably in 
function. There were some minor administrative changes, but it 
was already operating more or less as an Institute, with an 
intramural program and many authorities.

                       listing of nih facilities

    Mr. Miller. What facilities do you have outside of 
Bethesda, the main campus of NIH?
    Dr. Varmus. Well, we have facilities in Poolesville, 
Maryland; Baltimore, Maryland; and North Carolina--we could 
provide you with a list of them. We have quite a few.
    [The information follows:]

             NIH FACILITIES IN THE BALTIMORE/WASHINGTON AREA            
                       [Excluding Bethesda Campus]                      
------------------------------------------------------------------------
             Facility                             Location              
------------------------------------------------------------------------
NIH Animal Center................  Pooleville, Maryland.                
Frederick Cancer Research &        Ft. Detrick, Maryland.               
 Development Center (FCRDC).                                            
NIA/Gerontology Research Center..  Baltimore, Maryland.                 
NIDA/Addiction Research Center     Baltimore, Maryland.                 
 (lease).                                                               
NIMH/St. Elizabeth's Hospital....  Washington, D.C.                     
------------------------------------------------------------------------

    Mr. Miller. How about outside the greater Washington area? 
Do you have any?
    Dr. Varmus. Yes, we do. We have some in Montana, in North 
Carolina, in Arizona, and in quite a few other States, and some 
of those are requiring funds this year for upgrade of 
facilities. We could certainly provide you with a complete list 
of that.
    [The information follows:]

          NIH/FACILITIES OUTSIDE THE BALTIMORE/WASHINGTON AREA          
------------------------------------------------------------------------
             Facility                             Location              
------------------------------------------------------------------------
NIEHS............................  Research Triangle Park, North        
                                    Carolina.                           
NIAID/Rocky Mountain Laboratory..  Hamilton, Montana.                   
Primate Center...................  Perrine, Florida(\1\).               
Primate Center...................  Sabana Seca, Puerto Rico(\2\).       
Primate Center...................  New Iberia, Louisiana.               
NCI/Seattle Field Station (lease)  Seattle, Washington.                 
NIDDK/Phoenix Epidemiology &       Phoenix, Arizona.                    
 Clinical Research Branch                                               
 (agreement with Indian Health                                          
 Service facility).                                                     
------------------------------------------------------------------------
\1\ Ownership being transferred to the University of Miami, Florida.    
\2\ Property being execssed through GSA, ownership expected to transfer 
  to the University of Puerto Rico.                                     


    Mr. Miller. Are you planning more expansions around the 
country?
    Dr. Varmus. No, we're not.
    Mr. Miller. Is that a problem, having facilities around the 
country?
    Dr. Varmus. Well, we have, of course, reviewed all these 
institutions with regularity. There are a couple of small 
facilities that we have, one in your home State, Mr. Miller--
the Animal Center in Florida--and another small building in 
Puerto Rico, both of which we intend to transfer to the State 
or territorial authorities.
    Mr. Miller. Thank you very much, Mr. Chairman.

                            minority funding

    Mr. Stokes. Mr. Chairman, would you yield to me for just a 
moment?
    Mr. Porter. I would be happy to yield to you, Mr. Stokes.
    Mr. Stokes. Thank you, Mr. Chairman.
    Let me see if I can just clear up something that comes to 
my mind with reference to a question posed to you by Mr. 
Miller. He had asked you about the $1.2 billion of your budget 
which may in some manner impact upon minority health as a 
result of research in that particular area. You have indicated 
an allocation of about $1.2 billion, is that correct?
    Dr. Varmus. I would say that's probably a conservative 
number, because that number is determined by looking at 
projects that very clearly are intended to benefit minority 
health specifically, as opposed to, say, any cancer project, 
which, as you and I know, would be of benefit to minority 
populations, which do have a disproportionate burden of cancer.
    Mr. Stokes. I think it is important for the record to show 
the amount that remains in your budget after the application of 
the $1.2 billion. The $1.2 billion comes out of what budget 
total?
    Dr. Varmus. The total budget is $12.7 billion. Mr. Stokes, 
if I may, I understand where your line of questioning is going, 
but I would say that it's important to recognize that virtually 
everything we do is going to benefit the health of virtually 
everyone.
    Mr. Stokes. Hopefully.
    Dr. Varmus. Hopefully.
    Mr. Stokes. The disparity that we've been talking about as 
it relates to minorities, the disproportionate disparity, 
obviously is not affecting everyone.
    Dr. Varmus. Yes, but I would be hard-pressed to identify 
research which is disproportionately directed toward majority 
populations. Some, I'm sure, is, but----
    Mr. Stokes. The fact is that you are identifying 
approximately $1.2 billion that you feel has some impact upon 
the health of minorities, or--am I misstating you?
    Dr. Varmus. Yes, I think you are, with due apologies. I 
think that perhaps I'm not making myself totally clear.
    Mr. Stokes. Okay.
    Dr. Varmus. That research is identified by criteria that we 
will have to look at more closely, but it is research that is 
not just in any way likely to improve minority health, but is 
specifically addressed to a problem that has--in a way that 
investigates, for example, what might be the differences 
between stroke in African American and white populations or 
that uses a population of study patients who are largely 
minority, as opposed to a study of breast cancer, which is 
studying breast cancer generically and would have important 
benefits for the minority population because, as you know, the 
mortality rates for African Americans from breast cancer are 
higher. The study is of breast cancer per se, but I would argue 
strongly that it is very likely to have benefit for all people.

                           Concluding Remarks

    Mr. Porter. Could I suggest to the gentleman from Ohio that 
there is very little time left in the vote, but also that we 
are going to have NIH back again, and Dr. Varmus will be here, 
and this question can be raised at length, if you would like to 
do that.
    Mr. Stokes. I appreciate that, Mr. Chairman. Thank you.
    Mr. Porter. Dr. Varmus, this concludes our first round of 
NIH hearings, 13 in all, with 26 hours of testimony. You and 
your colleagues have been very patient to spend all these hours 
with us, and we are considering taking a little bit of money 
and making a laboratory in the basement of Rayburn for you----
    [Laughter.]
    Mr. Porter [continuing]. So that you can be here 
practically full-time.
    Dr. Varmus. I would appreciate that, Mr. Chairman.
    Mr. Porter. I think you realize how valuable these 
opportunities are for members of the subcommittee and how much 
we enjoy the sessions, and that's why we hope that you and your 
colleagues can return in May at the conclusion of our regular 
hearing cycle to discuss in more detail some of the issues we 
feel we haven't had sufficient time to discuss in this process, 
and we'll look forward to seeing you then.
    Thank you so much.
    Thank you, Dr. Kirschstein.
    The subcommittee will stand in recess until 2:00 p.m.
    [The following questions were submitted to be answered for 
the record.]

[Pages 2293 - 2429--The official Committee record contains additional material here.]

                               ----------

                                            Tuesday, June 10, 1997.

                     NATIONAL INSTITUTES OF HEALTH

                               WITNESSES

HAROLD VARMUS, M.D., DIRECTOR
RICHARD KLAUSNER, M.D., DIRECTOR, NATIONAL CANCER INSTITUTE
CLAUDE LENFANT, M.D., DIRECTOR, NATIONAL HEART, LUNG AND BLOOD 
    INSTITUTE
PHILLIP GORDEN, M.D., DIRECTOR, NATIONAL INSTITUTE OF DIABETES AND 
    DIGESTIVE AND KIDNEY DISEASES
WILLIAM PAUL, M.D., DIRECTOR, OFFICE OF AIDS RESEARCH
DENNIS P. WILLIAMS, DEPUTY ASSISTANT SECRETARY, BUDGET, DEPARTMENT OF 
    HEALTH AND HUMAN SERVICES
HON. GEORGE GEKAS, A REPRESENTATIVE IN CONGRESS FROM THE STATE OF 
    PENNSYLVANIA
 HON. CONSTANCE A. MORELLA, A REPRESENTATIVE IN CONGRESS FROM THE STATE 
    OF MARYLAND
 HON. GEORGE R. NETHERCUTT, JR., A REPRESENTATIVE IN CONGRESS FROM THE 
    STATE OF WASHINGTON
 HON. PATSY T. MINK, A REPRESENTATIVE IN CONGRESS FROM THE STATE OF 
    HAWAII

    Mr. Porter. The subcommittee will come to order. I am 
delighted to welcome back our panel of NIH witnesses for this 
hearing on the process NIH uses to set research priorities. It 
is a special pleasure for the subcommittee to have a second 
opportunity in the course of one hearing cycle to talk to 
representatives from NIH.
    We have invited this morning members who are not members of 
the committee, who have expressed an interest in this subject, 
and we expect that some of them will arrive in the course of 
the hearing this morning.
    Today's hearing is the outcome of discussions during our 
first round of hearings in which some members expressed 
concerns about whether NIH was appropriately taking into 
account various factors, such as health care expenditures, in 
allocating research dollars among various diseases. My own 
views on these matters are well established. I have stated 
scientific opportunity as judged by scientists, not 
politicians, should be the guiding principle in NIH resource 
allocation decisions.
    I do not believe that science fundamentally operates on a 
disease-specific basis. So much of the research that NIH 
supports is basic, unplanned, untargeted and unpredictable and 
serendipitous in its outcomes. As we have heard on many 
occasions, research aimed in one direction frequently provides 
benefits in an unexpected direction. Forcing a categorization 
of research in one disease area versus another can often be an 
exercise in futility and a hazardous diversion in funding 
debates.
    But I want to give an opportunity for a full airing of 
views on the subject. I am not without sympathy to the 
arguments that some of the disease groups raise. I understand 
how passionately they care about research and the victims of 
the diseases they represent. I intend to raise several 
questions myself that voice their concerns.
    I hope that today members will take advantage of this 
hearing to raise these issues that often simmer beneath the 
surface so the NIH leadership and the Institutes directly 
involved can respond. I hope this discussion will resolve some 
concerns before we approach markup. My first concern is to 
maintain the health of the NIH enterprise, and I fear that the 
fighting between diseases, this ``siblicide'', as one 
journalist dubbed it, represents a threat both because it 
undermines public support for NIH and because it could provoke 
ugly battles that result in NIH funding being cut overall.
    We will hear an opening statement from Dr. Harold Varmus, 
the Director of NIH, and other NIH representatives will be 
available to answer questions.
    I yield to Mr. Obey, our Ranking Member.
    Mr. Obey. Well, thank you, Mr. Chairman. I hadn't intended 
to make a statement, but let me simply make an observation.
    I have served on this subcommittee some 23 years, and 
during that time, two things have been self-evident. Number one 
is that this subcommittee has traditionally put as its highest 
priority support for biomedical research, which is largely 
funded through NIH. The second thing that has become abundantly 
clear to me is that there are tremendous political pressures 
which are brought upon both NIH and representatives in Congress 
on questions of funding levels for various Institutes to attack 
various diseases.
    I do not want to suggest at all that the process by which 
NIH arrives at its allocation decisions is absent political 
considerations. It is not. I think NIH is just as pummeled by 
political pressures as are Members of Congress. You have 
various groups who want dollars that you provide and they are 
going to find justifications to improve their bargaining 
position.
    But having said that, I would say that the dangers of 
political pressure on Congress resulting in bad allocations of 
resources in the biomedical field are infinitely larger than 
the dangers of political pressures on NIH itself, because what 
I find is that all too often, when Members of Congress get into 
this disease-of-the-month club business, they more closely 
resemble Daffy Duck than they do Jonas Salk.
    So it seems to me it is crucial that while this committee 
recognizes it has a legitimate right and indeed a 
responsibility to review the decisions made by NIH, it is also 
incumbent upon us to insist that the decisions that are made 
are free, are made as free as possible from political 
pressures. In fact, I think the intervention of this committee 
in any decisions made by NIH ought to be simply interventions 
that increase your ability to withstand political pressure, 
rather than decrease it.
    That is a distinction that I would draw, and I hope that 
this hearing will contribute in at least some small measure to 
ours and your ability to do so this morning.
    Mr. Porter. Thank you, Mr. Obey.
    Dr. Varmus, why don't you introduce your colleagues and 
then proceed with your statement.

                           Opening Statement

    Dr. Varmus. Thank you. Mr. Chairman, at your hearings over 
the last several weeks, and indeed the last several years, we 
have frequently had occasion to touch on decision-making and 
resource allocation at the NIH, and I am grateful to you today 
for providing this dedicated forum to discuss these important, 
contentious and unfortunately complex issues at greater length 
than usual.
    My job will be to present the process in general, to 
describe some of the underlying principles. Then, I will be 
joined by my colleagues, Dr. Claude Lenfant, Director of the 
National Heart, Lung and Blood Institute, Dr. Phil Gorden, 
Director, National Institute of Diabetes and Digestive and 
Kidney Diseases, Dr. Richard Klausner, Director of the National 
Cancer Institute, and Dr. William Paul, Director of the Office 
of AIDS Research, to answer questions about the specific 
processes, the specific mechanisms used in the different units 
of NIH in relation to specific programs.
    I think, before we get into some of the more contentious 
issues, it is useful to remember that over the past half 
century the NIH has enjoyed a good relationship with the 
Congress, the public, and the Administration; that very 
productive relationship has been responsible for many of the 
discoveries that have improved health around the world, 
deepened our knowledge of living organisms and placed the 
United States in the forefront of medical research and 
development.

          observations and principles for resource allocation

    Today we are meeting to discuss how we spend the money we 
receive from you each year, namely, what kinds of decisions 
must be made, who makes those decisions, and what factors need 
to be considered when making them.
    Underlying these simple questions are some fundamental 
issues. How much of our budget should be spent on plans to 
conquer specific diseases? How much should be invested in basic 
research? How should the NIH, as part of the Federal 
Government, generally respond to threats to health posed by 
specific diseases or injuries? And thirdly, where should the 
final authority reside in making important decisions about the 
distribution of our resources?
    In the interest of trying to consolidate the underpinnings 
of our decision-making process, I am going to confront these 
issues through 10 observations based on historical facts, on 
some operating principles and on my personal experience as 
Director of NIH that I believe help explain how we manage our 
budget.
    The first of these observations is that resource allocation 
is not a single issue. In fact, it embodies many decisions that 
are made during a complex process of deciding how to spend our 
money. So, first, the administration and the Congress must 
determine how much money is appropriate to give to each 
Institute and Center. Then each Institute and Center must 
decide how to allocate its funds to different kinds of 
mechanisms; that is, to investigator initiated grants, to 
contracts, to centers, to the intramural program, or to 
training programs.
    Then each Institute must also judge two additional things: 
which specific applications for grant support to fund and 
whether to emphasize certain research topics within its 
authorized domain.
    The net effect of these several decisions will be to 
determine how much across the NIH is devoted to certain 
categories, certain scientific disciplines or certain diseases.

                            commitment base

    The second perspective is a pragmatic one, well-known to 
this committee but worth emphasizing here: only a relatively 
small portion of our budget can be realigned each year. As you 
all know very well, many historical decisions provide a firm 
framework for our budget, decisions that led to the creation of 
Institutes, research centers that are supported by the 
Institutes, and the intramural research program.
    Furthermore, a very substantial portion of our funds are 
already committed to grant recipients as a consequence of 
giving multiyear awards and receiving annual budgets. As a 
result, a fairly small fraction of each year's budget, perhaps 
10 percent, can be affected by changes in funding policies.

                    limitations to planning science

    The third observation is a philosophical one, but important 
to remember, and that is, to echo a remark you made, our 
ability to plan science is limited and, indeed, excessive 
efforts to plan science can inhibit progress. Science attempts 
to discover what is unknown, and, in that sense, is inherently 
unpredictable. History has repeatedly shown the benefits of 
allowing some component of our research activity to be governed 
solely by the imagination of individual scientists. As a result 
of that policy, some of the research done by each Institute or 
Center may be difficult or, indeed, impossible to explain as 
part of a research program against a specific disease.
    Now, sometimes we can say about a research strategy that it 
can be planned, but it lies outside the boundaries of a 
specific disease. The genome project is a good example. But 
historically, we have many examples that fall into other 
paradigms. For example, the development of recombinant DNA 
research and the methods that now underlie the entire 
biotechnology industry and its production of important 
therapeutic reagents dramatically illustrates the need for 
unplanned, untargeted, high quality, fundamental science. There 
are many contemporary illustrations that will yield the same 
fruit: our efforts to understand cell death, our attempts to 
paint the three-dimensional structures of proteins, and many 
other areas that now can't be assigned to a specific disease, 
but, I believe, will be the foundations on which beneficial 
applications of our research will ultimately develop.
    So, overall, the Institutes cannot, and should not provide, 
entirely precise plans for their complete research portfolio.

                      criteria for decision making

    The fourth point is also an important one to remember, and 
that is that there are many criteria which have to guide the 
development and expenditure of our budget. There is no single 
criterion that applies. So when we try to answer the questions 
I raised earlier--how much to give to a singleInstitute, how 
much to devote to a certain discipline, how much to spend on a certain 
disease or certain grant mechanism or which applicant among many to 
fund--we have to consider many kinds of demands that we are responsible 
for answering.
    We need to respond to public health needs, but those needs 
themselves can't be correlated with research in any single way 
using any single metric. We need to be responsible to support 
work of the highest caliber. Excellence is our creed and we try 
to judge that by peer review.
    We are responsible for seizing scientific opportunities and 
we know all scientific opportunities are not equally 
approachable, regardless of their importance for public health. 
We have to depend on advisors of many kinds, including program 
managers in the Institutes, to help capitalize on recent 
advances.
    We also must be responsible for maintaining a diverse 
research portfolio so we feel we are advancing on all fronts, 
if at different speeds on different fronts, at all times.
    Finally, we need to help ensure a strong scientific work 
force and research facilities, so maintenance of the scientific 
infrastructure is also part of our domain.

                       advice in decision-making

    The fifth point is that we attempt to evaluate these many 
criteria for making decisions by seeking advice from a large 
number of sources. This is our outreach program. We have 
scientific review groups composed of accomplished investigators 
to review grant applications. We have national advisory 
councils with members of the public, and the medical and 
scientific community to review Institute policies. We organize 
large numbers of conferences, workshops and other studies to 
gather opinions on a variety of health and scientific and 
ethical and administrative issues. The Institutes and my office 
have coordinating committees and program offices that review 
scientific progress, develop long-range objectives, and 
formulate budgets and initiatives. We have extramural advisory 
groups that are asked to look at trans-NIH activities--that is, 
activities that extend across Institute boundaries: the 
clinical center, gene therapy, clinical research, my use of my 
one percent transfer authority.
    We consult frequently with members of other agencies and 
other components of the administration, Congressional Members 
and staff and, importantly, with professional and health 
advocacy organizations. But I have to emphasize, despite this 
large outreach of consultancy, despite these many means of 
gathering opinions and evaluating them, assembling each 
Institute's research portfolio is a difficult and highly 
imperfect process, and it is one for which the Institute 
directors and I must assume the ultimate responsibility.

                     imprecision of disease coding

    The sixth issue is one that causes us great difficulty. We 
know that numbers alone provide a hazardous way for assessing 
and designing a research portfolio. Now, the public and the 
Congress have a right to know how our money is spent, and we 
make great efforts to find out and determine those numbers for 
the public that provides the dollars by trying to account for 
the amount of money that we provide to specific diseases, to 
various research activities, and to separate grant mechanisms. 
But we know that the coding of funds by disease category, 
although useful as a general guide, is also inherently 
imprecise.

                          parkinson's disease

    I have provided for you, in the back of my written 
testimony, one example, in the context of Parkinson's disease. 
I point out to you the large difference between the number of 
grants that can be assigned specifically to research on 
Parkinson's disease--that is, specifically and unambiguously to 
Parkinson's disease--and the much bigger number of grants 
assigned to topics such as nerve cell biology, dopamine 
metabolism, nerve degeneration, topics that have obvious 
implications for understanding and treating this disease.
    The charts also show that many Institutes are involved in 
these activities; not just Neurology and Mental Health, but 
indeed virtually all the Institutes have some role in research 
that has an effect upon the development of our understanding of 
this disorder. And this is a reflection of the fact that beyond 
these widening circles, there is yet the other possibility that 
the most important discovery will come from a totally 
unexpected direction. For reasons of this kind, there is no 
right amount of money or right number of projects for any 
disease.

                      science cannot be purchased

    The seventh point is one which I find particularly 
important to emphasize in this context and that is that 
scientific work is not simply a commodity sitting on a shelf 
that we can purchase. To shift priorities in a way that makes 
effective use of our monies in these fiscally restrained times 
requires talent and ideas, not just budgetary realignments.
    Campaigns to expand research on specific diseases often 
focus on efforts to increase spending on those diseases. But in 
order to spend such money effectively, it is first necessary to 
identify scientific opportunities and use them to attract 
established investigators. We try to make use of several means 
to do this. We invite scientists to workshops that highlight 
new opportunity and needs in a field; we try to advertise an 
Institute's interest in increasing funding in that area; and we 
try to train new scientists to work in a designed area.

                         budgetary constraints

    The eighth point is a modern reality, and that is that the 
decision to increase support in one area of medical research 
now usually constrains the support of something else. Those who 
follow the history of the development of NIH know that there 
have been decisions over the years to create new Institutes and 
to markedly expand programs in certain areas, accompanied by 
dramatic increases in the NIH budget. No programs needed to be 
attenuated as a result of those large increases.
    This is no longer the case. Recent budgetary increases, 
while welcomed and appreciable, have been modest by historical 
standards and, therefore, when directed to spend more for 
certain diseases in certain areas, do run the risk of 
constraining spending in other areas, and even, perhaps most 
importantly, in our highly productive, nontargeted areas.

                       resource allocation by nih

    The ninth point is one of potential contention, and that is 
that methods for resource allocation at the NIH are, in my 
view, preferable to excessive congressional directives. We know 
that many fields of biomedical research deserve increased 
support and could move faster with more funds. But as I pointed 
out, resources are currently limited, so pushing funds 
vigorously in one direction is liable to impede funds in 
another. This situation compels caution.
    Our requests for increased funding are carefully considered 
by the Institutes, by my office, by me. Both of these we now 
feature in the NIH areas of emphasis which represent the 
results of prolonged deliberations between the Institute 
directors and me. These areas of emphasis aim to exploit recent 
discovery, such as theisolation of new genes for human 
diseases. They aim to encourage studies of diseases that have been 
relatively neglected, poorly controlled, or recently made more 
accessible to scientific study, and they aim to strengthen research 
technologies--computer science, imaging devices, neuroscience, gene 
mapping--that are applicable to a broad range of disciplines or 
diseases.
    The final point is that many novel and powerful means are 
available and should be used to heighten the interest of 
scientists and the public benefits of their research, that is, 
their application to disease. I understand, we at the NIH all 
understand, that the public and the Congress are often 
frustrated with the pace of progress, and that is so for a 
number of reasons.

