[House Hearing, 106 Congress]
[From the U.S. Government Publishing Office]



                 DEPARTMENTS OF LABOR, HEALTH AND HUMAN

               SERVICES, EDUCATION, AND RELATED AGENCIES

                        APPROPRIATIONS FOR 2001

_______________________________________________________________________

                                HEARINGS

                                BEFORE A

                           SUBCOMMITTEE OF THE

                       COMMITTEE ON APPROPRIATIONS

                         HOUSE OF REPRESENTATIVES

                       ONE HUNDRED SIXTH CONGRESS

                             SECOND 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               STENY H. HOYER, Maryland
 ERNEST J. ISTOOK, Jr., Oklahoma    NANCY PELOSI, California
 DAN MILLER, Florida                NITA M. LOWEY, New York
 JAY DICKEY, Arkansas               ROSA L. DeLAURO, Connecticut
 ROGER F. WICKER, Mississippi       JESSE L. JACKSON, Jr., Illinois
 ANNE M. NORTHUP, Kentucky          
 RANDY ``DUKE'' CUNNINGHAM,         
California                          

 NOTE: Under Committee Rules, Mr. Young, 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, Carol Murphy, Susan Ross Firth,
             and Francine Mack-Salvador, Subcommittee Staff
                                ________

                                 PART 4A

                      NATIONAL INSTITUTES OF HEALTH

                              

                                ________

         Printed for the use of the Committee on Appropriations

                                ________

                     U.S. GOVERNMENT PRINTING OFFICE
 64-155                     WASHINGTON : 2000

                       COMMITTEE ON APPROPRIATIONS

                   C. W. BILL YOUNG, Florida, Chairman

 RALPH REGULA, Ohio                 DAVID R. OBEY, Wisconsin
 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            STENY H. HOYER, Maryland
 TOM DeLAY, Texas                   ALAN B. MOLLOHAN, West Virginia
 JIM KOLBE, Arizona                 MARCY KAPTUR, Ohio
 RON PACKARD, California            NANCY PELOSI, California
 SONNY CALLAHAN, Alabama            PETER J. VISCLOSKY, Indiana
 JAMES T. WALSH, New York           NITA M. LOWEY, New York
 CHARLES H. TAYLOR, North Carolina  JOSE E. SERRANO, New York
 DAVID L. HOBSON, Ohio              ROSA L. DeLAURO, Connecticut
 ERNEST J. ISTOOK, Jr., Oklahoma    JAMES P. MORAN, Virginia
 HENRY BONILLA, Texas               JOHN W. OLVER, Massachusetts
 JOE KNOLLENBERG, Michigan          ED PASTOR, Arizona
 DAN MILLER, Florida                CARRIE P. MEEK, Florida
 JAY DICKEY, Arkansas               DAVID E. PRICE, North Carolina
 JACK KINGSTON, Georgia             MICHAEL P. FORBES, New York
 RODNEY P. FRELINGHUYSEN, New Jersey CHET EDWARDS, Texas
 ROGER F. WICKER, Mississippi       ROBERT E. ``BUD'' CRAMER, Jr., 
 GEORGE R. NETHERCUTT, Jr.,         Alabama
Washington                          MAURICE D. HINCHEY, New York
 RANDY ``DUKE'' CUNNINGHAM,         LUCILLE ROYBAL-ALLARD, California
California                          SAM FARR, California
 TODD TIAHRT, Kansas                JESSE L. JACKSON, Jr., Illinois
 ZACH WAMP, Tennessee               CAROLYN C. KILPATRICK, Michigan
 TOM LATHAM, Iowa                   ALLEN BOYD, Florida
 ANNE M. NORTHUP, Kentucky          
 ROBERT B. ADERHOLT, Alabama        
 JO ANN EMERSON, Missouri           
 JOHN E. SUNUNU, New Hampshire      
 KAY GRANGER, Texas                 
 JOHN E. PETERSON, Pennsylvania     
 VIRGIL H. GOODE, Jr., Virginia     

                 James W. Dyer, Clerk and Staff Director

                                  (ii)

                            C O N T E N T S

                              ----------                              

                               LABOR/HHS

                               VOLUME 4A

                                                                   Page

NIH Overview.....................................................     1

National Cancer Institute........................................   221

National Institute on Deafness and Other Communication Disorders.   545

National Human Genome Research Institute.........................   625

National Institute of Dental and Craniofacial Research...........   735

National Library of Medicine.....................................   819

National Institute of Child Health and Human Development.........   875

National Institute of General Medical Sciences...................   997

Fogarty International Center.....................................  1069

National Institute on Drug Abuse.................................  1139

National Institute on Alcohol Abuse and Alcoholism...............  1219

                                 (iii)

 
DEPARTMENTS OF LABOR, HEALTH AND HUMAN SERVICES, EDUCATION, AND RELATED 
                    AGENCIES APPROPRIATIONS FOR 2001

                                        Tuesday, February 15, 2000.

                     NATIONAL INSTITUTES OF HEALTH

                               WITNESSES

RUTH L. KIRSCHSTEIN, ACTING DIRECTOR, NATIONAL INSTITUTES OF HEALTH
YVONNE MADDOX, ACTING DEPUTY DIRECTOR, NIH
WENDY BALDWIN, DEPUTY DIRECTOR FOR EXTRAMURAL RESEARCH, NIH
MICHAEL M. GOTTESMAN, DEPUTY DIRECTOR FOR INTRAMURAL RESEARCH, NIH
ANTHONY ITEILLAG, DEPUTY DIRECTOR FOR MANAGEMENT, NIH
SUSAN E. QUANTIUS, ASSOCIATE DIRECTOR FOR BUDGET, NIH
DENNIS P. WILLIAMS, DEPUTY ASSISTANT SECRETARY, BUDGET, DHHS

                           Opening Statement

    Mr. Porter. The subcommittee will come to order. We 
continue our hearings on the budget for the Department of 
Health and Human Services this morning with the National 
Institutes of Health. We are very pleased to welcome Dr. Ruth 
Kirschstein, the Acting Director, one of our favorite people at 
an institution filled with favorite people.
    Ruth, we are delighted to have you here this morning. I 
want to welcome all the Directors and the people at the front 
table, with a special welcome to our former staffer, Sue 
Quantius, who is now your Budget Director at NIH. We are 
delighted to see you, Sue, as well.
    Dr. Kirschstein, if you would proceed with your statement, 
and then we will go to questions.
    Dr. Kirschstein. Thank you very much, Mr. Chairman. I want 
to, before I start my statement, introduce the people at the 
table. To my far left is Mr. Anthony Iteillag, who is the 
Deputy Director for Management; to his right is Dr. Michael 
Gottesman, the Deputy Director for Intramural Research; to his 
right, Dr. Wendy Baldwin, the Deputy Director for Extramural 
Research; and then I particularly want to introduce the person 
that I appointed as my Acting Deputy Director, Dr. Yvonne 
Maddox, who is to my immediate left; you have already 
recognized Sue Quantius, and we are delighted to have her; and, 
of course, Dennis Williams from the Department. And then I am 
very pleased to have behind me all the Institute and Center 
directors who have been remarkably supportive of me.
    Mr. Chairman, I am honored to appear before the 
subcommittee to present the President's budget for NIH for 
fiscal year 2001. And as you know, although this is the first 
time I have appeared to testify about the overall NIH budget, 
it has been my privilege to appear before this subcommittee 
annually for 19 years as the Director of the National Institute 
of General Medical Sciences and for six years as the Deputy 
Director. I am especially gratified, Mr. Chairman, to appear 
before you as you consider the NIH budget proposal for the last 
time as the head of this panel. Your support, in particular, 
and the support of all the members of the subcommittee has made 
a substantial difference in improving the public's health and 
well-being.
    Now, Mr. Chairman, all of us, we at NIH, Members of 
Congress, and the citizens we serve, have similar expectations 
for medical research. We want better ways to diagnose and 
treat, and, in the long run, prevent and cure disease. And we 
want the Federal dollars invested in medical research to result 
in the fulfillment of these expectations.
    In the last century, the scientific community, both public 
and private, worked in collaboration to prevent a devastating 
infectious disease, polio myelitis. And I was very fortunate to 
be at the forefront of the development of the polio vaccine, 
which was a truly monumental achievement. Other outstanding 
medical achievements followed in that century: organ 
transplantation, life-extending and life-saving cancer 
therapies, the identification of the AIDS virus and the drugs 
to treat AIDS, and discoveries involving the chemicals in the 
brain that are important in drug and alcohol addiction and 
mental illness, as well as identification of genes responsible 
for a large number of our normal functions and genetic 
diseases, such as Huntington's disease, cystic fibrosis, and 
certain forms of deafness, as well as many more. My colleagues 
will be telling you about them.
    In his budget plan for fiscal year 2001, the President is 
requesting $18,800,000,000 for NIH, an increase of 
$1,000,000,000, or 5.6 percent more than fiscal year 2000. The 
amount for NIH in fiscal years 1999 and 2000, both nearly 15 
percent increases, were dramatic and unprecedented and have 
allowed us to undertake many new and important programs. The 
funds requested for fiscal year 2001 will permit us to continue 
the initiatives of the past two years and allow us to begin new 
ones as well.
    We are very pleased that the public, the Congress, and the 
Administration place a high value on good health and understand 
the role that NIH and medical research has played in the health 
of the American public. We are aware, however, of our need to 
deliver to the public the two things that it most wants: 
research advances, year after year, that continue to improve 
the health of all members of society; and, secondly, assurance 
that we spend the public's money wisely.
    So let me mention just a few of the advances that occurred 
during the past year.


                           RESEARCH ADVANCES


    First, completion of the first sequence of a full human 
chromosome, chromosome 22. This chromosome has been implicated 
in the immune system function, congenital heart disease, 
schizophrenia, mental retardation, birth defects, and several 
cancers, including leukemia. And its 33,400,000 nucleotides 
comprise the longest continuous stretch of DNA that has ever 
been deciphered.
    Second, the discovery that months before symptoms appear, 
women who develop a precursor to a potentially fatal 
complication of pregnancy, eclampsia, have an imbalance between 
two chemicals, prostacyclin and thromboxane, which control 
blood pressure. Eclampsia and its precursor preeclampsia, are 
characterized by high blood pressure, excessive weight gain, 
severe headaches, and convulsions. New treatments to correct 
this chemical imbalance may prevent this severe condition. 
There is currently no therapy.
    Next, the identification of the gene that causes the 
Salmonella bacteria to be deadly. Salmonella that do not have 
this particular gene do not, when injected into mice, kill 
them. But, in addition, the Salmonella that are disarmed of 
this gene serve to provide protection against the deadly 
organism when the mice are injected with it. And this will open 
up possibilities for development of new antibiotics and 
vaccines.
    You will hear over the next several weeks from the 
Institute and Center directors who will provide you with many 
more examples.

                          FUNDING ALLOCATIONS

    Now to assure that funding will be wisely and well spent, 
we have developed a set of principles related to, one, 
responding to public health needs; next, studying a wide range 
of diseases; capitalizing on previous discoveries; seeking 
advice broadly, and particularly from the public; ensuring that 
we have first-rate scientists in the Nation's workforce as well 
as first-rate facilities; and lastly, but truly foremost, 
committing support to science of the highest calibre.
    Thus, in fiscal year 2001, we propose to emphasize clinical 
research, research on diseases and disorders that inordinately 
affect minority and underserved populations, the neurosciences, 
and bioengineering, bioimaging, and biomedical computing. And I 
will briefly highlight a few specifically proposed areas to 
which my colleagues will add many more.
    In diabetes research, there will be novel approaches to the 
imaging of functional islets cells and studies of islets 
transplantation as well as studies of immune tolerance, which 
is actually of importance to many diseases beyond diabetes and 
is an initiative of the National Institute of Allergy and 
Infectious Diseases as well as NIDDK.
    Studies of osteoporosis, which is often thought to occur 
only in women, will be undertaken in men. And also studies of 
the relationship of bone mass in men to prostate cancer.
    We will expand neuroimaging research in disorders of the 
central nervous system. This is of importance to the research 
missions of at least six Institutes.
    And one more study that I want to highlight that will be 
done this year is a collaborative clinical trial of activity in 
adolescent girls, to prevent the decline in physical activity 
and to reduce the development of obesity, beginning at the 
middle school level.
    Finally, Mr. Chairman, to ensure that NIH can support new 
initiatives that offer the most promise of expanding knowledge 
and improving health, and to ensure our ability to support a 
healthy number of new and young investigators, we will limit 
growth in commitments and in the size of awards for new and 
continuing grant awards to a 2 percent average increase.
    I will be happy to respond to questions.
    [Dr. Kirschstein's written statement follows:]




                    ALLOCATION OF [FUNDS]--RESOURCES

    Mr. Porter. Dr. Kirschstein, thank you very much for your 
statement. You said that the President's budget provides for a 
$1,000,000,000 increase. There is a tap, is there not, on NIH 
funds to fund AHRQ, health statistics, and other programs. How 
much is that tap?
    Dr. Kirschstein. It is $266,000,000.
    Mr. Porter. So the President's increase is really in the 
area of $740,000,000, not $1,000,000,000, when you take the tap 
into account.
    Dr. Kirschstein. Yes.
    Mr. Porter. Not that we focus a lot on the President's 
budget. [Laughter.]
    Dr. Kirschstein, the question that is on everyone's mind 
is, with the kinds of increases that this subcommittee and the 
Congress have provided over the last two years; and hope to 
provide this year and the following two years to meet a 
commitment to double funding for NIH over a five-year period, 
is this money being spent wisely. Are we buying good science or 
are we simply buying a lot of bad science? What evidence can 
you give us that the money is being spent for good science and 
will continue to be spent for good science if Congress sees fit 
to provide the same kind of increase in this next fiscal year? 
This is the real question that is on everyone's mind.
    Dr. Kirschstein. Indeed, Mr. Chairman. And we are very 
cognizant of this. And as I mentioned in my opening statement, 
we have thought long and hard about it. I mentioned just the 
highlights of some of the things that we consider to be very 
good science that have led to the discoveries that I 
highlighted for fiscal year 2000. I have told you how we plan 
to go about being sure that we provide serious thought to how 
we would spend increases in 2001, and I have given you some 
examples of that.
    First, and foremost, we want to support excellent science. 
The opportunities have never been greater. We know that through 
the activities that have occurred in molecular medicine, 
genetics, structural biology, and clinical research over the 
last several years, there are many questions that we can 
answer, and, at which we will work very hard. We think there is 
no question that we can spend the money wisely. We will not, I 
assure you, spend funds for what our advisors, our peer 
reviewers, my institute directors working with me, consider bad 
science. We would never do that.
    Mr. Porter. I guess I am more interested in your comparing 
what was happening in terms of the quality of the proposals 
three or four years ago and the quality of the proposals now. 
In other words, are there more good proposals being made that 
are peer reviewed and highly rated today? Are we dipping down 
so far that we are at ratings that are low by comparison? Can 
you give us an overview of where we are on peer-reviewed 
proposals and how far we are going down. Is there more good 
science or are we simply funding more science?
    Dr. Kirschstein. No, there is more good science. And one of 
the reasons is that because of the unprecedented increases that 
we have received over the last two years, there is confidence 
among the scientists who are working in our academic 
institutions, particularly the good scientists. They are 
reinvigorated. They want to do good science and they have 
wonderful new ideas.
    This year, fiscal year 2000, we will fund the largest 
number of research grants that we have ever funded. For regular 
research grants that will be over 31,000. If you add the small 
business innovation research grants into that, it will be over 
33,000. There is no dearth of superb science. Every discovery, 
and this is something I have noted over many, many years of 
being at NIH, leads to new questions and leads to creative 
minds developing new problems and new issues to solve. And I 
can assure you that we have not dipped down at all. In fact, 
our success rates are a little bit lower than we had projected 
was appropriate over the past few years, namely approximately 
one-third. The projections are somewhat lower. There is a great 
deal of new science to be done.

                                EARMARKS

    Mr. Porter. Another area where I think it is important to 
discuss is the effort that has been made on this subcommittee, 
on a bipartisan basis throughout its history and in our 
counterparts over in the Senate as well, to resist disease 
earmarks and to resist fine tuning the proposals for funding by 
Institute that is placed before our subcommittee, but rather to 
rely upon what we consider to be scientific judgement rather 
than political judgement that might come out of our political 
institution. We need, however, some assurance that that same 
thing is not happening within the Executive Branch, that what 
you submit to the Department and what you submit to OMB is not 
then put through a political filter before it is put into the 
President's budget and before the proposals are put before our 
subcommittee.
    So could you give us an idea as to what changes are made, 
and not just this year but perhaps in previous years, when you 
submit your budget to the Department, and when it submits the 
budget to OMB and the White House before we finally see what 
the suggestions for funding are by institute.
    Dr. Kirschstein. Mr. Chairman, of course the budgets that 
are submitted to the Department and to the OMB are subject to 
overall scrutiny. As you know, we have tried to work with the 
institute directors, with the Department to assure that the 
funds are used to support the very best science, with a view to 
the importance of the various studies that are being 
undertaken.
    We are mindful of the important and serious diseases that 
the public is concerned about. But we do not plan our science 
only based on that. We plan what we support based on scientific 
opportunities, the creativity of our investigators, and the 
information that we derive from the public. For example, as you 
know, based on, first, the IOM report, and, secondly, because 
we know it is the right thing to do, we have established a 
second Advisory Group to the Director of NIH. We have had, of 
course, for many, many years, the Advisory Committee to the 
Director, a body of more senior scientists and a few very 
senior members of the public. We have had two meetings and 
there will be a third meeting on April 6th of the new group, 
the Council of Public Representatives.
    Mr. Porter. Yes, but Dr. Kirschstein, what I am interested 
in is whether within the Administration there is the same 
respect for your scientific judgement as to where the money can 
best be spent, as we attempt to bring to the table in our 
appropriations.
    Dr. Kirschstein. I believe there is, sir.
    Mr. Porter. All right. There may be further questions as to 
why you believe that.
    Mr. Obey.

                         PROFESSIONAL JUDGEMENT

    Mr. Obey. Thank you, Mr. Chairman. Let me simply say before 
I start my questioning, that with reference to the comments 
that the President's budget should not be taken seriously, I 
would say it should be taken just about as seriously, or 
certainly it should be taken more seriously than the original 
determination of this committee last year to provide almost 
$7,500,000,000 in delayed obligations until the last day of the 
fiscal year. I do not think that decision was especially 
beneficial to orderly science either.
    Having said that, let me simply follow up on the Chairman's 
comments about the disease of the month or the year approach 
that some groups have to funding NIH. As you know, both the 
Chairman and I, and I think a good number of members of this 
subcommittee, have opposed that approach. We do not want to 
earmark specific dollars for specific diseases because we 
believe that political judgements are going to be inferior to 
scientific judgements in determining where money goes. The 
problem is that I think it is getting more and more difficult 
to defend that position because there are more and more people 
coming into this institution who do not share that attitude, 
who do not share that common experience. I think that means it 
is incumbent upon us and NIH to do a much more thorough job of 
responding to what you will see as increasingly more thoughtful 
approaches being pushed by a number of these specific disease 
groups out of their concern about individual maladies.
    Given that fact, I think it is essential that we ask harder 
questions about the way that money is used throughout the 
Government, including NIH. Time limits do not permit me to ask 
all of the questions I would like to ask and get an individual 
response from you on all of them. So I am simply going to ask a 
number of them at once. I would ask you then to respond to them 
as best you can here orally, and then give me further response 
in writing.
    I would also ask, since I asked the same question the last 
two years, if the agency gets the kind of money that we are 
talking about that leads to a doubling of NIH's budget over 
time, or even larger, for every additional billion dollars that 
you get, I would like to know ahead of time, rather than 
afterwards, where you would intend to put that money. I have 
asked that question for the last two years and, frankly, I have 
gotten back from NIH rather airy responses to that question. I 
would appreciate it if the air would be eliminated this year 
and we could get down to some specifics so that we know ahead 
of time where that additional money would go in your judgement, 
not in ours, if you got the extra money. Because otherwise, we 
are just throwing money and saying a prayer and hoping that 
some of it sticks in the right places. And I am not very 
enthusiastic about that approach.
    Let me just ask a series of questions. Last year, NIH got a 
large amount of money, but, when all the dust settled, only 
about a $700,000 increase over the request as I understand it 
went into the clinical research center line item. Why is that 
the right mix of money?
    Secondly, after getting a 15 percent increase in fiscal 
year 2000, why did the success rate for competing grants 
actually go down by 1 percent?
    You seem to be shifting away from emphasis on investigator-
initiated grants toward other mechanisms, such as centers and 
large collaborative grants. Is this really because that is the 
way the science is moving, or is this in fact just a convenient 
way to move more money out given the fact that you are getting 
a large increase?
    The Genome Project. You have, as you know, private firms 
out there racing to stay in the game and talking about seeking 
patents on the information they develop. Is this information so 
basic that it ought to remain free to all researchers, or is it 
all right for us to be going down the road of considering 
patents for some of this information?
    Also, in last year's budget justification, NIH estimated 
9,171 competing grants in fiscal year 1999 but ended the year 
with only 8,565, about 600 fewer. Can you explain why the 
actual number of competing grants was so much lower than the 
estimate?
    And could you also tell me what the impact would be on your 
budget if we were to renew last year's attempt to engage in 
this delayed obligation game that was attempted. Would there be 
a significant impact on your ability to efficiently deal with 
the problems you are supposed to deal with?
    And lastly, should the Congress ask the National Academy of 
Sciences, in light of Dr. Varmus' comments, to undertake a 
review of the entire structure at NIH?
    That's basically it. If you want to respond to any----
    Ms. Kirschstein. How much time do I have? [Laughter.]
    Mr. Porter. Your time is up. [Laughter.]

                            RESEARCH GRANTS

    Mr. Obey. Well take the time I did not get from an opening 
statement. And if you would, for a couple of minutes, pick out 
and answer it anyway you want. But I would like specific 
responses in writing to those questions before the markup.
    Dr. Kirschstein. We will give you specific, extended 
responses. I will try to hit a few of the highlights.
    First of all, Mr. Obey, I think I can assure you that all 
of us will, I and my colleagues will plan in detail and provide 
you in advance with what we think, is our best judgement will 
be what we would do with the increase that might be proposed, 
in specificity. I think you deserve that. I think we deserve to 
think about it that way. And I promise you we will do so.
    Secondly, let me talk a little bit about the number of 
research grants. I made the comment in response to a question 
from the Chairman that we were funding the largest total number 
of research grants in fiscal year 2000 that we ever had. You in 
turn, and rightly so, picked out the number of new and 
competing research grants. Now you know me from my years of 
testifying as the Director of the National Institute of General 
Medical Sciences, which is the basic science institute and 
whose very life blood for many years, was the individual 
research project grant. But a number of things have happened in 
science recently, and particularly in the biological sciences, 
that are worth discussing.
    First and foremost, over a number of years of constraints, 
research project grants, new and competing, were not funded at 
the levels that had been recommended by the peers for what the 
work required. And that inevitably meant that exciting science 
that was being done would be slowed down and could not be 
accomplished as rapidly as possible. While we did project early 
on that we were going to have a larger number of new and 
competing grants in both fiscal years 1999 and 2000 than we 
ended up, in the course of discussions all of us agreed that 
several things ought to be done.
    First of all, that we ought to make right this idea of 
funding research project grants at a level that was 
commensurate with what the peer reviewers felt was the science 
this should be done. Therefore, we fairly systematically, not 
in every case, but fairly systematically looked at increasing 
the size of each new and competing research grant to bring it 
back to a level that the scientist would feel would enable him 
or her to move forward rapidly. That ended up costing more 
funds than we thought it might, and we thought that was 
worthwhile. And so, to some extent, that was one of the reasons 
why the number of competing research grant numbers fell.

                          SCIENTIFIC RESOURCES

    Secondly, the science is changing. And one of the things we 
have learned from our investigators is that they need 
resources. They need databases for the information that comes 
out of the Genome Project, that comes out of many other studies 
that the institutes are performing; they need repositories of 
cells, of nucleic acid material so-called nucleic acid banks, 
they need all sorts of resources that help and expands their 
research, and in some sense can be considered as part of each 
of the individual research grants that they are participating 
in. And so we have, indeed, provided funds for these consortia, 
or contracts, or, in some cases, centers to provide those 
resources, because we, as a group, in consultation with the 
scientists out there, felt that was a way to move forward in 
this regard. And I can elaborate on that for the record because 
I want to talk about a couple of other points quickly.

                             GENOME PROJECT

    The Genome Project. I think we feel very, very strongly 
that it is essential that the information that is generated be 
publicly available. And as you know, all of the material that 
is generated through all of the National Humane Genome Research 
Institute, sequencing and mapping, is made available within a 
day of the time it is generated. And we feel very keenly that 
that must be done. We do not agree that there should be 
patenting of every little sequence. There are times when 
patenting is important to assure that a gene or a protein that 
is useful can be translated to an application quickly should be 
patented. But we do not think that these materials should be 
widely patented.

                          DELAYED OBLIGATIONS

    And finally, let me talk a little bit about the delayed 
obligations. It is wise and it would be helpful for us to plan 
carefully. And we do that by having the funds at the beginning 
of a fiscal year, knowing that we are going to have them before 
the fiscal year starts and doing careful planning. And we will 
continue to do that, and we will continue to do everything that 
is possible. If something prevents us from doing the orderly 
kind of planning that might be best, we will try to correct 
course and do what we have to do. We would prefer to do this in 
an orderly fashion.

                             REVIEW OF NIH

    I leave the question about the National Academy of Sciences 
undertaking a review of the entire structure of NIH to someone 
wiser than I. We have had many National Academy of Sciences 
studies; they are usually about every five to ten years. And 
having been here for forty-four years, I have been through many 
of them.
    Mr. Porter. Thank you, Mr. Obey.
    The Chair will remind Members that we are operating under 
the seven minute rule, unless you are going to ask questions in 
the way Mr. Obey asked them, in which case you get three 
minutes. [Laughter.]
    The Chair would also say in response to the gentleman from 
Wisconsin, he is correct that delayed obligations is a very, 
very bad way to proceed for any committee or subcommittee. Our 
subcommittee was unfortunately tapped to provide BA or outlays 
for other subcommittees and we were left to have to squeeze our 
bill within the limits of protecting the Social Security Trust 
Fund. I certainly agree that at no time did we believe or want 
to end up with the volume of delayed obligations that was 
necessary to make the numbers come out right. At it turns out, 
the Social Security Trust Fund was well protected and the 
delayed obligations were not necessary. But we certainly all 
agree it is not the proper way to proceed.
    Mr. Bonilla.

                                DIABETES

    Mr. Bonilla. Thank you, Mr. Chairman.
    Once again, welcome, Dr. Kirschstein. It is always a 
pleasure to see you. You are doing a great job over there and 
we hope you get the job permanently, if you really want it. 
[Laughter.]
    Dr. Kirschstein. No comment. [Laughter.]
    Mr. Bonilla. Right. I understand. I want to start out with 
one of my favorite subjects that I always start with on this 
subcommittee, and that is diabetes. The projections of people 
that are going to be affected by this disease are, 
unfortunately, bad; the numbers are expected to skyrocket. 
Considering that $1 out of our Medicare dollars is spent on 
treating the disease directly or indirectly due to the side 
effects, and this disease costs the Nation $100,000,000,000, I 
am oftentimes surprised that this doesn't get more attention. 
These are very, very large numbers and significant areas of 
health care that we ought to be concerned about.
    So my question is, how aggressive an approach does NIH plan 
to take with diabetes research? We know that prevention is 
important. If we can intercept a lot of these problems early 
on, we would not have the big price tag and the toll it takes 
on people's health in the end. So, what is NIH doing 
specifically to try to intercept this problem before it really 
starts to take off?
    Dr. Kirschstein. Mr. Bonilla, we, at NIH as a whole, and 
particularly as you will hear from my colleague, the new 
Director of the National Institute of Diabetes, Digestive, and 
Kidney Diseases, take this disease very seriously. We have 
studied the best ways to ensure that we do research on this 
disease. We have increased our funding for this disease 
considerably. And there are new things that we will be doing. I 
mentioned three of them actually in my opening statement.
    There are opportunities to image the islet cells now, to 
get a structural image through various mechanisms to look at 
them. There are opportunities to develop, and indeed we are 
developing, islet cell transplantation procedures. And finally, 
in regard to the disease, Type I diabetes, which is an 
autoimmune disease, we are working on concerns about immune 
tolerance. Now that, as I told you, is important for many 
diseases, but that will be one of the thrusts.
    But above and beyond that, we know that diabetes is a 
disease of importance to our minority and underserved 
populations, and we will be increasing our efforts in that 
regard. We also know that particularly Type II diabetes has an 
association with obesity. And so studies that are being done to 
learn about obesity and how to prevent it, are applicable to 
diabetes. I mentioned one during my opening statement, about 
physical activity in young girls. If we could start off our 
youth in a way to keep them from not just sitting all day, but 
exercising, worrying about their diets, we might be able to 
prevent diabetes. That would be much more useful than having to 
treat it once it develops.
    Mr. Bonilla. I would think, just as a final comment on this 
subject, that the most difficult thing to do oftentimes is 
change human behavior.
    Dr. Kirschstein. Exactly.
    Mr. Bonilla. And to convince them in the first place that 
they may become a victim of a certain disease or tragedy, 
because everyone out there when they are young feels 
bulletproof and as though they don't have to worry about their 
diet or exercise. But I hope that NIH looks seriously at 
education and prevention because, if somehow we can get the 
attention of these folks early on, obviously that intercepts 
the problem before it turns into a major disaster for not just 
the individual, but for the families. If one person in one 
family learns, they pass that value system on to younger people 
who are often predisposed genetically to get a disease like 
diabetes. So that is just something that I hope that you 
concentrate on.
    Dr. Kirschstein. We agree completely, sir.

                            IMAGING RESEARCH

    Mr. Bonilla. I want to move now to a different subject, Dr. 
Kirschstein. In your testimony on page 8, you state that one of 
NIH's research themes will be harnessing the expertise of 
allied disciplines. One of the disciplines you mentioned 
specifically in your budget justification is imaging. At the UT 
Health Science Center in San Antonio, they have developed an 
imaging center. They are doing a great job there, learning more 
about speech development, addiction recovery, the brain's 
response to the intake of glucose. All of this can relate 
directly to the development of obesity and diabetes. Can you go 
into more detail on NIH's efforts to expand imaging research? 
And can you remember and just keep in mind the UT Health 
Science Center as you look at this, because they are leading 
the way in South Texas and they are doing a great job.
    Dr. Kirschstein. Yes, sir. Actually, we will be glad to 
keep things in mind. Imaging is one of our foci this year. 
There are new opportunities, particularly in the neurosciences, 
and you mentioned the neurosciences, and several of our 
institutes are joining forces to assure that new imaging 
techniques are developed, that we will have new imaging 
facilities within our own hospital, and that we will be able to 
expand studies in this regard.
    I mentioned something that is fairly new to me, frankly, 
and that is the ability to be able to image the islet cells of 
the pancreas. Dr. Spiegel can elaborate on that.
    In addition, bioimaging is part of the whole area of 
bioengineering, bioimaging, and biomedical computing that is 
one of our emphasis areas. And in order to assure that this 
will be done collaboratively and coordinatively, we plan within 
a month or so to establish an Office of Bioengineering and 
Bioimaging within the Office of the Director. For the last 
several years, we have had a coordinating committee called 
BECON, and the activities of that coordinating committee, on 
which every institute is represented, will be subsumed and be 
expanded under this new Office of Bioengineering and 
Bioimaging.

                       RESEARCH FUNDING PER DEATH

    Mr. Bonilla. Thank you, Doctor.
    I have a question for the record. It is a short one, so 
hopefully you can respond in writing.
    In fiscal year 1999, how much did the NIH spend on research 
funding per death for each of the following diseases: cancer, 
diabetes, heart disease, HIV/AIDS, and stroke? I would 
appreciate if you would provide me those answers for the 
record.
    [The information follows:]



    Mr. Bonilla. Thank you again for your time. It is always a 
pleasure to see you.
    Dr. Kirschstein. Thank you, Mr. Bonilla.
    Mr. Porter. Thank you, Mr. Bonilla.
    Mr. Hoyer is recognized for three minutes because I know he 
is going to follow the example of the Ranking Member.
    Mr. Hoyer. Surely he jests. [Laughter.]

                          DELAYED OBLIGATIONS

    Doctor, welcome to the committee.
    Dr. Kirschstein. Thank you.
    Mr. Hoyer. Thank you for your 44 years of extraordinary 
service to the country, to NIH, to the health of Americans and, 
indeed, citizens throughout the world. You have made an 
extraordinary contribution.
    Dr. Kirschstein. Thank you, sir.
    Mr. Hoyer. Doctor, first of all, let me make a comment 
follow-up on Mr. Obey's comment. It is my understanding, in 
talking about the budget, that the budget chairman is going to 
adopt the baseline which reflects the 1997 Balanced Budget Act. 
Now if that is the case, then I would suggest that that will be 
the most unrealistic budget of all. That was, of course, what 
he did last year. Whether he does it this year or not I guess 
remains to be seen.
    Doctor, let me ask you about the delayed obligations. Mr. 
Obey asked you the general question. If we do not adopt the 
President's proposal to eliminate the delay of the 
$3,000,000,000, what will the consequences be? There is 
currently $3,000,000,000 that you still----
    Dr. Kirschstein. Yes, for fiscal year 2000. Yes. We will be 
spending all the funds. But we had planned, because we expected 
that we would have to delay them, we had planned an orderly way 
as to how to do that. It will not affect the number of awards 
we will make. We will make the same number of awards. It will 
allow us to spread this out over a longer period of time and 
will allow us to perhaps spread the workload out.

            ASSUMPTIONS AND PRIORITIES FOR BUDGET INCREASES

    Mr. Hoyer. Doctor, for the sake of time, if you could 
perhaps submit to us, not necessarily for the record which we 
will get many months from now, but as soon as possible what the 
consequences would be if we do not eliminate the delay.
    Dr. Kirschstein. If you do not eliminate? Fine. We will do 
that. We will make the same number of awards.
    Mr. Hoyer. My expectation is there will be a supplemental 
to come which will take care of that.
    Dr. Kirschstein. That is what we have heard, sir.
    Mr. Hoyer. When that does, we ought to have the 
justification as to why we are doing it.
    Dr. Kirschstein. Yes, sir.
    Mr. Hoyer. Let me ask you about the Administration's 
budget. The President has asked for a $1,000,000,000 increase. 
The Chairman observes that the caps will reduce that somewhat. 
The committee has increased the President's budget over the 
last few years under Mr. Porter's leadership. Do you have 
available for us, either now or in the near future, incremental 
consequences of increases, $500,000,000, $1,000,000,000, 
$1,500,000,000? In other words, if we increased over the 
President's request, what would be the consequences? What could 
you do and how would you spend that money? Because both Mr. 
Porter and Mr. Obey, and you in your own statement reflect that 
the public is, I think, very willing to invest if they think 
the investment is being wisely spent. Therefore, this committee 
ought to know if we increase, how we would spend that increase.
    Dr. Kirschstein. Yes, sir. We have been thinking about that 
and we will submit it for the record.
    [The information follows:]



                           DIABETES RESEARCH

    Mr. Hoyer. Let me ask you now a follow-up on Mr. Bonilla's 
question on diabetes. This entire committee, I know you as 
well, are interested in this disease. The Working Group report 
requested by Congress recommends a funding level of I think 
$827,000,000 for overall diabetes research. I think the budget 
reflects $525,000,000. Can you tell me, was the judgement made 
that the request was not appropriate, or that the resources 
were not available to request at the level suggested?
    Dr. Kirschstein. We studied the recommendations of the 
Diabetes Research Working Group very carefully. And most of 
them are extremely worthwhile, and we have accepted and are 
working on most of them. The size of the request from that 
group was very large. And within the context of other areas of 
important science, other important diseases that we needed to 
consider, we felt that the amount that was allocated for fiscal 
year 2000, which is, as you said, $525,000,000, was what was 
appropriate.

                         NEUROSCIENCE RESEARCH

    Mr. Hoyer. I understand. Let me ask you, this is probably 
going to be my last question, you mentioned in your statement 
breakthroughs in neurosciences. And you also I think in an 
answer to a question to both the Chairman and Mr. Obey 
mentioned that. Christopher Reeves, as you know, testified. 
Because of the genius of video imaging and computers, 
Christopher Reeves walks on a television public service 
announcement I suppose. That would be an end that all of us 
would hope for. What are your expectations of being able to 
accomplish that objective either for Mr. Reeves or for the 
hundreds of thousands who are similarly situated?
    Dr. Kirschstein. I think as the discoveries related to the 
central nervous system and neuroscience in general abound, and 
this is an area that is exploding, the expectations probably 
increase. But I don't think anyone would say we are there yet. 
And I think that there are possibilities that we can consider, 
and I would suggest, sir, that Dr. Fischbach will be 
elaborating on that.

                     DIRECTOR'S ADVISORY COMMITTEE

    Mr. Hoyer. Thank you. I have not heard the buzzer. I get 
one additional question I guess. The Congress, and we included 
report language, asked the NIH to reestablish the Director's 
Advisory Committee on Clinical Research. Has that been done?
    Dr. Kirschstein. No, sir, it has not. I have decided that 
we should revisit that. I and the institute directors will be 
talking about it in the next few months and we will determine 
what we think is wise.

                      CONSTRUCTION AND RENOVATIONS

    Mr. Hoyer. Thank you. Let me ask you then about lack of 
adequate research space in research institutions around the 
country. Dr. Varmus and I discussed that. Can you comment 
briefly on how big of a problem we believe that is and how we 
are going to address it.
    Dr. Kirschstein. There are, in some academic centers, needs 
for increased research space. The appropriation for fiscal year 
2000 provided $72,000,000 for construction and renovations. We 
will be addressing that by awards through the National Center 
for Research Resources. We will look at that very carefully.
    One of the things that is very clear is that our concepts 
of what is needed for both clinical space and basic research 
space have to change as the science changes. In clinical 
research, for example, the number of days that research 
patients spend in the hospital are shorter and they go for 
daycare and for outpatient studies and we have to accommodate 
that. In basic science research, shared instrumentation, large 
open spaces where scientists can talk to each other and work 
together also have to be considered. So we will be considering 
all of that as we develop the plans for how to work on that.
    We, in addition, are having a working group of the Advisory 
Committee to the Director which will look at the needs for 
construction.
    Mr. Hoyer. Is there any additional money in this budget?
    Dr. Kirschstein. There is $72,000,000, sir.
    Mr. Hoyer. In this proposed budget?
    Dr. Kirschstein. In the prospective budget, there is 
another $72,000,000 proposed.
    Mr. Hoyer. Thank you, Mr. Chairman.
    Mr. Porter. Thank you, Mr. Hoyer.
    Mr. Wicker.

                              IDEA PROGRAM

    Mr. Wicker. Thank you, Mr. Chairman.
    Dr. Kirschstein, it is good to have you back with us. Let 
me just observe that many of us are touching on the same 
themes. You do need to be mindful of the fact that there is a 
perception out there among some members of the House, and some 
members of the Senate that we talked to last week that we are 
just throwing more money at NIH research than you can actually 
handle in a year. As you know, the Chairman of this 
subcommittee is serving his last year as Chairman. He believes 
deeply in your agency, and I would be astonished, frankly, if 
at the end of the day the Chairman didn't get the funding level 
that he feels is appropriate. So that should be comforting to 
you. But still we need more than simply your assurance that the 
research money can be used adequately and that the extra 
dollars that we spend will actually result in a significant 
improvement in the research and in the welfare and health of 
Americans.
    As you know, I have an interest in the IDEA program, which 
seeks to fund research for those States that have not 
traditionally been awarded research grants. It is a companion 
to the EPSCOR program in the National Science Foundation. And 
it may be that by spreading more of the research to some of the 
traditionally ``have not'' States we can get more of a bang for 
our buck. I would point out to the subcommittee and to the 
record that 24 States received 93 percent of the NIH research 
grants, while the other 26 States split the remaining 7 
percent. Representative Istook has introduced H.R. 3115 which 
seeks to create a more level playing field. I know several 
members of this subcommittee are interested in that legislation 
and several members have cosponsored the legislation.
    Do you have any information about how the IDEA research 
compares to the research from these larger States that get the 
bulk of the research? For example, can you give me any 
information as to whether the IDEA research is of the same 
quality, because I know that the excellence of the research is 
what we are really looking for instead of just spreading the 
money around. Also, I am told by folks at my universities that 
the biomedical research is actually less expensive to perform 
in some of the NIH EPSCOR States. So I wonder if you can 
comment on the cost of the research and the quality.
    Dr. Kirschstein. Mr. Wicker, I share your concern about the 
fact that there are States that do not have a sufficient 
biomedical research component. As you know, I went down and 
visited the State of Mississippi a number of months ago and 
spent a really excellent day talking not only to the scientists 
at the University of Mississippi Medical School in Jackson, but 
they brought in people from the Oxford Campus, and then we went 
and visited the Jackson State facility as well. And there are a 
number of people who have excellent ideas there.
    What we did was ask them to begin to work with us to learn 
and see whether we could increase what they are doing. And so 
many of them have come up to visit with us, to spend time, to 
visit with the various institute staffs in order to develop 
their programs. We would like to do that in many of the States. 
I promised Mr. Istook when I spoke to him, and I promised Dr. 
Ed Brandt, who is from the State of Oklahoma and who used to be 
in the Department, that we would visit Oklahoma this year, and 
we will be doing that in the spring. And I think that we want 
to work with all the people who are doing research there, and 
we will do so, I promise.
    Mr. Wicker. Okay. And it may be that you will have to 
answer my specific questions on the record. Will you get that 
back to us because we want to be developing this legislation.
    Dr. Kirschstein. Yes, I would like to.
    [The information follows:]



                         PEER REVIEW COMMITTEES

    Mr. Wicker. You also might comment for the record, because 
I quickly have another question, on the disproportionate 
representation on peer review committees by the institutions 
which have traditionally been receiving the awards. So I would 
like for you to look into that as well.
    Dr. Kirschstein. We will comment on that, too.
    [The information follows:]

                         Peer Review Committees

    Peer review is based on the premise that scientists who are 
active researchers working in the area of research being 
proposed are the best judges of the scientific merit of that 
research proposal. An appropriate peer reviewer usually is an 
active researcher, who can understand and judge both the 
research goals and the research means being proposed by the 
applicants. Such persons are chosen because they are 
experienced researchers who are reasonably diverse in outlook, 
gender, and ethnicity and who have achieved recognition for 
their own research accomplishments. Such recognition usually 
includes successful competition for research grants. As a 
result, the major source of peer reviewers is found at the 
institutions that have significant research programs.
    In order to assure that appropriate consideration is given 
to new investigators from institutions that have traditionally 
received little or no NIH support, we are making real efforts 
to further diversify the population of scientists chosen to 
participate in our peer review groups.

                     FUNDING FOR DIABETES RESEARCH

    Mr. Wicker. Let me just echo the concern about diabetes 
funding and the political correctness of funding for research. 
As you know, in 1998, the American Diabetes Association 
delivered a rather critical assessment of the level of diabetes 
funding as compared to the level of AIDS funding. Since that 
time, the difference in funding for AIDS research and diabetes 
research has become greater. In other words, there is more of a 
disparity now than there was in 1998 when the American Diabetes 
Association was critical of the disparity. I want to quote one 
of the parents of a child who had diabetes. He said: ``Research 
funds are allocated on who is screaming the loudest. There 
doesn't seem to be any kind of standard, no basic criteria, no 
attention to the number of cases, number of deaths, the cost to 
the economy.'' What do you say to the Association as a whole 
and to this father of a child in response to this criticism?
    Dr. Kirschstein. I think I would say that I do not think 
that is true. I do not think we, as scientists, and as 
responsible administrators respond or should respond to those 
who are screaming loudest. We should respond, and we do 
respond, to the needs of what can be accomplished for the 
disease and the science of what could be done. In fact, over 
the last several years, the funds on a percentage basis of 
increase for AIDS has been, for fiscal year 2001 proposed to be 
a 5.2 percent increase, and for diabetes, 6.8 percent. So I 
think that allays some of the comments.
    In addition, although both diseases are devastating, they 
have a different type of devastation. One of them is an 
epidemic in the world at-large which is killing day-by-day 
large, large numbers of people. The other one is a disease 
which devastates children when they get it, and I understand 
the father's concerns. We attended a function recently with the 
Juvenile Diabetes Foundation individuals. We have to work on 
it, and we will. And I think we try to put those in a balance.
    Mr. Wicker. Thank you, ma'am.
    Mr. Porter. Thank you, Mr. Wicker.
    Mr. Jackson.

                           HEALTH DISPARITIES

    Mr. Jackson. Thank you, Mr. Chairman.
    Let me also thank you, Dr. Kirschstein, for taking time out 
of your very busy schedule to come and speak before our 
committee regarding your budget. Chairman Porter raised a 
question about increases in funding and Congress' desire to 
double NIH's budget over a five year period. He began by saying 
that if you could give us some distinction between good science 
and bad science. From my perspective, good science is not just 
the concern about getting the best bang for the taxpayer's 
buck, but it is also in how NIH prioritizes the use of those 
resources.
    You, your predecessor, Dr. Varmus, and I have had many 
frank discussions about health disparities and what the NIH is 
doing to eliminate them. I hope we can continue to talk about 
this subject and engage each other on different and creative 
ways to solve this very complex problem.
    This year your budget requests $18,800,000,000 for fiscal 
year 2000. Last year we appropriated $17,800,000,000, and in 
fiscal year 1999 we appropriated $15,600,000,000. I point this 
out not because I don't think the money is being well-spent, 
but because I think some people are not sharing in the research 
money. Dr. Kirschstein, how many of the 31,000-plus grants 
awarded for fiscal year 2000 were given to minority researchers 
or minority-serving institutions. I know the reporting on this 
data is questionable since information regarding race on grant 
applications is optional.
    Dr. Kirschstein. Mr. Jackson, as I have told you in 
conversations, and I will repeat here, I and my colleagues have 
a deep commitment and have made as one of our absolute areas of 
priority the concerns about the disparity between the health of 
the majority population and the minority and underserved 
populations.
    For many years, as the Director of the National Institute 
of General Medical Sciences, I was the head of an institute 
that gave considerable support to historically black colleges 
and universities, Hispanic-serving institutions, and indeed 
sought to support minority investigators in majority 
institutions. All of those efforts were not enough and all of 
them must be increased. My colleagues and I are dedicated to 
doing that. We are committed to making a difference, and it has 
been a very long time that we have not made sufficient 
difference.
    We have set up through the Office of the Director, as a 
starting point, and I raise very carefully, that it is a 
starting point, a Coordinating Center for Health Disparities 
through the Office of Research on Minority Health. There is in 
the budget $20,000,000 increased dollars for that. We plan in 
that regard to be sure that we address the priorities that you 
have been talking about.
    The way to get at those priorities is to make a plan, a 
strategic plan for all of NIH. And I have asked, on my behalf, 
two individuals to co-chair a committee of institute directors, 
and I have insisted that all the institute directors 
participate, and they have. I have asked Dr. Anthony Fauci, as 
the Director of the National Institute of Allergy and 
Infectious Diseases, and my new Acting Deputy Director Dr. 
Yvonne Maddox to chair that group, to put together an NIH plan 
which we will have ready for the 2002 submission of the budget. 
I have asked each institute director to also develop his or her 
individual strategic plan. We will be monitoring what is being 
done.
    Now the number of investigators who are minority who 
participate in research is, unfortunately, very small. We have 
worked very hard through training programs, through scientific 
education programs to increase that number. It is inching up. 
It has been 6.something percent; it is now 6.8 or 6.9 percent. 
But inching up is not good enough. We really have to do 
something about that, and we are working on it.

                     NIH'S COMMITMENT TO H.R. 2391

    Mr. Jackson. Dr. Kirschstein, this afternoon I am going to 
begin the process of exploring the depth of that commitment, 
starting with the Cancer Institute when they come before this 
committee. And I am so glad that all of the institutes, the 
centers, and offices are represented here today because even as 
you begin to work on your interim plan for addressing a 
significant problem that the IOM report indicated at NIH, I am 
certainly hoping that each of the institutes, the centers, and 
the offices that come before this committee can answer my 
questions in some very specific ways. Because every time they 
come before this committee, I keep getting broad and general 
responses to specific questions that we should be making 
significant improvements upon every Congress.
    So the Congress can go about its responsibility for 
overseeing the amount of monies that we are appropriating for 
these agencies, I would like to know in real specific terms 
what each of these institutes, centers, and offices are doing 
to address this fundamental issue of disparities and problems 
that are not only perceived, but factually documented at NIH.
    About a year ago, a good friend of mine, Dr. Louis 
Sullivan, the former HHS Secretary, spoke to Senator Specter's 
subcommittee about an IOM report that was somewhat critical of 
the National Cancer Institute. Senator Specter asked him for 
ways he might remedy the problems highlighted in the IOM 
report. Dr. Sullivan felt that elevating the ORMH to a free-
standing, autonomous center would be a start.
    I have subsequently sponsored a piece of legislation that 
is bipartisan, has more than 80 Members of Congress who are 
supporting it, for the purpose of better coordinating 
throughout the center. Dr. Varmus sat before this committee in 
the last Congress and made it very clear that each of the 
centers and institutes were at the level of center and 
institute status for the basis of being able to better 
coordinate amongst the various institutes and offices and 
centers these critical issues. And what became increasingly 
clear in the last hearings before this committee was that on 
the issue of health disparities there was a significant lack of 
coordination.
    Because of Dr. Sullivan's suggestions, and since there 
appears to be a dearth of minority researchers or minority-
serving institutions receiving grant dollars, again I 
introduced H.R. 2391, legislation that creates a National 
Center for Research on Domestic Health Disparities at NIH. 
There are four components to this legislation, and then I want 
to end with my question: (a) the legislation establishes a 
strategic plan for minority health research; (b) a seat at the 
table for the Director of Minority Health Research at NIH to 
participate in decisionmaking at the very highest levels and 
not be left simply to the jurisdiction or the responsibility, 
if you will, of benevolent directors at NIH who give specific 
requirements during their tenure based upon questions raised by 
this institution; (c) grant-making authority for the National 
Center for Research on Domestic Health Disparities; and (d) 
support for infrastructure improvements at minority 
institutions.
    What is it NIH is doing to meet the four goals contained in 
the legislation? And how does your budget proposal plan to meet 
these goals?
    Dr. Kirschstein. The first of those goals is the strategic 
plan. We are working on that. We also have as a request in this 
proposal for fiscal year 2001, as I said, $20,000,000,000 for a 
coordinating center. We look forward to working with you to try 
to satisfactorily work out this issue.
    The other issue is that we are requesting for this 
coordinating center, under exceptional circumstances as part of 
this appropriation bill, legislation to allow it to make some 
grants in areas where the center feels that there is not 
sufficient emphasis being placed within the institutes. And we 
hope to work further with you in this regard.
    Mr. Porter. Thank you, Mr. Jackson.
    The Chair would remind the gentleman from Illinois and 
other members that if you are in the process of asking a 
question and the time runs out, you are permitted to finish the 
question and the witness is permitted to answer. That is the 
rule.
    Mr. Jackson. Thank you, Mr. Chairman.
    Mr. Porter. Mrs. Northup.

                         RESEARCH BREAKTHROUGHS

    Mrs. Northup. Thank you.
    Welcome. I am always so fascinated and in awe of the work 
done at NIH. There are a number of questions that I have that I 
will just ask until my time runs out. I will give you time for 
an answer in between each one. [Laughter.]
    The first one is, the subject is how long it takes for a 
solution to come to the market. I noticed in a Newsweek or Time 
Magazine article recently about Alzheimer's. They talked about 
many new drugs that are being tested that seemed to have quite 
an impact on Alzheimer's, and then it said researchers are 
hoping that within fifteen years these drugs will be widely 
available. Now I am 52 and I can add 15, and I know I am going 
downhill. I don't mean to make a joke of it though.
    In all honesty, there are people with Parkinson's, ALS, 
Alzheimer's that are hearing about all these new breakthroughs 
that are so imminent and then when they hear fifteen years, 
that is somebody else that is going to benefit from that. I 
just wondered about the length of time it takes to actually 
have breakthroughs become available and what we could do to 
speed the availability of solutions that look so promising.
    Dr. Kirschstein. Mrs. Northup, NIH can only give you part 
of an answer to that question because there are so many other 
agencies involved. There is the regulatory aspect of drugs, 
there is the industrial aspect of drugs. What I can tell you is 
that in the many, many years that I have been here at NIH what 
has impressed me most is that the time is shortening, and 
shortening by a considerable amount, between an important 
discovery, a new drug, a new diagnostic, and the time to which 
it is finally applied. It may not be the time to which it is 
available to the entire public, but from the initial 
discoveries to when the first attempts at application are 
certainly shorter, and they are becoming shorter and shorter 
and shorter.
    But I do agree with you. I think it is very important to 
get things to the market as soon as possible. And it is my 
impression that things are moving more rapidly and that the FDA 
has been doing a much better job of that than in the past. We 
hope that will continue.

                            CLINICAL TRIALS

    Mrs. Northup. I think part of it is the drug approval 
process, and certainly we are all eager to streamline that 
process. But I think the other advice or suggestions I would 
hope NIH would make would be the ability to participate in 
possible life-saving testing, to expand and open that up. 
Because if you are diagnosed today with Lou Gehrig's disease, 
fifteen years is not a possibility for you. And what is the 
risk? I mean, what is the risk? There is no alternative but to 
take a chance. And for those people that want an opportunity, I 
would hope that NIH would bring to us the very best 
suggestions. I would point out to you that the research may 
have to progress further but some people would be willing to 
take that risk.
    Dr. Kirschstein. That is why I think all of our institutes 
are interested in expanding their clinical research activities 
and their clinical trials, to include in these clinical trials 
people who want to participate, and who, for example, through 
healthcare plans and other means of support could possibly get 
their care taken care of and NIH could participate in NIH 
supported research to get the research done. Many of our 
institutes are working on that. The Cancer Institute, in 
particular, would be pleased to tell you about that.

                   ALLOCATION OF [RESEARCH] RESOURCES

    Mrs. Northup. The next question I had is about the 
disparity in funding between disease groups. I think I have 
asked this type of question before. But it is my understanding 
that NIH puts research dollars where it looks like the most 
promising results will occur. And I think that is a good 
criteria. But if you have, for example, a lot of research going 
on in one area because of past NIH investments, then it is more 
likely that that disparity will increase, that you will have 
increasingly more good science coming from that particular 
disease, more promising results. And in areas NIH viewed as 
having the least opportunity, if I may, in breakthroughs five 
years ago, that the less it is funded the less likely it is 
that the disease group is going to turn up with really good 
research opportunities the following year. And it may be 
important to stimulate some of those areas where there is great 
disparity between the number of cases and the amount of 
research going on per case.
    Dr. Kirschstein. There is no doubt about that. We actually 
do plan changes from year to year and through five year 
strategic plans, which all the institutes have been putting 
together, we are doing such things. But there is also the 
element of not being absolutely sure as research progresses 
where it will be important. There was a marvelous article in 
the Washington Post on this some time ago. Many of the drugs 
that were developed and are being worked on currently as new 
drugs for AIDS in fact have been found to be extraordinarily 
useful for hepatitis C, another infectious disease. Therefore, 
there is a whole new set of drugs that nobody ever thought 
would be useful, and this was a disease that everybody was 
extremely worried about. And so I think you see how research in 
one area may progress into another.
    Mrs. Northup. I do. And that is one of the reasons that I 
really try not to politically influence the decisions that NIH 
makes about specific diseases. On the other hand, if you have 
an autistic child and you see no research moving forward or 
very little research moving forward, you wonder. It is hard to 
just hope that scientists stumble onto something or discover it 
by accident. I am just saying that what I do not want to do is 
begin to ordain, I would not want to see this committee begin 
to ordain how money is being spent. But I would ask NIH to 
focus in the big picture on areas that have been left behind, 
where there seem to be fewer opportunities. I don't know, maybe 
fund more investigator-initiated efforts, maybe have small 
grants that would help those researchers interested in that 
area to advance their studies.
    Dr. Kirschstein. That is precisely what we are doing. Over 
the last four years, we have had three or four institutes that 
have been working together on the disease you just mentioned, 
autism. We have increased the spending for that disease from 
about $40,000,000 to about $48,000,000 a year as a result. The 
institute directors meet together, discuss it, they have had 
several conferences along with autism families, and I think we 
are beginning to see some possible progress.
    Mrs. Northup. Thank you, Mr. Chairman.
    Mr. Porter. Thank you, Mrs. Northup.
    Ms. DeLauro.

                    OUTREACH TO COMMUNITY ADVOCATES

    Ms. DeLauro. Thank you very much, Mr. Chairman.
    Welcome, Dr. Kirschstein. It is a pleasure to have you here 
today and to have the other institute directors. I applaud the 
work of the NIH. There are always a lot of questions, but I 
think beneath all those questions is the absolute knowledge 
that we in fact have the best science and research in the 
world. And we are grateful to those of you at the NIH who 
engage in this effort.
    I have often asked this question before as well. It is an 
issue that is always on my mind. And with, as I say, great 
admiration for what gets done at the NIH, but in terms of 
translating what NIH does to get that word out on new research 
discoveries to physicians, to other providers who are on the 
front lines of treating patients, if you can talk to me a 
little bit about your work with the advocacy communities on 
this, if you can cite some examples, and what do you see with 
regard to increased collaboration and partnerships within the 
advocacy community.
    Dr. Kirschstein. Thank you, Ms. DeLauro. We indeed have, 
for a long time, had interactions with various advocacy groups 
and with units of advocacy groups that work together. In order 
to hear more from public members and from people who have been 
interested and been advocates, a little over a year ago we 
established a Council of Public Representatives. This consists 
of 20 people. We asked for nominations and received over 200. 
We asked people to request that they themselves be nominated, 
and we asked advocacy groups to nominate such people. We then 
screened those 200 plus applications and chose first about 35, 
and then winnowed the number down to 20.
    What we asked of these people was not that they come 
together and meet with us to advocate for any one particular 
disease, but that they leave their advocacy at the door. But 
that they come and join with us to discuss what is important 
for the public, how we transmit information to the public, how 
we hear from the public, how we learn what they and the public 
want from NIH. We had an initial preliminary meeting before we 
finally determined how to go about this, and then we appointed 
the people.
    We have had two meetings. We will have a third one on April 
6. The enthusiasm of these people is remarkable. We have 
involved them not only in these two meetings, but we have used 
them to advise us in other regards. The institute directors and 
the senior staff of NIH have a budget retreat each year and we 
asked several members of this Council of Public Representatives 
to join us in that discussion.
    In addition, as you know, it is a Federal law that we have 
to do an evaluation and assessment of our programs under the 
Government Performance Review Act. We had a wonderful day in 
which we presented to many people, about eight or ten being 
members of our Council of Public Representatives, a stack of 
scientific accomplishments for the past year, about this high, 
and they went through them in detail, discussed them, and were 
really very enthusiastic about it.
    They have organized themselves. They have asked that the 
people that did not get appointed to this committee be called--
the committee is a Council of Public Representatives, the 
acronym is COPR--and they have asked that the others become 
COPR associates. So they have expanded to about 250 as a 
result. They are putting out a newsletter and they are going 
out on behalf of science, not on behalf of NIH, but on behalf 
of biomedical research to communities all over the country.
    Ms. DeLauro. Is that list of the public representatives 
public information?
    Dr. Kirschstein. Yes, it is. It is on our web site and we 
can provide it to you.