                            pace of research

    Medical science is inherently hard and slow. Advances don't 
occur at equal rates against all diseases. Sometimes the long-
term relevance of the basic science that we do is relatively 
obscure, and scientists themselves may be deficient in 
comprehending or indeed communicating the connections between 
their work and its potential value to the public.
    I have argued here that the best solutions to such 
frustrations are not excessive directives to reroute dollars to 
specific diseases. Instead we encourage advocates for those 
specific diseases to advance their causes in a variety of 
innovative ways. For example, many of us have seen how 
advocates for the study of specific diseases can be effective 
either at the local or national level by visiting individual 
scientists or by visiting professional societies, and thereby 
stimulating the interest of working investigators in the 
unappreciated implications of those investigators' work. I have 
seen this strategy effectively used by proponents of research 
on a variety of diseases, most obviously cystic fibrosis, 
ataxia telangiectasia, scleroderma, and several others.
    The NIH often responds to concerns that research on a 
specific disorder is underserved by convening a workshop to 
evaluate opportunities, to bring potentially collaborative 
disciplines together, and to stimulate the interest of new 
investigators. We have had major workshops developed in this 
way on a variety of subjects. Perhaps the better publicized 
were on autism, spinal cord injury, and Parkinson's disease; 
another will be held soon on diabetes mellitus.
    One workshop brought together clinicians and geneticists 
who then collaborated to identify a new chromosomal locus that 
predisposes to a familial form of Parkinson's disease. The 
research opportunity created by this finding will attract new 
investigators and could be the basis for major advances against 
the more common, nonfamilial form of the disease.
    Mr. Chairman, thank you for the opportunity to talk at 
length on these issues. I and my colleagues will be happy to 
answer questions that you and your colleagues might have.
    [The statement of Dr. Varmus follows:]

[Pages 2439 - 2470--The official Committee record contains additional material here.]


    Mr. Porter. Dr. Varmus, thank you for that statement of 
principles.
    The subcommittee will operate under the 5-minute rule today 
because of the large number of Members who are present, and we 
will go back and forth between the Majority and the Minority. 
Although we would be delighted to have her, we are going to 
count Patsy Mink of Hawaii among the Majority instead of 
Minority because she is sitting on our side; and questions can 
be answered not only by Dr. Varmus but by anyone who would like 
to comment on them.

                    aids and scientific opportunity

    Dr. Varmus, you talked about scientific opportunity in 
allocating research dollars. This is a kind of chicken-and-egg 
situation, though, isn't it? In other words, don't you really 
create scientific opportunity in a sense when you allocate 
money to a particular research field, and that encourages 
talented scientists to move into that area?
    Advocates use the AIDS field as an example, asserting that 
the best scientists followed the AIDS dollars and shifted their 
work to that field. Isn't what is hot and new and interesting 
to scientists also part of this?
    And I wonder if you could explain whether you believe that 
scientific opportunity leads or follows the infusion of 
resources. In other words, can't resources create opportunity 
and encourage people to work in that field?
    Dr. Varmus. Well, it is a very complicated relationship, 
Mr. Porter. Needless to say, when the money is available, it is 
likely to lead to some findings that will then generate new 
opportunities. But that is a slow process.
    In the case of AIDS that you mentioned, I would argue that, 
in fact, the opportunities were fairly limited in the beginning 
until we knew that a retrovirus was the causative agent. At 
that point, it became clear that there were in fact already 
very deeply built-in opportunities, because a large number of 
investigators, myself included, have been working on 
retroviruses for other reasons for about 20 years. The result 
was that we knew a tremendous amount about that class of 
viruses.
    As soon as it was apparent that it was likely that AIDS was 
caused by such a virus, the accumulated knowledge was, in 
itself, the platform from which new opportunities for pursuing 
AIDS developed. We knew about the proteins made, we knew about 
enzymes that were made by these viruses. The methods for 
understanding pathogenesis and understanding the targets for 
drug intervention were already inherent in the problem.
    Mr. Porter. But don't you believe that once you put 
resources there, that you then tend to get a lot of proposals 
that follow the resources?
    Dr. Varmus. You get the proposals, Mr. Porter. The 
difficulty, of course, is deciding in a constrained 
environmentwhat is the most efficient use of resources.
    I do agree with you that if we applied a large amount of 
funds to a specific area, that eventually we would make 
progress and create some new opportunities, but the money 
itself is not sufficient. One has to ask in a period of 
constrained resources whether we should be--it is very 
difficult for us to stimulate all areas at once. We have to 
have a rationale for saying we are going to take money away 
from an area where money could be more productively used and 
add it to an area where opportunities, at the moment, may seem 
limited.
    Now, this is not to say areas of limited opportunity are 
not areas we would fund. We are funding them. But the question 
is, how do we assign the dollars that are flexible in each 
year's budget? I think we have to do that by taking into 
consideration a variety of factors. I think this is the place 
where our job is most difficult; namely, we hear, as you do, 
the stories that describe the impact of disease upon 
individuals, and we know that additional funds will be a 
benefit. But we have to make some decisions about where the 
benefits are likely to occur most quickly and most effectively 
at that time.

                     factors in resource allocation

    Mr. Porter. We often hear from disease or patient advocacy 
groups that you are not taking into account such things as the 
number of deaths attributed to a particular disease, the number 
of cases of a particular disease nationwide or worldwide, the 
indirect cost of the disease, the cost of the disease for 
government program such as Medicare, Medicaid, or Ryan White, 
the measurement of years of potential life lost, quality-
adjusted life-years or disability-adjusted life-years and the 
like.
    Can you tell us what role those kinds of things play in 
your decisions for allocating resources?
    Dr. Varmus. Well, Mr. Porter, your list of indices reflects 
part of the problem; that is, there are many ways to try to 
gauge the impact of disease upon society. Each of those gives a 
somewhat different outcome.
    We are of course extremely sensitive to our basic mission, 
which is to do science that benefits health; and we of course 
would be remiss if we were not spending large amounts of money 
on the diseases that have the greatest impact, by a variety of 
measures. But what becomes very difficult and, to my mind, not 
credible, is to try to take any single indicator and to use 
that as a metric by which to design a funding strategy.
    So if we were not supporting research on a disease that 
clearly had a major role in public health, we would be 
extremely remiss. But beyond that fairly proximate outline that 
tries to correlate our research spending with disease impact, 
the refinement of the process, I believe, needs to depend more 
heavily on the scientific opportunities.

                       committee report language

    Mr. Porter. What is appropriate for Congress to do in 
expressing our concerns? Obviously, I assume that you think 
that congressional appropriations that are specific to a 
particular disease would be inappropriate, but what about 
language in a report, directive language in a report or 
encouraging language? Why don't you tell us what you do with 
that.
    Dr. Varmus. We welcome that. We are a creation of the 
public will. We are one of the great manifestations of our 
democracy, and we believe that we should be responsive to the 
public, and you are the representatives of the public who 
indicate to us what public concerns are.
    There are a variety of ways for us to respond to such 
language. One is what I find the most pedestrian: to give you a 
report. What I find the most useful is for us to take your 
suggestions of an area of concern to try to bring together 
people who work on that problem and related problems, have a 
conference that addresses the public's concern about the 
issues, and seek the possibility that there are opportunities 
we have not seized adequately.
    We are imperfect and the process is imperfect. We have 
repeatedly heard this year that we are not providing adequate 
support for research on diabetes. My response and the response 
of my colleagues is not the defensive one of saying, no, what 
we do is perfect. Instead, we have organized a very important 
workshop that will be held the first week in September and will 
bring to Bethesda not only people in the diabetes field, but 
people working on research in fields related to diabetes, in 
hopes that we will identify new areas of research that will be 
beneficial to patients with the disorder.
    Mr. Porter. Well, you are imperfect, but Congress is more 
scientifically imperfect. But we obviously all have great 
concerns in certain areas and we feel free to express those in 
the report accompanying the bill, and you are saying you want 
to respond to that and state what the truth is, and I think it 
is a very good process.
    Mr. Obey.

                expenditures for aids and other diseases

    Mr. Obey. Dr. Varmus, let me follow up on the Chairman's 
questions that relate to your expenditures on AIDS versus other 
diseases.
    The argument is made that because many more people die of 
heart disease and cancer than die of AIDS that somehow we ought 
to look at those numbers and calibrate our expenditures to 
attack those problems accordingly. But I think there are other 
factors that ought to be taken into consideration.
    Since NIH was created, or over any other time frame that 
you care to cite, can you tell me how much has been spent, in 
total, on cancer?
    Dr. Varmus. Well, we have been spending--it will take me a 
little time to give you the precise numbers; I can give you 
those for the record, but since 1971 when the Cancer Act was 
passed, we have been spending, do you know, a billion dollars?
    [Clerk's note.--Later changed to ``$20 billion.'']
    Dr. Klausner. About $28 billion.
    Mr. Obey. Let me simply, if you don't have the numbers, my 
staff happened to have compiled them for me.
    Dr. Klausner. This is how we negotiate our budget.
    Mr. Obey. My understanding is, from 1967 to 1997 we have 
appropriated for the Cancer Institute some $35 billion; the 
Heart, Lung and Blood Institute, we have appropriated some $21 
billion; Diabetes, Digestive and Kidney Diseases, $12.5 
billion. AIDS, in comparison to the $34 billion for the cancer 
institute and the $21 billion for heart, lung and blood 
institute, over that period, AIDS, we have spent about $13 
billion. And I would point out that we spent hundreds and 
hundreds of millions of dollars prior to 1967 to attack cancer, 
to attack heart and other cardiovascular problems, to attack 
other diseases, simply because we didn't have AIDS until just a 
few years ago.
    And so it seems to me that there may be a very good reason 
why the expenditure per death is higher on AIDS than it is on 
other diseases, simply because we are starting from a zero 
knowledge base with AIDS, and we are still starting from a 
fairly low knowledge base, and we have had a lot of years to 
learn things about heart disease and cancer, and we haven't had 
as many years of research with respect to AIDS. So it just 
seems to me we ought to be very careful before we take the 
simpleminded approach of looking at only one index by which to 
measure what we are spending.

                            nobel laureates

    The second question, how many NIH officials over the past 
10 years have been the recipient of Nobel prizes in science?
    Dr. Varmus. Grant recipients?
    Mr. Obey. No, how many Nobel prize winners have been in 
positions of responsibility at NIH over the past decade or so?
    Dr. Varmus. It depends on what you mean by responsibility, 
administrative responsibility? Probably very few. At least one.
    Mr. Gekas. One is sitting here.
    Dr. Varmus. Equal to or greater than one.
    Mr. Obey. How many Nobel prize winners have sat on your 
peer review panels.
    Dr. Varmus. I would have to check. It depends on whether 
you ask before or after the receipt of the Nobel prize. 
Probably quite a number before. Fewer afterwards.
    Mr. Obey. My point is, it would be a significant number of 
people.
    Dr. Varmus. That is correct.
    Mr. Obey. How many Members of Congress have received Nobel 
prizes?
    Dr. Varmus. Peace or medicine?
    Mr. Obey. No, medicine. I think the answer is obvious.
    How many persons who serve in decision-making spots at NIH 
have received academic training in science and medicine?
    Dr. Varmus. Virtually all.
    Mr. Obey. How many members of this subcommittee have 
received academic training in science or medicine?
    Dr. Varmus. No one at the table today. There are some in 
the Congress.
    Mr. Obey. As I total it up, we have a lawyer, an insurance 
executive, a TV executive, a lawyer, another lawyer, another 
lawyer, a businessman, a teacher on the Republican side of the 
aisle; and on the Democratic side of the aisle we have a 
lawyer, a lawyer, a public official, a public relations 
consultant, a political activist and a fugitive from Russian 
studies. That is me.
    The point I am simply trying to make is, I think it is 
perfectly appropriate for us to exercise our responsibilities 
to taxpayers and to the average American citizen to see that 
you are making decisions absent political pressures. But I do 
think that there ought to be a certain modest sense of humility 
which accompanies those evaluations, given the fact that we are 
likely to be responding at least as much to political pressures 
as we are to our own scientific knowledge on this side of the 
table. And I would simply note that in case anybody on the 
subcommittee is even mildly interested.
    The only other thing I would say is with respect to AIDS, I 
think there are pressures on you, both up and down for funding. 
I mean, no matter how much you appropriate for AIDS it will 
never be enough for the AIDS activists, and no matter how much 
you appropriate to AIDS it will always be too much for gay 
bashers in this society. And I think it is our obligation to 
resist pressures in either direction, so you do have maximum 
opportunity to put the money where you have the greatest 
scientific opportunity rather than political opportunity.

                      managing public information

    The only other observation--this isn't a question; it is 
just another observation. I guess my main concern with the way 
NIH and the scientific community has operated the last 
generation has been, I think, their view that we must 
constantly feed the public with as much good news as possible 
in order to keep support out there for biomedical research, and 
I find that to be false.
    I happened to note Daniel Greenburg's article in the Post a 
couple of days ago with which I substantially agree. I think it 
is important for people to understand how little progress we 
have made in a number of these areas, not dismissing for a 
moment the importance of whatever breakthroughs we have had. 
But I think we have to resist this constant analogy that we get 
between the moon shot and, say, a cure for cancer or any other 
disease. We are able to go to the moon because we have reached 
a certain point in our understanding of engineering, in our 
understanding of ballistics, and in our understanding of 
trajectory and mathematics, in our understanding of propulsion; 
and when we reach that critical level of understanding in all 
those related fields, we are able to accomplish a relatively 
simple engineering feat.
    It is not a simple engineering feat to discover various 
forms of cancer or anything else, and it seems to me the best 
way that we can respond to the public's concern is to provide 
enough funding to basic research so that we eventually do reach 
that critical mass so that then what we spend in disease-
specific ways can have a greater chance of success, and I think 
that we have responsibility on this side of the table to 
remember that.
    Thank you, Mr. Chairman.
    Dr. Varmus. Thank you, Mr. Obey.

                congressional biomedical research caucus

    Mr. Porter. Thank you, Mr. Obey.
    We are pleased to be joined by a number of our colleagues 
who have been invited to sit in with us this morning, and 
George Gekas is the chairman of the Congressional Biomedical 
Research Caucus.
    And, George, we are delighted you are here.

 Statement of the Hon. George Gekas, a Representative in Congress From 
                       the State of Pennsylvania

    Mr. Gekas. Yes, I thank the Chairman. I also note the 
presence of our Cochair, the lady from California, Ms. Pelosi; 
and thank Dr. Varmus for giving us the opportunity several 
years ago to light the fire under the advocacy for biomedical 
research, which resulted in our forming the caucus. But I want 
Dr. Varmus to understand that the reason that he is Executive 
Director today of the NIH is because of Biomedical Research 
Caucus. That is going to be in my memoirs.
    But, in any event, it is a wonderful relationship we have 
struck up and has resulted in, we believe, education of the 
Members on many aspects of the subject to which Mr. Obey has 
alluded here today, and we want to continue cooperation between 
our caucus and the NIH, of course.

                            commitment base

    One thing that struck me from the testimony that you 
offered, Dr. Varmus--I don't find it in trying to look through 
the written part, but you alluded to the fact, or stated that 
only 10 percent of the total funding for a particular year 
really is allocatable; that is, with the ongoing grant 
contracts and work in progress, as it were, which has a 
multiyear feel to it, that when we start arguing about 
Alzheimer's and Parkinson's and cancer and diabetes, we are 
only talking about allocating, or reallocating, 10 percent.
    Dr. Varmus. That is it roughly. It will vary from year to 
year, indeed from institute to institute depending upon their 
commitment base for that year.
    Mr. Gekas. So we are really arguing here, when we try to 
apply congressional pressure to emphasize one disease or 
another on very little of the total package, and I think that 
is a message that we are responsible for transmitting to the 
public that work in progress, as it were--I can't think of a 
better term to use--receives most of the continued funding.
    Dr. Varmus. We do consider that a large number with respect 
to dollars and a major responsibility. Moreover, when we make 
decisions, those decisions tend to be perpetuated over multiple 
years because when a decision is made to develop a program it 
becomes part of the commitment base for succeeding years.
    Mr. Gekas. Where do we stand then in the proposition that 
we have referred to, to try to double the funding for NIH, the 
appropriations, to double the current level of funding over the 
next 5 years in which effort the Chairman of this committee has 
lent his name--in fact is a key part of. Would that go to that 
10 percent, shall we say in the next 5 years, but making it 20 
percent?
    Dr. Varmus. That would make a big difference with respect 
to the number of dollars that we had to mold to specific new 
opportunities and concerns.
    Mr. Gekas. But part of that would go to the ongoing work?
    Dr. Varmus. No, no, that would be new money for new 
initiatives and for expansion of existing ones.

                    coding for parkinson's reserach

    Mr. Gekas. Well, we want to continue that effort, and we 
will keep you apprised of the progress that we make in that. 
There is only one other question that I would like to ask.
    When you settled on Parkinson's disease as a way to give us 
an example of how related research awards, which may never have 
started with the idea of curing Parkinson's or--when you say 
they are related, that is what I want to know.
    Dr. Varmus. Yes, the reason I displayed the findings in 
that way was to show that there really are three cohorts of 
grants. One in which it is unambiguously clear that the grant 
is directed towards Parkinson's. It might be a clinical trial 
of a new drug against Parkinson's or the use of fetal tissue in 
transplantation research to treat Parkinson's. And then there 
is a collection, a cohort of grants in which the work is 
directed to, for example, dopamine metabolism. We know that 
dopamine is important in Parkinson's research, but also 
important in schizophrenia and other neurological and mental 
disorders.
    And then there is a third cohort of research that I could 
not display for example, on cell death. As you know, 
Parkinson's disease is dependent on certain cells in the basal 
ganglia. Cell death is the fundamental mechanism by which that 
disease arises. And yet it is possible for someone studying 
that cell death in a fibroblast, in tissue culture, to make the 
seminal discovery that turns our thinking about that disease. 
That research would not be funded as Parkinson's-related 
research because there would be no way to show the relationship 
at the time that the grant was awarded.
    Mr. Gekas. My point is that you could prepare such a chart 
for each disease, could you not?
    Dr. Varmus. Easily, yes.
    Mr. Gekas. And some would be related.
    Dr. Varmus. This is part of our coding problem, Mr. Gekas. 
I am glad you brought it up.
    Mr. Gekas. So that we return to the thesis that was first 
uttered by the Chairman in his opening remarks that basic 
research and the emphasis that we put on our scientific 
community on that level, seeps up, as it were, to reach all the 
diseases with which the public is so much concerned.
    Dr. Varmus. A very good example of that is the Genome 
Project, which is obviously built on the idea that we will 
identify all of the genes that contribute to the development of 
human diseases, and yet the Genome Project, per se, is not 
money attributable by this kind of accounting to one disease or 
another. Ninety-eight percent of the money that the Genome 
Institute spends on extramural research is not categorized by 
disease. Nevertheless, we know that as disease genes are found, 
the impact on the study of those diseases is dramatic and new 
opportunities are obviously created when you identify the 
precise gene that is involved in the causation of that disease.
    Mr. Gekas. With that, I want to thank the Chair for 
recognizing the value of the Biomedical Research Caucus, for 
his co-working with it on many different subject matters, and 
to allowing me to put myself on record as endorsing the 
Chairman's concept that the reliance on the new discoveries yet 
to be made should be placed on the scientific community with a 
nudge from the Congress as necessary. Thank you very much.
    Mr. Porter. Thank you, Mr. Gekas. The staff has reminded me 
that if I proceeded in the way that I first announced, I would 
be violating my own principle. So what we will do is recognize 
back and forth those who were present at the start of the 
hearing, and then we will recognize those Members in order of 
arrival so that from this point on, next will be Mr. Stokes, 
then Mr. Miller, then Mr. Nethercutt, Mr. Hoyer, Mrs. Mink, Ms. 
Northup, Mr. Istook, Ms. Pelosi, Ms. Morella, Mr. Oberstar and 
Mr. Moran.
    Mr. Stokes.