                                OUTREACH

    Ms. DeLauro. And in terms of the first part of the 
question, which was about getting information to the health 
community, physicians, to health providers, is that part of the 
mandate of this?
    Dr. Kirschstein. Well, that's part of their mandate. Their 
mandate would really be to provide information to the public. 
We feel it is NIH's responsibility and our scientists and our 
science administrators to provide information to physicians, 
and we do that in many ways, through scientific meetings, 
through scientific publications, through databases, through 
advertising our clinical trials, through our homepage on our 
web site which is available very easily, and now through a new 
clinical trials database which is up and running and will list 
all clinical trials that are either NIH-supported or non-NIH-
supported. A member of the public, physicians, other people can 
type in the name of the disease or the name of the entity or a 
symptom and get information.
    Ms. DeLauro. An issue which is one I am concerned about is 
the research regarding tobacco control and prevention and the 
current research at NIH on that, especially among ethnic 
populations and minorities.
    Dr. Kirschstein. That is of deep concern to us. We actually 
spend a great deal of money on concerns about tobacco-related 
diseases, both in institutes like the National Institute of 
Drug Abuse in the National Heart, Lung, and Blood Institute, 
because we know that cardiovascular disease is tobacco-related, 
and certainly in the National Cancer Institute, and many other 
institutes as well.
    Educational programs are very important. We know that. We 
have had, the country as a whole has had less starting of 
smoking and diminution of smoking in our adult populations.
    Ms. DeLauro. Not amongst kids.
    Dr Kirschstein. But you are absolutely right. We are deeply 
concerned about our youth. And I am personally, with my 
interest in women's health, particularly concerned about young 
women. And part of our concern relates to the fact that young 
women believe that the way to stay thin is to smoke, and they 
therefore are not concerned about quitting. And we have to, and 
we are, educating them about that and we will continue to do 
so.
    Ms. DeLauro. Thank you very much, Dr. Kirschstein.
    Thank you, Mr. Chairman.
    Mr. Porter. Thank you, Ms. DeLauro.
    Mr. Dickey.

                         FISCAL RESPONSIBILITY

    Dr. Dickey. Good morning.
    Dr. Kirschstein. Good morning.
    Mr. Dickey. I am concerned about the increases in NIH 
appropriations. I am sure you do not share that concern with 
me, do you?
    Dr. Kirschstein. No, sir.
    Mr. Dickey. But I am concerned, and in two respects. One 
is, I am afraid that the more we increase it, the more we keep 
funneling money there, the more grants that go out, the less 
chance there is of supervision of those grants and good 
stewardship. I am very concerned about that. It is the sort of 
thing like saying, well, obviously they are approving of what 
we are doing, and sometimes we do not even know and cannot find 
out what we are doing. That is number one of my concerns.
    Number two is, I want to be sure that we, because of the 
extra money, that we are going into areas that we have not been 
into in the past, some of the things that we have not done in 
the past and without losing ground with the main areas of 
direction.
    I would like for you to comment on those two things, and 
then I have two other questions after that.
    Dr. Kirschstein. Mr. Dickey, we could not agree with you 
more about the essential aspects of our stewardship. And we, as 
servants using the public money, want to be absolutely sure 
that we are good stewards. And we do that in many ways. We 
observe the peer review process. Our staff attends the peer 
review process. We make sure that the awards of grants are done 
reasonably. We make sure that the scientists send us progress 
reports once a year which we read, and if there are problems we 
do something about them. We go on site visits as much as we can 
to visit where they are and what they are doing. We do that 
particularly with large projects. We should do more of that. 
Some of it has been difficult to do because of some of the 
constraints in our administrative expenses. We agree with you. 
But we will work very hard at this within our capability 
because we know how important it is.
    In terms of areas that are not being studied, we try to 
assess this in many ways; by holding conferences related to 
diseases or conditions that have not gotten much attention, 
learning from the scientific community, learning from this 
Council of Public Representatives and the public what may be on 
their minds in order to be sure that we move in certain 
directions. We put out requests for grant applications in areas 
that have been either underfunded or less well funded. We do 
that in areas that have not necessarily been traditionally 
those that NIH has focused on.
    We have a new Office of Behavioral and Social Sciences and 
that office has been very active, as have the institutes, as a 
result in moving into further areas that we have not looked at 
before; areas such as do people who are on medications adhere 
to taking their medications; areas such as do people who have 
stopped smoking continue no longer to smoke, and how can we 
improve this.
    So we have many, many ways of moving into other areas. We 
are constantly assessing what we are doing. I think we have 
worked at this very hard and I think we have been relatively 
successful.

                           STEMCELL RESEARCH

    Mr. Dickey. Okay. Well we agree on that.
    I am going to mention something we do not agree on, and 
that is stem cell research. I am terribly concerned that we are 
taking tax dollars from people who work hard and contribute 
their taxes to the Treasury only to see those dollars being 
spent to do something that they think is morally not justified, 
and that is destroying a human embryo in any type of fashion. I 
am not asking you to agree with me as to the conclusion, but 
all I am saying is that there are many, many, many millions of 
people who will be disheartened and discouraged and demoralized 
by the fact that we are going to take Federal funds and support 
the tearing up of an embryo for stem cell research, 
particularly when we have adult stem cells that we can go to 
and fetal tissue and other things.
    I am more or less stating that my opposition is as strong 
as it has ever been. I think that we have gone to kind of 
double-speak when we talk about the ethical considerations on 
the human embryo prohibition that we already have in the law. 
We are going to do all we can to fight that for the sake of our 
Nation's conscience and hopefully so that we can keep the 
support of people who are paying the bills through their taxes.

                             STATE FUNDING

    My last point is more of a question, and that is Arkansas 
is getting very little of the funds from NIH. Do you know where 
our State is? It is across the Mississippi. [Laughter.]
    If you want to get some money, I could take it down in a 
sack. But I am upset that some 26 States are sharing 7 percent, 
as Mr. Wicker has already mentioned to you. Can you give me an 
answer about Arkansas whereas you might have given him one 
about Mississippi?
    Dr. Kirschstein. Yes, I can give you an answer because, as 
you know, Dr. Ruffin visited your State some few months ago. He 
is in the audience today. He met with the people that had been 
here at the hearing last year. We hope to be able to work with 
the individual with whom he met and a number of the people at 
the University of Arkansas, similarly to what we have done in 
Mississippi and what we hope to do in Oklahoma. And we are 
going to work very hard to see if we can increase appropriately 
the science base in that State.
    Mr. Dickey. You understand, in this regard I do not want 
fairness, I just want favoritism. [Laughter.]

                         NH allocation process

    Mr. Porter. Thank you, Mr. Dickey.
    We will have time for a second round of questions. There 
remains about twenty-three minutes before the noon hour.
    Dr. Kirschstein, going back to something I raised earlier, 
can you tell us in this budget cycle, the one that we are just 
beginning, did you send up to the Department a funding level 
for each of the institutes based upon the overall number that 
was indicated as going to be the President's increase in his 
2001 budget? In other words, was there a list with specific 
dollar amounts sent forward?
    Dr. Kirschstein. At the final stages, sir, yes.
    Mr. Porter. At the final stages. How was that number 
arrived at, and what participation did the Department and OMB 
and the White House have in allocations among the various 
institutes, if any?
    Dr. Kirschstein. The original allocations were made, in 
general, through the month of December by Dr. Varmus before he 
left. Shortly before the President's budget was submitted in 
final, there were some discussions with the Department and with 
the OMB which resulted in minor changes.
    Mr. Porter. Minor changes. And what was the nature of those 
discussions?
    Dr. Kirschstein. Well, for example, we had planned to 
develop the Coordinating Center on Health Disparities and there 
was discussion with the OMB and we arrived at this figure of 
$20,000,000. But that was done as a coordinated effort.
    Mr. Porter. Was there anything else that you can recall?
    Dr. Kirschstein. I think there may have been some minor 
things. I don't recall very many.

                         SCIENTIFIC MISCONDUCT

    Mr. Porter. All right. Dr. Kirschstein, when you pick up a 
newspaper and read that an investigator has falsified data, 
that to me is the worst thing that can happen to medical 
research. We know the nature of news, and I have said this many 
times, always tends to be negative. People see that and they 
say if we cannot depend upon the integrity of science, how can 
we depend upon the integrity of anything. And I think that is 
something that disturbs us all.
    What happens to an individual who falsifies data that is 
funded through an NIH grant? How far is this carried; have 
there been criminal prosecutions, have people been prohibuted 
from submitting applications? What do we do to a person that 
does that?
    Dr. Kirschstein. For a number of years, Mr. Porter, we have 
had, first housed at NIH and then moved to be housed within the 
Department, an Office of what is now called Research Integrity, 
it was previously called Science Integrity. For the last three 
years, all of the science agencies in the Federal Government, 
through the National Science and Technology Council and the 
Office of Science and Technology Policy, have worked together 
to try to develop a common set of requirements as to what would 
be considered scientific misconduct. The Department of Health 
and Human Services has had such requirements and there are 
indeed regulations and some legislation in that regard. But 
many of the other departments did not have it.
    I was privileged to be asked by the NSTC to co-chair 
initially and then, when my co-chair who was from NASA left, to 
finally chair the subcommittee of NSTC that put together what 
was a final common definition that all the agencies in the 
Federal Government could accept as to what was misconduct, and 
a set of principles that would outline how a scientist and his 
or her institution should be looked at in terms of misconduct, 
and what are the elements that should be investigated, and how 
eventually something should be done about this.
    In our Department, when a scientist is found to have 
committed scientific misconduct, there is a process which 
allows the individual to be debarred. That means that they will 
not be allowed to receive Federal funds for some specific 
period of time, and maybe forever depending on the seriousness 
of the misconduct. That was not true in all the departments. 
And I think it is fair to say that the Department of Health and 
Human Services, and NIH in particular, was a leader in this 
regard. So I am very proud of what we did.
    Now, that is scientific misconduct. There also are issues 
of how certain other types of research are done; for example, 
clinical research. And there we have had for even longer time 
than the Office of Research Integrity an office which works on 
behalf of all the Federal agencies that are involved in human 
subject research, the Office of Protection from Research Risks. 
And, indeed, it is not only currently concerned with human 
subjects, but the welfare of animals as well, this office 
considers. That office works under something that has long 
before been accepted by all the Federal agencies as the common 
rule for how to conduct human subjects and animal welfare 
research.
    We are as deeply concerned as you are about this and we are 
watching very carefully. We have been dismayed at some of the 
reports we have received. We are looking into what might be 
done. And in fact, because in the particular recent set of 
events that I am sure you are referring to, there were multiple 
agencies involved, the Food and Drug Administration and NIH, 
through its Recombinant DNA Advisory Committee, we are working 
together within the Department to shore up what should be done.

                            CLINICAL TRIALS

    Mr. Porter. Dr. Kirschstein, I am going to read this 
question because the staff has taken some time to prepare it 
and I think it is an important area. The death of a patient in 
a gene therapy trial has not only highlighted several problems 
in the oversight mechanisms in place to monitor these trials, 
it has also highlighted the high personal and financial stakes 
involved in this growth industry.
    Certainly no one institution or agency is at fault; the 
entire system failed. But there were plenty of signs that 
problems could develop if changes to the current oversight 
system were not addressed. For example, clinical research has 
evolved from individual or small group investigator studies to 
industry-sponsored studies. The sheer number of trials has 
grown tremendously; for example, the number of protocols at 
Duke University has grown from about 400 in the 1970s to 2,000 
today. The economic benefits of clinical research have 
skyrocketed, not only for the institutions conducting the 
studies but for the industry marketing the results of the 
studies. And the role of each entity responsible for oversight 
and what that responsibility entailed, as well as having 
adequate resources to do the job effectively, was lacking.
    As an agency, NIH was the closest to what was happening in 
this field. Why didn't someone see these changes and alert 
officials that the oversight system needed adjusting? Why 
wasn't something done sooner to keep pace with these changes?
    Dr. Kirschstein. Mr. Chairman, the relationship between NIH 
and the scientific community has always been based on mutual 
trust. And indeed, in the vast majority of situations, that 
trust is justified. You are correct, the science in many areas 
has moved very rapidly. The science in gene therapy has 
probably moved more rapidly than some of us anticipated.
    We did, however, have concerns about it. As early as four 
or five years ago, Dr. Varmus asked a working group of his 
Advisory Committee to undertake a study of gene therapy. The 
committee was headed by two very distinguished scientists, 
Stuart Orkin, from Massachusetts, and Arno Motulsky, from the 
University of Washington. They suggested that we continue to 
look at such therapy as research and to move slowly.
    In addition, the Recombinant DNA Advisory Committee, which 
was established to study and review all sorts of research in 
recombinant DNA long before gene therapy was even thought of, 
had changed in focus to become really a review body related to 
gene therapy protocols. And that committee was also studied it 
and some recommendations were made for change which were 
instituted. And we were in something of a transitional period 
when this dreadful event occurred.
    Now the important thing I think is that the Recombinant DNA 
Advisory Committee always meets and discusses issues in public 
so that the public may know all the protocols the committee 
looks at, particularly at the novel, unusual protocols. And 
that did happen. What transpired between the time that the 
review started for this particular situation and today is still 
under investigation by the Food and Drug Administration and by 
some activities of the Recombinant DNA Advisory Committee. So I 
cannot give you all the answers. But I can assure you that we 
are deeply concerned about this and that several of us working 
in the Department are planning very carefully to make sure that 
we put appropriate control processes in place immediately.
    Mr. Porter. Thank you, Dr. Kirschstein.
    Mr. Hoyer.
    Mr. Hoyer. Mr. Obey, before he left, asked me to ask you 
that in addition to the $3,000,000,000 consequence of the delay 
in outlay authority, if you would also address in that answer 
the consequences of the $7,000,000,000 original proposal? 
Obviously, that is so that if there is another instance in 
which such a proposal is made, we will have the knowledge as to 
what the consequences could be or would be. Thank you.
    Two additional questions, Doctor, about the Institute of 
Medicine's Report on Priority-Setting, which we have discussed. 
As an aside, I would say that I agree with the Chairman and the 
Ranking Member, and this committee generally agrees that the 
committee ought not to interpose its judgement on priorities. 
On the other hand, we have a direct responsibility to those who 
are paying the bill to assure that their money is being used in 
ways that they believe is appropriate. Within that framework, 
the dynamics of appropriate judgement on the committee's part 
reflected in many instances by questions and report language 
rather than earmarking in the bill, which I think is also 
appropriate because I think it creates the dynamic of sort of 
the democratic communication between you and your institute 
directors and the people. That is what we are for and I think 
that is appropriate.
    But the IOM's Report on Priority-Setting urged the NIH to 
better measure disease burden and invest research in specific 
diseases. My question is, can you tell me the status of your 
response to that and any observations that you might have on 
it.
    Dr. Kirschstein. Yes, sir. We considered that 
recommendation seriously. And we have held a series of meetings 
with medical economists, scientists, and many other people 
related to concerns about the burden of disease. Measuring the 
burden of disease in terms of the dollars that are spent on a 
particular disease is a very complex situation. There is not 
and cannot be any sort of one-to-one relationship; the state of 
science, whether the disease is an acute or a chronic one, 
whether the people who are ill have short lived illness or long 
periods of illness, whether quality of life is affected in the 
long run, the various ages of the population who are affected, 
et cetera.
    And it has been our experience that, in general, the 
scientists, the economists and social scientists, and others 
who study this are not of one mind about how one measures the 
burden of disease. It is a very difficult problem. They can 
give us some general recommendations. They have suggested we 
continue studying and collecting data, and we are doing so. But 
it is not an easy problem to solve.
    Mr. Hoyer. I think that your last statement, which I think 
is true, that the scientists are not of one mind themselves 
adds to the dynamic between the scientists and the public, 
through us, as to what we ought to be doing with their dollars.
    Dr. Kirschstein. That's right.

                          MENTAL HEALTH ISSUES

    Mr. Hoyer. My last question. Mental illness. The World 
Health Organization has estimated that four mental health 
diseases--schizophrenia, bipolar disorder, major depression, 
and obsessive compulsive behavior--are in the top ten most 
costly and disabling diseases. I guess this is sort of a 
follow-on on the IOM observations in question. What are we 
doing at the Director's level to address the priority-setting 
across institutes especially as they relate to disease burden? 
This is obviously a follow-on, but also in light of the mental 
health issues as well, which obviously the mental health 
illness and the physical illness clearly have a relationship.
    Dr. Kirschstein. It is not only true that we are thinking 
about this at the NIH level, but indeed the Department is 
thinking about this. There has just been released a Surgeon 
General's report on mental illness. The responsibility for 
putting that report together rested with two agencies 
primarily, and Dr. Hyman, who is sitting directly behind me, 
was deeply involved in this and I think he can probably speak 
to this better than I can.
    But I should say that many of our institutes are concerned 
about those mental illnesses. The major responsibility of 
course is, obviously, with the National Institute of Mental 
Health. But there is a group of people who meet and think about 
the relationship of the neurosciences, the physical changes and 
the chemical changes in the central nervous system related to 
mental health, to drug abuse and to alcohol abuse. We are 
thinking about it very deeply. And we put a great deal of money 
in that area. In fiscal year 2000, it is $1,200,000,000. In 
addition, of course, we have just come off a decade of the 
brain. And the Secretary herself has said that she thinks the 
next century is going to be the century of neuroscience. So we 
are all very deeply concerned.
    Mr. Hoyer. Doctor, thank you very much. As I sat here, I 
thought to myself that all of your colleagues who are sitting 
behind you and who have worked so long with you and know you so 
well must have been very proud at the very thoughtful answers 
that you gave, albeit you have had a lot of experience at this. 
But they were very thoughtful and good answers. Thank you.
    Dr. Kirschstein. Thank you.
    Mr. Porter. Thank you, Mr. Hoyer.
    Mr. Jackson.
    Mr. Jackson. Mr. Chairman, I really have no further 
questions. I wanted to once again thank Dr. Kirschstein who has 
been quite a pleasure to work with during my tenure and service 
on the committee. I look forward to meeting and listening to 
the testimony of the institute directors, centers, and offices 
before NIH. Thank you, Mr. Chairman.
    Dr. Kirschstein. Thank you.

                           MEASURING SUCCESS

    Mr. Porter. Thank you, Mr. Jackson.
    Dr. Kirschstein, I began my questioning by asking you about 
good science and is the money being spent wisely. We have 
always measured the success of any Institute by the increase in 
the success rate. But it seems to me that is no longer a very 
good way of determining what is happening. In fact, my 
understanding is that for all the Institutes and the centers, 
except two, the projected success rate is to decrease in fiscal 
year 2001. What kind of evidence is there besides anecdotal 
evidence of success, and it seems to me that is not a good way 
to measure success either. How do we tell that we are funding 
good science? What measure do we have to tell us that we are on 
the right path here?
    Dr. Kirschstein. I am not sure one can have any simple 
measure. The success rate which has been used for many, many 
years is an arithmetic figure derived by simply developing a 
percent of grant applications that are funded over the total 
number submitted.
    In the 1970s, when I first started testifying, that 
probably was an approximate measure. I think today there are 
many other measures. There are measures that indicate how we 
have increased the lifespan of the members of the American 
public, not all of them, and Mr. Jackson is quite right that we 
have not had all of our population sharing in that and that is 
the goal we must go forward to meet; how much impact there has 
been on particular diseases; how much the quality of life has 
increased even for people with chronic diseases; how people are 
productive as a result of being able to work despite some 
disability being corrected; how we need to make sure that our 
public understands the science and the health areas that we 
have been working on, all of these; the new science that leads 
to the discovery day after day after day of a new gene will 
eventually make a great deal of difference in a particular 
disease or complex diseases. We are struggling with this very 
much the same way you are, Mr. Chairman. We have a number of 
ideas but we have not quite gotten there yet.
    Mr. Porter. Dr. Kirschstein, the measures you suggest are 
historical and we know that those are going in the right 
direction in most cases and we are encouraged by that. But that 
does not tell us whether last year's funding really was going 
toward promising good science or not.
    What I would like to do is challenge NIH, because this is 
the question on the minds of most Members of Congress. You 
heard it today from many members here. I want to challenge each 
of the Directors when they come here to testify that they do 
their very best to address that question and to give us 
convincing evidence, if they have it, that we are in fact 
funding the best science and that we are making good progress 
and that this money is in fact being spent wisely. No one can 
guarantee results in science, obviously. But that the money is 
being spent for promising science that would historically, 
looking at the whole lifespan of NIH, be considered good 
science at any point in that lifespan.
    Dr. Kirschstein. Mr. Chairman, as we prepared for these 
hearings, I challenged them exactly the same way.
    Mr. Porter. All right. Wonderful. You have done an 
absolutely marvelous job this morning. We are delighted that 
you are there as the Acting Director. We have great confidence 
in your abilities and in the abilities of all the directors at 
NIH. And we look forward to hearing from each of them in 
respect to these concerns.
    Dr. Kirschstein. Thank you, Mr. Chairman.
    Mr. Porter. Thank you, Dr. Kirschstein.
    The subcommittee stands in recess until 2:00 p.m.



                                        Tuesday, February 15, 2000.

                       NATIONAL CANCER INSTITUTE

                               WITNESSES

RICHARD D. KLAUSNER, DIRECTOR
ALAN S. RABSON, DEPUTY DIRECTOR
RUTH L. KIRSCHSTEIN, ACTING DIRECTOR, NATIONAL INSTITUTES OF HEALTH
DENNIS P. WILLIAMS, DEPUTY ASSISTANT SECRETARY FOR BUDGET, DHHS
    Mr. Porter. The subcommittee will come to order. We 
continue our hearings on the appropriations for the National 
Institutes of Health with the National Cancer Institute. The 
subcommittee is very pleased to welcome Dr. Richard Klausner, 
the Director.
    Dr. Klausner, we are all in awe of the job that you are 
doing at NCI. We can't tell you how much we appreciate your 
work and look forward to hearing the progress that is being 
made toward fighting cancer. So why don't you proceed with your 
statement.
    Dr. Klausner. I will. First, let me introduce on my left, 
Dr. Alan Rabson, who is the Deputy Director of the National 
Cancer Institute. This is the fifth time that I am appearing 
before this committee as Director of the NCI. I am very pleased 
to be doing that.
    I would also like to recognize, however, that it comes with 
some personal sadness that this will be the last hearing that I 
will be appearing before our remarkable Chairman. And I know, 
speaking for all our colleagues, we will greatly miss you.

                            BURDEN OF CANCER

    In my written statement, I touch on many of the programs 
and initiatives of the NCI. What I would like to do, however, 
for the next few minutes, is to share with you both some new 
previously unseen data about the burden of cancer in this 
country. And then to illustrate what you have been patiently 
listening to from me for the last five years in terms of new 
programs.
    As I have done for the last three years, I have reported on 
where we are with one measure of the cancer burden, and that is 
the incidence in death rates that are monitored by the NCI in 
collaboration with the National Center for Health Statistics. 
These are unpublished, but we have the latest numbers from 
1997. Recall that for as long as we have been following cancer 
statistics, mortality rates were rising by about a half a 
percent per year, until around 1990, 1991, when the cumulative 
changes as we have talked about resulted in that stopping and 
finally coming down by about .6 percent per year.
    From 1995 to 1997, now, the latest numbers we have, that 
rate of drop has accelerated almost three-fold to a little less 
than 2 percent per year.
    On the right is the rise in the population of the United 
States over this time.

                     CANCER MORTALITY RATE FALLING

    Mr. Hoyer. I want to clarify what you just said with 
respect to the chart on the left. As I read the chart, in 1987, 
the death rate per 100,000 was approximately 172?
    Dr. Klausner. Right, in 1987, it was about 173. And it 
peaked at around 173 to 174.
    Mr. Hoyer. From 1987 to 1997, seems to me to be a reduction 
of approximately 9 per 100,000.
    Dr. Klausner. That's right.
    Mr. Hoyer. Okay.
    Dr. Klausner. That's exactly right. So that's the age 
adjusted rate. But of course, the total burden of cancer 
depends upon the number of people in the population, the 
changing demographics, and the aging of the population. The 
total population has gone up around 7.6 percent in that time. 
Actually the population over 65 where 70 percent of the cancer 
burden has gone up by 9.6 percent.
    The question is, in terms of the total burden of cancer, 
when or will we see a decrease in the rate of enough magnitude 
to catch up with the growing and aging population? And for the 
first time, as you will see in the next figure, we have done 
that.

                   ACTUAL NUMBER OF DEATHS DECREASING

    Notice that, in the first part of this, that this is the 
actual number of cancer deaths per year in the United States. 
Over the period of time of that last graph, from 1987 about 
479,000 deaths, to 1994 about 540,000 deaths. And because of 
this acceleration in the decline of the mortality rates, we 
have, I believe, another historic change in cancer statistics, 
the first time in this growing and aging population the number 
of deaths have stopped going up. We suspect that when we see 
the 1998 numbers, they will begin coming down.
    Now, for the last four years I have shared with this 
committee many of the new programs of the NCI. For the next few 
minutes, I would like to just illustrate one example about how 
some new and, we believe, innovative programs link together to 
move from basic discovery through technology to rapid 
application to affect the lives of patients with cancer.

                        GOALS OF CANCER RESEARCH

    It begins just with a little basic science of the nature of 
cancer. Cancer is, as you have heard me talk about, a disease 
of a single cell and its descendants. It is a disease whereby 
that cell gradually over time, and its descendants, changes its 
behavior. The behavior is changed because of accumulated 
changes in DNA. A set of genes are altered, the genes of the 
instruction set that determine the behavior of the cell.
    So the goal of cancer research in some sense, the biologic 
goal, is straightforward. If we could read and decipher all of 
these molecular changes, we know we would have new approaches 
to early detection, to prevention and to treatment targeted at 
those changes.

                    UNDERSTANDING MOLECULAR PROFILES

    Now, one other thing should change, and that is how we 
actually diagnose cancer. If each cancer is defined by its 
molecular profile, then we ought to be able to finally move 
beyond a century of diagnosing cancer by what it looks like 
under the microscope and where it comes from to a molecular 
classification, something we have long waited for. The core of 
modern successful medicine is correct diagnosis. If the correct 
diagnosis of cancer is a molecular diagnosis, this will be a 
sensible progress.
    Let me illustrate how we have rapidly moved that idea to 
new discoveries, just in the last three years. The example I am 
going to use is non-Hodgkins lymphoma. But it could just as 
well be any cancer. These are cancers from two different 
patients that both received the identical diagnosis. It is 
called diffuse large cell lymphoma. Is that one disease? Two 
diseases? Are there many diseases there? How are we going to 
choose the right therapy if we don't know whether we are 
lumping or separating diseases?

              MOLECULAR PROFILES GUIDE CLINICAL DECISIONS

    Now, to answer this, as you may recall, we first created a 
national project called the Cancer Genome Anatomy Project, or 
CGAP, an effort to identify tags for all human genes and to 
link them to all human cancers. And we have pretty much 
completed that process with about 1 million tags across 
virtually all cancers. So a researcher now, who wants to answer 
this question about the molecular profile of any cancer can go 
to a web site, and they would then look up lymph nodes. They 
can see the molecular profiles, just by clicking on lymph 
nodes, and get all the potential molecular tags associated with 
normal or abnormal lymphoid cells.
    However, which of these tags do you actually use to create 
a molecular diagnosis? We don't know. Maybe thousands.
    So to read the full molecular profile of the lymphoma 
required that we create a complex array. You have in front of 
you a slide of a chip, just in case you would like to do this 
at home. This slide contains 9,000 genes. The chart contains a 
chip with 18,000 genes, a little larger than the size of a 
penny.
    To develop and disseminate this array technology required 
novel funding mechanisms, and there are now about three dozen 
institutions around the country that have been set up to apply 
these technologies, and to use the discoveries from CGAP to 
finally answer the question about molecular profiling.
    How do we do that? We announced about a year ago something 
called the Director's Challenge for Molecular Classification. 
It simply was our challenge to the community to use all of the 
genes discovered, and to link to these array technologies to 
finally reclassify all human cancers, to try to create new 
diagnostic schemes.
    The first results for lymphoma were just published last 
week, as we see on the next slide. So what happens there?
    So again we go back to our two patients, they are given the 
same diagnosis, they are going to be given the same treatment. 
Now when we use these arrays we see that this type of lymphoma 
rapidly divides into two main classifications, there are two 
new diseases discovered, and in fact there are probably other 
subtypes.
    But does that mean something to the patient? Well, with 
this disease, we tell the patient we would recommend this 
therapy, and there is about a 40 percent chance of being cured 
with the particular therapy. Why a 40 percent chance? Well, we 
think one of the reasons is because we are treating different 
diseases, one of which responds and one of which doesn't. And 
in fact that's exactly what we just discovered happened.
    If we just do in our first separation of these two new 
diseases, we see that one group of patients with a disease we 
didn't know about a few months ago can be cured to the 80 
percent level with this treatment. Whereas the other group in 
fact is only cured to the 20 percent level. And we hope in the 
next few months to figure out the remaining 20 percent.
    You can see the impact that can have rapidly. We expect 
over the next year or so this to roll out for essentially all 
major human cancers. And I show this to you to try to stitch 
together these distinct funding initiatives that you have been 
hearing about, how they link together to try to achieve things 
that we know we need to achieve in cancer.
    Now, as I said, there are many issues that I hope that we 
can touch on. Let me just close my opening statement by 
pointing out that the President has requested a budget for the 
National Cancer Institute for fiscal year 2001 of 
$3,505,072,000 including AIDS funds, an increase of 
$193,385,000, a level that we believe will allow us to sustain 
these and many other programs we have initiated over the last 
four to five years.
    I am looking forward to answering your questions.
    [Dr. Klausner's written testimony follows. His prepared 
statement with associated color charts and pictures is also 
available at http://www.nci.nih.gov/legis/fy2001.html]



                    REDUCE CANCER MORTALITY BY HALF

    Mr. Porter. Thank you, Dr. Klausner.
    Mr. Wicker, will you take the chair? I have a telephone 
call that just came in I have to answer. I'm sorry.
    Mr. Wicker [assuming chair]. Thank you very much, Mr. 
Chairman and Dr. Klausner. It is wonderful to have you here.
    Before I yield to Mr. Hoyer, let me just ask briefly, our 
colleague from the Committee, but not from the subcommittee, 
has written a letter to all of us saying that we should have 
the goal, much as President Kennedy went before Congress and 
said we will put a man on the moon before the end of this 
decade, that a President of the United States should go before 
Congress and we should all agree that by the end of this 
decade, cancer deaths would be cut in half.
    I discussed this with you before we came to order. And I 
would like to ask you, would that be possible? Do you have an 
idea of how much of an increase in resources would be necessary 
for us to achieve this remarkable goal, which would basically 
be reducing the deaths, total deaths to 270,000 per year?
    Dr. Klausner. That will take an acceleration of the changes 
we are seeing. I, as you know, am hesitant about making these 
sorts of specific predictions. Because in fact, just over the 
short tenure that I have had as head of the NCI, our 
predictions about cancer death, death rates and death numbers 
have been wrong. We have dramatically overestimated, it turns 
out, our projections of cancer deaths, because we had 
underestimated the incremental progress that was being made in 
prevention and early detection and treatment.
    I do not know whether we can underestimate or overestimate. 
What I do is to try to lay out what I think it will take to 
maximize progress. I don't exactly know whether that's halving 
or more than halving.

                      PLANNING FOR CANCER RESEARCH

    But rather, the process we have engaged in is an extensive 
and open and widely participatory process of what I showed you 
with these examples, of trying to lay out what would it take to 
maximize progress, to capture the science, to capture the 
technology, to put them together and to make progress. That is 
what we present each year to the Congress, as the law requires, 
in my professional judgement budget.
    These numbers that I presented today would lead one to be 
quite optimistic that we will be able to continue to reduce the 
burden of cancer. We are particularly pleased that the drop in 
mortality rate is not only seen for the majority population, 
but is also being seen for the black Americans, who have a 
disproportionate burden of cancer incidence and mortality 
rates. But again, the numbers, not in all cases and not in all 
cancers, are beginning to move in the right direction.
    Our goal should be to accelerate them as rapidly as 
possible. And I think by this sort of planning process, I 
believe we can participate in that.

                          PREVENTION RESEARCH

    Mr. Wicker. Let me then ask you about not the death rate, 
but the incidence rate. And of course, that deals more with 
prevention than treatment. Can you tell us how we are doing on 
that front?
    Dr. Klausner. Incidence rates are also beginning to drop. 
They are not dropping quite as rapidly, because there are 
advances both in prevention but also in early detection and 
treatment. So we are getting better at treating the cancers 
that we see.
    But about a third of the drop that we are seeing in cancer 
mortality is due to decreased smoking rates over the past 30 
years by adults. And some of the rate is also due to a 
decreased incidence of colorectal cancer, the reason for which 
we are not entirely sure, perhaps it is early screening. We are 
trying to analyze that now.
    Most of the drop we think that we are seeing for the other 
major cancers, breast and prostate, we believe, are the result 
of treatment. The nature of the statistics leads us to conclude 
this.

                           RESEARCH CONSORTIA

    Mr. Wicker. Finally, let me ask you about this research 
that you alluded to, the poster there, application to people 
with cancer, concerning diffuse large B cell lymphoma, one 
diagnosis, many diseases. How many scientists in how many 
locations around the Nation participated in this research?
    Dr. Klausner. Yes, that is a very good question. Many. And 
in fact, the Director's Challenge, which is one of our new 
initiatives, resulted in funding 10 consortia of, I believe, 34 
institutions and now there is another whole round of 
applications.
    These programs, I really believe, have captured the 
imagination of the cancer research community. The researchers 
are putting themselves together into consortia so that dozens 
and dozens of institutions are all part of it. In essence, 
these large national consortia are solving these problems.
    Mr. Wicker. Okay, so you will be able to sort of on the 
record specifically answer my question as far as who 
participated in that?
    Dr. Klausner. Yes.
    [The information follows:]

    In the first round of the Director's Challenge there are 
148 scientists at 19 institutions receiving funding support 
through 10 five-year grants. Including an additional five 
unfunded collaborators, there are a total of 24 institutions 
involved in the first round of the Director's Challenge.

    Mr. Wicker. And you heard my colloquy with Dr. Kirschstein 
this morning. Can you tell me off the top of your head if any 
NIH EPSCOR type States participated in these consortia?
    Dr. Klausner. I will have to look for those consortia. For 
the lymphoma study, it involved people at the NCI, in Nebraska, 
in California, in British Columbia. I think that was the 
collection for the diffuse large cell lymphoma. I will have to 
look and I will get back to you about it.
    Mr. Wicker. Was research done at universities?
    Dr. Klausner. Yes, these were all at universities except 
for the NCI.
    Mr. Wicker. Thank you very much.
    Mr. Hoyer.

                    TOTAL FUNDING OF CANCER RESEARCH

    Mr. Hoyer. Thank you very much.
    Doctor, the budget calls for about $3,500,000,000. How much 
money is spent on cancer research outside of NIH?
    Dr. Klausner. Fifteen percent of our budget is spent----
    Mr. Hoyer. No, I am sorry, in addition to the 
$3,500,000,000, what other monies in the United States are 
spent through independent universities, universities which are 
not NIH grant dollars? What I am trying to find out is, what is 
the total expenditure in the United States on cancer research?
    Dr. Klausner. I do not have that number. I can tell you how 
much certain large funders outside the NIH spend but not the 
totality of private investment. Many of us have actually talked 
about trying to get a number. We do not think we have an 
accurate number, though.
    Mr. Hoyer. Do you have a factor of two, three, four?
    Dr. Klausner. Our own estimate would be that the NIH's 
support for cancer research would probably be about a half. But 
I must say, that really could be an inaccurate number. This is 
an estimate, and we are not sure.

                            TARGETED THERAPY

    Mr. Hoyer. The lesson here is that because we can now be 
more discrete in our evaluation, we can treat it better and 
diagnose more quickly?
    Dr. Klausner. Absolutely. You do not want to give an 
individual drugs that are not going to work or treatments that 
are not going to work. The history of modern medicine, as I 
said, is to align therapy with the correct diagnosis.
    Now, just having the correct diagnosis is not enough. We 
are going to have to develop new therapies that are then 
targeted for those new entities. From the chart you will see 
there is one that actually summarizes that. It is sort of the 
movement we want.
    Much of cancer research, in fact, even the successes we 
have had over the past several decades, have been quite 
empirical. We have had ideas about toxic therapies and we have 
tried them. It has been actually a remarkable process of trial 
and error, extremely high precision clinical trials that allow 
us to learn what works empirically.
    Our goal, however, is to move away from empiricism to what 
we call design. There are two steps to that. One is what I have 
just shown you, what I call tailoring, that we have to be able 
to define the entity directly, so we can tailor even the 
empirical therapies to the correct diagnosis. That is the first 
thing we will do.
    But the real challenge, which we then can move on to, is 
where I see the next decade of cancer research focusing on, 
getting past the tailoring and now to the targeting. What I 
mean by that, identifying through these chips or whatever those 
molecular machines that we want to create the new medicines 
against. And that is true for prevention or for therapy.
    We have some of them. This is the path that the National 
Cancer program needs to take.

                    EARLY DETECTION RESEARCH NETWORK

    Mr. Hoyer. Doctor, one of your comments during your 
presentation was in terms of assistance in diagnosis.
    Dr. Klausner. Yes.
    Mr. Hoyer. Presumably, one of the reasons for the better 
numbers is because of early diagnosis.
    Dr. Klausner. That is right.
    Mr. Hoyer. As you know, Judy died of stomach cancer. I can 
understand perhaps Southern Maryland missing it--they diagnosed 
the ulcer, which they thought was the problem she was having in 
her stomach. We went to Hopkins and it took them almost 60 
days. And once they diagnosed, the cancer was throughout Judy's 
stomach. They took her stomach out, but it was all over her 
stomach, and there was no possibility of survival.
    My question to you is, how are we proceeding? Obviously, as 
you know, the cancer she had did not tumor. It was in the 
lining of the stomach. Therefore, very difficult, obviously, to 
diagnose.
    But there have to be ways to diagnose that in the body 
without seeing either a tumor on an x-ray or MRI or some other 
thing. I mean, obviously, for some cancers we find blood, 
diagnosis that gives a diagnosis.
    Dr. Klausner. Let me tell you what we are trying to do 
about that. You are absolutely right, and what you are 
referring to is to try to find markers so we can have tests. 
They can be blood tests, they can be fecal tests, they can be 
urine tests, or whatever measures that the process that I 
showed you in that first poster is going on--the development or 
even the existence of cancer.
    Now, the systematic discovery of all the potential markers, 
that is what this CGAP and the genome gives us. They are all 
the potential markers. But how are we going to find the right 
ones?
    Well, once again, what we need is a research infrastructure 
to allow us to systematically test for markers, to develop them 
into usable clinical tests and to validate them. So as I put in 
my written statement, this year we funded a new national entity 
called the Early Detection Research Network. And it is to do 
just that, it is to capture all these potential markers.
    We have identified 18 different institutions that will be 
attempting to discover molecular markers for any cancer. And 
they have each divided themselves up into different groups of 
cancers. Then there are two validation laboratories, something 
we have never had. When you find a market, how do you actually 
validate it? How do you actually turn it into a usable test 
that can be shared between institutions, where you know the 
operating characteristics of the test, that it is sensitive, 
that specific.
    There will be 12 consortia of institutions that are already 
funded or being funded very soon that have access to groups of 
patients, either epidemiologic cohorts or clinical cohorts. So, 
for example, we can immediately examine 100 cases of gastric 
cancer; can you detect either in the serum or in the feces a 
marker that cancer is developing? This whole network is being 
brought together by a central data and statistical center at 
the Fred Hutchinson Cancer Center.
    So we think that this new infrastructure will allow us to 
capture the possibility of these molecular tags for early 
diagnosis and early detection that we have long hoped for.

                 DRUGS AND NATURAL PRODUCTS DEVELOPMENT

    Mr. Hoyer. I still have some more time. Last year, in 
answering one of my questions, you said that NCI was moving 
ahead in research for drugs or natural substances that can help 
prevent or reduce the risk of cancer. What kind of progress are 
we making there?
    Dr. Klausner. Well, as you know, last year we ended the 
first trial of the anti-estrogen tamoxifen, reducing the 
incidence of breast caner. Those results continue to hold up as 
we look over a longer time period for women. This year the FDA 
approved as a drug that I actually think I mentioned last year, 
in terms of being in trials. It is now approved a drug to 
reduce the incidence of a particular type of colorectal cancer, 
or at least the polyps that predispose to colorectal cancer, in 
individuals that are in families at high risk.
    And there are about, I think, 85 different drugs in trials 
now that we are supporting that are aimed specifically at using 
natural products and drugs to attempt to reduce the incidence 
of cancers of the prostate, skin, head and neck, lung, 
colorectal, and breast cancer. There may be some others.
    Mr. Hoyer. I have some other questions, but I will wait for 
the second round. Thank you, Doctor.

                       ATLAS OF CANCER MORTALITY

    Mr. Porter [resuming chair]. Thank you, Mr. Hoyer.
    Dr. Klausner, you recently published the Atlas of Cancer 
Mortality in the United States, 1950 to 1994.
    Dr. Klausner. Yes.
    Mr. Porter. It contains more than 250 computer color coded 
maps showing variations in cancer death rates during 1970 to 
1994 and compares them with corresponding maps for 1950 to 
1969. I realize these show mortality rates, but what 
conclusions can we draw from these studies, and does this mean, 
for example, that there is an environmental component to cancer 
in most cases? What does it tell us?
    Dr. Klausner. Per se, these maps do not give us answers. 
They really are important data that allow us to formulate 
questions. The previous maps, have only been done twice in the 
history of the NCI, and they were very useful. They allowed the 
NCI scientists to identify the reason in Montana for a high 
level of lung cancer associated with the Anaconda Copper 
Smelting Mine.
    We also noted the high incidence of mouth cancer among 
white women in the southeast. It looked environmental, and it 
was due to a local behavior pattern of using snuff.
    So these geographic patterns may mean many different 
things. People often forget that behavioral patterns are very 
geographically different, even the general age at which women 
get married and have their first children are different in 
different geographic environments.
    The most striking geographic pattern in those maps is of 
lung cancer. And it tracks with the geographic pattern of the 
use of tobacco. But there are hints there that may reveal what 
many of us are interested in, that is, can we find pollutants 
or toxins in the environment that we can identify as happened 
the last time.

                        ANALYZING THE ATLAS DATA

    So what do we do? We have task forces that analyze this 
data, we put it out on the web so all researchers can see it. 
We have announced a special funding plan that does two things 
linked to those maps. One, we asked for applications of 
individuals or researchers that look at those maps, have an 
idea, such as looking for a toxin or looking for a behavioral 
pattern or looking for different patterns of care, because 
these are mortality, as opposed to incidence rates, because we 
can't get incidence rates by counting. And that we will fund 
applications with proposals that are linked to these maps.
    The second thing we do is put out an announcement to 
develop the methodology to use these maps and link them to 
environmental information, to the development of these powerful 
geographic information systems.
    In addition, what we do is try to make everyone aware of 
these maps. We spoke with all of the State health officials, to 
help them understand the maps, help them provide information, 
if they have questions from the public or physicians or public 
health authorities, to understand these maps.
    These maps, however, are not answers. They are important 
clues or pieces of data that allow us to then formulate 
critical questions.

                        REFINING EARLY DETECTION

    Mr. Porter. Thank you. Can we go back to the second chart 
that you had there? I have a question that bothered me, and I 
may have asked it before. I guess it is the third chart.
    Dr. Klausner. The cartoon about the nature of cancer?
    Mr. Porter. That is it. If you have a normal cell and the 
chart, it seems to me assumes this, there are many times when 
you go through a first or second mutation where the body itself 
cures it and prevents it from going to the third or fourth.
    Dr. Klausner. Right.
    Mr. Porter. The chart seems to indicate that only one of 
the five ends up being a malignant cell and a serious problem. 
If you go back with early detection, so that you can, at the 
first mutation or the second, begin to cure or provide what are 
often very intrusive treatments, are we interrupting a process 
that may never lead to a disease in a way that is harmful to 
the patient rather than helpful? How do you know?
    Dr. Klausner. As always, a terrific question. One of the 
things we need, as we identify what we call pre-malignant 
lesions, one of the things we look for are markers that we can 
do research to ask whether they predict progression or not. 
This is very important. Or else, our technology may get us to 
the point where we all have that first row probably millions of 
times in our life. And we do not want to get into a state where 
our detection technology creates frightening diagnoses of pre-
cancer and results in more harm than good.
    So as we are doing this, one of the things we absolutely 
need to do is to try to learn how to prevent that from 
happening by understanding the predicted value of detecting 
pre-malignant lesions. Maybe I could just give one example of 
that with a very common problem, and that is detecting 
abnormalities on pap smears. We know the vast majority of 
abnormalities go away. So what we are trying to do is see 
whether we can add to that a test that predicts the subset that 
doesn't go away. For example, those that have a type of the 
human papilloma virus, a subtype that is associated with 
progression into cancer, so that you don't treat lesions that 
will go away by themselves.

                    INTERNATIONAL CANCER CONSORTIUMS

    Mr. Porter. Dr. Klausner, not too many people know, 
although I wish they all knew, that you have been involved in 
at least two instances where you have brought together into 
cancer consortiums people who don't work well with each other 
politically. One was in the Middle East in 1996, and most 
recently you got Ireland, all of Ireland, the North and the 
Republic working together on an All-Ireland Cancer Center. You 
used the words, captured the inspiration of people.
    I think people need to know this. This is the kind of thing 
that I just think is wonderful, where you get people who are at 
war with each other suddenly sitting down at the table and 
finding ways to cooperate to war on disease. Can you expand on 
this and tell us more about your efforts in this area?
    Dr. Klausner. Sure, I would be delighted. First I thought 
you were referring to the fact that the Harvard hospitals 
recently got together to become a single cancer center. 
[Laughter.]

                     MIDDLE EAST CANCER CONSORTIUM

    Dr. Klausner. I led a negotiation in the Middle East, 
starting actually Thanksgiving Day 1995 to bring together 
Cyprus, Turkey, Egypt, Palestine, Israel and Jordan, to create 
now an entity called the Middle East Cancer Consortium. It has 
not been an easy road, but they have all worked very hard. It 
is a standing organization.
    They have created cancer registries through the entire 
Middle East that talk to each other, that share data. Next year 
there will be the first publication of Cancer in the Middle 
East. There is a small grants program where they have to work 
together. That has been extremely successful. In fact, all the 
members of the board of governors will be in Washington in two 
weeks for the annual meeting.
    And it has been extremely moving to go, as I did a few 
years ago, to Gaza and see that for the first time, every case 
of cancer was being registered. The members of the Middle East 
Cancer Consortium, called the MECC, from Gaza, were in constant 
touch with their colleagues in Israel about treatment and 
diagnosis.
    Mr. Porter. Has anyone in the media picked up on this and 
let people in our country or elsewhere know about it?
    Dr. Klausner. There has been relatively little media, Mr. 
Porter. In fact, that was for purposeful reasons. The 
individuals who participated in this from the region actually 
felt that there were at some risk to do this. And the decision 
we all made, I say this now because we have all agreed that 
maybe now is the time, and one of the things we are going to 
talk about in the next few weeks is to communicate this more.
    But we kept it quite quiet, because there were lots of 
uncertainties, lots of tensions. But in fact the individuals 
from the different countries felt that they were at some 
personal risk and certain professional risks to do this. These 
are very brave and committed people, and it has been a real 
pleasure to work with them.

                     ALL IRELAND CANCER CONSORTIUM

    This October 3rd, in a separate agreement, we had a very 
wonderful ceremony in Belfast, where we signed an accord 
between the United States, which I signed, Northern Ireland and 
the Republic of Ireland, to create a completely All-Ireland 
Cancer Consortium linked to the NCI. Thursday evening I will be 
leaving to go to the first meeting of the board of that to see 
progress.
    And it is really quite remarkable. Because associated with 
this for the first time, the border for cancer disappears. In 
fact, individuals diagnosed with cancer in the northernmost 
three counties of the Republic are now seen at Belfast City 
Hospital. And all of that system is linked by fiber optics to 
the Bethesda campus. I think it is a model for how NIH can play 
a very special role in not only advancing causes of our 
approach to disease, but in fact getting people to talk to each 
other.
    Mr. Porter. Now, here you can publicize this. The people of 
Ireland can know about this, is that right?
    Dr. Klausner. Absolutely. And they do. It was very heavily 
publicized. There is a film that was made of the process which 
is going to be shown, I believe, in a few weeks on Capitol 
Hill. We will make sure everyone gets invitations.
    Mr. Hoyer. Mr. Chairman?
    Mr. Porter. Mr. Hoyer.
    Mr. Hoyer. Machiavelli would observe that one of the 
secrets to getting disparate interests together is creating, or 
identifying a common enemy.
    Dr. Klausner. And that is exactly what happened in both 
these of cases. It is really quite remarkable.
    Mr. Porter. That is wonderful. Thank you very much.
    Ms. DeLauro.

                        OVARIAN CANCER RESEARCH

    Ms. DeLauro. Thanks very much, Mr. Chairman.
    Dr. Klausner, always a pleasure. Thank you for your work. 
It is as simple as that. You make a difference in people's 
lives. Let me personally applaud you for the efforts to fund 
the two ovarian cancer spores, partially fund two others.
    I wanted to pick up the thread of what Mr. Hoyer was saying 
about diagnosis. Then what you talked about in terms of the 
identification of markers which help us to lead to the 
diagnosis.
    Fourteen years ago, as you know, I was diagnosed with 
ovarian cancer. Today still there is no effective way to detect 
whether or not someone has ovarian cancer, so that the whole 
question is of how one can make sense of this.
    I was stunned, though, not too long ago, to read that 
people were talking about a sonogram as the way in which, there 
might be a good way of that. That, quite frankly, is the way in 
which I was diagnosed, but that is 14 years ago.
    Dr. Klausner. Right.
    Ms. DeLauro. With all of the work that is being done, and I 
applaud every effort that is being made, what is, in your 
sense, the path that we are taking on ovarian cancer? I am not 
asking you to predict or use a crystal ball, etc. But you and 
the profession have some idea of where we might be on this road 
to being able to identify the marker, to identify the way in 
which we can get to early detection, so that we can deal with 
prevention.
    Dr. Klausner. Again, I am never very good at saying exactly 
when we can do something. But I feel confident that we have 
acted to do the things that have not been done and in some 
sense, couldn't be done, to make sure that we can get to 
markers for ovarian cancer. Again, that was one of the points 
of CGAP, when we started CGAP there were no known markers, 
molecular markers, genes that were uniquely expressed in the 
ovary that we knew about and were confirmed. Now there are 
something like 400 that were discovered, not by 400 different 
grants, but by creating this very rapid discovery process.
    We have, as I said before about this early detection 
research network, the reason we set this up, and it took 
several years of planning, is because the country did not have, 
we did not have in our research enterprise a systematic way to 
go from a lot of small studies that often came and went, to 
having all of the potential markers and having an 
infrastructure that allows us, one, to agree upon standards, 
what is a good marker, how do you determine operating 
characteristics.
    And having this structure, which I am quite optimistic 
about, I believe three of the centers are focusing on ovarian 
cancer. All of these investigators feel exactly the way you 
feel, it is time to try to definitively use now all this 
molecular and genomic information, these new technologies, to 
try to test not just one, not just two, but what we hope is all 
possible markers.
    Now, it doesn't guarantee that a marker will come out of 
that. But it means, I think, that we are moving through the 
possibilities much more quickly. I am actually quite optimistic 
that there will be markers from this process.
    Ms. DeLauro. Fully funding the spores in 2001 is in the 
cards here?
    Dr. Klausner. I believe so. We will have to see what the 
2001 budget is. [Laughter.]

                             SMOKING TRENDS

    Ms. DeLauro. We have to keep pushing.
    I want to find out if I heard you right on this issue, and 
then I have a final question on cervical cancer. I think you 
said one-third drop in the incidence of cancer mortality was 
because of a decrease in smoking.
    Dr. Klausner. That is right.
    Ms. DeLauro. And that is with all ages?
    Dr. Klausner. Well, of course, it is the adults that stop 
smoking, about 50 percent of the smokers over time stop, 
starting about with the Surgeon General's report in the early 
1960s. And then it took 20 years to see the accumulated benefit 
of that, just like we are going to see the accumulated disaster 
of the increase of youth smoking of we do not find ways for 
that to stop.
    Ms. DeLauro. Well, that is where I am going here. I think 
this is remarkable and I think we ought to have something that 
is laminated here to put this in front of us who have the 
wherewithal to do something about prevention and with underage 
smoking. We have 3,000 kids a day who start to smoke. And we do 
not have in all 50 States at the moment the kind of funding 
that is needed to work at trying to curtail underage smoking.
    And we could go further with this. I mean, we know what is 
causing this, and we sit back. On one hand, we spend millions 
of dollars in your shop to deal with this and on the other 
hand, we spend millions of dollars to promote the effort. I 
mean, let's be cost-effective in what we are doing. We sit 
around here, a lot of it jawboning about what is cost-effective 
and where we are spending our money and what we are doing. And 
we are increasing the incidence of smoking in this country, 
particularly with young people.
    I just think that it is a lot of wonderful words and a lot 
of wonderful talk here in what we do. Unless we are going to be 
serious about trying to deal with ending and preventing it from 
starting to smoke.
    I do not know what you are doing on the issues. I know the 
Chairman is interested--and I am--in Bedees and what is going 
on with the cigarettes that are coming from India which are 
flavored and how that is increasing.
    That was not meant to be a speech, but I think it is a 
powerful piece of information which we need to make sure that 
members of this body understand when we are talking about 
doubling the money for what you do and on the other hand, 
doubling not doing anything about preventing what we can be 
preventing with kids.
    Let me talk about cervical cancer for a moment here. Number 
one cause of mortality in women worldwide, the number of deaths 
from endometrial cancer increasing. Can we anticipate from NCI 
that you will move forward with a program of reviewing these 
two major gynecological cancers in fiscal year 2001?

                            CERVICAL CANCER

    Dr. Klausner. Yes.
    Ms. DeLauro. Do you anticipate in those areas that we might 
see the spores?
    Dr. Klausner. Yes, in fact, both of those will happen. We 
have this disease specific planning process called a PRG, 
Progress Review Group. And there will be one in 2001 for 
gynecologic cancers. And the spore program has now been 
announced as, it has always been targeted at a few cancers, we 
now have a five year plan to expand what we believe is a very 
successful program in translational research covering all 
cancers, including gynecologic cancers.
    I will say that last year I mentioned the development of a 
vaccine for human papilloma virus. We have the results of the 
phase I and II trials now. Every individual that was vaccinated 
proved the vaccine to be safe and remarkably effective at 
eliciting what we would predict would be a protective immune 
response. I have reviewed that data and it has allowed us to 
accelerate movement to a field phase III clinical trial, which 
we will be doing in collaboration with our colleagues in Costa 
Rica and Guano Coast Province. So hopefully we will be moving 
towards developing a preventive vaccine for the cause of 
cervical cancer.
    Ms. DeLauro. Thank you, Dr. Klausner, thank you, Mr. 
Chairman.
    Mr. Porter. Thank you, Ms. DeLauro.
    Mr. Cunningham.
    Mr. Cunningham. Thank you, Mr. Chairman.
    I have a lot of questions for you, Doctor, most of them 
softballs.
    Dr. Klausner. Thank you, Mr. Cunningham. [Laughter.]

                           MARKERS FOR CANCER

    Mr. Cunningham. Well, you have a stronger supporter here, 
and I think you know that.
    First of all, when you talk about the decline, I would have 
to think that Ms. DeLauro was talking about markers, that the 
PSA marker has caused a lot of that decline. The reason I say 
that is since I have been out speaking in the community telling 
people about getting PSA, Mayor Dick Lyons, which is in my 
district, Mayor Corky Smith, my own father-in-law, all had 
PSAs.
    And it wasn't just the early detection of cancer, but the 
quality of life. They are not impotent, they are not 
incontinent because of their early detection. So it is not just 
life, but the quality of life. I try to make it my 
responsibility to go out there and talk about not only prostate 
but breast cancer and ovarian cancer and the rest of it.
    Would you agree that we can find, like Ms. DeLauro was 
talking about, markers in ovarian cancer? I know last year we 
talked about maybe up to five of these markers possibly being 
discovered. Wouldn't all of those kinds of recoveries reduce, 
on your chart, reduce not only incidence but the number of 
deaths?
    Dr. Klausner. Yes, we would certainly expect so, and 
certainly hope so, particularly for ovarian cancer, where right 
now the majority of women diagnosed with ovarian cancer 
diagnose after it has spread.

                          NUMBER OF NEW GRANTS

    Mr. Cunningham. That leads me into my next question. It may 
sound partisan, but it is not, because I have a specific 
purpose for stating it this way. The President's budget right 
now does increase the money for NIH, although it decreased it 
last year, in the last budget. And it also increases it for 
NCI. But as I understand it, it reduces the number of new 
research grants for the program.
    The reason I say that, A, I have a daughter that wants to 
go into research. This bothers me, I want to make sure that the 
research grants are there.
    But secondly, what Ms. DeLauro was talking about, what I am 
talking about, new technologies. When I go to Dr. Bachorn in 
San Diego that has a group of people with prostate cancer, I go 
to the hospital with women that I talk to that have breast and 
ovarian cancer, they want something new. They want hope of what 
is on the horizon. If we eliminate these new research grants, 
then I think we are short-circuiting the potential for future 
growth.
    Would you agree, and if so, maybe for the record, what 
would you recommend for the new research grants that have been 
eliminated under this budget?
    Dr. Klausner. Well, as Dr. Kirschstein said this morning, 
the issue of the grant numbers in fact are only a piece of the 
picture of what we do. If you are asking me whether I would 
rather see an increasing number of grants, yes. But there are a 
lot of other mechanisms that we are using that are very 
important that we use. Clinical trials, technology development, 
as you say, that don't show up as grants.
    Dr. Kirschstein also made a very important point which we 
are seeing, and that is, the dollars per grant. The research is 
getting more expensive. It is not just that we have 
underfunded, which we have in the past. But it is also getting 
more expensive.
    And let me give you a flavor for that. This year, our 
program project grants, we predicted how many we can fund. The 
average cost of the new grants that are coming in have gone up 
almost 50 percent over what we predicted. The same thing is 
happening to many of our grants.
    So, for example, this year our pay line for investigator 
initiated research dropped from the 24th to the 22nd 
percentile. I know there have been some questions about why 
with a 15 percent increase. But the dollars going into the new 
grants are going up by 17.7 percent because of the increased 
number of applications and the change in different types of 
grants, and very importantly, the increase in the average cost. 
And I think we have to look at all of those.
    Mr. Cunningham. Let me shoot my own self in the foot here, 
because I have concern on the other side of it. I went to 
Scripps, and they are still looking at cancer like Dr. Salk 
looked at immunizations--actually injecting some of the virus 
into the individual. They are still looking at this in an old 
grant. But they are concerned that because of the new grants, 
they may lose this one, and they think they are right on the 
edge.
    So I am sort of like in a tennis match with myself on this. 
The genome program is also at Scripps, I see these machines, 
they are $100,000 apiece, and there are 25 of them laid out. 
You see these little genes, what took Mother Nature millions of 
years, and they are going through this research, it is 
exciting. They tell me that it is only just the mapping, but 
the new medicines that are being looked at.
    But I understand it, too, that in the future, we may take 
someone that says, well, you have a higher propensity 
genetically to get cancer or Alzheimer's or Parkinson's, and 
maybe we can start early treatment, whether it is eating a lot 
of tomatoes, like I do now, or even the diet. So one of the 
things that I would say is, some of my colleagues always say, 
well, tax breaks are always for the rich. Those devices for 
research cost $100,000 apiece. And those research and 
development tax breaks are able to fund those hospitals like 
Scripps, like UCSD and those to go forward also.
    I am especially glad to see Ireland in this, maybe even 
more than the Middle East with me. I had not heard that, and I 
am glad the Chairman brought that up, because I think it ought 
to be talked about. And the areas that we can possibly bring 
peace without that.
    I would also look at an area that Ms. DeLauro talked about 
that concerns me. My Uncle Frank died of lung cancer. He smoked 
probably five or six packs of Lucky Strikes a day, unfiltered. 
My Uncle Abe died of tongue cancer, it was smokeless tobacco, 
the chewing tobacco that he ate. Carrie, my oldest daughter, 
was in Spain, and I am not exaggerating, I bet 99 percent of 
the youth that I saw there smoked in Spain.
    I would be in support of the gentlelady on limiting the 
number, they haven't got the market here, they are killing 
people overseas. I think we ought to get into that environment 
with the tobacco industry as well. The only thing I will not 
support is the money going, billions of dollars, to the trial 
lawyers, so they then put it back into the DNC against us. That 
is one of the pitfalls of this thing and the politics that 
enter into it.
    But I think there are areas where we could really work 
together with this. Young people, we should do everything we 
can to keep cigarettes, you don't smoke in my house, my car, my 
boat, anything. Neither one of my parents smoke, and I am very 
thankful for that.
    But I want to personally thank you. I know there were some 
last year that said we were spending too much on medical 
research. They were not being mean spirited, they thought we 
took it out of other areas. Our priority in the Republican 
Conference is to increase medical research and to increase it 
at least by 15 percent again. We will continue to do that as 
long as we are in the majority, which is a long, long time, I 
will tell you, Doctor.
    Dr. Klausner. Thank you very much, Mr. Cunningham.
    Mr. Porter. Thank you, Mr. Cunningham.
    Mr. Jackson.
    Mr. Jackson. Dr. Klausner, I want to take this opportunity 
to thank you for coming before our Committee to discuss your 
budget. I have this funny feeling you know the line of 
questioning I am about to pursue, don't you?
    Dr. Klausner. I do.
    Mr. Jackson. You know the same line of questioning I 
pursued last year?
    Dr. Klausner. Yes.
    Mr. Jackson. So this year we should have some answers in 
this area.
    Dr. Klausner. We do.
    Mr. Jackson. I would like you, since you have the answers 
to the questions that you know I am going to ask already----
    [Laughter.]