                             strategic plan

    Mr. Stokes. Thank you, Mr. Chairman. Dr. Varmus, the 
previous Director of NIH instituted a strategic plan to help 
guide the Agency's direction in setting priorities. Can you 
describe the framework of that plan to the Subcommittee and 
tell us to what extent it has been updated under your 
directorship?
    Dr. Varmus. Well, I can tell you a little bit about the 
process of developing the plan. The plan itself has never been 
put into action. It involved reorganizing a number of aspects 
of the way in which we categorize our research. When I came to 
NIH, neither the Department of HHS nor I were willing to 
espouse the plan in detail.
    What I thought was extremely useful, about the notion that 
Dr. Healey put into practice, was the idea of engaging the 
extramural community more actively in the process of thinking 
through where the NIH was headed. Indeed, I and many of my 
colleagues here participated in very useful discussions at 
various locations around the country, trying to predict future 
directions as best we could, and thinking about what we would 
do with additional resources. The process was more important 
than the product.
    I have tried to emulate that in a somewhat different way. I 
am a little suspicious of efforts to develop one single plan 
for the entire NIH. Instead, I think it is more appropriate to 
consider reviews of special programs, reviews of Institutes, 
reviews, for example, of our extramural program, gene therapy 
research, and clinical investigation. I have tried to do that 
with as much involvement of extramural scientists, disease 
advocates, and professional societies as I have been able to 
do.

                      trans-nih disease categories

    Mr. Stokes. I understand that NIH tracks its investment in 
targeted diseases under the designated label--trans-NIH areas; 
is that correct?
    Dr. Varmus. Well, yes, we do have numbers for the 
expenditure on certain diseases or other activities across all 
the Institutes.
    Mr. Stokes. How do these diseases qualify for this label?
    Dr. Varmus. Frequently because in the past Congress has 
asked us to follow those numbers.
    Mr. Stokes. To what extent is there overlap in the 
reporting of funding amounts in these ``trans'' areas?
    Dr. Varmus. Very often there is considerable overlap for 
some of the reasons we just discussed with Mr. Gekas.

                  nih spending on minority initiatives

    Mr. Stokes. I would like to refer back for a moment, to our 
original hearings during this session of the Congress. At that 
time, pursuant to a question I posed, you indicated that NIH 
spends over a billion dollars on minority initiatives at NIH. 
You are familiar with that?
    Dr. Varmus. Yes, I am.
    Mr. Stokes. I am interested in knowing exactly how and 
where those dollars are being spent. When I use the term, 
``minority initiatives,'' I mean those funds that are being 
spent directly on minority programs, particularly on what the 
DHHS Secretary and others referred to as the 6 plus 1.
    As you know, in the DHHS report on minority health focused 
on cancer, cardiovascular disease, stroke, diabetes, unintended 
injuries, homicide, infant mortality, chemical dependency and 
AIDS. What I would like to have you do, and you can do it now 
or provide it for the record, is for each of these health areas 
tell us how much money has been allocated, and for what 
specific initiative.
    Dr. Varmus. I think we probably would need to do that for 
the record to be accurate. Obviously, in each of those areas, 
there are projects that are focused very heavily on the 
minority component. There is research that emphasizes the 
minority component and there is research that would work both 
ways as, of course, the research that is minority emphasized.
    The minority number I gave you at the previous hearing 
encompasses not just those seven categories, but several others 
as well. We can provide you with a breakdown by Institute and 
by disorder and we would be happy to do that.
    Mr. Stokes. That is what I would like to have you do for 
the record. For tracking purposes, how does NIH define minority 
health, women's health, children's health, senior's health, and 
aging research? How are these definitions used? What amount of 
funding is spent in each of these population categories?
    Dr. Varmus. I don't have the precise definitions with me, 
so I would have to provide those for the record, if I could.
    [The information follows:]

             NIH Definitions of Selected Population Groups

    The following are definitions that NIH uses to report 
funding for research on minorities, women, children,and 
elderly/aging. In using these definitions and in comparing 
funding reported for different population groups, it is 
important to keep in mind that there is considerable overlap 
among those populations groups and as a result, there is also 
some overlap in the research reported for each. For example, 
research on a disease that affects minority women 
disproportionately would be reported under both research on 
minorities and women's health research. Also, most definitions 
are developed in response to concerns of particular groups and 
have evolved as concerns and issues have changed. For this 
reason, definitions and data reported below are not consistent 
over time. Changes in definitions are noted below.

                                minority

    Research efforts related to individuals of non-Caucasian 
descent, and individuals of Hispanic descent.

                             women's health

    For research on diseases, disorders, or conditions that 
occur primarily in women (such as breast cancer, mammography, 
osteoporosis, etc.). This will include both clinical or applied 
research and basic research. Prior to reporting FY 91 data, 
women's health research reporting focused on single-gender 
diseases; studies to evaluate gender differences; and studies 
of diseases, disorders and conditions that are unique to women. 
Such an approach did not fully reflect the true scope of 
women's diseases, and NIH, in collaboration with other Public 
Health Service agencies; developed a more inclusive and 
consistent definition of women's health research.

                                children

    Research on children can be defined as studies in all 
categories of biomedical research (e.g., basic, clinical, 
epidemiological, behavioral, prevention, treatment, diagnosis, 
as well outcomes and health services) that relate to diseases 
conditions, or the health and/or development of neonates, 
infants, children, and adolescents up to age 21. This age 
grouping is consistent with recommendation by the NIH 
Director's Panel on Clinical Research, the NIH Inclusion of 
Children in Research Committee, and the American Academy of 
Pediatrics.

                            elderly (aging)

    According to the Research on Aging Act of 1974, which 
established the National Institute on Aging, research on aging 
encompasses ``biomedical, social, and behavioral research and 
training related to the aging process and the diseases and 
other special problems and needs of the aged.'' ``Elderly'' is 
often regarded as interchangeable with ``aged,'' and neither 
term is defined by any single, discrete chronological boundary, 
reflecting the fact that both normal and abnormal biomedical, 
behavioral, and social processes act on a continuum over the 
lifespan. Research on aging therefore focuses on issues of 
importance to health and quality of life of people in later 
stages of the lifespan through studies of a diversity of 
relevant events.

                    funding for population research

    Mr. Stokes. Also, if you would, provide for the record the 
current total funding investment in each of these population 
categories across the NIH. What is the percent change in the 
investment in each of these categories for fiscal years 1995, 
1996, and 1997, and fiscal year 1998 estimate? Provide for the 
record a chart that displays the amount and percent change in 
funding for each of the population categories, for each year--
for the period fiscal year 1984 to 1997, also include the 
fiscal year 1998 estimate. Would you do that for us?
    Dr. Varmus. I would be happy to do that. It will involve 
some hard leg work.
    I would also caution, Mr. Stokes, that there is going to be 
a subjective component to those assignations because, as you 
know, in all of our research activities there is going to be a 
component that we would like to believe benefits all. And there 
is research that is not categorized as minority that benefits 
minorities. There is research that is categorized as minority-
oriented research that, of course, benefits the majority. So 
there are not any clear-cut boundaries, but within the limits 
of our definitions, which we will provide for you, we will do 
those computations.
    [The information follows:]

[Page 2481--The official Committee record contains additional material here.]


    Mr. Stokes. I can appreciate that. I understand perfectly 
what you are saying. Let me go back to the previous question 
where you made reference to the use of the various definitions, 
I am assuming you can clearly identify the amounts.
    Dr. Varmus. Yes, we can identify them and you will see that 
the definition will be helpful, but nevertheless, there will be 
a subjective component in deciding how much of any single grant 
should be assigned to that category.
    Mr. Stokes. Thank you.
    Mr. Porter. Thank you, Mr. Stokes.
    Mr. Miller.

                        public relations for nih

    Mr. Miller. Dr. Varmus, welcome again.
    As one who is a very strong supporter of NIH, I am really 
excited to be on this particular subcommittee and to be able to 
express my support. I was interested in your tenth point, which 
was basically stating that you needed to do some better PR, and 
I see that all the time when we have Mohammad Ali who will come 
and testify on behalf of Parkinson's or Arnold Palmer on 
cancer. I think it is something that we need to push for as to 
the success and what a crown jewel that the NIH is and 
definitely be proud of how our tax dollars are used.
    As a strong fiscal conservative, I can argue very often 
against programs, but this is one that I argue for, and I think 
we need to develop a better program because so many people 
think that NIH funding is 10 percent that is intramural rather 
than the extramural. That, in effect, is what you point out in 
your tenth point. You don't want to use the word PR, but we 
need to market what good is being done there.
    And I agree with our Chairman and Mr. Obey that we need to 
be careful not to politicize it. For example, in the past 
couple of weeks I have had letters to the editor in my local 
paper criticizing me for not supporting the Mo Udall bill. It 
was targeting money for Parkinson's disease research. Last 
week, we had testimony about autism and it is very emotional.

                       aids research coordination

    AIDS is an issue that comes up, and maybe Dr. Paul, however 
you want to answer it, discuss the uniqueness of that. Why it 
developed the way it has, why its research is different overall 
affecting other diseases than, say, just cancer research or 
diabetes research and why the approach has been in that area.
    Dr. Varmus. I am not sure that it is inherently different 
from a disorder like diabetes, which also affects many organ 
systems. But, as you point out, Mr. Miller, one of the 
characteristics of the problem posed by HIV and AIDS is the 
multiplicity of organ systems affected by it. One of the 
consequences has been that we have a different mechanism for 
allocating our dollars for AIDS.
    That is, rather than absorb the administrative burden of 
creating a new institute to work on AIDS, we developed a 
coordinating office, which Dr. Paul leads. I will ask him to 
comment on this in just a moment. That office coordinates the 
funding through every NIH Institute and Center, each of which 
has some responsibility for the various components: the 
different organ systems that are involved in the manifestations 
of AIDS, and the different kinds of approaches that range from 
structural biology to behavioral research to drug abuse 
research to control of the opportunistic infections and cancers 
that occur during the disease.
    AIDS is one of the most complex problems we have had to 
confront. It is also an infectious disease, it affects young 
people and some of our most disadvantaged citizens and has 
posed a wide variety of problems, and it is a disease that we 
have had to respond to in fairly recent times, as Mr. Obey 
pointed out. The response has been acute because of public 
concern about the magnitude of the problem, the lethality of 
the disease, the unusual situation of having to cope with a 
viral infection for which vaccine efforts have been 
frustrating. We have had to develop for the first time 
effective pharmaceutical approaches to the control of the 
disease. We are very proud of the fact that, in conjunction 
with the drug industry, we have had remarkable successes doing 
that.
    We have also had the advantage of advance preparation due 
to a deep prior investment in virology, immunology, cancer, and 
many other basic research endeavors. This prepared the way for 
us to proceed with alacrity against this disease. Bill, you may 
want to comment.
    Dr. Paul. Yes, thank you. I think Dr. Varmus has laid out 
one of many of the important issues. I would like to emphasize 
one or two. HIV infection and AIDS is unusual in one very 
important respect. It is a disease which has come on the scene 
both suddenly and with frightening impact. Before 1980, we were 
virtually unaware of its existence at all. It is now the 
leading cause of death of young adults in the United States and 
it will shortly be the leading cause of infectious death in the 
world.
    It poses a remarkable challenge to us and a challenge which 
the government took up very quickly and did so within its 
normal mechanisms. The research on the various aspects of HIV 
infection was dispersed to the individual Institutes in a 
manner rather different than an established disease.
    Rather than form an Institute--and I think wisely the 
Congress did not move in that direction--the use of our 
established mechanisms, together with an office such as the OAR 
to coordinate that work, has allowed the Institutes to use all 
of their normal mechanisms without disruption of them. And yet 
for us to have a mechanism through the OAR which allows 
resources to be moved to the areas where opportunities are the 
greatest in a relatively rapid manner has been critical. We 
have been able to illustrate that.
    For example, in the last year or two, we have been able to 
change direction and markedly increase our resources devoted to 
vaccine research without having a marked disruption that might 
have been achieved had we not had a coordinating mechanism.
    So I would echo Dr. Varmus' statement. We face a new 
disease, a disease of still uncertain significance for the 
United States and the world, but a disease that has already 
established itself as a leading cause of death of young members 
of our society.
    Mr. Miller. Thank you, Mr. Chairman.
    Mr. Porter. George Nethercutt of Washington.

 Statement of the Hon. George R. Nethercutt, Jr., a Representative in 
                 Congress From the State of Washington

                           diabetes research

    Mr. Nethercutt. Thank you, Mr. Chairman. And thank you for 
allowing me to join this panel today. As a member of the 
Appropriations Subcommittees, I have a special interest in the 
subject of diabetes. And I certainly welcome all of you 
gentlemen here and thank you for all of your good work, because 
it is truly good work.
    Dr. Varmus, I heard you testify that the NIH would be 
remiss not to spend money on diseases that have the greatest 
impact, and I think you are correct. And so my question goes to 
the issue of diabetes and the relative spending that is done 
and has been done over the years on diabetes research and the 
Institute, NIDDK versus other Institutes. And I am not here to 
diminish the importance of other diseases, but I am here to 
emphasize the importance of diabetes because it has a 
tremendous impact on society. Something like $137 billion a 
year in costs that spans a wide range of complications from 
heart disease to kidney disease to blindness to amputations, 
all the horrors that all diabetics know about.
    So, my question is this: Do you acknowledge, Dr. Varmus, 
that there has been lesser emphasis on NIDDK spending and 
diabetes as opposed to the wide range of other diseases over 
the years? In other words, when NIH spending has gone up in 
other areas, my information is that NIDDK spending has gone 
down, and I am wondering if there is an explanation for that, 
and if so, what it is.
    Dr. Varmus. I don't think it is quite fair to say that 
diabetes research has suffered in comparison to all other major 
diseases. Over the last few years, there have been a number of 
new initiatives at the NIH that account for much of the 
increase in our spending: For example, increases in spending on 
AIDS, the creation of new institutes, and a number of other 
initiatives. Diabetes research has been well-supported for many 
years, and I think one would have to make the comparison with a 
large variety of other disorders to substantiate the claim that 
you just made.
    I would point out that my view of the proper metric here is 
not to try to correlate some number with the dollars that we 
assign to diabetes research. This is a number that is 
constrained by our ability to make the categorical assignments 
and the same problems that I described for Parkinson's Disease. 
But you have to consider the impact of a wide range of other 
research activities upon the creation of opportunities in 
diabetes research. For example, we have many kinds of studies 
of blood vessels. It isn't all categorized as diabetes 
research. Some of it is in cancer and some is in heart disease, 
and, of course, that all has an impact on the well-being of 
diabetics.

                    adequacy of spending on diabetes

    As you know, we have had many challenges from the diabetes 
advocacy groups about the adequacy of spending on diabetes 
research. I don't mean to defend absolutely what we do, because 
it is an imperfect process. That is why we have decided to have 
this very broad workshop, which is not intended to discuss 
recent research discoveries, but instead to bring together 
experts to evaluate our spending and our research initiatives 
in the area of diabetes, to ask whether the various components 
of diabetes research are all being pursued with the appropriate 
degree of enthusiasm and attracting the right kinds of 
personnel, because I do believe there are many opportunities.
    We also have opportunities to improve the lives of 
diabetics that the country has yet to take full advantage of. 
As you know very well from your own experience with the 
disease, we have learned a great deal through the work of the 
Diabetes Institute over the last several years about means to 
control the complications of diabetes. Yet we know that a very 
substantial number of patients with diabetes are not yet 
properly controlling their blood sugar. They are not seeking 
help for diabetic retinopathy at a significantly early stage. 
Those components of health care also need to be improved. We 
recognize that there are many ways that we can do better, and 
we are trying to look at ways in which we can pursue them.
    Mr. Nethercutt. I appreciate that and I think it is a wise 
move to have this diabetes research symposium coming up this 
fall. I have legislation I have introduced that would 
essentially do that gentle nudging to NIH that says, let's have 
a plan and decide in what areas and what specific subject areas 
would provide the greatest opportunity for curing this disease. 
And so I think the conference that is coming up this fall leads 
certainly in that direction.

                   nih resource allocation procedures

    Let me ask one other question as you talk about categorical 
assignments. I am wondering--and incidentally, I had a great 
visit to NIDDK earlier. I guess it was last year, and I am very 
well aware of the great basic research that is being done there 
and other places. What input is there, and what input do you 
use from the directors of the various Institutes of NIH in 
determining the allocation of funding for those respective 
Institutes? Is there a vote of some kind? Is there consultation 
regularly? I am just wondering from the committee's standpoint, 
what can we understand about the internal procedures for 
deciding who gets what?
    Dr. Varmus. Well, we are not sufficiently democratic to 
have a vote. I am not sure how well that would work. It might 
be one vote for each proposal. But there is an intense 
consultation process which begins within the Institutes, each 
having its own process for doing this, using the scientists who 
are grantees and intramural scientists of the Institute, 
advocacy groups, and other advisors, who are consulted during 
the course of the year to think about a number of issues--
including how grants are reviewed, what the criteria should be 
for funding, how much should be spent on various mechanisms, 
and whether there should be more centers or fewer centers, or 
increases in training in certain areas. The wide panoply of 
questions that I addressed in my testimony would be looked at 
either annually or every other year to try to determine whether 
the Institute is on the right course.

                           areas of emphasis

    Then, at a point during the development of the President's 
budget for NIH, I consult with each Institute director in a 
process that has been, frankly, evolving since I came to NIH. 
This year, for example, I asked each Institute director to 
bring to me candidate proposals for inclusion in what I called 
the NIH Areas of Emphasis.
    These are six broad areas in which I try to summarize, in a 
trans-Institute way, the major themes in modern medical 
research that I believe should be the vehicles for advancing 
medical science, particularly in the current restricted 
financial environment.
    What we try to do in building the budget is to provide the 
money for the commitment base and money to continue the support 
of investigator-initiated projects that simply depend upon the 
imagination and direction of investigators. In addition, we 
provide, through the Areas of Emphasis, new programs that are 
intended to either expand or initiate programs that we think 
are particularly valuable for fostering either broad research 
that may affect a variety of disciplines, or areas of research 
that we believe are currently undersupported, because NIH has 
not paid sufficient attention to them in the past, or because 
the discovery of a new gene has created opportunities that need 
to be pursued, or because a methodology has come about that now 
allows us to study the disease in a new way.
    For example, the Genome Project has made it possible for 
the Cancer Institute to begin to look at the anatomy, if you 
will, of a cancer in a different way by looking at the totality 
of expression of genes in each individual cancer, an advance 
that I believe will completely change our attitude toward the 
prevention, diagnosis and treatment of cancers over many years. 
Those investments are the ones that are highlighted in the 
areas of emphasis, and that is a document that is prepared by a 
series of consultations.

                     one percent transfer authority

    In addition, as part of our yearly assessment of what is 
going on during that fiscal year, we consider as a group 
initiatives proposed by the Institutes that can be funded by 
transferring money from one Institute to another. And only 20 
or 30 or 40 million dollars is usually transferred in that 
process. It is a combination of discussions among the Institute 
directors and advice that I receive from external advisors who 
are brought in to discuss these issues with me that result in 
the final determination that is then sent to your committee.
    Mr. Nethercutt. Well, I thank you very much for your good 
work. I have just commended to my colleagues on the panel, the 
recent editorial that was written in the Journal of NIH 
Research entitled, ``Mix Science and Politics? Of Course.'' I 
think it goes to a lot of the comments that you have made here 
today that there are a lot of influences that decides who all--
--
    Dr. Varmus. And I would point out that the Journal of NIH 
Research is not a journal written by the NIH.

                  final authority for decision-making

    Mr. Porter. Mr. Hoyer.
    Mr. Hoyer. Thank you, Mr. Chairman. Essentially, this 
committee has been a committee of advocacy for NIH. Doctor, in 
page 2 of your statement, you talk about where the final 
authority resides for making these important decisions, i.e., 
the allocation of resources. Notwithstanding the fact that we 
have lawyers, Indian chiefs, and refugees from Russian studies, 
the Founding Fathers put the authority here. What we try to do 
and what Mr. Obey and Mr. Porter have argued for is that we 
need to put a great deal of reliance on your judgment. But, 
ultimately the decision resides here, and, therefore, we have 
these hearings as opposed to simply saying, whatever Dr. Varmus 
says is what we do.
    It is interesting and important to note that the scientific 
community doesn't always agree.
    Dr. Klausner might want to answer one of the questions that 
I want to ask you. The New England Journal of Medicine 
published an article which is an update of the previous 
proposition that in the allocation of resources within the 
Cancer Institute or within NIH, we are spending too much money 
on trying to cure cancer as opposed to preventing and 
dissuading people from activities which lead to diseases.
    I think that is an interesting big picture item which we, 
nonscientists, will ultimately have to decide on. I have no 
doubt that we will continue the way we have gone, so I don't 
think it is going to change policy, but I think it is an 
appropriate question. I would like to hear your comments on 
this and Dr. Klausner's, comments, and perhaps other members of 
the panel, because ultimately, big dollars are put here because 
the people give those of us in Washington monies and hope we 
will spend it wisely. We have to try to decide how to do that.
    Dr. Varmus. Let me comment briefly before turning the 
microphone over to Dr. Klausner, about the initial comment you 
made about where the responsibility resides. I absolutely agree 
that the responsibility for giving out money to the Institutes 
resides with you, and of course, the administration. But there 
is that additional responsibility of deciding exactly how the 
money is spent within the Institute.
    Obviously, we are answerable to you because if you don't 
believe we spend it well, you give us less next year. But those 
decisions made within the budget that is given to any 
individual Institute, at the moment, at least, are our 
responsibility.
    Mr. Hoyer. And I do not want to be misunderstood. We agree, 
of course. The proposition that our Chairman and our Ranking 
Member were stating was that we have made a judgment that the 
best interest of the taxpaying public is that it is not a 
political decision. I think that is the position of the two 
most influential members of our committee, and I think we all 
agree on that. But in that context, the public does expect us 
to make judgments as to whether we are spending their money 
wisely.
    And then I go to this study where, having gone through a 
recent experience, I was very frustrated by the fact that we 
could not impact the situation that confronted our family. And 
every family in America has been confronted with this. After we 
spent a lot of money, how come we cannot impact the situation? 
As I understand, the proposition of the article is that we 
really have not made a whole lot of difference. Mortality rates 
are essentially the same. Not in every category, but 
essentially overall, adjusted for life expectancy, mortality 
rates are essentially the same and, therefore, what we ought to 
do is shift our priorities to a greater focus on prevention.