                 OFFICE OF RESEARCH ON MINORITY HEALTH

    Mr. Jackson [continuing]. To approach this question a 
little differently. I would like to know how you characterize 
the National Cancer Institute's relationship with ORMH?
    Dr. Klausner. I characterize it actually as a very 
productive one. Dr. Ruffin and I meet and talk regularly. He 
works very closely with our Office of Research and Special 
Populations. We develop plans together, Dr. Ruffin develops 
plans separately and we develop plans separately and then we 
engage each other on it.
    Mr. Jackson. How would you then characterize your 
relationship with Dr. Ruffin, personal, professional or both?
    Dr. Klausner. Both.

                     AFRICAN-AMERICAN CANCER BURDEN

    Mr. Jackson. So when Dr. Ruffin, I assume in his 
professional capacity, or in his personal capacity, approached 
the National Cancer Institute's Director, yourself, Dr. 
Klausner, and indicated that African-American cancer death 
rates were 35 percent higher than whites, and the incidence of 
rate for lung cancer in African-American men was 50 percent 
higher than white men, I am particularly interested in what 
your response to that was.
    Dr. Klausner. Well, I do not recall Dr. Ruffin coming to 
tell me that. I am well aware of that, and we know that data 
because of the monitoring that the NCI does, monitoring that we 
need to increase as we agreed and talked about last year, which 
I would be happy to talk about.
    Our goals are several-fold in dealing with those issues. 
One, we need to get that information. It is important that you 
and I and everyone know that information, which is why the NCI 
has a surveillance system that monitors, with high quality, we 
believe, the burden of cancer among different populations. We 
need to increase and enhance that. Because the beginning of 
intervention, of fixing things, is to not only document the 
information, which we do, that's where you get those numbers 
from, but also then to attempt to use that documentation to 
begin to understand why.
    Is it due to altered risk factors? Is it due to altered 
medical care? What sort of altered medical care, altered in 
terms of prevention, in terms of early detection, in terms of 
diagnosis and in terms of treatment? These are complicated 
issues, and it requires good data and an extensive research 
program.

              FUNDING FOR RESEARCH ON CANCER IN MINORITIES

    Mr. Jackson. I accept that, Dr. Klausner. Let me try and 
take it one step further.
    First of all, it is hard for me to imagine that Dr. Ruffin 
did not approach you about these alarming statistics. Secondly, 
the Chronicle of Higher Education indicated that at your 
particular institute, a 1993 story that less than 1 percent of 
grants from NIH were given or granted for the purposes of 
addressing this kind of research.
    So far there is no evidence, and maybe you are going to 
offer some evidence to the contrary of the statement I am about 
to make, that that information triggered at the National Cancer 
Institute more research grants in the area that those 
disparities appear to be most prevalent.
    Dr. Klausner. Well, first of all, there was a very 
significant disagreement about those numbers. That is a very 
important issue, because we need to be accountable, and we need 
to believe when we say we are spending a certain amount of 
money, that it is true or not. This is extremely important.
    So we had said that in 1997, which were the numbers that 
the IOM report looked at to reach the 1 percent, that we spent 
$124,000,000 in grants and projects aimed at the issue of 
disparity in minorities in cancer. Their calculation was that 
it was $24,000,000, not $124,000,000.
    Mr. Jackson. I agree. The IOM report claimed that you spent 
$24,000,000, NCI claimed that they spent $124,000,000. But out 
of a $3,000,000,000 budget, don't you think that $124,000,000 
is not enough to eliminate cancer disparities?
    Dr. Klausner. First of all, we did get an independent 
entity to review the dollars. Because this is important, to 
know what we spend. The issue is both what we target and where 
the answers are coming from. I think that is an important thing 
to distinguish, because not all of our research that is aimed 
at the issue of disparities is targeted by the dollars that go 
out the door.
    Let me explain how we evaluate them, and I think this is 
very important. Because we want to understand, we want to know 
whether our researchers are listening to what everyone is 
saying about the importance of this. So we reviewed the best 
measure of the outcome of our research, and that is, published 
information, information about the disparate burden of cancer, 
the causes, where it is, why.
    We identified hundreds of articles that were funded by NCI 
that produced that information. Interestingly, it turned out 
that only 20 percent of them were funded by the research that 
we coded as being directed towards the issue of the unequal 
burden of cancer.
    What I am trying to say is, I do not know exactly what the 
right percentage is. My view is, we need to make sure that we 
have a planning process that addresses all of the issues. Do we 
know the burden? Are we studying the reasons for the burden? 
Are we getting results from that? Are minorities participating 
in research as participants across the whole continuum? And 
then, we make sure that our programs are aimed that way.
    I think our evaluation is that they are. We need to do 
more. We can do more. Should it be 5 percent or 6 percent or 7 
percent, specifically directed at the disparity? It is not just 
talking about the money that is directed at the diseases that 
disproportionately affect certain groups in the United States, 
but the actual issue of the disparity itself.
    Whether that issue, and when you calculate that burden, I 
don't know exactly what number to come up with. Should it be 5 
percent, should it be 10 percent, I do not know where it is, 
exactly what the numbers should be. We need to be held 
accountable for, not these precise numbers, I believe, but 
whether we have the research programs that are addressing it.

                          MINORITY RESEARCHERS

    Mr. Jackson. Well, Dr. Klausner, I accept that. But maybe 
in light of the fact that some people go into research 
particularly for self-motivated reasons. Right now there is an 
absence of minority researchers, women, African-Americans, 
Hispanic researchers. In part because they argue that the 
market for research grants is closed to them. They can't get 
access to research grants to determine what indeed is 
appropriate for their level of research at minority 
institutions.
    So since in the final analysis, the money is where the 
rubber meets the road, maybe you can tell us today how many 
grants were awarded in fiscal year 2000, since it has been a 
year since I asked my questions last, to minority researchers 
or minority serving institutions, who are particularly 
interested in pursuing that data?
    Dr. Klausner. I can tell you that the dollars aimed at the 
issue of the unequal burden of cancer, which have gone up from 
$124,000,000 to $155,000,000. But one of the things that we 
recognize, in order to address what you are saying, and you are 
absolutely right, is how do we make sure that the research 
community is open to and is perceived as being filled with 
opportunities for people who have not been part of it.
    And working with many advisors over the past two and a half 
years to address this, during the course of the IOM report, we 
decided to establish two types of new funding initiatives. One 
is to create across the Nation new research enterprises called 
Special Population Networks. Our board originally approved this 
for $6,000,000 a year for 5 years. The idea of this is to 
create a funded infrastructure within different underserved and 
minority communities to support the development of research, 
learning how to do research, linking to research enterprises 
for cancer.
    We have set it up with the NCI Cancer Control Academy on 
our campus where all the people that are funded for this will 
come and be part of the Cancer Control Academy, where they will 
be linked to all the outreach cancer control prevention 
research within the communities. We were overwhelmed with 
applications.
    We have recently decided a funding plan, and we increased 
that program to about $60,000,000 over the next five years, the 
largest program as far as I know that we or anyone have ever 
done along these lines, and it covers minority communities that 
we have not addressed before.

            STRATEGIC PLANNING FOR MINORITY HEALTH RESEARCH

    Mr. Jackson. I recognize that my time has expired, Madam 
Chairman, but since there are only three of us, may I just ask 
the panel's indulgence for just one more question, and then I 
guess there is going to be a second round? Or how would you 
like to proceed, Madam Chairman.
    Thank you, Madam Chairman.
    Let me try and say that I could not disagree with that 
more. That is my first point. What I am hoping not to achieve 
here is a defensive answer to what appears to be a problem at 
NIH, according to Dr. Sullivan, the former HHS Secretary. By 
creating these kinds of special centers for research for 
specialized populations, from my perspective, to head down a 
very political road that is fraught with dangers in a very 
politically charged environment, affirmative action, some kind 
of little setaside for minority health issues at NIH designed 
to address some of these behavioral patterns, as opposed to the 
fundamental problem at NIH, that across the entire system, 
minorities through the 22 or 23 centers, offices and 
institutes, are receiving less than a reasonable fair share of 
opportunities to compete for grants across that center.
    You indicated by your own admission that Dr. Ruffin had not 
brought to your attention certain statistics that are already 
obviously known. But the response that the institute itself did 
not determine that finding a way to review its grant process 
and determine why minority institutions and minority 
researchers are not receiving and beneficiaries of these 
grants, I find to be deeply troubling and problematic.
    So we proposed a piece of legislation that Mr. Wicker 
supports, a number of members in the majority support, to 
establish a strategic plan for minority health research, a seat 
at the table, along with yourself and the NIH Director, grant 
making authority for that center, support for infrastructure 
improvements at minority research institutions.
    And I want to know, as opposed to heading down the pathway 
of setting up some kind of specialized centers, what your 
opinion is on better coordination amongst the institute, center 
and office directors, with the present ORMH director for the 
purpose of addressing some of these fundamental disparities, 
that exist not just in the society, but NIH in particular?
    Thank you, Madam Chairman.
    Dr. Klausner. I think there should be better coordination. 
I think there has been a lot of coordination. But we do 
disagree about the fact that if we have a process of planning 
involving many people who care about this problem, and they say 
one of the most important funding initiatives to get grants to 
individuals would be to create these funding programs, as we 
have done over the past couple of years, we just disagree.
    We have a planning process to address these issues. We are 
trying to. They are difficult issues to address. The fraction 
of our training grants that are aimed at minority populations 
are growing. They have grown from 6 percent to 7.5 percent to 
next year being 11 percent. The number of training slots from 
the Cancer Institute for post-graduate training aimed at 
minority participation has grown over the past two years by 55 
percent.
    So I think, I'm not sure what you mean by this is just a 
setaside. This is part of our very serious commitment to trying 
to address the issues that you raised, that I think we are not 
disagreeing about. I happen to think these special population 
networks are exactly one of many funding initiatives that 
represent the type of activities that, if they are successful, 
will move towards redressing these inequalities in the NIH 
granting system and research system that we have for a long 
time been trying to fix.
    Mr. Porter. Thank you, Mr. Jackson.
    Mrs. Northup.

                          RESEARCH CAREER PATH

    Mrs. Northup. Doctor, can you tell me how new 
investigators, lead investigators, usually get there? And just 
a short version of it. Is it because they rise up in an 
existing research program, say become second or third in 
command and then get attracted by another institution to lead 
their program?
    Dr. Klausner. No. The most common way that individuals get 
their own research program is very early in their career they 
finish their training period, which is called a post-doctoral 
fellowship, they are being mentored. And then when they finish 
that mentoring period, maybe three years or four years or five 
years where they have been mentored, they then go off on their 
own and apply generally for their first NIH grant.
    Mrs. Northup. Well, it seems to me if we are interested in 
raising the number of minority leaders in these programs, that 
that can't be done tomorrow, that we need to sort of assess 
where in these post-graduate doctor programs, which you say is 
almost the single or main source of future lead scientists, 
whether or not they are open and available to minority 
populations.
    Have you all done that?
    Dr. Klausner. Yes, we have. We did a fairly extensive 
analysis in terms of the cancer program of this idea, the 
question of the pipeline, where are the individuals, where are 
they leading the pipeline. The issue is that there is a lack of 
individuals at all points along the pipeline, in undergraduate 
science, even the question of interest in science, as high 
school students.
    So when we analyzed that, one of the things we did is we 
gave money to our cancer centers that are in communities all 
around the country to develop relations with schools and local 
institutions, to bring them in. So we are trying to address it, 
but there is no one point.

                    ATTRACTING MINORITY RESEARCHERS

    Mrs. Northup. One of the past concerns that we have looked 
at on this committee and subcommittee is the concern for the 
number of students that have the potential to be top rate 
scientists, actually going to med school, the remunerations are 
greater, the opportunities to be in control of their career is 
greater. And we found that in all populations, that there is a 
great number of we might wish we could attract into research 
that are in med school.
    Would you say this is true for minority populations, too?
    Dr. Klausner. Yes, I believe it is. And Dr. Kirschstein may 
have some more to say on that.
    Dr. Kirschstein. Mrs. Northup, we do find that is a big 
problem. Now, within the intramural program of NIH, we have 
authority to bring those medical students and college students 
to work for us and to forgive the debt. We have that authority 
in the intramural program.
    Mrs. Northup. If they want to be researchers.
    Dr. Kirschstein. If they want to be researchers.
    Mrs. Northup. But if they want----
    Dr. Kirschstein. What has not been available to us, through 
our authorities, is to do the same thing, and it would be 
particularly important for minority students who are studying 
at our universities, medical schools, be they HBCUs, Hispanic 
Serving Institutions or other schools. We do not have that 
authority at present. We have been asking for that authority 
for several years and indeed we have asked for it again this 
year through the appropriations process. This has the potential 
to increase the number, particularly, of minority students very 
significantly.
    It is an authority to allow the students who work part-time 
for us in the summers as researchers or work in research 
laboratories for a year not to have to pay the debt they incur 
if they go to medical school. The Government would pay off the 
debt for them. We have been looking for that authority for many 
years. We hope we will get it this year, finally.
    Mrs. Northup. Okay. But the point is, the challenge that we 
have is attracting top rate scientists into research when they 
have the opportunity to go to medical school. Because what has 
been a problem for this committee is, how do we keep them in 
research.
    Let me ask you another question about the parity issue, the 
opportunity issue. If you get an application, you said, as 
someone at this hearing said, that it is a choice whether or 
not you disclose your race, is that correct? So how do you know 
what the percentage is?
    Dr. Kirschstein. The individual has to self-identify. If an 
individual does not wish to identify his or her race or 
ethnicity, we do not push that.
    Mrs. Northup. And it is the lead investigator?
    Dr. Kirschstein. Yes, this is the lead investigator.
    Mrs. Northup. Usually, the programs that I am aware of, 
there is a lead investigator, there are several top assistants. 
There may be some med school participants, there may be some 
Ph.D. assistants. Do they identify everybody that is in the 
program? Is there a space for that?
    Dr. Klausner. No, it is only the principal investigator.
    Mrs. Northup. So in fact, you could have, for example, you 
know, the lead investigator in 10 percent of the cases might be 
a minority, but if they are the only one that exists, you would 
have 1 percent, maybe, of the people actually participating and 
likewise, at every level. So have you done research to 
determine at every stage what the percentage is? Is there any 
way to determine that since it is not identified?
    Dr. Klausner. No, we have not done that.
    Dr. Kirschstein. It is extraordinarily difficult to do it 
that way. What we do have are data that are collected by the 
National Science Foundation on the number of Ph.D. scientists 
and M.D. scientists in the biological field who are in 
research. We know that unfortunately that number is 
extraordinarily small for minorities. We have been working very 
hard for a long time to increase the number.
    And I do believe that we have found through both our 
intramural program and some of the other programs we have been 
running for a long time, the MARC program and the MBRS program, 
that there is an enormous interest among minority students in 
research careers. But because of the economic situation, and 
the fact that they are more in debt very often than are even 
majority students, we cannot give them this opportunity that 
they have in our limited intramural program. I believe this is 
a very important facet.

                    ATTRACTING MINORITY RESEARCHERS

    Mrs. Northup. So you believe that there are students out 
there that have the interest, but that the question is in terms 
of scholarship availability, grant availability for them to 
participate in graduate school, scientific efforts.
    Dr. Kirschstein. To some extent, I believe that. That is 
not the whole answer, but it is a big part of the answer.
    Mrs. Northup. I believe that many of these questions, and I 
will look forward to when the Department of Education comes 
before us, because I have always believed that we fail kids 
when they are five years old, six years old, seven years old, 
so that a child who has all the academic ability when they are 
a sophomore in high school to become a doctor or researcher, 
that because of what was not done in sixth grade and seventh 
grade and eighth grade, they are not in a position to make up 
their mind to choose their choice at that point.
    Dr. Kirschstein. We agree with you.

                               RURAL POOR

    Mrs. Northup. And I think that those questions need to be 
asked.
    Mr. Chairman, can I have the indulgence, since a little of 
my time was passed? I do want to pursue one more question along 
this line, and that is the question that we have in Kentucky. 
There is the very important research about populations that are 
at greater risk. We have that in Appalachia. Our rural poor, 
the incidence of cancer and other illnesses are very high.
    But unfortunately, based on your definition of what is 
included in these populations, you do not have a category and 
you cannot accept rural poor. So while we have researchers in 
Kentucky that are eager to receive grants, they do not receive 
them under these grants.
    Dr. Klausner. Just going back to this particular enterprise 
of the special populations network, it does include the rural 
poor. And in fact, part of our planning about the unequal 
burden of cancer relates to not just minorities, but the 
underserved.
    Mrs. Northup. You mean it is included in health 
disparities? Your health disparities recognizes rural poor?
    Dr. Klausner. Yes.
    Mrs. Northup. Because I have been specifically informed by 
my State that it did not qualify.
    Dr. Klausner. Yes, and one of these special population 
networks in fact is specifically in Appalachia.
    Mrs. Northup. Okay. Thank you, Mr. Chairman.
    Mr. Porter. Thank you, Mrs. Northup.
    Dr. Klausner, you would characterize yourself as a 
molecular biologist, would you not?
    Dr. Klausner. I used to. [Laughter.]
    Mr. Porter. But your background is in molecular biology?
    Dr. Klausner. Yes, it is.

                     BEHAVIOR AND NUTRITION CANCER

    Mr. Porter. I wonder, because we know that, or at least we 
think we know that there is a mental component to the disease 
and there maybe a dietary component to the disease. How many of 
your grants or how much of your total spending is spent on 
biology as opposed to other areas?
    Dr. Klausner. Well, of course, the intersection between 
nutrition and biology and behavior and biology is not precise. 
One of the things that we have done is to reorganize, as many 
things, completely, our approach to cancer control, creating a 
new division that would really be able to grow and achieve what 
I think it already has, an international prominence in 
behavioral and other approaches to cancer.
    I am actually very proud of that at the institute. Barbara 
Rimer is the Director of this new Division. Our commitment to 
programs in behavioral sciences actually have grown I believe 
the fastest of any area, both in terms of setting up a basic 
behavioral program, a new program in health communications, 
communications research, applied behavioral research in terms 
of whether people engage in healthy behaviors, or helpful 
behaviors, how they make decisions, aimed at tobacco, aimed at 
cancer survivorship issues and behavioral issues and 
psychological issues around that.
    So this has been an area where we have been very successful 
recruiting and actually have quite a new program that has grown 
to, I believe this year, $192,000,000 in behavioral research at 
the NCI.

                         HIGH DOSE CHEMOTHERAPY

    Mr. Porter. Thank you. There is some concern among clinical 
researchers that experimental treatments, such as bone marrow 
transplants for breast and ovarian cancer, have not been proven 
more effective than standard treatments, such as chemotherapy. 
Researchers are also concerned because so many patients are 
opting for these experimental treatments that there are not 
enough willing to participate in a clinical trial to prove 
their effectiveness.
    What do you think about this? Is it a problem? If so, what 
should be done?
    Dr. Klausner. What you raise is a very specific issue of 
high dose chemotherapy that destroys the bone marrow, requiring 
bone marrow rescue. It's primarily for women with breast 
cancer. It also is being looked at for women with ovarian 
cancer.
    You described the issue very well, and that is, there was 
great enthusiasm for the potential benefit of this therapy, 
without it being subject to the definitive and rigorous testing 
of a randomized clinical trial. This was a very high priority 
for the NCI, and it took way too long, eight to nine years, to 
get answers. We still do not have the complete answers.
    Five studies were presented last year at the American 
Society of Clinical Oncology. There is little question in 
anyone's mind that one of the difficulties is that because of 
the sense that this therapy ``worked'' and what you would offer 
a woman when you had nothing else, many women received this 
therapy outside of the clinical trial setting, and that 
profoundly not only competed with, but also discouraged people 
from participating in clinical trials, both the physicians and 
the patients.
    This meant that the answers were a very long time in 
coming, which did not serve these women well. As you probably 
know, the answers appear to be, from the clinical trials that 
were performed, that there is at this point no discernible 
benefit between this high dose, very toxic and, at times fatal 
therapy with stem cell rescue and the standard best practice 
chemotherapy. That answer only came because of clinical trials.
    Mr. Porter. Dr. Klausner, multiple votes have been called. 
While we have many more questions for you, I do not think it is 
fair to ask you to stay while we go over and vote. So we are 
going to submit the remaining questions for the record.
    As always, you do a magnificent job of not only explaining 
complex matters, but the enthusiasm that you show and the 
evident tremendous degree of interest in educating us is very, 
very much appreciated. You are showing great leadership in so 
many areas. As I said earlier, we stand in awe of the work that 
you are doing there.
    Thank you very much.
    Dr. Klausner. Thank you very much, Mr. Chairman.
    Mr. Porter. The subcommittee will stand in recess until 
10:00 a.m.



                                      Wednesday, February 16, 2000.

    NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

                               WITNESSES

DR. JAMES F. BATTEY, JR., DIRECTOR, NATIONAL INSTITUTE ON DEAFNESS AND 
    OTHER COMMUNICATION DISORDERS
DR. DONALD H. LUECKE, DEPUTY DIRECTOR, NATIONAL INSTITUTE ON DEAFNESS 
    AND OTHER COMMUNICATION DISORDERS
WILLIAM DAVID KERR, EXECUTIVE OFFICER, NATIONAL INSTITUTE ON DEAFNESS 
    AND OTHER COMMUNICATION DISORDERS
PATIENCE T. SPARKS, BUDGET OFFICER, NATIONAL INSTITUTE ON DEAFNESS AND 
    OTHER COMMUNICATION DISORDERS
DR. RUTH L. KIRSCHSTEIN, ACTING DIRECTOR, NIH
DENNIS P. WILLIAMS, DEPUTY ASSISTANT SECRETARY, BUDGET, DHHS
    Mr. Porter. The subcommittee will come to order and 
continue our hearing with the National Institute on Deafness 
and Other Communication Disorders. We are pleased to welcome 
Dr. Battey. Please proceed.

                       Introduction of Witnesses

    Dr. Battey. Thank you, Mr. Chairman. Joining me at the 
table are Ms. Sparks, Budget Officer; Mr. Kerr, Executive 
Officer; Dr. Luecke, Deputy Director for the Institute; and you 
know Dr. Kirschstein and Mr. Williams.
    Before I begin my formal remarks, I would like to add my 
thanks to that of Dr. Alexander for your remarkable leadership 
on this subcommittee and for the subcommittee's remarkable 
support of the National Institutes of Health and the National 
Institute on Deafness and Other Communication Disorders. I 
think after you heard what Dr. Alexander told you and what I 
will tell you and what all of the other directors will tell 
you, you will realize that you made a great difference for the 
Nation's health and that difference will be felt for many, many 
years; and I give you my sincere thanks for that support.

                           Opening Statement

    I am honored to appear before you as the Director of the 
National Institute on Deafness and Other Communication 
Disorders or NIDCD. Within the last year, we have witnessed 
outstanding research progress in hearing, balance, smell, 
taste, voice, speech, and language by NIDCD-supported 
scientists and clinicians, progress further accelerated by our 
collaborations with other NIH institutes. Today, I would like 
to highlight a few of NIDCD's many science advances that are 
relevant to hearing and hearing impairment throughout the human 
life span.
    In humans, auditory sensory cells, hair cells, and other 
internal parts of the ear form as early as the third month of 
development. These hair cells establish connections with the 
central nervous system and are essential for the hearing 
process. Loss of, or damage to, these hair cells following 
injury is permanent and results in deafness or hearing 
impairment.
    If I can direct your attention to my poster, what you see 
is three parallel rows, which are the tops of cylindrical hair 
cells that you see down below. You see the beautiful symmetry 
and order, those cells are responsible for the fine tuning of 
the auditory response. On the right side they are wiped out or 
grossly distorted; that ear on the right has been exposed to 
excessive noise; and you can see that the hair cells have been 
completely damaged.
    Mr. Hoyer. Is that from a rock concert?
    Dr. Battey. A teenager going once to one rock concert will 
not damage their hearing. What is required to get noise-induced 
hearing loss would be to be the guitar player sitting next to 
the speaker every night.
    NIDCD investigators have recently provided direct evidence 
of the mechanism that regulates the number of progenitor cells 
that develop as hair cells, providing important clues about the 
molecular processes critical for hair cell development and the 
potential for hair cell regeneration. NIDCD-supported 
investigators have also shown that in the mouse, the Math1 gene 
is essential for regulating the development of hair cells and 
progenitor cells. Mice deficient in this Math1 gene develop no 
hair cells in their inner ear.
    These findings provide insight into the molecular 
mechanisms regulating hair cell differentiation and 
specification and provide the initial clues as to how we might 
ultimately regenerate these hair cells which are so often the 
cause of hearing loss. Immediately after birth, the ears of a 
newborn are filled with the new sounds of his or her 
surrounding environment. Unfortunately, not every newborn will 
be able to hear these sounds. It is estimated that as many as 
12,000 babies each year are born in the U.S. with significant 
hearing loss, making it a far more common congenital disorder. 
NIDCD-supported research has shown that the detection of 
hearing impairment and intervention within the first 6 months 
after birth are very important for optimizing language 
development in young children.
    In a 5-year multi-center study, NIDCD-supported scientists 
determined the optimal test procedures for neonatal hearing 
screening. This study was the first controlled comparison of 
normal hearing and hearing-impaired infants assessing multiple 
physiological responses to sound. The development of precise 
and timely diagnostic screening procedures is the first 
important step in providing early intervention strategies that 
will optimize the development of either spoken or signed 
language skills. Not only is hearing screening becoming 
available for all newborns, but breakthroughs in medical 
genetics will enable clinicians and scientists to determine 
precisely the genetic changes which cause hearing impairment.
    About one child in 2,000 is born with hereditary hearing 
impairment which compromises the development of normal spoken 
language skills. The first gene where mutations result in a 
regrettably common form of hereditary hearing impairment was 
mapped to a region of chromosome 13 in 1994. Three years later, 
scientists discovered that mutations in a gene called GJB2 were 
the cause of deafness in families with DFNB1.
    Since this discovery, scientists studying the nature of 
mutations in this deafness gene have learned that about one-
third of all recessive hereditary hearing impairment in the 
United States is caused by mutations in GJB2. This is a major 
player among the tens to hundreds of genes where mutations can 
cause hearing impairment. With the identification of mutant 
genes, genetic testing becomes possible, but the technical 
capability does not necessarily mean the genetic testing is 
appropriate for widespread clinical application.
    The NIDCD is particularly interested in research to develop 
and validate diagnostic genetic tests to assess the impact of 
genetic testing on various cultural groups and individuals and 
to provide education and counseling to facilitate informed 
decisionmaking about reproductive issues and treatment 
strategies. Last year, I had the opportunity to describe 
NIDCD's research on the cochlear implant. In fact, I brought a 
cochlear implant for you to see.
    This is a bioengineering advance that restores the 
perception of sound to both children and adults with profound 
hearing impairment. The cochlear implant is an array of roughly 
22 electrodes inserted into the inner ear that converts sound 
into electrical impulses that directly stimulate the acoustic 
nerve thereby bypassing the damaged hair cells that I told you 
about a few minutes ago. If I can direct your attention to my 
second poster you will see a 4-year-old girl. She is wearing a 
cochlear implant, although you can barely tell. You have to 
look closely to see the wire. She received her implant at 2, 
she is now 4 and her caregiver reports to me that she is on age 
level for language development and, in fact, describes her as 
chatty which is remarkable given the fact that she has never 
heard a sound in her life other than the sounds through the 
cochlear implant that she received at 2 years of age.
    Scientists supported by the NIDCD conducted a study to 
measure language achievement in children with cochlear 
implants. The study compared a group of children who received 
cochlear implants and a second group who were using hearing 
aids and saw significant differences in language achievement 
favoring the children with cochlear implants.
    As research moves forward to reduce the burden of disease 
in America, the NIDCD is committed to the idea that all 
segments of American people should benefit from this progress. 
In comparison to the general U.S. population, Native American 
children have one of the highest rates of otitis media. NIDCD 
is continuing its support of a study on the epidemiology of 
this disorder and hearing loss among Native American infants 
from birth to age 2 at the White Earth Reservation in 
Minnesota.
    Recent assessment shows that intervention programs should 
focus on parental smoking as a significant risk factor for 
otitis media in Native American infants. The study also 
includes prevention strategies to reduce the burden of otitis 
media such as promoting breast feeding. Understanding the 
natural history and risk factors is vital to gaining insight 
into the epidemiology of otitis media in both majority and 
minority populations.
    Loss of hearing can occur in childhood, but also later in 
life. The NIDCD is conducting research on neurofibromatosis 
type 2, a genetic disorder that often leads to tumors on both 
acoustic nerves causing deafness in children and adults. 
Scientists supported by the NIDCD have determined that specific 
mutations in the NF2 gene result in different levels of 
severity of the disease. There is a correlation between the 
severity of the mutation in the gene and the progression and 
severity of the disease. This finding will facilitate earlier 
DNA-based diagnoses and improve disease management and increase 
the preservation of hearing in NF2 patients.
    Regrettably, the surgery required to manage this disease 
often results in resection of both acoustic nerves so that 
sound perception cannot be restored with cochlear implants. 
NIDCD-supported scientists have developed a specialized 
auditory prosthesis that is implanted directly into the ventral 
cochlear nucleus of the animals, that is the portion of the 
central auditory system where the acoustic nerve fibers make 
their initial connections. These animal studies have 
demonstrated the safety of this technique and deaf NF2 patients 
are scheduled to be fitted with these devices within the next 
few years with the hope of restoring auditory perception.
    A recent NIDCD-supported study has demonstrated a clear 
genetic component for age-related hearing loss or presbycusis. 
It is likely that different mutations in the same genes that 
cause profound hereditary hearing impairment in children also 
cause age-related hearing loss later on. With the ability to 
predict who is at risk for age-related hearing loss, better 
strategies to minimize or delay hearing loss within the aging 
population can be developed.
    The older population of the U.S. is large and growing. As 
they live longer, they have a greater chance of developing 
hearing impairment. Hearing aids are the most common means for 
assistance for persons with hearing loss. Roughly 20 million 
Americans have hearing aids right now. The Department of 
Veterans Affairs and the NIDCD conducted a multi-center trial 
which included elderly volunteers to compare the efficacy of 
three commonly used hearing aid circuits. Data from the trial 
showed that performance differences among the three hearing aid 
circuits were minimal. Of greater importance, the trial 
demonstrated that each circuit improved speech recognition with 
improvements observed under both quiet and noisy listening 
conditions. We remain committed to supporting research leading 
to smaller and better hearing aids, capitalizing on 
bioengineering advances in micro electronics.
    My colleagues and I will be happy to respond as best we can 
to your questions.
    Mr. Porter. Thank you, Dr. Battey.
    [The written statement of Dr. Battey follows:]



                             ANIMAL MODELS

    Mr. Porter. You have mentioned that--first of all, what 
kind of animals are used in these experiments?
    Dr. Battey. That animal model would be either the 
chinchilla or the guinea pig typically. They are chosen because 
the size of their ear is relatively large compared to the size 
of their head so it is simpler to do the experiments in those 
animal models than in mice, for example.