                         cancer mortality rates

    Dr. Varmus. We do have some differences with regard to Dr. 
Bailar's article. I think Rick might want to comment on them.
    Dr. Klausner. Yes, I would be delighted to. The main take-
home message of Dr. Bailar's analysis, which is a reanalysis of 
what the American Cancer Society and the NIH have done using 
public numbers, is that we agree that something remarkable has 
happened. Cancer mortality rates were going up all century. 
They were going up. And around 1990, the overall rate stopped 
going up and since then we all agree they are beginning to 
drop.
    Now is cancer defeated? Absolutely not. A disease that is 
going to kill about 550,000 people this year is not defeated. 
But the sound bite from the New England Journal has been that 
efforts devoted to cancer have been a failure. I must say I 
don't feel I am being defensive, but the numbers don't support 
the sound bite. They are dropping. The mortality rates are 
dropping.
    Where I disagree with Dr. Bailar is why and what are the 
implications for policy. We agree about the numbers.
    Dr. Bailar says treatment will fail, that we have been 
promised it for years. The problem is cancer is not one 
disease. It is many diseases. And if you are now going to go 
from the aggregate lumping of total mortality, whether we look 
at total mortality of all diseases, you are not going to learn 
anything until you look disease-by-disease. The reality is when 
we look disease-by-disease, the mortality rates are really 
falling.
    The answer for some is prevention. With lung cancer, we 
have not made much progress for treatment. We think we know how 
to prevent it. Gastric cancer is plummeting and we actually 
have no idea why. Breast cancer mortality rates are really 
beginning to fall. That is ascribed to a combination of early 
detection and treatment, and I will propose that the vast 
majority is the use of adjuvant therapy, which has been 
recently shown for colorectal cancer to reduce mortality by 20, 
or 30 percent. Forty years ago, people argued childhood cancer 
couldn't be cured. Don't try it, they said. Now, 80 percent of 
our children with cancer are cured.
    Now, Dr. Bailar says that is not enough, the numbers are 
not enough. What do we say on prevention? Again, the question 
is what are the numbers? The NCI spends 38 percent of its 
dollars on what the prevention community broadly defines as 
prevention, and we keep looking for new leads and investments.
    A blue ribbon panel was constituted last year by me of 
experts from throughout the country on prevention. This report 
will be given to me next week, in fact, about how we should be 
studying prevention better. But we currently spend 38 percent 
of our dollars on prevention. Prevention requires knowing 
causes. It is not simple. There is no more likely going to be a 
magic bullet for a single cure for cancer than a magic bullet 
in prevention.
    An article that I am sending to the New England Journal is 
subtitled from a quote from Yogi Berra, and that is ``When You 
Come to a Fork in the Road, Take It.'' What do we mean by that? 
When we look at the reason we are making incremental progress, 
progress that we all agree is too slow, it is being made for 
many reasons. It is a combination of prevention, early 
detection and treatment.
    We need to take our victories where we can. When we come to 
the fork in the road where we are seeing progress in both 
treatment, and as he says, early detection--but early detection 
doesn't cure anything without an effective therapy--and 
prevention, we need to do all of it. We spend about 31 to 35 
percent of our dollars directly on treatment versus 38 percent 
on what we talk about as prevention; that is, prevention, 
intervention, understanding the cause--you can't do prevention 
if you don't understand cause--epidemiology, predisposition, 
environment, et cetera.
    Mr. Hoyer. Doctor, I have one last question, but the 
article, I think, would be interesting for the Members to have.
    Dr. Klausner. I will have to submit it through the New 
England Journal. They have asked me to write it and we will 
have to see if they accept it.
    Mr. Hoyer. It would be interesting, even if they don't 
accept it.
    [The information follows:]

                        Cancer Research Article

    Upon completion of the article, I would be pleased to 
submit it for the record.

                           funding for autism

    Mr. Hoyer. We had some very compelling testimony from a Dr. 
Rothman, whose brother is a Member of Congress from New Jersey. 
His testimony really crystallized what we are talking about. He 
has a child with autism. There are apparently 380,000 cases of 
autism in the United States. He made the analogy between 
autism, cystic fibrosis, and M.D., and referred to how Jerry 
Lewis raises a lot of money. He made the comparison between 
about a $33.88 expenditure on autism per afflicted individual, 
$1,000 on muscular dystrophy, and $1,200 on cystic fibrosis.
    His point was that you have $20 billion in consequential 
expenses relating to the 380,000 autistic children and adults, 
but we were doing very little to combat it. Chairman Porter 
made a very compelling statement you know, we have got to 
listen to the scientific community. We will put report language 
in, but, ultimately, we do not want to make a political 
decision.
    I thought the Chairman's comments were on target and I 
agree with him. But on the other hand, from this parent who 
happens to be a medical scientist and a doctor's standpoint, he 
compares a telethon and a lot of dollars at the NIH, on M.D. 
and cystic fibrosis which have far fewer individuals afflicted. 
This doctor says to himself, how are you making these 
decisions? How do we answer that individual?
    Dr. Varmus. Let me answer with respect to autism. I don't 
find it extremely useful to try to do the comparison disease-
by-disease. But I do find it useful to focus on autism as a 
disorder. We recognized a few years ago that autism was a much 
more complex brain-based disorder than had commonly been 
thought.
    A workshop was carried out in part in response to a 
congressional suggestion in 1995 and organized by the Child 
Health and Human Development Institute. A great deal was 
learned in that workshop about, first of all, the idea that 
autism was probably not a single disorder, but instead as many 
as five or six different disorders. There were also clues 
available as to anatomical abnormalities in the brain.
    It was agreed among the members that were involved in this 
workshop that we needed to place additional emphasis on the 
families that had been studied, attempting to identify genetic 
components, and to do more neurophysiological and 
neuroanatomical studies of this disease.
    The result has been a new initiative involving several 
Institutes at the NIH. There is a small coordinating group. 
This year I have used my one percent transfer money to help 
underwrite the genetic studies of autism. I believe that we are 
going to see, as a result of the process, there will be a quite 
similar result to what I tried to describe in my opening 
testimony for Parkinson's Disease. I think that this is one 
place where advocacy and a few new scientific developments have 
synergized to allow us to identify some ways to promote the 
study of this disease.
    Mr. Hoyer. Thank you. And thank you, Mr. Chairman, for the 
extra time you gave me.
    Mr. Porter. We will take it off your next series of 
questions.
    The Chair has eight Members on the list. This would take us 
somewhere between 12:15 and 12:30. Dr. Varmus, do you and your 
colleagues have time to stay with us?
    Dr. Varmus. I certainly do, and my colleagues would be 
agreeable.
    Mr. Porter. Patsy Mink of Hawaii.

Statement of the Hon. Patsy Mink, a Representative in Congress From the 
                            State of Hawaii

                      detection of ovarian cancer

    Mrs. Mink. Thank you very much, Mr. Chairman. I certainly 
want to thank you, Mr. Porter, for inviting me to participate 
in these hearings this morning. I do not serve on the 
Appropriations Committee, so this is a rare opportunity that is 
being extended to some of us who care deeply about what is 
happening in the whole area of health, particularly the impacts 
of research and other activities at NIH, and the implications 
that it has on the general fears and concerns of our 
constituents.
    While I certainly support the comments of the Chair and the 
Ranking Member that it would be inappropriate to politicize the 
whole question of the areas of research that are being 
conducted in NIH, I would be remiss if I did not take this 
opportunity to express my very deep concerns about the minimal 
efforts that have been done in the last 6 or 7 years in the 
whole area of ovarian cancer.
    I came upon this issue in 1990 when I returned to Congress 
and found at that time less than $7 million that we could 
identify with the assistance of NIH to ascertain exactly what 
was being spent in direct research and studies and explorations 
in this area.
    Today, after nearly 7 years, we have somewhat less than $40 
million being expended. I hope that because of the efforts of 
some of us, that increase has been able to be attained. But the 
point is that we are not here to make choices for the NIH. I 
believe that the staff and the experts there have to make that 
determination. But I do feel that the Congress has the 
responsibility to express the frustrations and anxieties of the 
population as large. And we are talking about 28,000 women who 
are diagnosed with ovarian cancer each year. We also know that 
14,000-plus die of ovarian cancer each year, and these are 
fairly steady figures that have not diminished in any way over 
the last 6 or 7 years.
    The frustration is not an anxiety with respect to 
prevention or cure. The anxiety comes from the fact that there 
is really no early detection process for the assurance that 
women can get because of periodic checks to ascertain that they 
do not have this dreaded disease. Most frequently, the disease 
is discovered too late, and as a result only 25 percent of 
those that have been diagnosed with ovarian cancer can expect 
to survive more than 5 years.
    It seems to me with this picture of the historic reality of 
this disease, that somewhere in NIH, there must be a 
combination of interest, talents, and motivation to get more 
research into this area for the one aspect of it, and that is 
the early detection. And I would like to know from yourpoint of 
view, Dr. Varmus, are we advancing our best research in this one area, 
and how close are we to giving assurances to the women in this country 
that in a short period of time there will be tests available in the 
hands of practicing physicians that have the chance of detecting this 
type of cancer?
    Dr. Varmus. Thank you for the question, Mrs. Mink. I 
believe that we are making progress in this area. I am going to 
turn the microphone over to Dr. Klausner of the Cancer 
Institute to answer in detail. I would draw your attention to 
one unexpected benefit that came from the studies of genetics 
in breast cancer. We now know that two recently discovered 
genes that were pursued initially because they were believed to 
be involved in hereditary breast cancer also predispose 
strongly to ovarian cancer. Knowledge of mutant forms of those 
genes is an important clue to women who may be highly disposed 
and particularly appropriate targets for early detection 
methods. But I think to discuss some of those methods and what 
is being developed, I will turn to Dr. Klausner.
    Dr. Klausner. You described the difficult situation with 
ovarian cancer perfectly. You are absolutely right. We need 
early detection for that reason. Dr. Varmus, before, described 
a new initiative of NCI called Cancer Genome Anatomy Project. 
Instead of waiting however long it might take, decades, to 
discover a possible flag, a marker like PSA, but hopefully even 
better than PSA for cancer, what we now have the opportunity to 
do through the Cancer Genome Project is to quickly try to 
identify all expressed molecules, all expressed genes in any 
cancer.
    We have begun that. It is up and running, and there are 
five cancers chosen in the first year to initiate the project, 
one of which is ovarian, and it is moving very quickly. Now, I 
don't know what to promise from that. I don't know whether we 
will discover a PSA or a better than PSA--which I think we can 
do better--with this project, but I think this is the quickest 
way to once and for all give us the tools to ask whether there 
are markers to provide a blood test or some other sort of test. 
I can go on to other things that we are doing, but I think that 
is actually the most significant ones, and we chose ovarian as 
one of the five for exactly the reason you talked about, 
because we so desperately need new markers.
    Mrs. Mink. Thank you, Mr. Chairman.
    Mr. Porter. Mr. Istook.
    Mr. Istook. Thank you, Mr. Chairman.

                     factors in resource allocation

    Dr. Varmus, I appreciate the chance for the hearing today. 
I must say, I remain disturbed and, frankly, suspicious about 
some things I am hearing. I recognize, and I think we all 
recognize the need to pursue scientific opportunity. The 
opportunity should be pursued, but when we talk about the need, 
also, to pay attention to the incidence of diseases and of 
deaths in society and make that a significant factor in the 
allocation of resources also, I think that NIH protests too 
much; the vigor with which I hear actual denouncements of 
efforts to do that.
    If we talk about that, it is characterized not as us trying 
to take our proper congressional role in public policy and 
spending public money, instead it is characterized as an 
excessive congressional directive. We are treated as though we 
don't pay attention to scientific opportunity and the other 
things that you properly consider, but there is such an effort 
to avoid having NIH priorities expressly take into account the 
number of people afflicted with different diseases, the number 
of people who die from them, the cost to society and the cost 
to the families and the financial cost as well, whether it be 
to the Federal Government through Medicare and Medicaid 
spending, things that go through HCFA, whether it be the cost 
to private insurance companies or the cost to the individuals 
or the lost man-hours at work, whatever it may be. I, frankly, 
am tired of the NIH pooh-poohing and belittling those factors, 
and I believe you are doing so, even though you don't do it in 
quite those words.
    The jealousy with which you try to say the pursestrings 
should be under the control of persons who know better than the 
rest of us is an attitude that is not healthy in our society, 
and we are here trying to talk about public health.
    I see ratios that are so out of proportion. We have seen it 
analyzed in different ways. If you look at what NIH is doing 
per patient in this country that either has AIDS or HIV, there 
is $2,100 a year being spent on research on that. But per 
patient with breast cancer, it is only a tenth of that, $200. 
For overall cancer it is $338. Alzheimer's, $81; heart disease, 
$74; Parkinson's disease, $34; diabetes $20. But diabetes has 
16 million Americans that are afflicted with it. People who 
face amputations and all sorts of other complications because 
of it. It is a horrible disease in what it does to people. 
Sixteen million people, $20 each; AIDS or HIV, the larger 
category, 700,000 Americans at best, $2,100 each.
    I realize you should not be driven by a strict sense of 
having to have percentages and proportions. We both agree that 
would be wrong. That is not the approach anybody advocates, but 
when you look at the overall results and the disparity, the 
system that you have now is one where all roads lead to you, 
Dr. Varmus, in the decision-making. I realize that you did 
research in this area before you came to NIH. You are a very 
capable and accredited scientist who has the public good at 
heart. But there are many others who also have the public good 
at heart and there is such a disproportion here.
    And I think there is a lack of recognition that 34 million 
Americans with Parkinson's disease are paying for this 
research. And 8 million Americans with cancer and 2 million 
women with breast cancer and 16 million with diabetes, and 13.5 
million with heart disease, these are the people who are paying 
for the research. To be told that those numbers are at best a 
negligible factor or that Members of Congress that bring it up 
are being excessive is an attitude that I find extremely 
disturbing.
    What do you say to the administration when they overlook 
your budget? When the White House exercises a role in your 
spending priorities, do you subject them to the same criticism? 
I am very disturbed.

                            priority setting

    And I would like to know, Dr. Varmus, in the descriptions 
that you have given us of the priority setting, are your 
priority setting meetings open to the public? Are they open to 
the representatives of the administration and to the White 
House? Are they?
    Dr. Varmus. I do not know for sure what priority setting 
meetings you are talking about. As I mentioned, there are many 
sessions.
    Mr. Istook. Do you accept White House and administration 
efforts to be involved in the prioritization process?
    Dr. Varmus. I am not sure which step in the process you are 
referring to, Mr. Istook.
    Mr. Istook. All right. Do you have communications on behalf 
of the White House that come to you saying we want these 
priorities to be established in research funding?
    Dr. Varmus. That happens occasionally. We, of course, 
develop our budget with the OMB and with the White House. And 
frankly, Mr. Istook, I don't think you are hearing what I am 
trying to say.
    Mr. Istook. I don't think you are hearing what I have been 
trying to say, but please go ahead.
    Dr. Varmus. We are discussing priorities here. We do meet 
with many members of the committee; we meet with your staffs. 
There is a tremendous amount of to and fro between Congress and 
the NIH. And we welcome that. You are representatives of the 
public.
    I think you are painting me in the position of greater 
authority and arrogance than is true. For example, I must take 
particular care to point out that although you say all roads 
lead to me and that I worked in an area of research that is 
HIV/AIDS-related in the past, that the imputation that the size 
of the AIDS budget is the result of my single-handed 
determination to make the budget that large is really 
incorrect.
    Mr. Istook. I agree. It is not an effort to do that 
because, frankly, I don't think there is any other disease that 
has had the political involvement, you know, people in 
Hollywood wearing ribbons, the media attention to it, the 
millions of dollars that are given to political campaigns by 
people who have a specific interest in this disease. I would 
agree it is not, in that case, that all roads lead to Dr. 
Varmus. But I think it is a mistake to pretend that politics 
are not involved in the process and in the result we have seen 
with the disparate funding for that research. It is not that 
AIDS is not a terrible disease, because it is, but it is not 
the only terrible disease.

                    nih expenditure on aids research

    Dr. Varmus. My point is, that although I strongly defend 
the money that we spend on HIV/AIDS, the current funding level 
was actually established before I came to the NIH. It was 
established by a large number of factors, including 
congressional appropriations, administration wishes, public 
health concerns manifested by many components of the public, 
and as well as by scientific opportunities. So, you know, if 
you look back at the history of the development of funding for 
AIDS research, you will see that the funding was at an 
extremely low level initially in the course of the epidemic, 
when it was difficult to know how this disease appeared.
    Many have argued, perhaps appropriately, that the 
government was slow to respond. There was also a shortage of 
experimental opportunities. We didn't know how the disease 
arose. The CDC was heavily involved in trying to find the cause 
of the disease. Once we knew that the disease was caused by a 
retrovirus, there was tremendous opportunity because the virus 
is one that we had tremendous information about. With the virus 
spreading through the population, affecting young people, and 
being universally lethal, with little prospect of a vaccine, 
there was tremendous public support for pursuing this in a 
vigorous way.
    Mr. Istook. And there should be significant resources for 
it.
    Dr. Varmus. And increases occurred up to fiscal year 1994 
at which point the level of funding has stabilized. We believe 
that within the context of that budget we have been very 
successful in trying to pursue the vast myriad manifestations 
of the disorder. Because of many concerns about the AIDS 
research portfolio, 2 years ago we asked over 100 
investigators, many of whom do not work on HIV/AIDS, to conduct 
a study of our research portfolio. First of all, they thought 
that the level of funding was approximately appropriate and 
that there was no need for increased funding. But they made a 
number of suggestions about moving allocations from one area of 
AIDS research to others, more emphasis on vaccines, and many 
other suggestions.

                      stabilizing aids infections

    Mr. Istook. Would you say, Dr. Varmus, with CDC reporting 
decline in the incidence of AIDS, that a decline in the AIDS 
research proportion I am going to say, not absolute numbers, 
but proportion should be anticipated?
    Dr. Varmus. There has been a stabilization in the number of 
new infections. Dr. Paul may want to speak to this, as well. Of 
course, the problem is not solely confined to this country, and 
as Dr. Paul pointed out a moment ago, AIDS will soon be the 
number one cause of infectious disease worldwide--a disorder of 
mass destruction in many parts of the world, especially in 
Africa and Asia, and still the major cause of death among our 
young adults in this country. So it is not a problem that is 
going away by any means. The fact that we have achieved some 
level of control is not, in my view, a reason to say that the 
battle is over, far from it.
    Mr. Istook. I don't think anybody would say the battle is 
over. The question is not whether there should be significant 
resources there, because I believe everybody agrees there 
should be. It is a horrible and deadly disease. The question is 
one of prioritizing with other deadly diseases that affect a 
far, far larger number of Americans.
    Dr. Paul. Mr. Istook, I might comment if that would be 
appropriate.
    Mr. Istook. Sure, I think I am about to lose my time from 
the Chairman.
    Dr. Paul. I think Dr. Varmus has made some of the most 
important points. In HIV, we face an unusual situation. Like 
you, I recognize there are many other terrible diseases and 
that as a Nation we have an obligation to attack them 
vigorously. Here we are facing a disease which has appeared on 
the scene relatively recently and of still uncertain potential. 
While you rightly point out the number of infections has 
stabilized within the United States in recent years, we know 
this disease is running rampant throughout the rest of the 
world.
    It continues to evolve because it is a relatively recent 
pathogen for humans. It is not like influenza or measles which 
has been evolving for a millennia. We cannot predict with 
confidence how this virus will interact with different 
populations as it continues to move through the rest of the 
world until we have a reliable means to prevent transmission--a 
vaccine or other preventive means--or effective treatment for 
populations who are at risk and will remain at risk.
    It is my own view that this is an opportunity we have been 
given to try to deal with the disease now and not leave it to 
our children or grandchildren to face what may be a more severe 
epidemic. So my own view is that we are facing an unusual 
challenge and we have adopted an unusual mechanism. I would 
argue that this is an appropriate action that the Nation as a 
whole has undertaken.
    Mr. Istook. Just in final statement, Mr. Chairman, I think 
it is important that we understand that the research dollars 
that go through NIH in AIDS are only about 20 percent, 
approximately, of the overall Federal spending that is related 
to this particular disease. Maybe there is some management of 
the overall numbers that are in order, because I certainly 
agree and I want to commend your efforts on researching this.
    The Human Genome Project, I absolutely agree with you with 
the extreme significance of that and other things; but I just 
finally reiterate my concern that there are so many other 
diseases that I feel are not getting proper priority in NIH 
allocations.
    Thank you, Mr. Chairman.
    Mr. Porter. Thank you, Mr. Istook.
    Ms. Pelosi.

                         aids research funding

    Ms. Pelosi. Thank you very much, Mr. Chairman.
    I want to join you in thanking our distinguished guests for 
their fine testimony today--more importantly, for their 
leadership and the important work they do at the NIH.
    You are very fortunate, I think, because you have the power 
to cure. Hopefully, we can match the opportunity to scientific 
opportunity you have with resources so we don't miss any 
opportunities. Because we certainly don't want to engage in 
pitting one disease against another at the expense of missing 
an opportunity someplace along the way.
    Since I came so late in the game in terms of questions and 
answers and had the opportunity to hear the questions of my 
colleagues, it enables me to move on to another issue.
    First, though, I want to thank you, Dr. Varmus and Dr. 
Paul, particularly, for the justification you presented today 
on the AIDS research funding. I think it holds up on the 
criteria established in your presentation, Dr. Varmus.
    I want to thank all the members of the panel for making 
themselves available today, but also Dr. Klausner has visited 
San Francisco where there is a very high incident of breast 
cancer. Yes, we have a great deal of activism on the outside. I 
don't call that politics; I call it America. It is good when 
people speak out about a subject of which they are aware to 
make sure we have the full benefit of their views in making a 
judgment.
    I am certain, Dr. Varmus, that you could make a chart like 
this about AIDS as well in terms of the benefit it can give to 
other diseases as well as aspects of--areas of NIH which 
receive funding on AIDS research, is that right?
    Dr. Varmus. As you know, the budget is coordinated by the 
Office of AIDS Research but goes to every Institute at NIH.

                     unanticipated research results

    Ms. Pelosi. I thank you. That is a level of politics I 
couldn't possibly understand, and I appreciate how you manage 
to pull that off. But I commend you for doing so, because I 
know it is a challenge.
    I wanted to talk about the future a little bit, because in 
your remarks you talk about there are limits to ability to plan 
science, the developments of recombinant DNA methods. It 
illustrated the need for unplanned, untargeted, high-quality 
fundamental science, as you said. The Human Genome Project, 
which follows on that, of course opens so many avenues. I know 
that the discovery of DNA was a culmination.
    Are there any inspirations in the Genome Project which you 
foresee which would inquire a huge infusion of funds? My 
question comes to the point of, A, what do you anticipate your 
needs down the road to be; and, B, if there were a will in the 
country to double the NIH budget in the next 5 years, could you 
absorb that?

                    genetics research opportunities

    Dr. Varmus. Well, there is very little doubt that whenever 
the pursuit of human genetics identifies a disease involved in 
the cause of disease, we create new possibilities for 
investigation. Many examples have accrued over the last few 
years in the area of cancer. We believe we are on the threshold 
of such discoveries in Parkinson's disease, hopefully in 
autism, and in many other neurological disorders.
    When a gene is discovered, you read about it in the 
newspaper. To the naive reader this seems like, a--if you will 
excuse the expression--a culmination. But in our view it is 
just the beginning. We now have the tool. It is directed in a 
multiplicity of directions.
    Can we use this tool to develop tests to indicate 
predisposition to disease or early diagnosis? Can we use this 
gene to understand the basic mechanism by which the disease 
arises? Can we use the gene and the protein that the gene 
directs the cell to make to develop new therapeutic approaches? 
It is that set of new experimental possibilities that are now 
created by having a gene in hand that demands additional 
resources be devoted to that disorder.
    So the Genome Project, as we mentioned earlier, is not 
classified by disease. Indeed, the entire extramural genome 
budget is not classified by disease. But the outcome of the 
research is to generate opportunities that clearly fall into 
categorical disease areas.
    Ms. Pelosi. And these are all not predictable.
    Dr. Varmus. Well, in some cases, we can say yes.
    If we look backward, we can say we knew there was going to 
be a gene for cystic fibrosis, which is a disease of inherited 
nature. The gene was discovered several years ago, creating new 
opportunities for thinking about therapy and diagnosis and 
understanding of the disease.
    In other cases, it is a little more difficult to know. For 
example, in the case of autism, which we talked about a moment 
ago, or hypertension or diabetes, it is difficult to know 
exactly how many genes are involved, and what the discovery of 
those genes will provide.
    In the area of diabetes, just last year two new genes were 
identified as being important in a disorder called maturity 
onset diabetes of the young. Those genes had, in fact, 
previously been identified and not suspected as being diabetes 
genes. But we already knew something about them. That, 
obviously, creates all kinds of new inspirations, if you will, 
for trying to understand diabetes more generally.

                         doubling nih's budget

    Ms. Pelosi. You didn't say whether you could absorb the 
doubling of the NIH budget.
    Dr. Varmus. Well, as you know, Ms. Pelosi, NIH funds 
currently about 25 percent of its grant proposals. A doubling 
of our budget, we would assume, would occur in increments. Yes, 
we certainly could absorb that.
    We also recognize that we are not the only agency that 
seeks more funds in government. The Administration has many 
other objectives that the intention of the Congress and the 
public is to reach----
    Ms. Pelosi. Is there scientific opportunity for that?
    Dr. Varmus. Absolutely.
    Ms. Pelosi. So that takes me to my final point, which is we 
have a problem. Because certainly if there is scientific 
opportunity and we have the ability to put the resources there, 
we have, I think, a moral responsibility to do so. However 
important that we all clearly view the work of the NIH, it is 
the same old thing. It is not the price. It is the money. And 
the money just doesn't seem to be here, unless, as I say, there 
is a will in the country to change that readily.
    I know our Chairman would--if there was any way to have the 
money, he has certainly been your champion. But instead of 
having this pitting of one disease against the rest, I would 
hope that we could all channel our energies toward a bigger 
602(b) allocation for our committee; and so much bigger that 
any increase in the NIH would not come at the expense of other 
lambs in our lamb-eat-lamb allocation--job training, Head 
Start--you know the list very, very well.
    So what is important for me to hear from you today is that 
there is scientific opportunity for not incrementally but a 
drastic increase in the funding. We have to take it to the 
American people to see if they want to live within the budget 
constraints, which are difficult at best, and now, with the new 
budget numbers in light of the budget agreement, almost 
unlivable for us.
    But the challenge of scientific opportunity to be matched 
by the resources is one that I find irresistible. But, on the 
other hand, we need the scientific community to help us with 
our entire budget so you are not benefiting at the expense of 
other functions within our subcommittee.
    I did want to just make one other point, Mr. Chairman; and 
that is to say that all of what we do here really saves money 
in the end. If we are helping people be well, if we are finding 
cures, if we are adding to productive years of life for people, 
I wish we could have a dynamic scoring on the investments at 
the NIH. But I leave that to our Chairman. Thank you all very 
much again.
    Thank you, Mr. Chairman.
    Mr. Porter. Thank you, Ms. Pelosi.
    Now, the congresswoman who has the privilege of 
representing many of the NIH scientists and has the NIH campus 
in Bethesda within her district, Connie Morella of Maryland.

  Statement of the Constance A. Morella, a Representative in Congress 
                       From the State of Maryland

    Mrs. Morella. Thank you, Mr. Chairman. Thank you for 
inviting me to this briefing. I was sitting in the corner for 
most of it, so I did hear the responses and the questioning 
that took place.
    I must say I am very, very proud, obviously, of the 
National Institutes of Health and the progress that has been 
made through the years; and it only happens because of 
leadership, leadership from the top and the leadership that you 
all have provided as Members at the top.
    You also--I think we are pretty fortunate in having such a 
good subcommittee of the Appropriations Committee. It is a 
pleasure to--not as a member, as someone who is not a member of 
the committee--to work with that committee in terms of getting 
the kind of funding that they need; and you can tell by the 
questioning, by and large, how they feel.
    I am going to a meeting on lupus and then osteoporosis, I 
was in the Race for the Cure, and my sister died of cancer 
years ago. I am very much involved in HIV/AIDS, particularly in 
women where the fatality rate has increased 3 percent over the 
years; and, of course, worldwide will be a problem. I think we 
need to push more the breakthroughs as spin-offs, the ripple 
effect. When you move into the field of HIV/AIDS and a 
discovery occurs, it is one that might well be applicable in so 
many other areas, so that research in these areas pays off.

                          information transfer

    I wonder if you might indicate what is the rule? How do you 
handle that? How do your other institute centers people know 
about breakthroughs in one area so they can apply it?
    Dr. Varmus. Fortunately, the world on the outside is not 
categorized by Institutes and Centers. That is only true at the 
NIH.
    But when one is an outside scientist, as I was for many 
years, one thinks of oneself as publicly supported by the NIH. 
You are a member of a scientific community that may identify 
itself as cell biology or virology or genetics. One goes to 
meetings and reads journals and hears about research 
developments through a wide variety of mechanisms--gossip, 
telephone, the New York Times and, of course, through the usual 
scientific processes.
    There is an issue with respect to moving information among 
the institutes, among the program managers. We have made a real 
effort over the last several years to try to develop the 
appropriate mechanisms for coordinating efforts among our 
institutes when multiple institutes are involved in the pursuit 
of any single problem.
    As you have seen from the charts and much of the 
discussion, it is almost inevitably the case that any single 
discipline or disease-oriented area of research will command 
the attention of multiple institutes. So we do that at one 
extreme by having an office like the Office of AIDS Research, 
with its major fiscal and scientific oversight 
responsibilities. At the other end, there may be an informal 
relationship in which program managers or Institute directors 
from two or three Institutes will meet informally at regular 
intervals to see how research is progressing and what kind of 
applications they have received each year to study that 
discipline.
    We believe that through those two extremes, or through 
coordinating committees or offices in the Office of Director or 
other mechanisms, we are able to do a pretty good job of 
coordinating research.
    Mrs. Morella. So you think that works. It is an internal 
process.
    Dr. Varmus. I don't think it is always perfect. One of the 
ways we try to be responsive to Congress is to develop such 
bodies for coordination when the Congress perceives, or the 
public perceives, we are not doing as good a job as we should 
at that.

                effect of public and congressional input

    Mrs. Morella. Because I think it is a good way of heralding 
how the hipbone is connected to the thighbone and other things.
    One area of your testimony, you talked about how there is a 
balancing act in determining areas of research. One segment of 
that balancing act includes public input. I know this is a 
difficult thing because the public may be clamoring for more 
research, you know, for cancer. You and I talked about Sam 
Donaldson's Million Man Woman March for Cancer Research, but I 
wondered about the effect of public input.
    Also, I know Mr. Istook is not here, so I can mention this. 
Also the fact that the President came up with that mission 
statement with regard to we will have a vaccine, you know, 
against AIDS within the decade.
    I am also reminded of the Office of Research on Women's 
Health, and I know Dr. Kirschstein is here who is in the period 
of the genesis of it. But had we not had Congress looking in on 
where our priorities are or are not, if we had not had the 
public then entering the picture, we might still only have a 
little bit of an Office of Research on Women's Health. We might 
not include them in clinical trials and protocols as we now do.
    So I think that that says that there is a strong role for 
congressional involvement and public input not overwhelming 
what you as scientists know. But would you like to comment on 
that?
    Dr. Varmus. Well, I think you touched on an important 
point. We are responsive to Congressional and public interests; 
and I agree that we have made important advances in our 
approach to women's health issues through the interest of women 
advocates, the creation of a women's health office and the 
writing of guidelines for inclusion of women and minorities in 
research. Those have been extremely important.

                        aids vaccine initiative

    With respect to your remark on the President's interest in 
the AIDS vaccine, I would make a minor correction in what you 
said and say that the President didn't say we will have it. He 
gave us a challenge, not a promise. He gave us what I call 
inspiration. That is, he has responded to our belief that the 
prospects for an AIDS vaccine have improved.
    There are no guarantees. I come back to Mr. Obey's point 
earlier about moon shots. We acknowledge that this is not an 
engineering feat we are undertaking. We are trying to do 
something the guidelines for which are not clearly spelled out. 
We are attempting to find new means to approach AIDS vaccine 
development. I believe having the President speak out on that 
public occasion about the possibility of doing this provides 
leadership and excitement and could have a very significant 
and, at this point, dollar-free contribution to the way in 
which we approach the AIDS epidemic.

                       cost savings from research

    Mrs. Morella. Finally, just a statement. I very often, in 
comments to groups, will point out how much money we have saved 
in terms of health, the health of the Nation by virtue of 
something that has come from the NIH in the way of research. It 
is a good way of bringing the point home to people in terms of 
the value, tangibly, that they can see.
    So thank you all very much and thank you, Mr. Porter, for 
the opportunity.
    Mr. Porter. Thank you, Mrs. Morella.
    Ms. DeLauro.

                             ovarian cancer

    Ms. DeLauro. Thank you, very much; and I want to thank all 
of you for being here today and discussing with us the 
priorities within the NIH and how the research funds are 
prioritized. Obviously, the topic here is to--strong feelings 
amongst members of what are the areas of research that ought to 
be looked into, what are the areas that are considered 
underfunded.
    My commitment, as you know, has been to women's health. I 
want to say thank you, though she has left, to my colleague 
Patsy Mink for talking about the issue of ovarian cancer, being 
one of the few survivors of ovarian cancer, and that we are 
providing this amount of money in terms of diagnosis, 
treatment. So I am very excited about the Genome Project, and 
ovarian cancer is included in it.

                         politics and research

    I think--while Members try to influence decisions or 
really, for the most part, try to provide informed views on the 
direction, I think we do need to concede that politicians--and 
I am proud to be one--are not the final arbiters in this 
effort.
    I think one area that has been mentioned, the Parkinson's 
disease--and I don't want to get into a debate about this--we 
are in the business of cutting off avenues of research to look 
at, you know, Parkinson's fields of research or other means. I 
think if we inject the politics into this process, then we wind 
up truly not serving the best interests and best health of the 
public.
    So we put a lot of faith and responsibility in the 
judgments of NIH and the research funding priorities--not an 
easy admission for those of us who are here.

                           clinical research

    One of the things I wanted to inquire about--and I have 
asked this question in different ways over the last several 
months. That is, while basic research is critically important 
in generating fascinating, powerful insights into disease, 
without the kind of transfer, the clinical research, the 
discoveries cannot really help to improve the care that 
Americans receive in their doctors' offices and hospitals.
    So the balance between basic research and clinical research 
has been the topic of some conversation. Along with several of 
my colleagues, we have introduced legislation to raise that 
profile of clinical research. I want to get a sense from the 
NIH of how do we ensure that the discovery--the remarkable 
discovery that you are making in basic research----
    And let me say with regard to the AIDS research, when you 
are looking at research into blood and into suppressed 
immunities, this carries over into cancer and a whole variety 
of areas. This is not one specific area.
    But what are the steps that we are taking at the NIH to 
ensure that the discoveries that we make in basic research, 
with being tested in the clinical trials, are hitting doctors' 
offices across the country where that is--where the people 
receive the benefit?

                          technology transfer

    Dr. Varmus. Let me point out that there are at least three 
vehicles for doing what you outline. First, something I won't 
talk about in detail is technology transfer. As you know, 
Congress became concerned in the late 1970s about getting the 
products of our research into development, and the Bayh-Dole 
Act was one way to do that. We of course, are not the only game 
in town, and we want to believe the basic discoveries we make 
are picked up by pharmaceutical and biotechnology firms and 
carried forward into the production of benefits that can be 
delivered to patients. We believe there has been a very 
successful change in the way business is done.

                           clinical research

    The second concern has to do with clinical research. I 
don't mean to distinguish clinical research from basic 
research; indeed some clinical research is basic. When I 
arrived at NIH there was a concern that clinical research was 
in a state of crisis for a variety of reasons having to do with 
a decrease in the number of trained individuals going into 
clinical research and the potential for underfunding of 
academic research centers where clinical research is carried 
out because of changes in health care reimbursement. And there 
were concerns that NIH might not be adequately supporting 
clinical research.
    As I think you know, Ms. DeLauro, we put together a panel 
of clinical research investigators and medical school leaders 
to look at the clinical research portfolio whether we support 
it adequately and whether we are adequately attracting new 
investigators into clinical research activities, particularly 
patient-oriented research. A number of things have come about 
as a result of the panel's activities over the last 2 years. 
One has been the simple recognition that NIH's investments in 
patient-oriented or clinical research are already very 
appreciable. In dollars, about 37 percent [Clerk's note.--Later 
corrected to ``38''] of our grant money is going to clinical 
research activities, and nearly 30 percent [Clerk's note.--
Later connected to about 27''] of our grants are in the 
clinical research arena.
    Secondly, we agree that there is concern about recruitment 
of new clinical investigators. We are in the process of trying 
to identify ways to support new clinical investigators on 
faculties. We have recently established a new training program 
that allows medical students to come to NIH and spend 1 or 2 
years with us to develop their interests in clinical research. 
We are hoping over the course of the next couple of years to 
develop loan repayment programs to create incentives for 
clinical investigation in the extramural sector.
    We are also looking closely at the operation of our 
clinical center at the NIH, the largest center for clinical 
studies anywhere in the world. Your committee has been helping 
us maintain at a high level of productivity through the 
generation of a new building andmany new programs within the 
clinical center.

                       information dissemination

    The third area of concern is how we get information about 
our discoveries into doctors' offices. We have a considerable 
degree of activity in communications to advertise our results. 
This is an imperfect process; it is one other agencies of 
government and professional societies must help us with, 
because it is a huge and expansive problem. It is one where I 
think, in general, the biomedical establishment has not been 
totally successful.
    We talked earlier about obtaining as much benefit as would 
be possible from discoveries in the area of diabetes over the 
last several years. We know the science has run ahead of 
clinical practice there. It is extremely important that we find 
better ways to support the instruction of physicians in new 
methods and new findings, and we do that. But we can't do that 
alone because it is simply too expensive. It is much more 
effective for us to work in conjunction with advocacy groups, 
physicians and scientific societies.

                             ovarian cancer

    Ms. DeLauro. It is an area we really ought to talk about, 
because with regard to ovarian cancer, many of the women who 
have been diagnosed are not getting the kind of care and 
treatment they need. That is statistical data, and I understand 
the difficulties in ovarian cancer, and I don't know if the 
science is outpacing what is being passed on, as you mentioned 
with diabetes.
    But with a disease which is as insidious as it is and with 
the high death rate, if we have it and we are not then properly 
treating it, then, my God, to what end are we engaged, so 
whatever ways in which we can assist in that third opportunity, 
I think we need to explore those ways. And it is not just your 
responsibility; it becomes all of our responsibility as well.
    Thank you very much, Mr. Chairman.
    Mr. Porter. Thank you, Ms. DeLauro.
    Mrs. Lowey.

                         congressional support

    Mrs. Lowey. Thank you, Mr. Chairman, and I do apologize. 
Because of a commitment in New York, I missed part of the 
testimony, but I want to join my colleagues and thank all of 
you for the outstanding leadership you have shown. And I am 
very pleased that the Chairman, who is probably your strongest 
advocate--and I know most of us would join with him and wish we 
could double our 602(b).
    It is absolutely criminal to know that only 25 percent of 
the grants are funded, when you think of all those 
opportunities to deal with the challenges in medical research 
that we are not pursuing--in my judgment, it is a real tragedy.
    I, too, don't like to see one illness pitted against 
another, but I think it is so important that we say, loud and 
clear, and understand that we all advocate on behalf of so much 
of the research that is done, whether it is in AIDS or diabetes 
or breast cancer, that does affect other illnesses.
    And in the area of AIDS, we know, and you have certainly 
expressed to us, that so much of that research has helped us to 
advance in other areas, and to not take advantage of 
opportunities that exist in AIDS research is criminal as well. 
So I want to applaud you in that area.
    I remember when I got to Congress in 1988, looking back, if 
we had not had the input of activists and congressional 
members, certainly in the area of women's health, we would not 
have had that partnership and moved as fast as we have moved. I 
want to personally express my appreciation and thank you for 
the Women's Health Initiative, for all the work you have done.
    I remember talking--Dr. Kirschstein remembers as well--I 
remember talking to the American Women's Medical Association, 
and I remember them talking to us about their medical school 
classes where they would spend 5 minutes on estrogen and a 
couple of hours or a couple of days on testosterone.
    And I also remember the days when there were just three 
gynecologists on the staff at the NIH, so I want to personally 
thank you for that cooperative effort that has moved us so far 
ahead in those areas. And as a passionate supporter of 
research--and I want to assure you, I care about prostate 
cancer and heart disease and diabetes, and we can go on and on, 
but my particular concern is with regard to the Office of 
Women's Health; and I want to thank you for your concern in 
just making sure we have a healthier society.

                    orwh's priority setting process

    We know that a primary function of the Office of Research 
in Women's Health is its role in identifying research vital to 
women; that should be conducted and supported by the NIH. Could 
you update us in how the office is functioning, how its agenda 
is determined? Following up on the original Hunt Valley 
conference, how is it continuing to analyze and reevaluate 
priorities? I think it would be helpful for us to hear.
    Dr. Varmus. I can do that very briefly, Mrs. Lowey.
    About a year and a half ago Dr. Pinn, who is the director 
of the office, put together a standing advisory committee 
composed of outstanding physicians and investigators around the 
country who were particularly concerned with women's health. 
They are helping her adjust the research portfolio and set new 
priorities.
    The office continues to provide supplements to grants, 
working closely with the many Institutes and centers, all of 
which, of course, have an investment in women's health. The 
purpose of most of those investments is to augment the level of 
activity on grant projects that have already been approved by 
the Institutes in order to provide them with extra resources, 
to expand their efforts in the gender-specific aspects of the 
work.
    In addition, the office has responsibility for trying to 
encourage the careers of women in science and provides a number 
of programs that allow women to reenter the work force and stay 
in the work force despite domestic responsibilities.
    Another issue I should perhaps raise with you is one I know 
you are concerned about: the inclusion of women and minorities 
in research projects, and the guidelines that have supported 
our activities in those areas that were written jointly among 
offices in the Office of Director, including the Office of 
Women's Health. Dr. Pinn has been involved in evaluating the 
success of those efforts, and as far as we can tell, the 
success has been very great; that is, we see very little 
difficulty in helping our investigators to achieve compliance 
with the recommendations of those guidelines.

              priority setting interaction of orwh and nih

    Mrs. Lowey. In looking at the Office of Women's Health over 
the past few years, is there any difference in setting 
priorities there compared to the way you set priorities with 
the entire Institute, and what is the interaction?
    Dr. Varmus. Well, I think the reasons I would say the 
differences are not so great is because Dr. Pinn and her 
colleagues are in fact working with the other Institutes. 
Therefore, the input that goes to the other Institutes is 
amalgamated into the decision-making process that goes on inthe 
Office of Research on Women's Health.
    Mrs. Lowey. I think that is so important because I think 
the research is done across the board in almost every area. As 
you revitalize the NIH clinical center, perhaps you could share 
with us what considerations have been made with regard to 
women's health issues.
    Dr. Varmus. Women's health is part of virtually every 
research endeavor. It would be difficult for me to say what 
special concerns have been addressed in the plans we have 
carried out so far. Most of the energy that has surrounded 
revitalization of clinical center activities has had to do with 
recruitment of new clinical investigators to the NIH, training 
programs, the construction of the new facility, and changes in 
governance of the clinical center. We believe that in every one 
of these, equity is provided for gender-specific research.
    I think there has been a very significant change in 
attitude over the last several years. I don't believe that 
there is an ingrained discrimination of a gender-specific 
source at this point. If you feel there are ways in which 
women's health issues are being slighted in those activities, I 
would be more than pleased to entertain your views.
    Mrs. Lowey. No, in fact, again in closing, I want to 
emphasize I think in the last decade there has been 
extraordinary progress in the attention given women's health 
needs; and as we stated before, the research is done across the 
Institutes and all the institutions involved.

                        clinical research report

    Just in closing, I wanted to thank you for the report that 
you have provided regarding your efforts on behalf of clinical 
research. I must say I haven't read it as yet--we just received 
it--but I want to thank you for the report, and I look forward 
to discussing it with you. And once again I hope that we can be 
of help to our Chairman and that the 602(b) will be increased 
as my colleague Ms. Pelosi mentioned so we can fund a greater 
share of those grants.
    Thank you again.
    Mr. Porter. Thank you, Mrs. Lowey.
    Mrs. Northup.

                   information transfer in prevention

    Mrs. Northup. Yes, Dr. Varmus, I would also like to talk to 
you about transfer of information and results that come from 
research.
    In many of the medical areas, there are the dollars and the 
economic reasons to transfer technology very quickly. For 
example, AIDS research, then pharmaceutical companies become 
involved in developing a drug that addresses the problems. That 
is not so true in some quality-of-life issues, I guess you call 
them prevention issues. And prevention is becoming much more 
the issue in health, and I just wondered what you all are doing 
to promote that.
    I will give you a couple of examples. For example, drug 
rehabilitation and questions of addiction. What sort of effort 
does the Institute make when you come to certain conclusions 
about rehabilitation, or prevention altogether, to transfer 
that information to HHS so that the grants and the funding of 
prevention actually follow what the research shows is most 
effective.
    I will give you one other example, and that is learning and 
learning disabilities. We had quite a bit of testimony about 
what the best way of teaching kids to read who are at risk, and 
remediation for kids who have fallen behind. But in fact there 
is very little evidence that the Department of Education funds 
those kinds of programs, and in fact the President has proposed 
a reading initiative that is as far away from that as you can 
get.
    So could you share your comment with me? There is no 
pharmaceutical incentive or money incentive or medical 
incentive or insurance incentive to have the transfer go in 
those cases?