                              GENE THERAPY

    Mr. Porter. It seems to me that with the identification of 
the genes that cause certain hearing problems, that perhaps--am 
I correct we have not had any successful gene therapy yet?
    Dr. Kirschstein. Mr. Chairman, there were just two reports 
at the American Society for Hematology meeting in New Orleans 
about a week ago of some success. One in severe combined 
immunodeficiency disease and the other one in hemophilia B. 
Those are preliminary results. There were abstracts presented 
and it looks very promising, but we cannot be sure until we see 
the full papers.
    Mr. Porter. We have put a great deal of our reliance on the 
mapping of the human genome with the thought that we can, after 
successfully learning the basis of disease or health problems, 
manipulate or change the genes in some way and correct them. 
Would it be likely in your area of deafness and communication 
that this might be the place where we might look for early 
success? In other words, is it simpler here than it might be 
with respect to a complex disease?
    Dr. Battey. I hold out great hope for the promise of gene 
therapy, in the fullness of time, for correcting genetic 
defects which in the inner ear result in deafness.
    Having said that, I recognize that there are some rather 
imposing technical challenges that must be met. For example, we 
must learn to instruct the right cells to express the new genes 
at the right time and at the right levels. Until we understand 
the normal mechanisms that regulate these processes, it is 
going to be difficult for scientists to design the right 
vectors, called expression vectors, that will both deliver the 
genes to the right cells and give the proper pattern of gene 
expression.
    A second issue is gene delivery. We will need a way to 
somehow be able to infuse solutions that contain these genes 
into the inner ear and have that DNA taken up by the right 
cells and in adequate amounts and then to get sustained 
expression not just for days or months, but for years. My own 
sense is that there is a fair amount of rather basic work 
understanding these fundamental processes that will need to 
take place before we attempt to replace a defective gene in the 
inner ear.
    One piece of good news about the inner ear is that it is a 
very small closed compartment which means that the amount of 
solution that would have to be delivered and the region of the 
body that would need to receive the solution is relatively 
small and that would be, I think, a point in favor of gene 
therapy attempts in the inner ear as opposed to other 
circumstances.
    Mr. Porter. We often talk of completing the map of the 
entire human genome as an end in itself, but it is basically 
the beginning. There is a great deal more that needs to be done 
to move it to an application stage where we really are changing 
defects that we can now identify.
    Dr. Battey. I think your remarks are absolutely right on 
target. Having the sequence of the genome will be an enormous 
help; but it will require many, many years of additional work 
to understand what regulates gene expression at different 
points in development and in different organs. Those issues 
will be absolutely critical to our ability to leverage fully 
the data and the information that will come in what my 
colleague, Francis Collins, calls the post-genomic era.

                       COCHLEAR IMPLANT RESEARCH

    Mr. Porter. Dr. Battey, there are some people among the 
deaf community that don't believe that research to find a way 
for deaf people to hear is a worthy goal. The National 
Association of the Deaf, until recently, opposed the use of 
cochlear implants. What kind of impact does that have on the 
research that you do?
    Dr. Battey. We feel that the major important goal for NIDCD 
is to promote communication skills and language development. 
That can be done in an oral auditory mode with cochlear 
implants. In many children, we see dramatic positive results. 
It can also be accomplished by teaching American sign language. 
As a matter of fact, it is as important to teach American sign 
language at the right time when the neuralsubstrate for 
language is ripe to incorporate language skills, as it is to 
provide oral auditory language experience.
    So the NIDCD's position is that we need to do research into 
both ways of empowering the language and communication skills 
of young Americans with hearing impairment and that parental 
choice is the most important determining factor in deciding 
which mode is the better mode for a given child in a given 
home.
    Mr. Porter. Thank you. Mr. Hoyer.
    Mr. Hoyer. What would be the criteria for judgment on the 
answer to that question?
    Dr. Battey. I am sorry?
    Mr. Hoyer. You leave it up to each parent to make the 
choice between presumably facilitating or enhancing auditory 
capability as opposed to other ways of communication. I am 
asking you what would be the criteria if you were a parent 
making that choice?
    Dr. Battey. I think a key role for health care providers in 
this regard is to provide the parents with a full complement of 
information on the pluses and minuses of either way of enabling 
language skills and that once the parents are fully informed, 
the decision should rest with the parents.
    Mr. Hoyer. I understand that. What I am trying to get at, 
is on what basis would I make a determination as a parent not 
to enhance the auditory skills of my child?
    Dr. Battey. One possible----
    Mr. Hoyer. Let me add as you answer the question, which 
does not preclude alternative ways of communicating obviously?
    Dr. Battey. That is correct. One could make the argument 
that if, in fact, both the parents of the child were hearing 
impaired themselves and were users of American sign language 
that they would be more comfortable raising their child in the 
same language and culture that they found themselves.
    Mr. Porter. Would the gentleman yield?
    Mr. Hoyer. Sure.
    Mr. Porter. I have the same question. Why would a parent 
choose signing rather than the cochlear implant if they knew 
that the cochlear implant would provide real hearing? Is this 
the only circumstance where this would occur?
    Mr. Hoyer. It seems to me Dr. Battey has given us the 
answer, and what I glean from the answer is this is a very 
controversial and sensitive issue where parents believe they 
may be somehow diminished in their relationship with their 
child if their child is a hearing child through the use of a 
cochlear implant and will be less likely to be able or inclined 
to communicate with them as readily.
    Mr. Porter. Is that the only circumstance where a parent 
would maybe decide that?
    Dr. Battey. I would say that is the most likely 
circumstance. There are individuals in the Deaf Culture who 
feel that using American sign language is every bit as rich an 
experience as a hearing individual. Because I can never know, 
nor can any of us who have heard since we were born, what it is 
like to be a deaf individual, I feel that it is important that 
we respect that perspective.
    Mr. Hoyer. Doctor, I agree with that. My wife was on the 
board at Gallaudet and was a supervisor at the end but a 
teacher, that was her main focus in life. She taught hearing 
children to sign and to make letters in sand. In other words, 
she taught multiple ways to communicate because she believed 
that enhanced the child's ability to use each of the ways of 
communicating. It is an interesting----
    Dr. Battey. Yes. I think you have hit upon the key theme. 
What is tragic is to have an individual cut off because they 
cannot communicate by any means. The key thing that NIDCD seeks 
to do is to see to it that never happens if we can avoid it.

                    AMERICANS WITH DISABILITIES ACT

    Mr. Hoyer. Let me ask you a follow-on question. I was very 
involved in the adoption of the Americans With Disabilities 
Act. We are making reasonable accommodation in this hearing for 
those who may be hearing impaired by having a signer present. 
Based upon your discussions with the hearing impaired 
community, and obviously you deal with them all the time, what 
is your thought on the success we have had with the ADA and 
what areas do you see perhaps of further attention?
    Dr. Battey. One of the limitations to using the cochlear 
implant technology on a more widespread basis is the fact that 
cochlear implants are expensive. The device is expensive to 
purchase in the first place. The surgery to have them implanted 
into the inner ear is expensive, and between $20,000 and 
$30,000 is needed in rehabilitation once the implant is in 
place to allow the individual to fully capitalize on its use.
    There are many instances where individuals or families 
simply cannot afford the cochlear implant and third party 
payers are failing to provide the resources to support cochlear 
implantation even though the amount of money that would 
probably be saved by providing a cochlear implant in a timely 
fashion to a young child vastly exceeds the amount that will be 
lost over a lifetime in earnings and income and other 
potential. I think this might be an area for further 
consideration.

                     COMPUTER MODELING IN RESEARCH

    Mr. Hoyer. Excellent. I will pursue that.
    You mentioned the use of animal studies. Can you tell me 
the relative advantages of use of animals versus computer 
modeling? I presume that they are cumulative in many instances, 
but are we able now to use more computer modeling in our 
research?
    Dr. Battey. Yes, computer modeling is an important part of 
trying to understand how the inner ear works, and in our 
intramural research program we have a mathematician who is 
using computer modeling studies to try to understand how, 
within the inner ear, a specific frequency is detected by only 
a small band of those three rows of hair cells that you saw on 
my first poster. He has derived some very interesting models.
    However, once you have developed the model, the only way to 
know that it is right is to test it and that unfortunately 
involves the use of laboratory animals. We used them as 
carefully as we can, as humanely as we can, using as few 
animals as are needed to answer the question. We have very 
close scrutiny both at the NIH and at institutions where we 
sponsor research over the care and use of laboratory animals.
    Mr. Hoyer. Thank you, Doctor. My time is up.
    Mr. Porter. Thank you, Mr. Hoyer. Dr. Battey, I have 
appointments beginning at 4:00. What I am going to do is turn 
over the Chair to Mr. Wicker. Let me thank you for the fine job 
that you are doing. We can't tell you how much we appreciate 
the intellect that all of you bring to bear on the afflictions 
of humans. You are doing a wonderful job and it is inspiring to 
hear you explain all of the progress that is being made.
    Dr. Battey. Thank you. Mr. Porter, I will miss seeing you 
in your familiar chair next year.
    Mr. Hoyer. We want him here, but one chair over.
    Mr. Wicker. Speak for yourself.
    Mr. Hoyer. I was. The ``we'' referred to this side.

                          ALLOCATION OF FUNDS

    Mr. Wicker. I will be glad to take the Chair. Really I just 
have a quick question; and, of course, I just want to echo the 
comments of Mr. Hoyer and Mr. Porter about your testimony. We 
very much appreciate what you are doing. Just tell me a little 
about your research. Who is doing it and how many locations? To 
what extent are you involving universities?
    Dr. Battey. We have about 710 research grants and contracts 
in the extramural community. They are spread out among 44 
States. I can't tell you exactly how many universities but a 
large number of universities within those States have NIDCD 
grants. Some of the finest people I know are our grantees. 
These folks work 60, 70 hours a week for a lot less money than 
a lot of other people make, and I find these grantees and the 
work of their fellows to be absolutely inspirational. I am 
merely their mouthpiece. If you are impressed by what you hear 
me say, it is because our extramural researchers and intramural 
researchers did the fine research that allows me to bring these 
things to your attention.
    Mr. Wicker. How much is extramural and how much intramural?
    Dr. Battey. Our Division of Intramural Research is a little 
over 8 percent of our budget. Roughly 70 percent of our budget 
is in research projects and grants and another--I cannot 
remember exactly how many percent, but another portion is in 
research centers. We have research training that is extramural 
which is another few percent of the budget. But if you sum 
intramural research, which is about 8 percent, and research 
management and support, which is the 4 percent that we use to 
keep the place running, you are left with about 88 percent and 
that is provided to the extramural community.
    Mr. Wicker. That is interesting. Feel free to follow up 
with more detailed information on the record about the number 
of universities.
    Dr. Battey. We will give you a listing of the number of 
universities and their location by State.
    [The information follows:]



                        USES OF ADDITIONAL FUNDS

    Mr. Wicker. Wonderful. Let me ask what have you been able 
to do because of the increases that you have received in the 
last 2 years that you might not have been able to do otherwise?
    Dr. Battey. The increases have come at a phenomenal time 
for us. As the subcommittee knows, many of the States are now 
implementing newborn hearing screening which means that 
thousands of infants will be found with mild, moderate, and 
severe hearing impairment, found in time to intervene and 
optimize their language skills. We know that intervening early 
makes all of the difference.
    What we don't know is what the optimal intervention 
strategy is for a mild, moderate, or severely hearing impaired 
child. We don't know under what circumstances hearing aids 
should be used, and we don't know if they should be fitted 
exactly the same way as an adult's hearing aid. We don't know 
if the developing ear is more sensitive to noise and therefore 
the aids should be turned down.
    So we will need research to determine the optimal 
intervention strategies for these infants so we can capitalize 
in making the early diagnosis. NIDCD set aside dollars to 
stimulate research in this area. We have one grant funded. 
Other grants are submitted. We plan to extend this program 
announcement, and I am very gratified by the response in that 
area. The progress in the area of genetics has been absolutely 
astounding. Four years ago, we knew of not a single gene that 
caused non-syndromic hereditary hearing impairment. We now know 
of 12, and we know the map location of nearly 60. That research 
was stimulated in large measure by the substantial increases 
that this subcommittee provided.
    Mr. Porter spoke of the post-genomic era. Knowing the 
sequence of the genome will be great, but there is a lot more 
to do. We need to know which of those 100,000 or more genes are 
expressed in those critical hair cells in the inner ear. Even 
when we know the whole genomic sequence, we will not know which 
genes are actually expressed in cells that we know are 
important to hearing, balance, smell, and taste, research areas 
of primary responsibility for NIDCD. The way to learn that is 
to develop gene expression libraries, collections of all of the 
genes that are expressed in a given cell, and to sequence those 
libraries and determine which of the genes are expressed. We 
began an initiative to do that within the last year and that 
work is being supported with the generous increase provided by 
the administration and the Congress and we thank you for that.
    Mr. Wicker. Thank you, Dr. Battey. Mr. Hoyer, are there any 
further questions?
    Mr. Hoyer. No, thank you.
    Mr. Wicker. So the hearing is concluded and we will 
reconvene at 10:00 a.m. tomorrow morning. Thank you.



                                          Wednesday, March 1, 2000.

                NATIONAL HUMAN GENOME RESEARCH INSTITUTE

                               WITNESSES

          FRANCIS S. COLLINS, M.D., Ph.D. DIRECTOR, 
          ACCOMPANIED BY:
ELKE JORDAN, Ph.D., DEPUTY DIRECTOR
CHARLES E. LEASURE, JR., DIRECTOR, OFFICE OF ADMINISTRATIVE MANAGEMENT
KATHY L. HUDSON, Ph.D., DIRECTOR, OFFICE OF POLICY AND PUBLIC AFFAIRS
ERIN S. BURGESS, BUDGET OFFICER
RUTH L. KIRSCHSTEIN, M.D., ACTING DIRECTOR, NIH
DENNIS P. WILLIAMS, DEPUTY ASSISTANT SECRETARY, BUDGET, DHHS
    Mr. Porter. I think we had better proceed. The subcommittee 
will come to order. We continue our hearings on the budget of 
the National Institutes of Health, with the National Human 
Genome Research Institute. We are delighted to see Dr. Francis 
Collins, the Director, who always gives us a fascinating update 
of what he is accomplishing there. Dr. Collins, you are doing a 
wonderful job, and we are anxious to hear what you have to tell 
us.

                              Oral Remarks

    Dr. Collins. Thank you very much, Mr. Chairman.
    Let me begin by introducing the people at the table with 
me. Dr. Elke Jordan, the Deputy Director of the Institute; Mr. 
Charles Leasure, who is our Executive Officer; Dr. Kathy 
Hudson, who is our Director of Policy and Public Affairs; Ms. 
Erin Burgess, our Budget Officer; to my right, as you know, Dr. 
Kirschstein, the Acting Director of NIH; and Mr. Dennis 
Williams from the Department.
    It is an honor to appear before you today for the seventh 
time as Director of the National Human Genome Research 
Institute. Since I know, Mr. Porter, this is the last time I 
will have the honor to appear before you, I want to express my 
personal thanks to you for the leadership and the thoughtful 
and enthusiastic support that you have provided to NIH, in 
general, and to the Human Genome Project, in particular. I 
think it is fair to say the Human Genome Project would not be 
where it is today were it not for the enthusiastic support of 
this subcommittee. That is much appreciated, and you will be 
sorely missed, Mr. Chairman.

                         SEQUENCING MILESTONES

    The NHGRI consumes less than 2 percent of the overall 
budget of the NIH, but we represent the flagship of the Human 
Genome Project in the United States and around the world.



    Dr. Collins. On this first poster that Dr. Jordan is 
pointing to, you can see some of the milestones already 
achieved through the Human Genome Project's efforts. This is 
only a partial list. Listed there are sequences of several 
model organisms, which are of enormous utility for 
understanding how DNA sequence informs biology.
    In fact, the first meeting I chaired when I came to direct 
what was then the National Center for Human Genome Research was 
in 1993. We sat around a table and tried to decide how much 
actual genomic production sequencing could be done in a 5-year 
period from 1993 to 1998 because we were in the process of 
writing a new 5-year plan. After vigorous debate, we decided 
that we could work very hard, and we could produce 80 million 
base pairs of sequence in that 5-year period. Many people in 
the room thought we had overstepped reality.
    Well, we achieved that. And remarkably, just 2 years after 
the completion of that 5-year period, I can now tell you that 
last week we did 80 million base pairs of human DNA sequencing. 
What took us 5 years, now takes us 1 week.
    [The information follows:]



                       HUMAN SEQUENCE PRODUCTION

    Dr. Collins. The next poster shows you, in graphical form, 
the accumulation of that human DNA sequence production over the 
course of the last 4 years. I think you can see by the steep 
slope of the curve what is going on in regards to mapping out 
the sequence of the human genome. As of last Friday, we had 
produced 1.72 billion base pairs of human sequence. Recognizing 
that the genome is approximately 3 billion, you can see that we 
are on track towards our goal of covering 90 percent of the 
sequence in a working draft form in the very near future.
    [The information follows:]



    Dr. Collins. The next poster shows a different view, a 
graphical one, of the coverage that I told you about last year. 
Notice this says March 1999. When I appeared before you in that 
hearing, we had sequenced 405 million base pairs, 13.5 percent 
of the genome, and we were pretty proud of that. The graphical 
presentation of the human chromosomes shows you, by the colored 
areas, where the work had been done. You see at that point 
there were a lot of areas in white where no sequencing had yet 
been done.
    [The information follows:]



    Dr. Collins. Well, if you will do the fold-over, we will 
update this and fast forward by a year, and you will see where 
we are now, March of 2000. Now virtually every chromosome is 
heavily colored in with activity. I will not go into the color 
codes, but you can see that we have touched on most of the 
genome in one way or another. In fact, the summary up there in 
the corner indicates they are approaching 60 percent of the 
genome being covered now in this working draft form.

                     HUMAN CHROMOSOME 22 SEQUENCED

    I particularly draw your attention to chromosome 22, which 
you see completely filled in, because a very significant 
milestone occurred in December with the publication in a 
journal called Nature, of the complete sequence of this human 
chromosome. This is the first time that has ever been done. 
There is a big foldout in this particular journal, which 
crosses several pages.
    I must say, from my own personal experience, to be able to 
look at this diagram of 35 million base pairs of sequence, 
containing hundreds of genes, many of which had never been 
known to be there before, is really a milestone of the highest 
order. It is a historical moment, where, for the first time, we 
have an entire mammalian chromosome and all of its details laid 
out in front of us. This chromosome includes genes involved in 
schizophrenia, in immune disorders, in cancers and in birth 
defects. The causes of those entities will now be much clearer 
because of having this first chapter in the ``book of life'' 
revealed before us.

                 FREE ACCESS TO FUNDAMENTAL INFORMATION

    The ultimate goal of the human genome sequencing effort is 
to get all of the chromosomes finished in the same fashion as 
chromosome 22. We will get that sequencing done by 2003 or 
sooner. All the data will be freely accessible, released every 
24 hours onto the Internet--without patents, without licenses, 
without secrecy agreements or subscription fees or other 
barriers--for any scientist who has a good idea about how to 
understand it. From the outset, the Human Genome Project has 
aimed to provide that information, with truly free access, to 
any scientist with an Internet connection. We feel this is how 
this fundamental information will most benefit the public and 
we will not waiver from that principle.
    [The information follows:]



                         OTHER GOALS OF THE HGP

    Dr. Collins. The last poster brings me to a very important 
point. While the human sequence--up there at 12 o'clock of our 
diagram of the power tools that the Human Genome Project is 
trying to produce--is one of our most visible efforts, it is 
not the only part of the Human Genome Project. We have seven 
other current goals that you see arrayed around that power 
tool. We are in the business of building lots of those power 
tools and then making them available to anybody. I will not 
have time to go into each of the icons that you see there, but 
I will point out a couple.

                        HUMAN SEQUENCE VARIATION

    The one called human sequence variation, where you see two 
people carrying two different flags, and one of them has a 
``G'' and one has a ``T,'' that is to represent our interest in 
studying the .1 percent of the human genome where you and I 
differ. Most of those differences are not particularly 
significant, but a small subset of them will carry the 
significance of predisposition to various illnesses; things 
like diabetes, Parkinson's disease or cancer.
    In a highly productive partnership with the private sector, 
NIH is engaged in building a publicly accessible catalogue of 
those human sequence variations and then connecting them up 
with their health consequences. Using this strategy, we predict 
we should be able to understand the major genetic contributions 
to virtually all diseases in the next 5 to 7 years.

                          COMPARATIVE GENOMICS

    Next to that icon, you see one of a mouse, labeled 
comparative genomics. The mouse is there representing a number 
of other genomes and animals as well, whose DNA sequence we aim 
to try to unravel. The comparisons between those organisms, 
particularly the mouse and human, will illuminate in major ways 
how the human DNA sequence actually works. Overall, the mouse 
sequence is 40 percent the same as the human, but in the areas 
that code for protein, it is 85 percent alike. If you had one 
tool that you could apply to the human sequence, which we are 
about to have in front of us, to find all of the genes, it 
would be the mouse sequence. That would be the single most 
useful way to identify what are the important parts of this 
human ``book of life.'' So based on that logic, we began 
sequencing the mouse genome last fall, and we aim to have a 
working draft of that genome by 2003 or quite likely sooner.

                          FUNCTIONAL GENOMICS

    Going around to the next icon on the poster, these 
explorers are puzzling over the DNA. We are vigorously pursuing 
other innovative ways to understand how genes work and doing so 
in a fashion that allows the study of many genes at once. You 
have at your place one of these chips that is changing 
everything in terms of our ability to understand genomes. Under 
that postage-stamp sized piece of glass is a piece of silicon, 
and on that silicon has been synthesized pieces of all of the 
genes of baker's and brewer's yeast, one of those organisms 
whose genomes we derived 3 or 4 years ago.
    This chip allows you to look at the function of all 6,400 
of those yeast genes in one experiment. In the old days, we had 
to look at one gene at a time, but now we can look at all 6,400 
in one afternoon. Out of this has come a vast number of 
insights about how genes interact with each other in both 
normal and abnormal situations. We will soon be able to do the 
same things for the human genome.

                         COMPUTATIONAL BIOLOGY

    The next icon is relevant here because the challenges for 
data analysis with this kind of very powerful tool are quite 
significant. One of our grantees, who works with this yeast 
chip, says it currently takes an afternoon to do the 
experiment, but 6 months to analyze the data because it is so 
rich in details.
    So bioinformatics, also called computational biology, is 
becoming an increasingly important part of the Genome 
Institute's portfolio. A major part of the new initiatives for 
us in fiscal year 2001 will be in this very area. We will soon 
have vast databases of genome sequence information on the human 
and a number of other organisms. The ability to mine through 
these databases and find the nuggets of information will depend 
upon sophisticated algorithms developed by experts trained in 
both computational methods and in biology.

                ETHICAL, LEGAL, AND SOCIAL IMPLICATIONS

    Finally, on this diagram, I would like to point to the ELSI 
program, the Ethical, Legal and Social Implications of genome 
research, here represented by the scales of justice. The study 
of those ELSI issues has been, from the beginning, a central 
part of our agenda. We feel quite strongly that not only do we 
have to advance the science of genomics, we have to advance the 
understanding of its implications for society.
    In that regard, it was a great personal pleasure for me to 
participate in the signing of the first Executive Order of the 
millennium, on February 8th, by the President of the United 
States. This banned the use of predictive genetic information 
in the Federal workplace. That action now protects 2.8 million 
Federal workers from such discrimination and will, hopefully, 
be seen as a model of what needs to happen for the rest of the 
American workforce. It is my fervent hope that Congress will 
take action this year to ban the discriminatory use of genetic 
information in both the workplace and in health insurance.

                        BENEFIT TO HUMAN HEALTH

    Finally, how will all of this rapid-moving research on the 
genome benefit human health? Surely, that is the major concern 
of this committee and mine as well, as a physician and a 
scientist. The power tools you see represented are already 
being applied to unraveling the mysteries of a host of 
diseases.
    Families all over the world are participating in this grand 
adventure. Consider the case of Emanuel and Martha. Brother and 
sister, both in their forties, both recently diagnosed with 
diabetes, both living in Ghana. Through a ground-breaking 
research study that is being carried out by our intramural 
program in collaboration with Howard University, and wonderful 
colleagues, indeed, we have there, and with strong support from 
John Ruffin and the Office of Research on Minority Health, 
Emanuel and Martha are participating in a study of the 
hereditary factors in adult-onset diabetes. West Africa 
represents the geographic origin of modern-day African 
Americans, but hereditary factors in diabetes are easier to 
study in West Africa since there are fewer confounding 
environmental factors such as diet.
    We are also part of a large consortium with other groups 
studying diabetic families in the United States, Europe and 
Scandinavia. I can predict for you that, based upon the power 
tools provided by the Human Genome Project and the 
participation of these families from many different ethnic 
groups and backgrounds, we will uncover the major hereditary 
contributions to adult-onset diabetes in the next 5 to 7 years. 
Out of that will come the ability to make more precise 
diagnoses and, ultimately, designer drugs which will be much 
more effective and free of side-effects, more likely to reverse 
the underlying causes of the disease rather than treating 
downstream symptoms. That is a vision that I think we can all 
share.