                          drug rehabilitation

    Dr. Varmus. Yes, you are making a very good point, and it 
is one we are concerned about. I am sure that more detailed 
explanations of what is being done could be provided on those 
two topics. I would point out in the case of drug 
rehabilitation, that Dr. Leshner, Director of NIDA, works 
closely with at least a couple of other agencies that are 
involved, like SAMHSA and other departments within the HHS. He 
also has been working closely with General McCaffrey and his 
colleagues on drug control. So there are other ways to try to 
translate the scientific findings into public policy.

                      early childhood development

    As you know, the White House has had a high degree of 
interest in early childhood development. We hope that from the 
initiatives that have been put into place by the President in 
the last year to try to emphasize the role of early childhood 
development on learning, that there will be increased 
interagency activities.
    Mrs. Northup. I think my question specifically to you is, 
what does your agency do to make the people making public 
policy and appropriating money aware of your most recent 
findings?

                 information transfer to other agencies

    Dr. Varmus. I think almost all agencies involved in public 
policy in those areas are aware that we do research in those 
areas, and see that we are consulted. There is also an 
opportunity through the National Science and Technology Council 
for spreading our information among the various agencies that 
are involved in those public policy decisions.
    So in the area of health, for example, there is a whole 
committee of the National Science Technology Council that is 
devoted to health and safety, and multiple representatives of 
the NIH are at those meetings.

                   research on learning disabilities

    Mrs. Northup. I worry because I sometimes have the feeling 
that if they don't call--and, quite honestly, I think that was 
really true of learning disabilities and problems--that you all 
do the research; and then, in a sense, the Department of 
Education until recently was not aware of what the most recent 
research was. Considering the dollars we are spending and how 
concerned we are about that issue, I think it is important that 
you initiate an effort to disperse the results of what your 
considerations are.
    Dr. Varmus. Well, I remember your interesting conversation 
with Duane Alexander, Director of NICHD, on this topic before, 
and I hope to get back to you about what is being done.
    [The information follows:]

Information Dissemination of Research Findings on Learning Disabilities

    The NICHD has in place a successful program aimed at 
research information dissemination and in the last year has 
intensified its efforts in this regard in the area of reading 
development and disorders, and other learning disabilities. The 
extensive work of the Institute's investigators in the area of 
learning disabilities research is being published widely in 
research, education, and general interest publications. The 
NICHD is producing information such as fact sheets and 
brochures that are being distributed by the Institute and other 
agencies in both the government and private sectors. The 
Institute responds daily to many requests for information from 
the public and special interest groups on this subject. In 
addition, the Institute annually publishes a book that 
describes the year's progress in learning disabilities 
research. The NICHD worked cooperatively with the Department of 
Education to produce a set of information materials called 
``Learning to Read--Reading to Learn'' that is being 
disseminated widely by the Department of Education and other 
agencies. The NICHD is working actively with the learning 
disabilities organizations to disseminate information to parent 
and education groups about the progress that is being made. In 
addition, the scientist directing the Institute's learning 
disabilities research program has testified before the Congress 
and, upon request, provided information to a number of state 
legislatures and parent groups in states around the country 
about the results of this research. In April of this year, the 
NICHD together with the Learning Disabilities Association 
sponsored a Learning Disabilities Summit in Washington, D.C., 
with the concluding event on Capital Hill, to further 
disseminate the research results in this area. The Institute is 
working with the Department of Education to develop a national 
assessment of research in reading development, reading 
disorders, and other learning disabilities and, where 
appropriate, a national strategy for the dissemination of that 
information to the Nation's teachers and schools.

    Mrs. Northup. What I am worrying about again, if we don't 
ask the right questions and somebody doesn't call up, nobody 
ever knows, and that is important.

                      Earmarks in DOD for research

    I would like to ask you one other question. I absolutely 
agree with us not making scientific determinations here, but of 
course it is sometimes hard when you are in Congress not to 
think that you can't make all the rules. We try to repeal the 
laws of economics sometimes and all sorts of things.
    I have noticed that the defense appropriators have decided 
that they are going to earmark appropriations for such things 
as prostate cancer, ovarian cancer, Parkinson's disease and 
bone marrow. I was wondering if you would comment on, at least 
for us, why those appropriations being earmarked by defense 
aren't a good way or why they run counter to the best interest 
of research.
    Dr. Varmus. Well, I think that we at the NIH are 
interested, have been interested in working closely with our 
colleagues in the Department of Defense to make optimal use of 
those appropriations. As you know, there is very strong 
biomedical science in the Department of Defense through Walter 
Reed and the Office of Naval Research and other components of 
the Defense Department.
    You are right. The monies appropriated for research are in 
some cases conspicuously earmarked. We have a variety of 
interactions on virtually every topic on which they received 
earmarking that allows NIH scientists to interact with our 
counterparts in the Defense Department, and we welcome those 
interactions. In addition, the Defense Department has been 
working with us in clinical trials that include Department of 
Defense personnel.
    So there are many ways in which we interact with them, and 
to the extent to which most are appropriate for specific 
diseases, we try to do the best we can to provide advice that 
will allow those monies to be most wisely used.
    Mrs. Northup. Okay, thank you.
    Mr. Porter. Thank you, Mrs. Northup.

                         NIH Budget for FY 1998

    I think this has been an excellent hearing, and we want to 
thank you, Dr. Varmus, and your colleagues and all the members 
of the audience this morning. I might say that I found 
everything that you had to say highly credible, except 
defending the President, who is now--and I might add, this also 
includes the members of the Budget Committee and our leadership 
negotiators, who have now got the NIH budget down to a 1.2 
percent increase for the next fiscal year.
    I am sure you find that just as unacceptable as we do, and 
I hope that the expressions about our 602(b) allocation that 
have been made by members of the panel this morning are ones 
that come true, because it will make it very, very difficult 
for us; and I am afraid the leadership of both the White House 
and the Congress have made it very, very difficult to make that 
a high priority and made our job much, much more difficult in 
the process.
    I think this is a subject that all of us have to address in 
the coming calendar year and make certain that the substance, 
the resources follow the advocacy. The advocacy is always 
welcome, but not if it is not supported by resources.
    Dr. Varmus, thank you very much.
    The subcommittee will stand in recess until 10:00 a.m. 
tomorrow, which is our last hearing of the year.

[Pages 2509 - 2552--The official Committee record contains additional material here.]










                           W I T N E S S E S

                              ----------                              
                                                                   Page
Adderly, Donna...................................................  2155
Alexander, Duane.................................................  1635
Baldus, A.C......................................................  2001
Baldwin, Wendy...................................................     1
Barros, C.F......................................................  1915
Beldon, Bill...................................................711, 805
Benowitz, S.C....................................................  2249
Berkowitz, S.J...................................................   583
Burgess, E.S.....................................................   495
Bursenos, S.J....................................................  1443
Casady, D.S......................................................  1635
Cassman, Dr. Marvin..............................................  2095
Collins, F.S.....................................................   495
Counts, G.W......................................................   583
Cushing, Mary....................................................  1377
Du Buy, Y.H......................................................  1737
Dufour, Dr. Mary.................................................  1091
Fauci, A.S.......................................................   583
Ficca, S.A.......................................................  2249
Fitzsimmons, W.T.................................................  1809
Fivozinsky, C.L..................................................   419
Fulton, B.E......................................................  1635
Gekas, Hon. George...............................................  2431
Gorden, Phillip..............................................1177, 2431
Gordis, Dr. Enoch................................................  1091
Gottesman, Michael...............................................     1
Grady, Dr. P.A...................................................  1377
Hall, Dr. Z.W....................................................  2001
Haseltine, Dr. F.P...............................................  1635
Hausman, Dr. S.J.................................................  1491
Hodes, R.J.......................................................  1915
Hodgkins, G.E....................................................  2095
Hudson, Kathy....................................................   495
Hyman, S.E.......................................................  1809
Itteilag, Anthony...............................................1, 2249
Jaron, Dr. Dov...................................................  1573
Johnson, Laurie..................................................   711
Jones, D.M.......................................................   983
Jordan, Elke.....................................................   495
Katz, Dr. S.1....................................................  1491
Kerr, W.D........................................................   805
Kerza-Kwiatecki, M.S.............................................  1491
Kirschstein Dr. R.L...........................1, 1377, 1443, 1915, 2249
Klausner, R.D.................................................199, 2431
Kleinman, D.V....................................................  1737
Kupfer, Carl.....................................................   419
Laurence, L.E....................................................  1177
Leasure, C.E., Jr................................................   711
Lenfant, Dr. Claude...........................................865, 2431
Leshner, A.I.....................................................   983
Levine, S.U......................................................  1309
Lindoerg, D.A.B..................................................  1309
Lipman, D.J......................................................  1309
Little, Francine.................................................     1
Long, Stephen....................................................  1091
Luecke, D.H......................................................   805
Maddox, Dr. Y.T..................................................  1635
McGowan, J.J.....................................................   583
McLaughlin, Jack.................................................   419
McManus, Edward..................................................   419
Merritt, Sheila..................................................   865
Miller, Richard..................................................  1443
Millstein, R.A...................................................   983
Mink, Hon. P.T...................................................  2431
Moore, Marshall..................................................   805
Morella, Hon. C.A................................................  2431
Moul, Ellen......................................................  1377
Nakamura, R.K....................................................  1809
Nethercutt, Hon. G.R., Jr........................................  2431
Olden, Kenneth...................................................   711
Paul, W.E....................................................2155, 2431
Penn, Dr. A S....................................................  2001
Pine, J.R........................................................  1809
Pine, Martha.....................................................  2095
Poppke, D.C......................................................  1309
Rabson, Alan.....................................................   199
Ramm, Dr. L.E....................................................  1573
Richardson, C.M..................................................  1091
Rosenthal, Laura.................................................   983
Ross, KS.........................................................  1915
Roth, Dr. Carl...................................................   865
Schambra, P.E....................................................  1443
Shafer, Dr. W.S..................................................  2095
Sherbert, R.L., Jr...............................................  2001
Slavkin, H.C.....................................................  1737
Smith, K A.......................................................  1309
Snow, J.B., Jr...................................................   805
Sparks, P.T......................................................   805
Strachan, R.J....................................................  1491
Summers, A E.....................................................  1573
Taylor, E.S......................................................  1737
Trusty, M.K......................................................  1091
Vaitukaitis, Dr. J.L.............................................  1573
Varmus, Dr. Harold.....1, 199, 419, 495, 583, 711, 805, 865, 983, 1091, 
     1177, 1309, 1491, 1573, 1635, 1737, 1809, 1915, 2001, 2095, 2155, 
                                                             2249, 2431
Vennetti, J.C....................................................   495
Wehling, James...................................................   865
Weiblinger, G.M..................................................  1809
Wertheimer, Wendy................................................  2155
Wetle, TelTie....................................................  1915
Williams, D.P........1, 199, 419, 495, 583, 865, 983, 1091, 1177, 1309, 
     1377, 1443, 1491, 1573, 1635, 1737, 1809, 1915, 2001, 2095, 2155, 
                                                             2249, 2431
Williams, T.D....................................................   583
Wilson, S.H......................................................   711
Zellers, C.R.....................................................  1177











                               I N D E X

                              ----------                              

                 National Institutes of Health Overview

                                                                   Page
Administrative Costs.............................................    53
AIDS/HIV:
    AIDS and Minorities..........................................   111
    AIDS Research................................................    83
    Culminations in HIV Research.................................     3
    HIV Vaccine..................................................    29
    Inspiration in HIV Research..................................     4
Areas of Research Emphasis.......................................    79
Awareness Relating to Biomedical Research........................    67
Biomedical Engineering Research..................................   116
Budget Estimates:
    Budget Estimates.............................................    11
    Budget Estimates, Justification of...........................   148
    Five Year Budget.............................................    91
    FY 1998 Budget Request.......................................    43
    Funding for NIH..............................................    96
    Impact of 7.5 Percent Increase...............................    22
    1st President's Budget Proposal..............................     5
    Professional Judgment Budget.................................    11
Cancer:
    Ovarian Cancer...............................................    33
    Advances in Ovarian Cancer Research..........................    34
Child Abuse and Neglect..........................................   134
Child Development and the Brain..................................    34
Clinical Research:
    Clinical Research at Academic Medical Centers................   143
    Clinical Research Panel....................................129, 144
    Clinical Research Program....................................    80
    Funding for Clinical Research................................    80
    Initiatives for Clinical Research............................   145
    IOM Recommendations................................19, 81, 142, 145
    Peer Review of Clinical Research.............................   145
    Progress in Support for Clinical Research....................    22
    Subscribers Participation in NIH Protocols...................    21
    Third Party Payments, Impact of..............................    35
Cloning:
    Cloning......................................................    13
    Cloning of Humans............................................    26
    Earlier Cloning Experiment...................................    14
    Ethical Implications.........................................    17
    How Genes Turn On and Off....................................    16
    Legislating Cloning..........................................    18
    Medical Uses of Cloning......................................    15
    Scientific Significance of Cloning...........................    15
    Use in Bone Marrow Transplants...............................    16
Comparison of Medicare Costs and Disease Research Costs..........    36
Congressional Earmarks...........................................    85
Consensus Development Panels.....................................    23
Contraceptive and Reproductive Health Training Programs..........   136
Contraceptive Research...........................................    70
Coordination with Other Agencies.................................    82
Culminations of Research.........................................     2
Department of Defense, Collaboration with........................    89
Department of Education, Cooperation with........................   130
Diabetes:
    Commitment to Diabetes Research..............................    30
    Diagnosis and Detection of Diabetes..........................    31
    Increase in Diabetes Research................................   131
    Initiatives for Diabetes Research............................   131
    New Approaches to Pathogenesis...............................    65
    NIH-Wide Diabetes Research Efforts...........................    64
Direct and Indirect Costs........................................    72
Director's Discretionary Fund, FY 96 and 97......................    45
Employment Rates for African-American Males......................   120
Ethical, Legal and Social Implications Working Group.............    94
Ethics Training..................................................    29
Extramural Construction..........................................   107
Extramural Programs..............................................    86
Full Time Equivalents (FTES):
    FTE Detail by Grade Level....................................    59
    FTE Ceiling..................................................    61
    FTE Total by Institute.......................................    48
    FTE Total by Mechanism.......................................    49
Human Embryo Research............................................    92
Grants:
    Administrative Burdens on Grantees...........................    88
    New and Competing Research Project Grants....................   142
    Number of Applications.......................................    51
    Research Project Grants......................................   104
    RPGs as Priority.............................................   113
    Success Rates...............................................12, 110
Imaging Research.................................................    32
Indirect Cost Cap................................................    66
Inspirations of Research.........................................     3
Instrumentation..................................................    61
Intramural Programs..............................................    87
Mammography:
    Mammography..................................................   108
    Mammography Policy...........................................    25
Medicare Spending by Disease, 1995...............................    37
Minorities:
    Inclusion of Minorities in Clinical Research.................   122
    Investment in Minority Research Programs.....................   116
    IOM Study....................................................   103
    Minority Health Standing Advisory Committee..................   102
    Minority International Research Training Program.............   100
    Minority Investigators.......................................   113
    Number of Minority and Women Investigators...................   105
    Pipeline.....................................................   127
    Research Centers in Minority Institutions....................   128
    Research Related to Minorities...............................    95
National Bioethics Advisory Commission...........................    28
National Center on Sleep Disorders Research......................    52
Needle Exchange..................................................    24
Neuroscience.....................................................   126
Obstetrics and Gynecology, Research in.........................135, 138
Offce of Research in Minority Health (ORMH):
    Funding for Offce............................................96, 97
    ORMH Co-funding..............................................    99
    Role of the ORMH.............................................   103
Opening Statement................................................     6
Oversight and Administrative Activities..........................     4
Panel on Potential Research on Marijuana.........................    24
Pediatric Research:
    Number of Intramural Pediatricians...........................   138
    Pediatric Research...........................................   137
Permanent Separations Profile....................................   121
Pipeline for Young Investigators.................................    93
Population Research..............................................    70
Prenatal Research................................................    71
Public Education.................................................    50
Pulmonary Hemorrhage Among Cleveland Infants.....................   104
Priority Setting:
    Allocation of Research Dollars...............................    40
    Criteria for Funding Allocations.............................    40
    Establishing Priorities......................................    12
    NIH Priority Setting Process.................................42, 73
    Priority Setting at NCI......................................    76
Reducing Health Care Costs.......................................    41
Research Infrastructure..........................................   114
Research on Learning.............................................   130
Research Management and Support (RMS):
    Cap on Management and Support Costs..........................    94
    One-Percent Evaluation Funding In............................    49
    RMS Funding 1990-1998........................................    50
Research Spending Per Death for Selected Disease.................    67
Research Training................................................    86
Shannon Awards...................................................    61
Small Business Innovation Research Grants........................   115
Spending by Disease..............................................    56
Taps and Assessments:
    One-Percent Evaluation Set-Aside.............................    61
    Taps and Assessments.........................................    63
Toll-Free Numbers................................................    54
Women in Clinical Trials.........................................   141

                       National Cancer Institute

Abortion and Breast Cancer.......................................   255
Access to Care...................................................   236
Advances Against Cancer..........................................   273
Angiogenesis.....................................................   231
Areas Impacting on Cancer........................................   232
ASSIST...........................................................   252
Behavioral Research..............................................   321
Breast Cancer-ABMT...............................................   236
Cancer Genetics..................................................   259
    Cancer Genetics Network......................................   260
    Cancer Genetics and Molecular Biology........................   305
    Genetics Testing.............................................   261
Cancer Survivors...............................................230, 272
    Breast Cancer Survival.......................................   235
    Five-Year Survival Rates.....................................   230
    Office of Cancer Survivorship................................   242
Cancer Vaccines..................................................   263
Cancer Centers Program Review Group..............................   269
Cancer Genome Anatomy Project....................................   269
Cancer Mortality by Race.........................................   317
    Decline in Cancer Mortality..................................   271
Cancer Prevention................................................   203
Clinical Trials................................................204, 278
    African American Women and Clinical Trials...................   299
    Breast Cancer-Molecular Markers..............................   207
    Clinical Trials in FY 1998...................................   286
    Clinical Trial Educational Efforts...........................   267
    Clinical Trial Agreement with The Department of Defense......   265
    Clinical Trial Agreement with The Veteran's Administration...   266
    Dissemination of Clinical Trial Results......................   284
    Women in Clinical Trials.....................................   328
Clinical Treatment...............................................   236
Cloning..........................................................   318
Collaborative Efforts............................................   307
Combination Therapies............................................   308
Comprehensive Cancer Centers.....................................   251
Construction.....................................................   246
Coordination Efforts with DOD..................................237, 238
Coordination of the National Cancer Program......................   251
Detection Technologies For Breast Cancer.........................   225
    Other Detection Technologies For Breast Cancer...............   224
Diet and Cancer................................................258, 311
Dissemination of Cancer Information..............................   319
Environmental Links to Breast Cancer.............................   233
    San Francisco Bay Area.......................................   234
Environmental Justice Research Activities........................   313
    Environmental Justice Collaborative Activities...............   315
Estrogen and Breast Cancer.......................................   325
``Five A Day'' Program...........................................   249
FTE Decrease.....................................................   245
Funding Allocation Decisions.....................................   226
Funding for NIH..................................................   228
Gynecologic Cancer Research......................................   328
Human Papillamovirus.............................................   241
Imaging..........................................................   263
    Imaging Technologies.........................................   297
Infectious Causes of Cancer......................................   294
Institute of Medicine Cancer Study...............................   317
Intramural Program at Frederick..................................   244
Justification of The Budget Estimates............................   331
Mammography....................................................221, 295
    Mammography Imaging..........................................   265
    Screening....................................................   223
Measure of Successes.............................................   268
Minorities and Cancer............................................   229
    Advances in Minority Health..................................   227
    Cancer in Minority Population................................   312
    Excess Cancer Death Rate.....................................   271
    Office of Special Populations................................   229
Molecular Characteristics of Cancer..............................   310
NCAB Subcommittee................................................   224
NCI Panels and Advisory Boards...................................   329
New Cancer Drugs.................................................   268
NIH Reauthorization..............................................   231
Opening Statement................................................   199
Ovarian Cancer.................................................240, 327
Professional Judgment Budget.....................................   238
    Opportunities................................................   239
Prostate Cancer................................................236, 278
    Prostate Cancer Initiatives..................................   300
    Prostate Cancer Treatment and Early Detection................   302
    African Americans and Prostate Cancer........................   304
Radiation Therapy................................................   246
Role of Stress in Cancer.........................................   277
San Antonio Cancer Institute.....................................   251
Science Information System.......................................   323
    Implementation of The Science Information System.............   324
Statement of The Director........................................   212
Tobacco Use and Children.........................................   247
Biology of the Brain.............................................   431
Cataract Surgery.................................................   437
Contact Lenses...................................................   437
FDA Approval.....................................................   429
Fetal Tissue.....................................................   434
Glaucoma Gene..................................................427, 429
Introduction of Witnesses........................................   419
Long-Range Research Plan.........................................   436
Macular Degeneration...........................................429, 434
Marijuana use for Glaucoma.......................................   434
Neuron Survival..................................................   428
Nutritional Supplements for Retinitis Pigmentosa.................   436
Opening Statement................................................   419
Private Foundations..............................................   435
Professional Judgement Budget....................................   426
Radial Keratotomy Versus Laser Technique.........................   428
Retinopathy of Prematurity.......................................   430
Statement of Director............................................   422
Transplanted Retinal Cells.......................................   433
Vision Conditions Needing More Research..........................   437
Budget Increase..................................................   506
Bureaucratic.....................................................   531
Center for Inherited Disease Research.....................497, 529, 543
Cloning:
    Cloning and Ethics...........................................   547
    Cloning Humans...............................................   515
    International Cooperation....................................   511
    Potential for Hoax...........................................   514
    Scientific Opportunities...................................507, 536
    Why a Sheep..................................................   515
Designer Drug Strategies.........................................   513
Diversity........................................................   544
Ethical, Legal, and Social Implications........................499, 535
Finding the Gene...............................................497, 505
Finishing Faster:
    Additional Funds Needed......................................   525
    Finding A Cure...............................................   507
Future Health Care Delivery......................................   512
Genetic Discrimination and Privacy.............................519, 529
Genetic Testing:
    Breast Cancer................................................   508
    Counseling and Control.......................................   510
    Guidance.....................................................   526
Health Insurance Portability and Accountability Act of 1996......   537
Howard University Center.........................................   543
Human Embryo Research............................................   516
Human Genome Project:
    Creation of..................................................   541
    Mapping Progress.............................................   534
Intramural Program...............................................   540
Minorities and Women.............................................   533
Newest Research Institute.................................495, 523, 532
Opening Statement................................................   501
Oral Remarks.....................................................   495
Ovarian, Breast, and Cervical Cancer.............................   546
Prostate Cancer..................................................   496
Protection of Patient Medical Information........................   538
Sequencing:
    Complete DNA Sequence........................................   498
    Beyond the First Sequence....................................   498
    Large Scale Sequencing.......................................   528

         National Institute of Allergy and Infectious Diseases

Introduction of Witnesses........................................   583
Opening Statement................................................   583
AIDS:
    AZT...................................................586, 588, 618
    Behavioral Research..........................................   614
    Clinical Trials............................................602, 606
    Global Threat................................................   612
    Minorities...................................................   632
    Office of AIDS Research......................................   611
    Pediatric....................................................   657
    Protease Inhibitors..............................601, 605, 614, 623
    Therapy....................................................605, 608
    Treatment Strategies..................................586, 605, 612
    Vaccines.........................................593, 601, 609, 633
    Women........................................................   654
Asthma...........................................................   636
Basic Research............................................594, 599, 601
Benefits of AIDS Research........................................   654
Budget Estimates, Justification of...............................   661
Cholera..........................................................   619
Chronic Fatigue Syndrome.............................603, 623, 631, 641
Clinical Trials..................................................   649
Cloning..........................................................   640
Diarrheal Diseases.............................................602, 630
Drug Issues......................................................   617
Emerging Infectious Diseases.....................................   647
Grant Success Rate...............................................   648
Hansen's Disease.................................................   620
Hemophilia.......................................................   617
Hepatitis A......................................................   626
Lyme Disease.....................................................   603
Malaria........................................................618, 633
Media Involvement................................................   616
Multiple Sclerosis...............................................   603
Patient Registries...............................................   639
Primary Immune Deficiency........................................   622
Priority Setting.................................................   628
Research Accomplishments.........................................   643
Rotavirus........................................................   602
Sexually Transmitted Diseases........................602, 628, 652, 658
Topical Microbicides.............................................   655
Tuberculosis.........................................619, 626, 630, 640
Vaccines.............................................596, 597, 603, 642

           National Institute of Environmental Health Siences

Air Quality......................................................   763
    Air Quality Standards.................................730, 736, 745
Artificial Sweeteners............................................   725
Asthma.........................................................728, 763
Autism...........................................................   731
Beryllium........................................................   770
Breast Cancer....................................................   766
Budget...........................................................   747
Budget Formulation...............................................   762
Cancer...........................................................   764
Clinical Program...............................................748, 750
Clinical Research................................................   754
Clinical Trials..................................................   762
Cloning..........................................................   756
Collaboration with Industry......................................   723
Collaborations...................................................   757
Congressional Visit..............................................   719
Contract Mechanism...............................................   727
Endocrine Disruptors...........................................719, 723
Environmental Genome Project.....................................   720
Environmental Health Hazards.....................................   756
Environmental Justice..........................................752, 767
EPA..............................................................   749
Funding Increase.................................................   717
Grant Funding Mechanisms, Major..................................   758
Gulf War Syndrome................................................   724
Justification of the Budget Estimates............................   772
Knowledge ``Bottleneck''.........................................   754
Link Between Science and Public Health...........................   721
Minorities, Improving Health of..................................   752
Mixtures.........................................................   718
Nanofabrication..................................................   726
National Toxicology Program....................................734, 768
New Testing Methodologies......................................720, 734
Opening Statement................................................   711
Particulate Matter...............................................   736
Pulmonary Hemorrhage Among Cleveland Infants, Epidemic of........   764
Retesting of Chemicals...........................................   728
Secondhand Smoke.................................................   746
Smoking..........................................................   730
Statement of the Director........................................   713
Success Rate.....................................................   759
Superfund......................................................734, 750
Toxicity Test Systems............................................   747
Vitamin D and Prostate Cancer....................................   718

    National Institute on Deafness and Other Communication Disorders

Autism Research..................................................   811
Balance Disorders in Elderly.....................................   816
Clinical Trials................................................818, 831
Cloning Technology...............................................   828
Collaborative Effort in Hearing Aid Technology...................   822
Eating Behavior and Nutrition....................................   815
Government Performance and Results Act...........................   818
Hair Cell Regeneration...........................................   811
Hearing Aid Research.............................................   827
Hearing Impairment:
    Consensus Conference Findings................................   813
    Incidence....................................................   824
Introduction of Witnesses........................................   805
Investigator-Initiated Research Applications.....................   832
Justification of the Budget Estimates............................   834
Loss of Voice....................................................   816
Multi Cultural Language Assessment...............................   830
Opening Statement................................................   805
Otitis Media.....................................................   823
Partnership Program..............................................   832
Public Information Activities....................................   821
Presbycusis......................................................   826
Research Funding.................................................   821
Sense of Smell...................................................   816
Sensory Regeneration.............................................   815
Specific Language Impairment.....................................   820
Statement of Director............................................   807
Stochastic Resonance.............................................   812
Vaccine for Otitis Media.......................................819, 826

               National Heart, Lung, and Blood Institute

Allocating Funds.................................................   888
Asthma.........................................................876, 928
Benefits from Research...........................................   890
Cardiovascular Disease in Mississippi..........................887, 926
Cell Death.......................................................   875
Child and Adolescent Trial for Cardiovascular Health (CATCH).....   916
Chronic Obstructive Pulmonary Disease..........................921, 922
Clinical Trials and Research..............................925, 939, 942
Comprehensive Heart, Lung, and Blood Center......................   911
Cooley's Anemia..................................................   882
Cost Recovery....................................................   902
Diet and Blood Pressure..........................................   936
Education Programs........................................893, 900, 932
Folic Acid.......................................................   918
Gender Differences...............................................   930
Gene Therapy..............................................875, 878, 914
Government Performance and Results Act...........................   895
Heart Disease Death Rate.........................................   915
Heart Diseases...................884, 892, 902, 912, 926, 927, 932, 938
Human Clonine Research.........................................892, 941
Hypertension and Children........................................   935
Hypertrophic Cardiomyopathy......................................   905
Imaging Technology.............................................866, 873
Infants and Congenital Heart Disease.............................   934
In Utero Bone Marrow Transplantation.............................   874
Knowledge ``Bottleneck''.........................................   940
Lung and Blood Diseases..............................868, 880, 887, 896
Lung Volume Reduction Surgery..................................895, 924
Major Opportunities..............................................   927
Minority Health............................879, 881, 925, 931, 933, 938
Organ Damage.....................................................   935
Primary Pulmonary Hypertension.................................906, 909
Salt Intake......................................................   901
Selected Areas of Research.......................................   898
Select Pay.......................................................   903
Service Centers..................................................   894
Sleep Disorders Research.........876, 893, 901, 907, 908, 922, 923, 936
Smoking........................................................884, 927
Specialized Centers of Research..................................   899
Statement of the Director........................................   870
Stroke Research................................................877, 919
Women's Health............................................913, 920, 944

                    National Institute on Drug Abuse

AIDS and Drug Abuse..............................................  1002
AIDS/HIV and Drug Abuse..........................................  1017
Alaska Needle Exchange...........................................   995
Alcohol and Substance Abuse......................................   993
Biology of the Brain.............................................  1028
Brain Development in Adolescent Drug Users.......................  1050
Brain Imaging....................................................  1032
Bupropion........................................................  1006
Clinical Research................................................  1038
Clinical Trials..................................................  1041
Cloning..........................................................  1040
Cocaine Craving..................................................  1009
Cocaine Medication...............................................   999
Cocaine Medication Development...............................1005, 1006
Collaborative Effort.............................................  1027
Comparing United States Drug Abuse...............................  1003
Cost to the Nation...............................................  1029
Craving............................................................1012
Demographics of Addicts..........................................  1003
Disease Specific Budgets.........................................   996
Drug Abuse Budget Increase.......................................   994
Drug Abuse Costs.................................................  1009
Drug Intoxication................................................  1030
Effect of Welfare Reform on Addicts..............................  1052
Effective Drug Treatments........................................  1009
Effectiveness of Prevention Programs.............................  1007
Essense of Addiction.............................................  1001
Extent of the Problem............................................  1020
Genetic and Environmental Influences.............................  1034
Impact of Drug Abuse.............................................  1030
Improving the Health of Minorities...............................  1037
Information Dissemination....................................1007, 1048
Introduction of Witnesses........................................   983
Justification of the Budget Estimates............................  1054
Knowledge ``Bottleneck''.........................................  1039
Marijuana for Medical Purposes...................................  1026
Medical Marijuana Concerns.......................................  1008
Medical Use of Marijuana.........................................   997
Methadone Treatment..............................................   998
Minority and Women's Health......................................  1044
Minority Related Research........................................  1004
National Institutes of Health Disease-Specific Budgets...........   996
Needle Exchange...............................................997, 1023
Needle Exchange and AIDS.........................................  1008
Needle Exchange Programs.........................................  1004
Nicotine Addiction............................................994, 1000
NIDA-SAMHSA Coordination.........................................  1053
Opening Statement................................................   983
Our Nation's Youth...............................................  1047
Outreach.........................................................  1037
Prenatal Drug Use Study..........................................  1007
Prevention Increase..............................................  1008
Prevention Principles Book.......................................  1006
Prevention Program...............................................  1005
Prevention Programs for Elementary and Secondary School Students.  1016
Prevention Research..............................................  1012
Progress.........................................................  1031
Relationship Between Marijuana and Abrupt Termination of 
  Pregnancy......................................................  1011
Relationship with ONDCP..........................................   992
Research.........................................................  1012
School Based Drug Prevention.....................................  1014
Search for a Cure................................................  1046
Statement of the Director........................................   988
Successor Drugs of Abuse.........................................   999
Tobacco..........................................................  1014
Vaccine Development..............................................   992

           National Institute on Alcohol Abuse and Alcoholism

Adolescent Consumption, Trends of................................  1101
Alcoholics Anonymous, Evaluations of.............................  1103
Animal Models....................................................  1092
Brain Function in Adolescents....................................  1140
Chromosomes Associated with Alcoholism...........................  1123
Clinical Research................................................  1136
Clinical Trials..................................................  1139
Cloning..........................................................  1138
Comparing Drug and Alcohol Use and Abuse.........................  1108
Consumption......................................................  1109
Coordination.....................................................  1122
Coordination of Research Findings................................  1142
Cure for Alcoholism..............................................  1105
Dissemination of Research Findings...............................  1131
Effects of Alcohol on Development................................  1110
Estrogen, Effect of Alcohol on...................................  1112
Extent of the Problem............................................  1124
Fetal Alcohol Syndrome, Correlation of Heavy Drinking to.........  1111
Fetal Alcohol Syndrome...........................................  1125
Fetal Alcohol Syndrome and Early Childhood Development...........  1143
Genetic Testing..................................................  1107
Genetics Research, Practical Applications of.....................  1107
Incidence by Gender..............................................  1121
Institute of Medicine Assessment.................................  1132
Justification................................................1145, 1176
Knowledge of ``Bottlenecks''.....................................  1137
Liver Transplantation for Alcoholic Liver Disease................  1113
Major Research Opportunities.....................................  1125
Medications for Alcohol Treatment................................  1104
Medications, Promising...........................................  1118
Minorities, Improving the Heslth of..............................  1135
Moderate Drinking................................................  1117
Naltrexone Research..............................................  1133
New Opportunities for Developing New Drugs.......................  1119
Opening Statement................................................  1091
Pregnancy........................................................  1128
Prevention.......................................................  1094
Prevention Research versus Behavioral Research...................  1121
Project Match, Rigorous Design and Findings of...................  1101
Project Northland: Positive Outcome and Lower Drug Use...........  1121
Research Advances, Application of................................  1093
Research Dissemination...........................................  1095
Safe and Drug Free Schools.......................................  1115
Serotonin........................................................  1112
Significant Research Opportunities...............................  1125
Statement of the Director........................................  1096
Tobacco and Alcohol Use..........................................  1134
Treatment Research...............................................  1094
Vulnerability to Alcoholism......................................  1091
Welfare Reform...................................................  1141
Witnesses, Introduction of.......................................  1091

    National Institute of Diabetes and Digestive and Kidney Diseases

Administrative Issues............................................  1218
Artificial Pancreas..............................................  1194
Budget Estimates, Justification of...............................  1184
Chromium Diabetes Study..........................................  1236
Clinical Research................................................  1251
Clinical Trials..................................................  1254
Clinical Trials--Participation...................................  1249
Cloning..........................................................  1253
Collaborative Efforts........................................1225, 1246
Cooley's Anemia..................................................  1209
Costs of Treating Diabetes.......................................  1194
Crohn's Disease..................................................  1257
Diabetes Education Program.......................................  1191
Diabetes Education and Research..................................  1224
Diabetes Emphasis................................................  1184
Diabetes Gene....................................................  1243
Diabetes in African Americans....................................  1256
Diabetes in Minorities...........................................  1244
Diabetes Initiative..............................................  1240
Diabetes Prevention..............................................  1237
Diabetes Prevention Trials.......................................  1225
Diabetes Regimen.............................................1209, 1219
Diabetes Research............................................1228, 1231
Digestive Diseases...............................................  1205
Disease Funding..................................................  1214
Drugs That Work Selectively......................................  1204
Effects of Alcohol...............................................  1201
End-Stage Renal Disease..........................................  1241
Funding for Diabetes Research..........................1189, 1217, 1223
Genetics of Diabetes.............................................  1191
Helicobacter Pylori..............................................  1249
H. Pylori Applications...........................................  1202
Health Status of Women and Minorities............................  1245
Hepatitis........................................................  1207
Hepatitis C......................................................  1214
Identifying Areas of Research Emphasis...........................  1184
Immune Modulation in Diabetes....................................  1185
Impact of Diabetes Trial.........................................  1210
Improving the Health of Minorities...............................  1251
Intramural Decision-Making.......................................  1196
Intramural Research..............................................  1195
Introduction of Witnesses........................................  1177
Justification of the Budget Estimates............................  1258
Knowledge ``Bottleneck''.........................................  1252
Liver Disease in Children........................................  1221
Liver Disease Information........................................  1219
Locating Diabetes Information....................................  1193
New Methods for Treating Diabetes................................  1237
Newly Diagnosed Diabetics/Early Intervention.....................  1227
Nutrition........................................................  1200
Nutrition and Diabetes...........................................  1255
Obesity..........................................1211, 1222, 1241, 1244
Opening Statement................................................  1177
Organ Donations..................................................  1250
Outside Input for Diabetes Research..............................  1226
Peer Review......................................................  1230
Polycystic Kidney Disease..............................1208, 1217, 1255
Prevalence of Diabetes...........................................  1188
Professional Judgment Budget.....................................  1189
Prostate Cancer..................................................  1247
Prostatitis......................................................  1206
Public Education Activities......................................  1216
Public/Private Research Partnerships.............................  1255
Research Centers.................................................  1215
Restoring Insulin Production.....................................  1187
Review Process for Clinical Studies..............................  1226
Risk for Diabetes................................................  1239
Small Business Research..........................................  1197
Special Research Areas in Diabetes...............................  1192
Statement of the Director........................................  1180
Stress in Diabetes...............................................  1185
Treating and Preventing Diabetes.................................  1223
Ulcer Diagnosis and Treatment....................................  1203
Ulcers.......................................................1199, 1228
Upcoming Diabetes Conference.....................................  1192
Urology......................................................1206, 1218
Women's Health...................................................  1193

                      National Library of Medicine

Bioinformatics...................................................  1325
Electronic Patient Records.......................................  1338
Genetic Databases............................................1336, 1346
Gpra Standards...................................................  1341
High Performance Computing...................................1337, 1347
Human Genome Map.............................................1316, 1324
Iaims Program....................................................  1337
Internet.........................................1312, 1326, 1331, 1339
Justification of The Budget Estimates............................  1355
National Information Infrastructure..............................  1309
Next Generation Internet Initiative..........................1326, 1352
Opening Statement................................................  1309
Outreach.....................................................1324, 1330
Personal Services Contracts......................................  1337
Project Phoenix..................................................  1342
Pubmed.......................................................1339, 1348
Statement of the Director........................................  1319
Telemedicine.........................1314, 1327, 1328, 1334, 1343, 1351
Toxicology Center................................................  1337
Underserved Populations..........................................  1345
User Fees........................................................  1349
Video Tapes......................................................  1349
Visible Humans...................................................  1310
World Wide Web...............................................1333, 1343

                 National Inatitute of Nursing Research

Aging............................................................  1402
Alzheimer's Disease..............................................  1400
Breast Cancer....................................................  1399
Breast Self-Exams................................................  1389
Cardiovascular Disease...........................................  1378
Cardiovascular Disease in Children...............................  1396
Chronic Illness..................................................  1395
Clinical Research Conference.....................................  1385
Collaborative Efforts............................................  1401
Communication with Health Care Providers.........................  1384
Counseling for Genetic Screening.................................  1389
Cultural Diversity...............................................  1378
Currency with Research...........................................  1386
End of Life......................................................  1379
End of Life Care.................................................  1397
Future Research Emphases.........................................  1379
FY98 Budget Request..........................................1379, 1413
Infant Colic.....................................................  1396
Irritable Bowel Syndrome.........................................  1378
Justification of the Budget Estimates............................  1384
Minority and Women's Health......................................  1406
Minority Researchers.............................................  1403
Nurse Education Act--FY 1988 Budget..............................  1393
Nursing and Oncology.............................................  1410
Nursing Publications.............................................  1385
Opening Statement................................................  1377
Opportunities for Ethnic Nurses..................................  1392
Outreach and Information Dissemination...........................  1405
Pain Research................................................1377, 1399
Professional Judgment Budget.....................................  1384
Provider Care....................................................  1398
Quality of Care..................................................  1393
Quality of Life..................................................  1394
Research Training Issues.........................................  1387
Rural and Ethnic Populations.....................................  1391
Sister to Sister Study...........................................  1405
Stroke...........................................................  1406
Targeted Research................................................  1404
Transplantation..................................................  1379
Traumatic Brain InJury........................................1386, 397
Women's Health...................................................  1411
Women's Health Issues............................................  1388

                      Fogarty International Center

Biodiversity Program.............................................  1455
Budget Increase..............................................1460, 1461
Emerging Infectious Diseases.................................1463, 1464
External Panel Review............................................  1452
Fellowship Programs..........................................1450, 1451
Former Soviet Union--State of Science............................  1454
Human Frontier Science Program...................................  1453
International Agreements.........................................  1460
International Activities Expenditures........................1458, 1459
Justification of Budget Estimates.............................1466-1489
Minority International Research Training Program.............1462, 1463
Opening Statement................................................  1443
Other Countries Leading in Biomedical Research...................  1450
Vitamin A Supplementation....................................1464, 1465

 National Institute of Arthritis and Musculoskeletal and Skin Diseases

Antibiotic Treatment.............................................  1507
AIDS Research....................................................  1529
Arthritis Treatment..............................................  1522
Breast Cancer and Osteoporosis...................................  1535
Breast Implants and Autoimmune Diseases..........................  1512
Budget Estimates, Justification of...............................  1537
Budget Request, FY 1998..........................................  1494
Cartilage Repair.................................................  1512
Central Nervous System Lupus.....................................  1514
Clinical Research................................................  1530
Clinical Trials..................................................  1533
Collaborative Research...........................................  1515
Depression and Osteoporosis......................................  1513
Epidemiological Data Concerning Repetitive Motions Injuries......  1520
Ergonomics...................................................1500, 1502
Fibrodysplasia Ossificians Progressiva...........................  1514
Funding for Disease Areas........................................  1517
Gender and Autommunity...........................................  1511
Gulf War Syndrome................................................  1513
Human Cloning....................................1502, 1503, 1505, 1532
Health Status....................................................  1528
Low Back Pain....................................................  1518
Minority Health Research.........................................  1530
Musculoskeletal Disorder.....................................1500, 1518
Osteoarthritis...................................................  1526
Osteoporosis...........................................1493, 1509, 1510
Psoriasis........................................................  1535
Professional Judgment Budget.....................................  1507
Repetitive Motion Injury.....................................1499, 1525
Research Centers.................................................  1517
Research Opportuoities...........................................  1522
Research Challenges..............................................  1532
Rheumatoid Arthritis.............................................  1493
Sexualy Transmitted Diseases.....................................  1536
Skin Cancer..................................................1493, 1524
Statement of the Director....................................1491, 1495
Stress and Arthritis.............................................  1511
Success Rate.....................................................  1536
Systemic Lupus Erythematosus.................................1493, 1528
Total Joint Replacement..........................................  1492
Trauma Injuries..................................................  1521