                      GREATEST INTELLECTUAL MOMENT

    I would like to close by reading a couple of words from 
Matt Ridley, who is the author of a book just published on the 
genome. He writes, ``Sometime within the next few months, we 
shall have a rough first draft of the complete human genome. 
This is routinely reported as an event of medical and perhaps 
ethical significance. I believe it is more than that. I believe 
it is the greatest intellectual moment in history. Bar none. 
Some may protest that a human being is more than his or her 
genes. I do not deny it. There is much, much more to each of us 
than a genetic code. But until now, human genes were an almost 
complete mystery. We will be the first generation to penetrate 
it.''
    You might say those words are perhaps a bit grandiose, but 
I think, in fact, when history looks back on this enterprise, 
that this will have been recorded as the grandest adventure 
that humankind had ever mounted, this reading of our own 
instruction book.
    Mr. Chairman, members of the subcommittee, I would be happy 
to answer your questions.
    [The written statement of Dr. Collins follows:]



                      INCREASE IN SEQUENCING RATE

    Mr. Porter. Dr. Collins, thank you so much.
    Tell us, if you will, what technology and where was it 
developed that allowed you to increase the rate of sequencing 
so rapidly from what you were doing before?
    Dr. Collins. It is no one, single technology development. 
It is a series of advances that occur in the instrumentation, 
in the basic ways in which we break the genome into manageable 
pieces and in the automation that one needs to bring to a 
production line that is going to crank out 80 million base 
pairs of sequence a week. Most of those technical advances 
were, in fact, developed in academic centers over the course of 
the last 10 years, many of them with funding from the National 
Human Genome Research Institute.
    The private sector has played a critically important role, 
particularly in the development of the automated sequencing 
machines, which are used now in virtually all of our genome 
centers, but which had their origins some 15 years ago through 
the work of Dr. Leroy Hood at Cal Tech.
    These combinations of efforts--and if you go to one of our 
genome centers like the Whitehead Institute in Boston or the 
Washington University Center in St. Louis or the Baylor Center 
of Medicine, you will see a whole host of automated systems in 
place, and they are not exactly alike from one center to the 
next, everybody has their own favorite way of doing things--
have come together, particularly in the course of the last 
year, to make possible the kind of prodigious production rates 
that we had dreamed of, and that we were not quite sure we 
could achieve, and achieving them at a cost that is actually 
substantially less than even the most optimistic would have 
guessed 5 years ago.
    Though there have not been quantum leaps forward, a brand-
new, bolt-from-the-blue development in technology that changed 
everything overnight, these incremental series of additive 
advances have, over the course of the last 8 or 10 years, 
improved our production and brought down our cost by more than 
an order of magnitude.
    Mr. Porter. Well, if it went from 13.5 percent, after 
working for a number of years, to 57.5 percent, it seems 
revolutionary, rather than evolutionary, to me.
    Dr. Collins. I agree with you. Especially living through 
the last year, it has felt like a revolution on a daily basis. 
We did not seriously begin our efforts to sequence the human 
genome until 1996. We just did not have powerful enough tools 
to take that on, and so most of the sequencing was devoted to 
model organisms with smaller genomes.
    In 1996, we began a series of pilot projects which carried 
us through a 3-year, very clearly defined, period to find out 
where the problems were and what kinds of efficiencies could be 
achieved as we scaled up this enterprise. It was just about a 
year ago, about the time I was in front of this committee last 
year, that we had the chance to look and see the full flowering 
of the results of those pilot projects and concluded we were 
ready, we were ready to go for broke. We were ready to scale 
this enterprise up and let it run. The consequence of that 
scale-up is, as you can see over the course of the last year, a 
dramatic speeding up of the accumulation of sequence 
information.

                         PRIVATE SECTOR GROWTH

    Mr. Porter. Dr. Collins, was it foreseen by you or others 
in 1993 that there would be a corresponding growth of effort in 
the private sector to do the same kind of sequencing that you 
are doing?
    Dr. Collins. Not entirely. I think there was an 
understanding that sequence information is of great interest 
and that there was likely to be, on a modest scale, a good deal 
of sequencing going on in the private sector. In 1993, and 
1994, and 1995, for instance, a number of companies, such as 
Incyte, Human Genome Sciences, set up operations not to try to 
sequence entire genomes, like the human, but to look at the 
parts that are expressed, the so-called ESTs, which are parts 
of things called cDNAs. It is the part of the genome that codes 
for protein and, therefore, is likely to have the greatest 
commercial value. And large-scale efforts were carried out to 
do that kind of sequencing and those databases were then held 
by those companies for their own use or for use by their 
private partners.
    I think there was concern that this was important 
information and that academic scientists ought to also have 
access. Interestingly, Merck, a private company, stepped 
forward and said, ``We agree with that point of view,'' and 
then funded the development of a publicly accessible database 
of the same sort, which was carried out by the sequencing 
center at Washington University.
    I do not think, though, until about a year-and-a-half ago, 
there was much expectation that sequencing the entire human 
genome or the entire mouse genome or other large genomes of 
this sort would be a commercially attractive business plan. 
This is information which is clearly of a very fundamental 
sort, and the majority view, in both the public and private 
sectors, had been that this kind of information ought to be 
publicly accessible. Therefore, to set up an enterprise to try 
to derive a large amount of sequence on a profitable basis, had 
somewhat of an uncertain prospect of being an effective 
business plan.
    Those things have changed, as you know. There is a good 
deal of interest now in trying to derive large amounts of this 
information and place it in a database for which access is, in 
significant ways, limited, in order to derive a profit from 
that. And while that may make a reasonable plan for deriving 
profits from the enterprise, I think there is broad and deep 
concern, in both the public and private sectors, about whether 
it is a good thing for something as fundamental as the sequence 
of the human genome, the ``book of life,'' to be in any way 
restricted..

                       GENOMES OF DIFFERING SIZES

    Mr. Porter. I want to ask you a short question before my 
time runs out. The mouse genome has approximately the same 
number of base pairs as the human genome, about 3 billion; is 
that correct?
    Dr. Collins. That is correct.
    Mr. Porter. But other sequencing that you have done, yeast, 
for example, has far fewer, correct?
    Dr. Collins. Much fewer, right.
    Mr. Porter. Is there anything that has more, do we know? I 
am just curious about this.
    Dr. Collins. Yes, there are, and perhaps that is a bit of a 
dint on our view of the world. But, in fact, there are genomes 
that are ten times bigger than ours. It may be reassuring to 
hear that those genomes, many of which are in plants, seem to 
have arrived at their very large size by picking up an 
inordinate amount of junk along the way and carrying around a 
lot of repetitive sequences that do not seem to be doing very 
much.
    In terms of gene count, the number of actual genes 
contained within the genome, the number of instructions, 
mammals are probably among the most complex, if not right at 
the top of the list. But the amount of filler varies 
significantly enough from one genome to the next that the 
correlation between numbers of genes and sizes of the genome is 
not always precise.
    Mr. Porter. Thank you.
    Mr. Obey.

                     PATENTING OF THE HUMAN GENOME

    Mr. Obey. Thank you, Mr. Chairman.
    Dr. Collins, two sets of questions: First of all, following 
up on something that the Chairman got into with you, I am 
concerned about the issue of patenting by private groups of 
segments of the human genome.
    I am not sure what the exact policy ought to be. I am not 
sure what the right decisions would be if they were to be made 
by the Patent and Trademark Office, and I am not sure we fully 
appreciate the implications of what is being done in the 
private sector.
    I would like to ask what concerns do you have about 
patenting by private organizations? I saw, for instance, a very 
interesting--and I do not normally have a very high regard for 
the way network news explains complicated subjects--but Robert 
Krulwich did a very understandable piece on ABC News the other 
night on the genome, which I happened to catch.
    I would very much like it if you could take that piece and 
simply expand on it and respond to it for the records, if you 
would evaluate virtually every comment in that piece, I think 
that would help everybody to have a better understanding of 
what is at stake here.
    Dr. Collins. I would be happy to do that.
    [The information follows:]



    Mr. Obey. And I would like you to respond here, how do you 
think public policy ought to be changed; what do you think the 
law ought to say to protect the public interest; what are the 
implications if we do not make those choices; and should we 
consider accelerating the funding of your project to try to get 
as much done on your hook? Would that have any value in helping 
to minimize the problem that we might face with this private 
patenting?
    That is question one, and then I have one other for you.
    Dr. Collins. Mr. Obey, I appreciate the question very much 
because I think this is a very important issue, and you have 
phrased it well. The question is, what is in the public 
interest? That is why we have patent laws. It is not to make 
inventors rich, it is to try to benefit the public.
    In that regard, I think a gene discovery that leads you 
fairly directly to a product that the public needs is an 
appropriate topic for consideration of intellectual property 
protection because it allows a company that is going to need to 
invest hundreds of millions of dollars to bring that product to 
market to have some protection against unfair competition.
    On the other hand, DNA sequence information, whose 
functional significance is unclear or perhaps unknown 
altogether, does not seem to meet the expected standard of 
utility that most scientists would have in mind or that I, 
personally, would have in mind when it comes to setting a bar 
for what is appropriate to allow intellectual property 
protection.
    The Patent and Trademark Office has very recently issued 
for public comment a set of possible policy changes that they 
are considering with regard to the issuing of patents on DNA 
sequences. That public comment period expires March 22nd. There 
is a meeting tomorrow, organized by the American College of 
Medical Genetics and Vanderbilt University, to consider this 
issue.
    Harold Varmus and I have exchanged some letters with 
Commissioner Dickinson about this issue. And while we welcome 
and congratulate them for some of the steps they have taken to 
say that a DNA sequence of no known functional information does 
not meet the standard of utility that they would now seek to 
apply, we are still concerned about sequences where the utility 
is largely theoretical because a computer analysis has implied 
a certain possible function, but that function has not yet been 
demonstrated by genetics or by biochemistry.
    Our sense is that to allow patents on that kind of 
theoretical utility places a great risk downstream of the 
genome being balkanized in such a way that truly interesting 
experiments that seek to study the function of tens of 
thousands of genes at one time may not be doable without months 
of paperwork and thousands or tens of thousands of dollars of 
licensing fees. This would represent a true deterrent to our 
ability to understand how the genome functions. That would be a 
truly tragic outcome.
    I appreciate your suggestion that one solution to this is 
to speed up what we are doing because it is all being put in 
the public domain every 24 hours, and we would welcome that 
opportunity, of course, and we will not waiver from that 
commitment. But I think, actually, we need a number of steps 
here to try to make sure that this ``book of life'' does not 
end up in private hands.
    Mr. Obey. Just one last comment. As you know, at the 
beginning of this project, I was concerned about moving forward 
with it because I did not feel that we would take an adequate 
account of the ethical considerations and of privacy 
considerations. We run into the same thing in the field of 
diabetes, when you appear to have some research with stem cells 
that offers real opportunity and yet you run into a wall of 
controversy every time you mention stem cell research.
    But I am beginning to wonder whether or not, because of the 
aggressiveness of the private sector, whether or not we should, 
in fact, accelerate your program so that, if we are going to be 
in a race, the good guys are sure to win.
    With respect to privacy, just one last question. I 
congratulate the President for his Executive Order. I think 
that is great. It helps Federal employees, but we still have a 
lot of private-sector employees who have problems.
    Dr. Collins. Yes we do.

                     AVAILABILITY OF GENETIC TESTS

    Mr. Obey. Could you tell us what are the most common 
diseases or conditions for which there is currently a genetic 
test available, a predictive test, that could be used to 
discriminate against people today, and are patients being fully 
and adequately advised and treated, in your view, when they do 
have this information available?
    Dr. Collins. Mr. Obey, it is still early days for a full 
unraveling of the genetic susceptibility factors for many 
diseases, but we are seeing that happening already. This kind 
of genetic testing is available for individuals who come from 
families with large numbers of breast cancers or ovarian 
cancers.
    The same kind of testing is available for families where 
colon cancer has appeared at unusual frequency. Similarly, even 
in some cases of diabetes, where we now understand the precise 
genetic abnormality, it is possible to make a prediction about 
who is going to develop diabetes. That predictive ability is 
not true for most cases of diabetes, but in some families it 
now is. Of course, there is a long list of neurologic disorders 
for which prediction is available, ranging from things like 
Huntington's disease to Alzheimer's disease. For many of those 
diseases, there is something you can do if you are at high 
risk, but unfortunately for some of the others there is not.
    All of those kinds of tests, if applied to an individual, 
could place them currently at risk of health insurance 
discrimination or of workplace discrimination based on this 
predictive information. The effort--which I agree with you we 
need to push over the finish line and not satisfy ourselves 
simply by protecting Federal workers--is to provide those 
protections to all, because it is about all of us. We are all 
walking around with 40 or 50 of these glitches that place us at 
risk for something. Why should we discriminate against the 
people who are unlucky enough to have their glitch found first, 
when, in fact, we are all in the same boat. A system that 
allows that kind of discrimination is not only unjust, it is 
unworkable.
    With regard to people getting information in an accurate 
way, I think, in general, if they are being seen by physicians 
with training in genetics or by genetic counselors, yes. But we 
have a big educational challenge ahead of us to get primary 
care providers ready to become the genetic counselors and the 
genetic medicine providers of the future because most of them 
are not ready yet. In that regard, we have a big initiative 
organized with the AMA and the American Nurses' Association to 
try to achieve genetic literacy in primary care in the next 3 
to 5 years. It is going to be a tough road to go, but I think 
the way to do it is to encourage the professional societies to 
join up with us to try to achieve that goal.
    Mr. Obey. Thank you.
    Thank you, Mr. Chairman.
    Mr. Porter. Thank you, Mr. Obey.
    Mr. Wicker.
    Mr. Wicker. Thank you, Mr. Chairman.
    Dr. Collins, a few moments ago you did a very bold, risky 
and unusual thing. You departed from your prepared text.
    [Laughter.]

                      GREATEST INTELLECTUAL MOMENT

    Mr. Wicker. And you gave us a quote which my staff and I 
have been scratching for ever since. So I want you to give it 
to us again, the Matt Ridley quote. The whole row behind you 
has been abuzz trying to find a copy of that.
    [Laughter.]
    Mr. Wicker. But I want to hear it.
    Dr. Collins. Well, sure. In fact, it is part of an entire 
book, which has just come out in the last couple of weeks.
    Mr. Wicker. Called ``The Genome.''
    Dr. Collins. Called, ``The Genome: The Autobiography of a 
Species in 23 Chapters,'' because each chapter is about a 
particular gene on a particular human chromosome. It is very 
compellingly written. If one reads through all of those 
examples, you learn a lot of human genetics along the way.
    Mr. Wicker. And this is by Matt Ridley, an author of----
    Dr. Collins. He is an author.
    Mr. Wicker [continuing]. Of whom you approve.
    Dr. Collins. I certainly like his book. I have never met 
him.
    [Laughter.]
    Dr. Collins. He is a British citizen who has been a writer 
for The Economist in the past. But he has gotten very excited 
about genetics.
    Mr. Wicker. Okay. He is excited. So give us that exciting 
sentence that woke me from my revery and sent my staff 
scrambling.
    [Laughter.]
    Dr. Collins. I am guess, perhaps--
    Mr. Hoyer. What is happening over at that end of the table?
    [Laughter.]
    Dr. Collins. ``Sometime within the next few months,'' he 
writes, ``we shall have a rough first draft of the complete 
human genome,'' which is what I have been talking about. ``This 
is routinely reported as an event of medical and perhaps 
ethical significance. I believe it is more than that. I believe 
it is the greatest intellectual moment in history----''
    Mr. Wicker. The greatest intellectual moment in history. 
All right.
    Dr. Collins [continuing]. ``Bar none.'' I am quoting him.
    [Laughter.]
    Mr. Wicker. But you quoted with approval. Do you agree with 
that?
    Dr. Collins. I think I said at the end of this quote that 
this may be a little on the grandiose side, and it probably is 
a bit ``over the top.'' But I will say, Mr. Wicker, as compared 
to any other scientific adventure that we have undertaken, I 
would stack the Human Genome Project up against any other 
project for its significance for our future, for our 
understanding of ourselves, both in terms of its promise to 
better human health--for the ways in which we understand how we 
are similar and how we are different--and how we relate within 
society. It is hard to beat this.
    Splitting the atom? I think that was awfully important, but 
I would put this one up one notch above that. Going to the 
moon, fantastic adventure. I am a big fan of the space 
program--
    Mr. Wicker. It probably made for better television than the 
human genome.
    Dr. Collins. Probably. You know, we do have a problem 
there. We do not send up space shuttles and have photogenic 
moments. If you go to one of our genome labs, it is a little 
hard to turn that into a story for the evening news, although 
it occasionally happens.
    Mr. Obey. Hire Krulwich.
    [Laughter.]
    Dr. Collins. Robert Krulwich is clearly a good guy to have 
on your side.

                        BENEFIT TO HUMAN HEALTH

    Mr. Wicker. Take us then a quarter century into the future, 
looking back on perhaps the greatest intellectual moment in 
history, and tell us what we will have achieved for our Federal 
investment and for our scientific endeavors, from this the 
greatest intellectual moment in history, perhaps.
    Dr. Collins. I think that is the right question--how is 
this going to make a difference.
    Well, we will uncover the susceptibility factors for 
diabetes, and heart disease, and Alzheimer's disease, and 
virtually every condition because they all have hereditary 
factors. By 25 years from now, we will have figured out how to 
use that genetic information to make individual predictions of 
future risk of illness, allowing each of us to practice a 
program of individualized preventive medicine focused on 
keeping ourselves well. Not in a one-size-fits-all approach, 
which is what we are currently relegated to doing, but in an 
approach that is ideally suited for that person.
    If you fall through that preventive medicine safety net and 
get sick anyway, the treatments we will have available, and 
some will be gene therapies and many others will be drug 
therapies based on an understanding of genes, will be much more 
precisely tuned for the problem that you have and will be 
available at an earlier stage. Our diagnosis will come along 
much sooner and before the symptoms have become so advanced, as 
they currently often do, and we will be able to develop 
designer approaches that are targeted at the molecular problem, 
as opposed to some downstream symptom. This is all too often 
what we currently do in medicine, because it is the best we 
have.
    So this new generation of therapies, which is probably 
going to come along first for cancer--and I am sure Dr. 
Klausner talked extensively about the ways in which our 
understanding of cancer are leading us already in that 
direction--will come along for other diseases as well. And by 
25 years from now, both the preventive aspects of medicine and 
the therapeutic aspects will be almost unrecognizable and will 
be more powerful in many ways than we can currently guess. We 
will have to experience this to believe it when we get there.
    Mr. Wicker. And the way that we insure for them will be 
quite different, obviously.
    Dr. Collins. That is one thing I cannot predict, how will 
we handle our medical care system.
    Mr. Wicker. Well, are you willing to predict that because 
of your efforts that the cost of medical care will be less?
    Dr. Collins. That is a very hard question. New developments 
in medical technology that come out of research often, as you 
know, initially do not reduce the costs. They may be for a time 
adding to the costs because they are novel and often involve 
equipment that is rather expensive. But those are short-term 
half-way technologies.
    Ultimately, yes, I believe these advances will result in a 
reduction in costs. Just to focus on a preventive approach, 
especially if it works, is likely to greatly reduce the ways in 
which we spend money on health care. So, I think the answer 
will be, yes. It is much harder for me to predict the timetable 
over which that expenditure requirement will go up and then 
will gradually come down.

                           FUTURE OF THE HGP

    Mr. Wicker. I notice you have in the budget justification 
you refer to a 5-year research plan.
    Dr. Collins. Yes, sir.
    Mr. Wicker. And I suppose you are in your third year now of 
that 5-year plan?
    Dr. Collins. Right. It was published in October of 1998.
    Mr. Wicker. But do you foresee a time when your institute 
will be out of business or a quarter of a century now will the 
Human Genome Research Institute still have a mission?
    Dr. Collins. In the genome business it is hard to see 
beyond 5 or 6 years in terms of what the research will involve 
because things do come along rather quickly. I certainly think 
we will have plenty to do for the next 5 or 6 or 7 years. The 
diagram on the easel indicates the number of areas that will 
keep us very busy, even after the human sequence is completed, 
which we will expect will be done in 2003 or possibly a little 
sooner, because we will need to understand that sequence.
    We are very concerned that we not set ourselves up to 
compete with the other institutes of the NIH because all of 
them, as you no doubt have been hearing, are very enthusiastic 
about the way that genomics is going to provide answers to the 
diseases that they are invested in solving. We celebrate that 
and will do everything we can to encourage that and partner 
with them.
    But there will be central areas of research like general 
technology developments for the next generation of genomics 
that we are particularly well suited to address. Computational 
methods, are another place that we will have a very important 
role to play and that is why it is one of our major initiatives 
for next year. So, I do not know that I can answer your 
question beyond 6 or 7 years. I think we have plenty to keep us 
busy during the next interval and more than we can probably do. 
We will be thoughtful about selecting topics that are 
complementary to what NIH is doing in other institutes and not 
in a way to be competitive.
    Mr. Wicker. Thank you.
    Mr. Porter. Thank you, Mr. Wicker.
    Mrs. Lowey.

                 ETHICAL, LEGAL AND SOCIAL IMPLICATIONS

    Mrs. Lowey. Thank you, Mr. Chairman, and thank you, Dr. 
Collins, for your thoughtful presentation.
    You and I have talked before about the implications the 
Genome Project's work has for the privacy of individuals and I 
would like to follow-up with Mr. Obey's comments on privacy. 
And I think your thoughtfulness has been very helpful as we try 
to sort through proposals to protect medical records and 
prevent genetic discrimination.
    Last year, we did discuss your 5-year plan of ethical, 
legal and social implications or ELSI, as you call it. We have 
all heard the horror stories of genetic discrimination, the 
case of the woman whose fetus tested positive for cystic 
fibrosis during pregnancy and then the child could not get 
coverage and there are just so many of these horrid stories.
    My first question is, number one, I would like to know if 
you feel ELSI is proceeding fast enough, if you can give us an 
update on the plan and where you see it is heading? And 
secondly, in a related area on pharmacogenetics, you have 
commented publicly on your concern that pharmacogenetics may 
also lead to cases of genetic discrimination. Is that because 
pharmacy records would contain information about prescriptions 
that can be shared with the employer or insurer?
    So, I would really like you to comment on both, ELSI and 
then how the whole privacy issue involves pharmacogenetics and 
your comments on that.
    Dr. Collins. Thank you, Mrs. Lowey. And again, I appreciate 
your leadership on these issues to try to prevent 
discrimination from a host of different perspectives when it 
comes to genetics.
    The ELSI program has as its primary goal the support of 
research efforts that will illuminate the issues of where the 
study of genomics brings us into a circumstance where society 
needs some warning and some protections in place. How can we 
make sure that these advances are used to benefit people and 
not to place them at risk?
    In addition to the ELSI research program many of us are 
vigorously involved in trying to disseminate what we conclude 
from that research program with regards to ways that it might 
need to be known by policy makers. We have partnered-up with a 
variety of organizations, particularly the National Action Plan 
on Breast Cancer, to try to achieve some of those policy option 
development efforts. And it is gratifying to see the next phase 
of this effort which is the taking up of these issues by 
legislatures, both State and Federal, and bills coming to pass 
for issues like discrimination and privacy. Although as already 
pointed out, we are not there yet, at least there is gathering 
recognition of the importance of the ELSI issues.
    The part of this equation that we, at the Genome Institute, 
perhaps have the most ability to influence is the research 
part. That is what we fund. Our ELSI program since the 
beginning has been 5 percent of our budget and we are very 
proud of that. This is a new experiment. This has never really 
been tried before, where you study the research about the 
consequences at the same time that you do the science.
    We did, as you mentioned, last year talk a little bit about 
our new ELSI plan. It is particularly focused now on trying to 
understand the consequences of the study of human variation. 
That has become a very significant part of our goals, for good 
reasons, because we believe it will help us understand the 
causes of virtually all diseases. But that same variation can 
be used for nonmedical purposes. People are very interested in 
how this will play out in the study of behavior, how will it 
influence our understanding of ethnicity and racial identities, 
how will it be used even in the justice system, for instance. 
We have just funded a whole new set of grants that we solicited 
to try to address those particular goals, the ethical 
consequences of studying variation. It is a very exciting set 
of proposals. So, I think we are on a good track.
    We have also partnered-up with the National Heart, Lung and 
Blood Institute to study a particular condition called 
hemochromatosis, which many of us believe will be the first 
disorder for which adult population screening will be offered. 
This is an iron-storage disorder. It affects one in 300 people 
and it is entirely treatable. Simply by giving blood a little 
more often than other people, you can keep your iron stores 
down. The gene has now been identified and there is a lot of 
enthusiasm for offering testing to virtually everybody to 
identify those who need this treatment.
    We believe that in order to do that right we should carry 
this out on a pilot basis and, so, with the National Heart, 
Lung and Blood Institute we will be screening 100,000 people in 
a research program to find out how this works. That will be a 
paradigm-setting experience; it will set the way, show the path 
for other adult-onset disorders.

                           LEGISLATION NEEDED

    Where I am perhaps most powerless and most in need of your 
help when it comes to the ELSI issues and whether the future is 
going to turn out the way we all want, is at this interface 
between the research program and the policy decision making and 
the legislation. I am gratified that folks like you have raised 
these issues to the level of recognition that we have received 
to the point.
    I am gratified to see support in both parties, in both 
houses for doing something about the ELSI issues, and the 
number of bills that are being considered in the current 
Congress. I hope that the year 2000 will not just be known as 
the year of the President's Executive Order but also as the 
year where Congress actually got legislation passed and provide 
the kind of reassurances to the people that we see in our 
clinics every day, who are afraid to get genetic information 
about themselves for fear it might be used against them.

                           PHARMACO GENETICS

    Your other question was about pharmacogenetics. This is a 
very exciting field. It offers the potential to predict an 
individual's response to a drug therapy and know whether that 
is the therapy that is going to work for them, and also to know 
whether that therapy is the one that will give a bad side 
effect and they had better stay away from it. This study of 
human variation will lead us to that kind of possibility.
    It is also true that the kind of testing you might do to 
predict somebody's drug susceptibility may also tell you 
something about their future risk of illness, even if they do 
not get that drug. So, one cannot ignore the same kinds of 
issues that relate to susceptibility testing in general. And 
certainly if the pharmacy were to have access to that 
information and were not paying attention to confidentiality 
there would be privacy issues as well.
    But I think, in general, it is an approach which has, just 
like the preventive medicine effort enormous potential to allow 
each of us to know what is going to be best for our health. We 
just have to pay attention and make sure that the information 
does not get used against people in improper ways. We would all 
recoil from that, and preventing those outcomes is going to 
take good public policy.
    Mrs. Lowey. Thank you. I have a feeling I am out of time.
    Mr. Porter. You are right.
    Thank you, Mrs. Lowey.
    Mr. Hoyer.
    Mr. Hoyer. Thank you very much, Mr. Chairman.
    Dr. Collins, I do not know whether I am in revery at this 
end of the table but I do know I am in awe of the threshold of 
which you speak or perhaps the threshold we have crossed and 
are now expanding into the room.
    I was interested, I happened to pick up a--which I have not 
read--``Time's'' observation of who the Man of the Century 
was--and obviously, as you know, it was Einstein--as you 
answered the question and as I heard the perhaps over-
expansive--one I guess could get into a theological discussion 
pretty quickly on what the greatest intellectual moment in 
history is but putting that aside----
    Dr. Collins. We could and we probably should if we are 
being honest about it.
    Mr. Hoyer. I think it is not too far off that really 
science does affect us as a humankind.
    Dr. Collins. Yes.

                   AHEAD OF SCHEDULE AND UNDER BUDGET

    Mr. Hoyer. Not perhaps more. And it was interesting that 
``Time'' observed that the three great movements of the 20th 
Century were the Civil Rights Movement: Women in the early part 
of the century voting and expanding upon that, obviously, in 
the middle part of the century, Gandhi, Martin Luther King; 
then the success of democracy, how we govern ourselves as 
peoples around the world; and then, third, the scientific, and 
ultimately ``Time'' concluded that the scientific had made the 
greatest impact which is interesting in a century that had 
Roosevelt and Churchill and Gandhi and King and giants, who 
have affected us as societies, but perhaps none more so than 
Einstein, who I presume much of what he thought then and 
hypothesized then is now still very relevant to what you are 
doing even.
    In any event, having said that, I will get off my revery 
and ask you: You observed that you are ahead of time and under-
budget. What is under-budget mean?
    [Laughter.]
    Dr. Collins. Well, that is a good question. We are rather 
proud of that set of words, being ahead of schedule and under-
budget. Mr. Porter generally smiles when I say those things and 
I am very proud to be able to come in front of this Committee 
and make those claims and I will be happy to back them up.
    There are various ways that one can do this accounting 
because the original budget projections for the Human Genome 
Project were made in 1990 at a time where the goals for the 
project were scoped out over a 15-year period in a fashion that 
people thought at the time was pretty darned aggressive and 
ambitious. Many goals were, in fact, ridiculed as being totally 
unrealistic. We have now achieved almost all of those goals. We 
will finish the human genome sequence in the relatively near 
future.
    If I look at the money that has been spent since 1990 for 
this enterprise, combining what the NIH has spent and what the 
Department of Energy has spent and correcting for inflation, it 
still falls substantially under the $3,000,000,000 that had 
been put forward as that original projection.
    But I think that calculation actually understates 
significantly the way in which this project has come in under 
expectations as far as costs. During these 10 years, because of 
the success of various parts of the project, we have added 
other highly relevant and necessary goals that we thought we 
would have to wait until 2005 to start on, the study of human 
variation, for instance. We are now spending a good chunk of 
that total budget on those other new enterprises which have 
been started way ahead of schedule.
    If you just look at what we have spent on a working draft 
sequence of the human genome, it adds up to about $250,000,000. 
Obviously, way under the original projections of what that 
would cost. So, I think no matter how you do the accounting and 
which things you say are inside the box and which are outside, 
it is entirely legitimate for us to say this is a project that 
has outstripped expectations in terms of costs and times of 
delivery.
    Mr. Hoyer. I think that is an important point because so 
often we make projections of what things are going to cost and 
almost everybody invariably believes we will spend 20 percent, 
50 percent, 100 percent-more than that. And I think it is a 
testimony to how fast this thing is going and how effectively 
we are being assisted by these supercomputers to get to 
conclusions much faster than obviously we otherwise could have. 
We obviously could not have done this, I suppose, without that.
    Let me ask you, Doctor, in the time I have left, about 
various neurological disorders. I am very interested and have 
been for years in Rett's syndrome, which is a neurological 
disorder. What, if anything, have you done with that or have 
you done anything with that specifically?
    Dr. Collins. That is a wonderful question because it has 
been an incredibly exciting revelation just in the last few 
months.