                 National Center for Research Resources

National Center for Research Resources.......................1573, 1604
Broader Participation............................................  1602
Clinical Research................................................  1591
Chimpanzees in Research..........................................  1579
Chimpanzee Retirement........................................1580, 1581
Coordination of Imaging Activities...............................  1586
Education........................................................  1597
Euthanasia of Research Animals...................................  1583
Extramural Construction..........................................  1600
Extramural Facilities Construction...............1585, 1587, 1588, 1592
Extramural Programs..............................................  1596
Faculty Investigators............................................  1598
Funding for Selected Programs....................................  1588
General Clinical Research Centers................................  1583
Interest in Biomedical Research..................................  1590
Introduction of Witnesses........................................  1573
Minority and Women's Health......................................  1600
Minority Research Investigators..................................  1597
NCRR Appropriations..............................................  1595
NCRR Strategic Plan..............................................  1582
Near Infrared (University of Kentucky)...........................  1590
Office of Research on Minority Health............................  1597
Opening Statement............................................1573, 1575
Pipeline.........................................................  1596
RCMI Clinical Initiative.........................................  1601
RCMI Cofunding...................................................  1600
Regional Primate Research Centers............................1586, 1587
Research Centers in Minority Institutions........................  1592
Research Infrastructure in Minority Institutions.................  1595
Review Committees................................................  1598
Shared Instrumentation Grants....................................  1588
Use of Animals in Research.......................................  1579
Virtual Laboratories.............................................  1585

        National Institute of Child Health and Human Development

AIDS.............................................................  1681
Alcohol and Drug Addiction.......................................  1673
Asthma...........................................................  1649
Autism...........................................................  1643
Autism Centers...................................................  1644
Autism Research Investigators....................................  1644
Child Day Care...................................................  1674
Childhood Nutrition..............................................  1667
Children with Learning Disabilities..............................  1660
Children with Reading Disabilities...............................  1655
Clinical and Basic Research......................................  1689
Clinical Research................................................  1665
Clinical trials..................................................  1691
Cloning..........................................................  1691
Diabetes Research................................................  1679
Drug Dosages for Children & Pediatric Pharmacology Res. Units....  1653
Drug Use before Pregnancy........................................  1657
Early Child Care.................................................  1646
Funding--Disease Areas...........................................  1671
Grant Funding....................................................  1666
Health Status of Minority Children...............................  1684
Infant Mortality.................................................  1676
Infertility Research.............................................  1656
Infertility......................................................  1673
Intervention Programs............................................  1660
Intramural Clinical Research.....................................  1669
Justification....................................................  1693
Learning Disabilities............................................  1688
Learning Disabled Children.......................................  1644
Learning to Read.............................................1648, 1654
Maternal Mortality...............................................  1656
Middle School Children...........................................  1662
Minority Representation in Basic Research and Training...........  1689
National Center for Medical Rehabilitation Research..............  1672
Obesity Research.................................................  1680
Opening Statement................................................  1635
Perinatology Research--District of Columbia......................  1665
Phonics Based Reading System.....................................  1659
Phonics Based System.............................................  1661
Phonics..........................................................  1663
Premature Labor and Delivery.....................................  1646
Prevention Problem Behavior......................................  1651
Protection from Asthma...........................................  1650
Pulmonary Hemorrhage in Infants..................................  1687
Research Bottlenecks.............................................  1690
Research Centers.................................................  1670
Research on Fatherhood...........................................  1663
Research Opportunities...........................................  1685
SIDS Back to Sleep Campaign......................................  1645
SIDS.........................................................1670, 1688
Spinal Cord Injury...............................................  1668
Strengthening Families...........................................  1670
Teenage Drug Use and Pregnancy...................................  1658
Vaccine Development..............................................  1666
Web Page.........................................................  1649

                 National Institute of Dental Research

50th Anniversary.................................................  1772
AIDS/HIV.........................................................  1775
Biomimetics......................................................  1749
Bone Research................................................1762, 1780
Cleft Palate.....................................................  1755
Clinical Trials..................................................  1768
Clinical Research................................................  1777
Cloning..........................................................  1778
Congressional Justification......................................  1782
Dental Amalgams..................................................  1748
Dentist Scientist Program........................................  1756
Diabetes, Oral Complications of..................................  1750
Flouridation.................................................1749, 1754
Future Expectations..............................................  1750
Health Status....................................................  1767
Immune Systems...................................................  1770
Introduction of Witneses.........................................  1737
Knowledge ``Bottleneck''.........................................  1771
Medicare Coverage for Dental Care................................  1755
Minorities, Improving the Health of..............................  1776
Minority Groups, Reaching Ethnic and.............................  1762
NIDR Strategic Plan..............................................  1759
Opening Statement................................................  1737
Oral Cancer............................................1757, 1764, 1769
Osteoporosis and Oral Bone Loss..................................  1751
Pain Research................................................1752, 1780
Priority Setting.................................................  1760
Public Education.............................................1774, 1780
Research Centers.............................................1759, 1765
TMD..........................................................1750, 1753

                  National Institute of Mental Health

Basic Neuroscience...............................................  1852
Brain as the Touchstone of NIMH Research......................1828-1829
Brain Development and Mental Illness..........................1840-1842
Children............................................1854-1856 1866-1867
    Prevention of Childhood Mental Illness....................1823-1824
    Proceedings of Workshop (Inclusion of Children in Clinical 
      Research)...............................................1837-1839
    Research Needed on Childhood Disorders....................1829-1830
    Treatment of Mental Illness in Children...................1834-1840
Circadian Rhythms and Mental Illness..........................1843-1844
Clinical and Services Research...................................  1852
Eating Disorders.............................1844-1845, 1849-1850, 1856
Funding Amounts FY 1996--FY 1998.................................  1846
Gene Therapy..................................................1868-1869
Global Burden of Disease......................................1818-1819
Table 1..........................................................  1811
Inclusion of Women and Minorities.............................1865-1866
Initiative to Track Enrollment of Women and Minorities...........  1827
Justification of Budget Estimation............................1870-1913
Managed Care..................................................1857-1858
Mental Illness in the U.S.....................................1859-1862
Mental-Physical Relationship..................................1867-1868
Minority Employment..............................................  1826
Minority Investigators and Research Subjects..................1825-1827
Needle Exchange Programs......................................1821-1822
New Drugs for Schizophrenia...................................1831-1832
Nutritional Factors...........................................1850-1851
Opening Statement of Director.................................1809-1817
Prevention of Childhood Mental Illness........................1823-1824
Proceedings of Workshop (Inclusion of Children in Clinical 
  Research)...................................................1837-1839
Regulation of Emotion............................................  1853
Relationship of Mental Illness to Other Physical Illnesses....1842-1843
Research Needed on Childhood Disorders........................1829-1830
Schizophrenia....................................................  1859
Setaside for Mental Health Services Research.....................  1821
Sexual Abstinence in AIDS Prevention.............................  1823
Social Work Research.............................................  1830
Suicide and Suicide Prevention................................1862-1865
Training.........................................................  1858
Training of Minority Researchers.................................  1831
Translation of Research into Treatment........................1832-1834
Treatment of Mental Illness in Children.......................1834-1840
UNOCCAP (Use, Needs, Outcomes, and Costs for Child and Adolescent 
  Populations)................................................1819-1820
Victims of Torture............................................1846-1849
Vulnerability....................................................  1854
World-wide Burden of Disease (Table 1)...........................  1811
World-wide Burden of Depression...............................1824-1825

                      National Institute on Aging

Aging--The Exercise and Nutrition Linkage........................  1955
AIDS.............................................................  1963
Alzheimer's Disease and Ibeprofen................................  1941
Alzheimer's Disease..................1915, 1934, 1935, 1948, 1954, 1960
Alzheimer's Disease Genetic Discoveries..........................  1917
Biological Processes.............................................  1958
Biology of Aging.................................................  1920
Caloric Restriction..............................................  1949
Collaborative Activities.........................................  1959
Demographic Reaearch.............................................  1934
Demography of Aging..............................................  1921
Disability Research..........................................1933, 1956
Embryo Research..................................................  1936
Falls in the Elderly.............................................  1939
Genetic Research.................................................  1943
Health Care Savings..............................................  1937
Health Status and Clinical Trial Participation...................  1861
Hypertension.....................................................  1952
Immune System....................................................  1963
Long Term Care...............................................1943, 1965
Managed Care.....................................................  1955
Menopause........................................................  1964
Number of Chronically Disabled Americans Age 65 and Over.........  1924
Nursing Homes--Individualized Care...............................  1950
Opening Statement............................................1915, 1926
Osteoporosis.....................................................  1937
Predictive Testing...............................................  1944
Projected Population Age 100 Years and Over......................  1931
Prolonging Independence-Delaying Disability......................  1956
Prostrate Cancer.................................................  1940
Protective and Risk Factors for Alzheimer's Disease..............  1919
Quality of Life..................................................  1936
Research Centers.................................................  1946
U.S. Life Expectancy at Age 85, 1900-1995........................  1932
Unraveling Longevity.............................................  1963
World Population by Age..........................................  1922

        National Institute of Neurological Disorders and Stroke

Accident Prevention..............................................  2048
Alzheimer's Disease..............................................  2039
Amyotrophic Lateral Sclerosis....................................  2022
Brain Diseases in Children.......................................  2039
Childhood Diseases...............................................  2035
Clinical Research................................................  2041
Clinical Trials..................................................  2044
Cloning..........................................................  2043
Congressional Justification......................................  2051
Diseases of Aging................................................  2010
Epilepsy Research............................................2033, 2040
Estrogen and Stroke..............................................  2020
Future of Brain Research.........................................  2011
Human Embryo Research............................................  2023
Introduction of Witnesses........................................  2001
Knowledge Bottleneck.............................................  2042
Mad Cow Disease and Prion Hypothesis.............................  2021
Minority Research Investigators..................................  2037
Multiple Sclerosis...............................................  2034
Neurodegenerative Disease Initiative.........................2018, 2019
New Treatments and Discoveries...................................  2038
Nicotine, Possible Therapeutic Effects of........................  2020
NINDS Budget Increases...........................................  2012
Opening Statement................................................  2001
Parkinson's Disease..........................................2016, 2028
Prion Hypothesis and Mad Cow Disease.............................  2021
Research Centers Grants, NINDS...................................  2026
Specific Disease Funding.........................................  2026
Spinal Cord Injury Research......................2012, 2016, 2024, 2049
Statement of Director............................................  2005
Stroke Research......................2010, 2020, 2031, 2036, 2047, 2049
Targeted Research................................................  2018

             National Institute of General Medical Sciences

Biology of the Brain Initiative..................................  2121
Budget Policy....................................................  2142
Budget Tables....................................................  2144
Cell Biology and Biophysics......................................  2130
Compliance with NRSA Payback Requirement.........................  2112
Employment Prospects for Research Trainees.......................  2110
Evaluation of National Research Service Award Training...........  2112
Gender Differences in Response to Trauma.........................  2115
Genetics and Developmental Biology...............................  2133
Goals of the Director............................................  2108
Goals to be Accomplished and Priority-Setting Process............  2140
High Risk Research...............................................  2109
Inclusion of Underrepresented Minorities.........................  2118
Innovations in Management and Administration.....................  2141
Interim Funding..................................................  2108
Introduction.....................................................  2123
Justification of Budget Estimates................................  2124
MARC Program.................................................2122, 2138
MBRS and HBCU Participation......................................  2120
MBRS Program.................................................2119, 2137
Medical Scientist Training Program...............................  2112
Minority Opportunities in Research...........................2117, 2137
New Approaches to Pathogenesis...................2132, 2133, 2134, 2135
New Investigators................................................  2110
NIGMS Organizational Chart.......................................  2125
Opening Statement................................................  2095
Other Areas of Interest..........................................  2141
Percentage of Ph.D's Awarded to Minorities.......................  2114
Pharmacology Research Associate Program..........................  2140
Pharmacology, Physiology, and Biological Chemistry...............  2135
Protease Inhibitors..............................................  2118
Rationale for Stipend Increases..................................  2112
Research Advances................................................  2130
Research Areas Pursued by Young Investigators....................  2113
Research in Chemistry and Physical Sciences......................  2108
Research Training Collaborations with Industry...................  2111
Scientists Employed as Temporary Workers.........................  2111
Special Initiatives..............................................  2138
Special Programs.................................................  2137
Stimulation of Research Fields...................................  2110
Stipend Levels...................................................  2116
Story of Discovery: From Chemistry to Gene Therapy...............  2129
Training Programs of the Howard Hughes Medical Institute.........  2114

                        Office of AIDS Research

AIDS Statistics..................................................  2163
AIDS in Minority Populations.....................................  2170
AIDS in Minority Populations.....................................  2203
AIDS Research Proportion of NIH Funding..........................  2171
AIDS Research Addressing Minorities..............................  2170
AIDS Research Proportion of Total NIH Request....................  2167
Benefits of AIDS Research to Other Diseases......................  2164
Changing Faces and Scientific Priorities.........................  2190
Clinical Trials of New Therapeutic Agents........................  2188
Cooperation with Industry........................................  2183
Demographic Groups With Increasing AIDS Cases....................  2163
Direct Support for OAR...........................................  2174
Federal Biomedical Research Plan.................................  2175
Flexibility for OAR to Change ICD Distributions..................  2165
Inclusion of Minorities in AIDS Research.........................  2193
Justification................................................2205, 2248
Latest Advances in AIDS/HIV Therapies............................  2202
Minorities on Research Training Grants...........................  2168
Minority Participation in Clinical Trials........................  2197
Needle Exchange..................................................  2187
NIH Panel on Principles of Therapy for HIV Infection.............  2181
OAR Discretionary Fund...........................................  2176
OAR Collaboration with ORMH and ORWH.............................  2192
Opening Statement................................................  2155
Pediatric AIDS...................................................  2178
Prevention Science Working Group.................................  2172
Projected AIDS Deaths Without a Vaccine..........................  2164
Proportional Increases for NIH Institutes........................  2171
Prospects for International Availability of an AIDS Vaccine......  2163
Recipients of AIDS Research Funds................................  2177
Reluctance of Monitories to Participate in Clinical Trials.......  2171
Research Plan....................................................  2186
Role of the Office of the Director...............................  2167
Small Business Innovation Research Grants (SBIR).................  2196
Social and Behavioral Factors of AIDS............................  2192
Status of Minority and Women's Health............................  2167
Status of the Development of an AIDS Vaccine.....................  2186
The Investment in Minority Research Programs.....................  2196
The New Generation of AIDS Researchers...........................  2172
Three Percent Transfer Authority.................................  2166
Total AIDS Research Funding......................................  2166
Training for HIV Researchers.....................................  2184
Witnesses, Introduction of.......................................  2155

          Offfce of the Director and Buildings and Facilities

Administrative Cost Study........................................  2264
Area Program.....................................................  2301
Behavioral Research..............................................  2335
Budget Request for ORMH..........................................  2338
Building and Facilities..........................................  2257
Child Abuse and Neglect..........................................  2324
Cholestin........................................................  2262
Clinical Research Issues.........................................  2304
Concluding Remarks...............................................  2292
CRC Advanced Appropriations......................................  2262
CRC Cost Estimates...............................................  2263
Credit Card Purchases............................................  2303
Decrease in OD Funding Level.....................................  2323
Electronic Grant Submissions.....................................  2311
Employment Separation Rates......................................  2345
Enrollment for Women's Health Initiative.........................  2308
Extramural Associates Research Development Awards Program........  2328
Extramural Biomedical Facility Construction Research 
  Infrastructure.................................................  2344
Grant Scoring....................................................  2310
Herbal Medications...............................................  2266
Inclusion of Women and Minorities in Clinical Trials...2309, 2332, 2347
Institute of Medicine............................................  2343
Introduction of Witness..........................................  2249
Justification of Budget Estimates................................  2358
Listing of NIH Facilities........................................  2290
MARC and MBRS Programs.......................................2270, 2334
Medical Nutrition Therapy........................................  2266
Minority Health Initiative.......................................  2300
Minority Programs................................................  2336
    Funding for Minority Programs............................2338, 2345
    Funding for Minority Researchers.............................  2271
    Inclusion of Minorities in Research..........................  2330
    Increasing Minority Participation............................  2327
    Minorities in Clinical Trials................................  2351
    Minority Funding.........................................2270, 2291
    Minority Research Grants.....................................  2272
    Minority Researchers.........................................  2337
    Recruitment and Retention of Minorities......................  2350
    Representation of Minorities in Research Protocols...........  2349
    Underrepresented Minorities..............................2326, 2352
National Agenda on Research on Women's Health....................  2269
National Biomedical Research Service Positions...................  2298
National Foundation for Biomedical Center........................  2315
New Component for Women's Health Initiative......................  2308
NIH Organizational Structure.....................................  2289
Office of Alternative Medicine.........................2265, 2318, 2323
    Alternative Medicine Research................................  2316
    Office of Alternative Medicine Budget........................  2301
    Office of Alternative Medicine Clearinghouse.................  2302
Office of Behavioral and Social Sciences Research................  2315
Office of Dietary Supplements....................................  2266
Office of Research on Minority Health and NIEHS Collaborations...  2293
Opening Statement................................................  2249
Opening Statement--Dr. Kirschstein...............................  2251
ORMH-Standing Advisory Committee.................................  2341
ORWH's Budget Level..............................................  2268
Pediatric and Neurodegenerative Initiatives......................  2306
Plans for New Institutes.........................................  2290
Progress of Minority and Women's Health..........................  2326
Quotas...........................................................  2274
Radioisotope Contamination.......................................  2295
Radiology and Imaging............................................  2262
Recombinant DNA Advisory Committee...............................  2314
Renovation of Clinical Center....................................  2263
Research Needs of Children.......................................  2323
Research of Human Subjects.......................................  2313
Re-Submission of Unfunded Grant Applications.....................  2313
SBIR Grants......................................................  2295
Science Education Activities at the NIH..........................  2275
Senior Biomedical Research Service Positions.....................  2295
Status of Minority and Women's Health............................  2326
The Ryan Commmsion...............................................  2316
Unified Information Technology System............................  2264
Women and Minorities in Biomedical Careers.......................  2333
Women in Biomedical Careers......................................  2269
Women's Health Initiative........................................  2298
Adequacy of Spending on Diabetes.................................  2484
Advice In Decision-Making........................................  2435
AIDS:
    Expenditures for AIDS and Other Diseases.....................  2473
    NIH Expenditures on AIDS Research............................  2494
    Research Coordination........................................  2482
    Research Funding.............................................  2495
    Scientific Opportunity.......................................  2471
    Stabilizing Infections.......................................  2494
    Vaccine Initiative...........................................  2500
AIDS and Scientific Opportunities................................  2471
AIDS Research Coordination.......................................  2482
AIDS Research Funding............................................  2495
AIDS Vaccine Initiative..........................................  2500
Areas of Emphasis................................................  2485
Biography, William E. Paul, M.D..................................  2468
Biography, Harold E. Varmus, M.D.................................  2459
Biography, Dennis Williams, Ph.D.................................  2470
Budget:
    Constraints..................................................  2436
    Doubling NIH's...............................................  2497
    NIH Budget for 1998..........................................  2508
Budgetary Constraints............................................  2436
Cancer:
    Mortality Rates..............................................  2488
    Ovarian......................................................  2501
    Ovarian......................................................  2503
    Ovarian, Detection of........................................  2490
    Research Article.............................................  2489
Cancer Mortality Rates...........................................  2488
Cancer Research Article..........................................  2489
Clinical Research............................................2501, 2502
Clinical Research Report.........................................  2505
Coding for Parkinson's Research..................................  2477
Commitment Base..............................................2434, 2476
Committee Report Language........................................  2472
Congressional Biomedical Research Caucus.........................  2475
Congressional Support............................................  2503
Cost Savings from Research.......................................  2500
Criteria For Decision-Making.....................................  2434
Curriculum Vitae, Phillip Gorden, M.D............................  2467
Curriculum Vitae, Richard Klausner, M.D..........................  2460
Curriculum Vitae, Claude Lenfant, M.D............................  2465
Detection of Ovarian Cancer......................................  2490
Disease:
    Imprecision of Coding........................................  2435
    Trans-NIH Categories.........................................  2478
Doubling NIH's Budget............................................  2497
Drug Rehabilitation..............................................  2506
Early Childhood Development......................................  2506
Earmarks in DOD for Research.....................................  2507
Effect of Public and Congressional Input.........................  2499
Expenditures for AIDS and Other Diseases.........................  2473
Factors in Resource Allocation...................................  2492
Factors In Resource Allocation...................................  2472
Final Authority for Decision-Making..............................  2486
Funding for Autism...............................................  2489
Funding for Population Research..................................  2480
Genetics Research Opportunities..................................  2496
Imprecision of Disease Coding....................................  2435
Information Dissemination........................................  2503
Information Dissemination of Reaearch Findings on Learning 
  Disabilities...................................................  2507
Information Transfer.............................................  2499
Information Transfer in Prevention...............................  2506
Information Transfer to Other Agencies...........................  2506
Learning Disabilities:
    Research on..................................................  2507
    Information Dissemination of Reaearch Findings on............  2507
Limitations To Planning Science..................................  2434
NIH Budget for 1998..............................................  2508
NIH Definitions of Selected Population Groups....................  2479
NIH Health Funding By Group......................................  2481
NIH Expenditures on AIDS Reaearch................................  2494
NIH Resource Allocation Procedures...............................  2485
NIH Spending On Minority Initiatives.............................  2479
Nobel Laureates..................................................  2474
Observations And Principles For Resource Allocation..............  2433
One Percent Transfer Authority...................................  2486
Opening Statement of the Director NIH............................  2433
ORWH's Priority Setting Process..................................  2504
Ovarian Cancer................................................250, 2503
Pace Of Research.................................................  2437
Parkinson's Disease..............................................  2436
Parkinson's Disease And Related Research Awards, FY 96...........  2457
Politics and Research............................................  2501
Prepared Statement Of Director, NIH..............................  2439
Priority Setting.................................................  2493
Priority Setting Interaction of ORWH and NIH.....................  2505
Public Relations for NIH.........................................  2482
Research on Learning Disabilities................................  2507
Resource Allocation By NIH.......................................  2437
Science Cannot Be Purchased......................................  2436
Stabilizing AIDS Infections......................................  2494
Statement of the Hon. George R. Nethercutt, Jr...................  2484
Statement of the Hon. George Gekas...............................  2476
Statement of the Hon. Patsy Mink.................................  2490
Statement of the Hon. Constance A. Morella.......................  2498
Strategic Plan...................................................  2478
Technology Transfer..............................................  2502
Trans-NIH Disease Categories.....................................  2478
Unanticipated Research Results ..................................  2496