                    RETT'S SYNDROME GENE INDENTIFIED

    Mr. Hoyer. I got a lot of calls about your work and I 
wanted you to put this on the record.
    Dr. Collins. I bet you did. So, Rett's syndrome is a very 
frustrating disorder which affects only girls. These little 
girls are born appearing completely normal and develop normally 
for a while, a few months, and then gradually begin to lose 
milestones and ultimately end up autistic with a typical hand-
wringing kind of motion, withdrawn and unable to interact with 
their environment, a heart-breaking situation.
    Investigators at Stanford and at Baylor, using the tools of 
the Human Genome Project, developed particularly for the X 
chromosome where the Rett syndrome gene was thought to lie, 
announced last October that they had accomplished something 
which many of us thought would be many years off because the 
clues as to the location of this gene were really quite 
sketchy. They identified the gene. They showed that it was a 
particularly interesting gene in that it controls the way in 
which whole blocks of genes, maybe even a whole chromosome, is 
turned on or off. So, it not only provides a remarkable 
revelation about the cause of this disease, it provides some 
fundamental information about the regulation of the entire 
human genome, and who would have thought those two things would 
come together?
    This discovery almost immediately, makes it possible to 
diagnose this illness precisely, which has been a big problem 
in the past because it has been a purely clinical diagnosis. 
And, of course, the hope is that the revelation of the 
mechanism will supply some good ideas about how to turn this 
around and help those unfortunate girls that suffer with this 
disease, and their families.
    So, Rett's syndrome, after many, many years of being behind 
a curtain and paid little attention to, has suddenly become the 
hottest story in genetics. In part, this has happened because 
of the brilliance of those investigators, but I must also say 
because of the tools that were available for them through the 
Genome Project.
    Mr. Hoyer. Mr. Chairman, you know the story of Christy 
Smith, who has Rett's syndrome. I wish I remembered the year, 
but it had to be 10 years ago perhaps. Dr. Kirschstein, you may 
remember, when I put $500,000 in this bill for the purposes of 
asking NIH to look at Rett's syndrome. And it is an incredibly 
good feeling to know that for a relatively small sum of money--
you have expanded it by the way, you added money that was not 
specifically added, you being NIH--but it is an extraordinary 
story and it is the kind of thing that makes these investments 
worthwhile.
    Now, this happens to be a very specific, defined area, but 
that story is replicated millions of times over, and will 
continue to be. It is very exciting.
    Thank you, Mr. Chairman.
    Mr. Porter. Thank you, Mr. Hoyer.
    Mr. Bonilla.

                        GENE-BASED RISK BEHAVIOR

    Mr. Bonilla. Thank you, Mr. Chairman.
    Dr. Collins, I also want to congratulate you on the great 
work that you are doing and I find it fascinating and I am sure 
it is extremely rewarding for you, personally, and for all the 
researchers that are working with you. In listening to your 
dialogue with Mr. Wicker earlier it was fascinating to think 
about a few years down the road when we have the genetic makeup 
all mapped out and we know so much about what we can prevent 
and so forth as you were discussing, I wonder how much better 
people will react to that than they do now based on the 
research that is not genetic research but historically we did 
not use to know, for example, 30, 40 years ago, maybe that what 
a significant impact weight loss would have on a person's 
health, how much of a factor smoking is on lung cancer, how 
much your diet has to do with heart disease and stroke and now 
that we know all of these things for a while you see people 
paying more attention and adapting their lifestyles and 
behavior, I wonder if--what I am trying to say is that the 
reaction has not been as significant as it should be. We know, 
for example, what prevents diabetes to a great degree but 
people still continue to ignore the facts and choose to live, 
have poor eating habits and poor exercise habits and they will, 
nonetheless, even though we know what can lessen your chances, 
will continue to do the wrong things and wind up sick anyway.
    So, I am hoping--I do not know if you can project or 
anticipate that the knowledge we acquire from your research 
will affect the public any differently?
    Dr. Collins. Mr. Bonilla, I think that is an excellent 
question and, in fact, this is one of our ELSI initiatives for 
fiscal year 2001. We aim to try to get more information about 
how people will use genetic information about themselves to 
make decisions about health behaviors. I think we cannot be 
naive and just imagine, if you tell people this behavior for 
you is going to be more dangerous than the average person that 
they will not do it.
    We have to understand how that information is received, how 
it is integrated into somebody's view of themselves, and then 
translate it into an actual change in health behavior. How is 
that change affected by numerous other factors, including their 
previous experience with the medical care system, their 
educational level, socioeconomic status, or cultural 
traditions. We aim to study that interaction in a rather 
systematic way through this new research initiative.
    I think we have a lot to learn from that. You are right, we 
already know a lot of health behaviors that are quite dangerous 
and yet many people continue to practice them, smoking being 
the obvious example. We cannot be Pollyannish about this notion 
that if we have the genetic factors figured out everybody will 
then do exactly the right thing with that information.
    Mr. Bonilla. Right.
    Dr. Collins. So, it is an area that deserves a lot of 
research attention. We are going to make that a very high 
priority. I do not know quite how it will turn out. I can guess 
that like most things there will be a lot of folks who welcome 
this information, who understand--after some explanation--what 
it means and who take appropriate actions. There will be other 
folks for whom this just does not seem very relevant.
    Mr. Bonilla. It is somewhat discouraging for a lot of us 
who--my background is not in health but I have certainly 
learned a lot on this Subcommittee going on my eighth year now, 
that we have so much wonderful information out there, you are 
giving us more, but we still, people still choose to either 
ignore or not--in some cases they choose to not even try to 
learn what they need to know to make themselves healthier. So, 
it is just something that I am glad you are looking into that 
aspect of it as well in terms of how people will be more likely 
to use this kind of knowledge.
    Dr. Collins. I think when such knowledge is individualized 
that will add an additional value to it in people's view.
    Mr. Bonilla. Like here is your map, kind of?
    Dr. Collins. That this is not just about everybody. Because 
a lot of people manage to convince themselves, oh, that is not 
going to happen to me. That is somebody else.
    Mr. Bonilla. Right.
    Dr. Collins. But, if it is based upon your own information, 
your own genome, then it becomes somewhat more difficult to 
turn around and walk away and say, well, that is not so 
relevant. I think that will be an additional motivator. It will 
not be perfect.

                           DIABETES RESEARCH

    Mr. Bonilla. I am curious to learn more about how this work 
will translate into therapies for particular diseases. In your 
budget justification you mention your institute study of 
leukemia, cystic fibrosis, and diabetes in the African American 
population. Could you further elaborate on the current status 
of genetic research related to diabetes, in particular, Type I?
    Dr. Collins. Sure. As you may know, our extramural program 
is devoted largely to accomplishing the goals of the Human 
Genome Project, which provides maps and sequences and 
technologies that all of the institutes use in their searching 
for the causes and cures of illness. Our intramural program has 
a different philosophy and it is using those tools to attack 
important problems in research. We have in the intramural 
program significant efforts on diabetes, although it is 
primarily Type II.
    My own research lab, which I still manage to go to now and 
then, has as its major focus trying to uncover the genetic 
factors in adult-onset diabetes. We are particularly involved 
in a study in West Africa trying to identify these factors in 
the ancestral origins of modern day African Americans. It turns 
out it is easier to study those factors in an environment such 
as West Africa where the diet is less of a confounding factor 
than it is here.
    In Type I diabetes, clearly a great deal has been done, 
both in the U.S. and in Europe, to study families in which more 
than one child has had juvenile-onset disease. We have learned, 
and this is work in the U.S. largely supported by NIDDK, about 
the existence of as many as a dozen genes that play a role in 
this disease. Although many of those are still neighborhoods 
and we do not have the precise genes yet, for three of them we 
do know exactly what the gene is and we have a pretty good idea 
about what the mechanism might be.
    The goals are much like the ones that I talked about 
earlier. This information could be used to identify which kids 
are at the highest risk. If there is an environmental trigger, 
as many people believe there might be, understanding the high-
risk individual might also point you to what the environmental 
trigger might be, and then give you an idea about how to avoid 
that.
    So, the process of going from gene identification, to 
better diagnostics, to better therapeutics is being played out 
for Type I diabetes and for many other disorders, one after the 
other.
    Mr. Bonilla. Dr. Collins, it is nice to see the excitement 
and enthusiasm you have over at the NIH and keep up the good 
work. We are proud of what you are doing.
    Dr. Collins. Thank you very much, Mr. Bonilla.

                  CHROMOSOMES--NUMBERS, SIZES, SHAPES

    Mr. Porter. We will have time for a second round.
    Dr. Collins, just for my edification, what is the 
significance of the different sizes and shapes of the 
chromosomes?
    Dr. Collins. Human chromosomes, which you can actually see 
under the microscope, are not all the same size. The biggest 
one, which we call Number One, is cartooned there on the poster 
but if you were looking at it, that is the one that--I am not a 
cytogeneticist--I can always pick out chromosome Number One 
because it is the biggest one, and chromosome 22 is the 
smallest. The X and the Y chromosomes are the sex chromosomes. 
If you have an X and a Y you are a boy. If you have two X'es, 
you are a girl.
    How they ended up in this particular set of sizes and 
shapes is a very interesting question and we can, in fact, make 
comparisons with some of our close relatives in the animal 
kingdom and begin to figure out how chromosomes have reshuffled 
over time.
    It is very much part of our identity, our karyotype, we 
refer to it. Each one of those chromosomes has thousands of 
genes on it. There is no chromosome for the liver and a 
chromosome for the kidney. The genes are scattered all around, 
the chromosomes basically representing their houses but the 
residents of those houses do not necessarily belong to the same 
family. They are all mixed in together.
    Mr. Porter. Now, would a mouse have the same number of 
chromosomes as a human and does every living thing have the 
same number?
    Dr. Collins. No. Actually there is quite a lot of 
variability in chromosomes. Mice have 20. They tend to be of 
almost the same size. So mouse chromosomes are much harder to 
study than human chromosomes because they all look a lot alike. 
Some organisms have as many as 60 or 70 chromosomes. Some of 
the simpler ones may only have three. It is a characteristic 
feature of the biology of that organism but it is all over the 
place.
    Mr. Porter. All right. Now, my understanding is that you 
are sequencing one individual's genome. You have talked here 
about everybody having their own map and it has taken you all 
these years to get where we are today. How fast will an 
individual's genetic map be able to be produced in the future 
and is it not going to be a huge undertaking just to do that?
    Dr. Collins. Yes. There are two levels of an answer to 
that. You are right that what we are doing right now is to 
sequence basically a representative genome. Actually the 
sequence that we are producing does not come from one specific 
individual. It is a patchwork of a small number of 
contributors. That will give us a very good idea about the 99.9 
percent that we all have in common. But if I was going to look 
at my genome map or yours I would also be interested in the .1 
percent that is different.
    Mr. Porter. And how do you find that?
    Dr. Collins. And how do you find that? That is, in fact, 
why we have this other goal of identifying sequence variation. 
I had the cartoon up there, and maybe Dr. Jordan will put it 
back up if it has not disappeared, of the two individuals 
carrying their flags and one has a ``G'' and one has a ``T.'' 
You know most human variation is ancient. It has been with us 
since we were all together in Africa, about 10,000 of us about 
150,000 years ago.
    Mr. Porter. So, you would know where to look?
    Dr. Collins. You would know where to look, precisely. So, 
you do not have to look at all 3 billion base pairs to find 
most of the variation. You can look in about 10 million places 
and you will see most of it.
    Now, ultimately, in maybe 20 or 30 years we will be good 
enough, I suspect, at sequencing DNA--and I made this 
prediction in a ``Scientific American'' article that came out 
in December--that we would be able to sequence your entire 
genome, all 3 billion base pairs, for such a low cost that it 
is easier just to do it that way instead of picking out the 
places where the variants are most likely to be. But that will 
not come along right away.
    Mr. Porter. Now, when you do other sequences; of laboratory 
mice or chimpanzees or whatever, would you be able to 
eventually find the perfect laboratory mammal for certain types 
of study by--in comparing the human genome and the genome of 
this particular mammal? In other words, would you be able to 
say that to study a part of the brain we would be able to use 
the dolphin as a laboratory animal even though it is very 
unwieldy?
    Dr. Collins. Mr. Porter, you ask wonderful questions. In 
fact, that is the kind of question that many folks in the 
biological community are asking themselves right now. Clearly, 
the ability to sequence genomes is here. I think everybody 
would agree that after the human, the mouse is going to be the 
one model from which we derive the greatest amount of 
additional incremental information. In part, because there has 
been so much work done on this organism as a model of human 
diseases. There are mouse models of almost any disease you can 
think of and using these models are wonderfully powerful ways 
to study the disease. Also there is a lot of experience with 
the genetics of the mouse to help you along.
    But if, as you are saying, your goal is not necessarily to 
study the genome of an organism that is globally useful but may 
be useful in a specific way, what would you choose? Well, I 
suspect if you were trying to understand higher brain function 
you might be interested in knowing what are the differences--
the 1.6 percent differences--between us and chimpanzees, for 
instance. Or moving a little further down in the primate or the 
pro-simian lineages, what is going on with that suite of genes 
that is involved in the brain? So, you might make that kind of 
choice.
    If you were interested in studying physiology of the heart, 
for instance, you might very well want to pick an organism that 
is fairly similar to human. A lot of people study pigs for that 
reason, both in terms of size and the way that the system 
operates. So, it would be predicated very much on what was your 
question. For some of those questions right now there would be 
genuine disagreement about the answer, but it is the right 
question and it will be one that gets asked a lot.
    Mr. Porter. And presumably you can take all orders of life 
and in an exact way say which are the most similar to humans--
--
    Dr. Collins. Yes.
    Mr. Porter [continuing]. Once you sequence them all?
    Dr. Collins. Yes. Even by sampling them to a modest 
statistical level you can begin to get a pretty good sense of 
what that answer is going to be. You do not have to sequence 
their entire genomes to get a pretty good idea of the 
similarity once you have the complete human to compare it to.
    Mr. Porter. And do we assume, therefore, that the 
chimpanzee is the closest to humans or we to they?
    Dr. Collins. That is correct. Ninety-eight-point-four 
percent seems to be the identity between us and chimpanzees. 
Gorillas are close but not quite.
    Mr. Porter. So, this tends to corroborate Darwin's theory?
    Dr. Collins. It is certainly consistent with Charles 
Darwin's observations, yes, indeed.

                  HEALTH OUTCOMES IN DEVELOPING AREAS

    Mr. Porter. All right. Now, you have talked about how we 
can find genetic defects in diabetes or heart disease or other 
diseases. But we are, in the United States, about 6 percent of 
the world's population and a great deal of the world's total 
population lives in developing countries where, they do not 
live long enough many times to have diabetes or heart disease. 
They die of infectious diseases, like malaria--we talked about 
this with Dr. Fauci this morning--malaria or tuberculosis or 
HIV-AIDS or influenza or something else.
    What are the genetic implications of infectious diseases? 
In other words, how does your work bear upon those diseases? 
And secondly, if it does, how will we translate the work into 
health outcomes when you do not have a health infrastructure 
that today can even deliver vaccines for some of the most 
understood diseases?
    Dr. Collins. That is a very important question, Mr. Porter. 
I spent some time myself in Africa working a couple of stints 
in a mission hospital, and I am fully aware, by that 
experience, of just how difficult it is to deliver medical care 
in a situation where public health measures are hard to come 
by, and where access to therapies or diagnostic methods is 
really quite limited.
    It is certainly the case that infectious diseases continue 
to be the scourge in much of the undeveloped world. Although as 
one looks at these trends, one sees more and more the emergence 
of the chronic diseases that we consider Western: diabetes, 
heart disease, cancer. So clearly, those are going to be 
increasingly a problem. We do somewhat better with the 
infectious disease management.
    It is very clear that genetics also plays a role in 
susceptibility to infectious illnesses. A lot of really 
interesting work has been done with AIDS in that regard. We 
understand that some fraction, probably 1 percent, of the 
American population is genetically immune to AIDS because they 
lack a certain cell surface receptor that the virus needs to 
get inside the cell. Knowing that, obviously, suggests some 
ideas about how you might develop that same genetic resistance 
by an acquired method as opposed to one you have to be born 
with.
    There was a very interesting study in West Africa a couple 
of years ago that was published in the New England Journal of 
Medicine, which looked at tuberculosis. The researchers 
identified a particular variant in a particular gene, that is 
involved in the pathogenesis of TB, that had a pretty strong 
effect on whether or not that person ended up with severe, 
prolonged cavitary pulmonary tuberculosis or whether they were 
able to fight off the infection. We have a lot to learn that is 
relevant to that category of illnesses, and certainly NIAID and 
Dr. Fauci have been quite enthusiastic about the interface 
between their interest and our own.
    Your harder question, and the one that I do not have an 
easy answer to--and I guess I take comfort that others do not 
as well, although I wish we collectively did--is how are we 
going to translate these advances that we hope for in this 
country, with all of its richness and benefits, to the rest of 
the world, because that is our obligation.
    My hope, my dream, would be that genetic approaches to 
illnesses will become transportable, exportable in an 
inexpensive way. Whether that dream comes to pass as swiftly as 
you and I would like will depend a lot on how much effort we 
put into it, so we have to continue to consider that a high 
priority. Certainly, one of the things we need is to do a 
better job of training folks outside of the US to be prepared 
to take on these new challenges in medicine. The Fogarty Center 
has certainly had some interesting ideas in that regard that we 
have been talking with them about it.
    Mr. Porter. Do you foresee, for example, a time when you 
can discover the genetic predisposition to, let us say, 
malaria, and a type of vaccine can actually be developed, where 
you could vaccinate whole populations without even determining 
whether they happen to be subject to that, and prevent the 
disease; is that possible that way?
    Dr. Collins. Certainly if you could come up with----
    Mr. Porter. I do not know what the delivery mechanism would 
be, but if it is a simple one and can be done easily, then I 
assume you could do it broadly.
    Dr. Collins. Right. A couple of things. One is we already 
understand one of the major factors in malaria susceptibility: 
that is whether or not you are a carrier for sickle cell 
disease. That is the reason why sickle cell anemia is so common 
in individuals whose geographic origins are in endemic areas 
for malaria, so we already have a pretty good handle on one of 
the major contributors in that regard.
    We are studying the malaria genome in collaboration with 
other international efforts. NIAID has taken the lead on that 
for NIH, but there is a lot of investment in that from the 
private sector and from the Wellcome Trust. The hope is that by 
studying that parasite genome, we will come up with new and 
better ways to develop vaccines. Obviously, if a vaccine were 
truly universally effective, you probably would not bother to 
go out and genotype all of the folks who are at risk. You would 
simply offer it to anybody who might get exposed to the 
parasite. But you could predict outcomes where the vaccine 
might work better in some populations than others. This is 
vaccino-genetics as opposed to pharmacogenetics. I suspect 
those kinds of scenarios will come to pass, where you figure, 
well, there are these three vaccines, and for you this is the 
best one, and for you, you ought to take that one, and the 
genotype will help you make that decision.

                        GENOMES TO BE SEQUENCED

    Mr. Porter. How many species and organisms do we need to 
sequence? I mean, is there a point beyond which where we say--I 
know we will always be curious to do it, because we can do it, 
and human curiosity is going to lead us to it, but is there a 
point then in which you say, ``Well, we have done all that we 
need to do to help human health?''
    Dr. Collins. I think we will get the maximum yield of 
information from the first several that we do, but I think 
there will continue to be, for specific reasons, and some of 
them you referred to in an earlier question, reasons to go on 
and do additional genomes. Fortunately, I think this is going 
to work out pretty well, because the cost of sequencing is 
going to continue to come down. We are experiencing almost a 
Moore's Law right now for sequencing, where the cost is 
dropping by a factor of two every couple of years. If that 
continues, and obviously, we need to invest in technology to 
make sure of that--that is why we have the sequencing 
technology goal, and I showed you an example of a gadget of 
that sort last year--but if that continues, we could afford to 
do many other genomes 5, 6 years from now, even if one could 
not argue that base pair for base pair they gave the same 
medical value that doing the human or the mouse did.
    I would hope, because the information is so fundamental, 
that we will not lose our nerve, and we will sustain an 
operation which is now gloriously productive, for some time. 
Because the value of the information, in many ways as yet 
untested, is likely to be even greater than we expect in ways 
that we cannot entirely predict.
    I have to add to that, this will only come to pass if that 
information is available to all, and I have to come back to 
that as a fundamental theme. I believe in the value of all 
manner of activities in both the public and private sector to 
add value to the sequence information to make it more 
meaningful, but the fundamental DNA sequence--and I would say 
this applies to any genome, not just the human, not just the 
mouse--the fundamental sequence information ought to be where 
everybody can use it. It is rather like this system that you 
have in the Congress, where if you want to learn about a bill 
or you want to learn about something in the Congressional 
Record, you go to Thomas and you get the information. That is 
free, and any citizen has access to it.
    Now, you can also go and pay for a more elaborate way of 
searching what is there, and getting additional annotation of 
the information, and that is great too, but we need to be sure 
we have a Thomas for genomes. That the fundamental DNA sequence 
information is accessible to any scientist with a good idea. If 
we make a mistake and lose that accessibility, we will regret 
it for years to come.

                        PARTNERSHIP ON FRUIT FLY

    Mr. Porter. That leads me to the final question that I want 
to ask. You did a sequencing of the fruit fly genome in 
partnership with a private company, Celera.
    Dr. Collins. Yes.
    Mr. Porter. And apparently, their method of sequencing, 
their part of it was different than your method of sequencing, 
your part of it, and yet you were able to take the two 
databases and merge them into a final product; is that not 
correct?
    Dr. Collins. Yes.
    Mr. Porter. All right. What did you learn from this? How 
did you do this, and is this likely to be the approach used in 
the future for similar type sequencing?
    Dr. Collins. It has been a very interesting chapter in the 
story of sequencing genomes. The publication of the draft 
sequence of the fruit fly is expected in about 3 weeks, but the 
information was recently presented at the AAAS meeting. Celera 
took a strategy where they broke the sequence into small 
pieces, regardless of where those pieces came from and then 
sequenced them. So they ended up with many, many bits of 
information, sentences, if you will, from this book of the 
Drosophila genome.
    Our grantee, Gerald Rubin at UC-Berkeley, took a different 
strategy, where he basically would take a page at a time and 
sequence it rather lightly, but he would know that the 
information came from that page.
    Because sequence is essentially digital information, it is 
possible to combine the results of these two approaches, and 
take those sentences that came out of Celera's approach and see 
what page they fit on, because you have things to overlap them 
with, and that is what was done. The indications are that it 
was pretty darn good. It still has something like 1,600 gaps 
that will require work to close them over the course of the 
next year, maybe a little more. But it does seem, at least for 
this genome, which is 1/30th the size of the human, that this 
strategy was effective.
    Already, in part because of this but in part because of 
other developments, there is a lot of enthusiasm in the public 
international sequencing effort to approach the mouse in a 
similar way, to do a combination of what we call the whole 
genome shotgun approach, and the page-by-page--or we call it 
BAC-by-BAC--approach, and then merge the two together. That is 
probably how we will sequence the mouse. So it is an 
interesting set of scientific developments and it has turned 
out pretty interesting.
    Mr. Porter. But it is not really complete because there are 
some gaps because of using the Celera method.
    Dr. Collins. Dr. Rubin will now be spending his time trying 
to close those gaps.
    Mr. Porter. They may not be significant gaps, but they are 
still gaps.
    Dr. Collins. They need to be worked on, this is not a 
finished sequence, and that will occupy him for many months to 
come.
    Mr. Porter. Dr. Collins, it is incredibly fascinating for 
us to listen to you. I have enjoyed immensely the last 7 years 
of watching this project grow and the success that you have 
had, and it is just amazing. I think the quote that you made 
probably is pretty close to accurate. It has been a wonderful 
time for me. You and other Directors have said how nice it was 
to appear before our Subcommittee and wish me well in my 
retirement, but the gain on this side has been much, much 
greater than the gain on that side. I will leave this position 
enriched and enlightened greatly from my experience with you 
and your colleagues at NIH, and we just cannot tell you how 
much we appreciate the work that you are doing. Thank you.
    Dr. Collins. Thank you, Mr. Porter. It has been a privilege 
to appear before you today as always.
    Mr. Porter. Thank you, sir.
    We will stand briefly in recess.



                                       Thursday, February 17, 2000.

         NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

                               WITNESSES

DR. HAROLD C. SLAVKIN, D.D.S., DIRECTOR, NIDCR
DR. DUSHANKA KLEINMAN, D.D.S., DEPUTY DIRECTOR, NIDCR
YVONNE du BUY, EXECUTIVE OFFICER, NIDCR
GEORGE J. COY, BUDGET OFFICER, NIDCR
DR. RUTH L. KIRSCHSTEIN, ACTING DIRECTOR, NIH
DENNIS P. WILLIAMS, DEPUTY ASSISTANT SECRETARY, BUDGET, DHHS
    Mr. Porter. Dr. Slavkin, why don't you proceed, because our 
time is short. I must leave at noon because I have a speech off 
the Hill, so we only have about 45 minutes, unfortunately. Why 
don't you proceed right away.

                       Introduction of Witnesses

    Dr. Slavkin. Thank you very much, Mr. Porter.
    Before I begin, I would like to introduce to you again Dr. 
Ruth Kirschstein and Mr. Williams, who were both kind enough to 
join us. Then we have our team from the institute, Wendy 
Liffers, Office of Science Policy, Yvonne du Buy, our Executive 
Officer, Dr. Dushanka Kleinman, our Deputy Director, and Mr. 
George Coy, our Budget Officer.

                           Opening Statement

    Thank you for this opportunity to provide you with a sense 
of your investment in the National Institute of Dental and 
Craniofacial Research and a sense of the return on the 
investment.

              RETURN ON INVESTMENT IN ORAL HEALTH RESEARCH

    Mr. Porter, when you were 10 years old, a study was 
conducted in your hometown of Evanston, Illinois. You were in 
the experimental group testing the fluoridated drinking water 
compared to Oak Park, Illinois, which was the control group.
    Mr. Porter. You know, I remember that. Seriously, I 
remember that very well.
    Dr. Slavkin. That was really the beginning in the 20th 
century of one of the most significant public health 
interventions ever done.
    As a consequence of that, now 50-some odd years later, the 
American people save $4 billion every year on dental bills, 
which is significantly more than the entire appropriation to 
the Institute over its 52-year history. So I believe that that 
is an example of a modest investment that translates into a 
significant return.
    Mr. Hoyer. Would the Chairman yield one second?
    Mr. Porter. I yield.
    Mr. Hoyer. Does the Chairman remember it as a communist 
plot?
    [Laughter.]
    Mr. Porter. The gentleman from Maryland might find this 
very interesting, because at home with us lived my mother's 
mother, my grandmother, who was, herself, a Roman Catholic who 
had converted to Christian Science, and she raised us 
religiously and we went to Sunday School in the Christian 
Science church.
    When this came along, there were objections by Christian 
Scientists that this was imposing on them medications that they 
did not want to take, and that began my gradual movement away 
from Christian Science. I have always appreciated the 
connection of faith and belief with healing and good health, 
but I thought that went away from what common sense told me was 
the right direction. So it was kind of interesting, now that 
you asked.
    Mr. Hoyer. A plot by any other name, I understand.
    Mr. Porter. Yes.
    Dr. Slavkin. Now, what I would like to do in the remaining 
time is give you a sense of your current investments and the 
return on those investments. In your packet from us are a 
series of graphics that we are going to refer to over here on 
this easel.
    Clearly, one of the things that has happened over these 52 
years is that today the problems are not simple. They are 
highly complex. Today the society is a polyglot amalgamation of 
all kinds of people and we have learned from our investments in 
genetics and pharmacogenetics that one treatment does not fit 
all. There are a number of new frontiers, and I would like to 
highlight them for you.

                    BURDEN OF DISEASES AND DISORDERS

    On the second of our graphics is a sense of the burden of 
disease as we see it--and ``we'' means CDC, HRSA, ourselves, 
HeadStart, the WIC programs, a variety of surveillance groups 
at the Federal and State level who are looking at changing 
demography, changing diversity, and changing patterns of 
disease.
    So we are looking at birth defects, including--and I will 
point this out in a few minutes--low-birth-weight premature 
babies, that are correlated with oral health.
    Dental caries, which are now expressed in about 20 percent 
of the population, strictly correlated with a socioeconomic 
gradient in this country.
    The issue of dental orthopedics--severe malocclusions 
occurs in about 23 percent of the population.
    The loss of all of the dentition--52 years ago, half of the 
adult population had no teeth. Today it is roughly 10 percent, 
and we would like that number to get significantly lower.
    Head and neck cancer--oral, pharyngeal, laryngeal, and 
tonsilar cancers, represent the sixth most common cancer of all 
of them; and in the African American male population, it is the 
fourth most common malignancy in our country.
    Osteoporosis, bone loss, is also a major factor as our 
population lives longer and wants to live better. Osteoporosis 
is a major challenge for keeping teeth in people's mouths.
    Head and neck trauma, orofacial trauma, is especially 
significant to children and includes child abuse issues, both 
intentional and non-intentional injuries.
    Chronic pain--essentially, 25 percent of the adult 
population experiences some kind of severe chronic pain.
    Periodontal diseases affects about 67 percent of the 
population.
    Over 15 million Americans are at risk for oral 
complications of systemic diseases such as diabetes, 
osteoarthritis, Parkinson's, and a host of other systemic 
problems.
    Salivary gland dysfunction is associated with 
immunodeficiency, medically-compromised individuals.
    Oral complications of cancer therapy--both chemotherapy and 
radiation--manifests in the mouth. These very ugly yeast 
infections are associated with immunodeficiency and medically-
compromised issues.
    Now in all of these, the most significant focal point, from 
our point of view, is children and their caregivers. About a 
year-and-a-half ago we began studying to develop a strategy to 
work with other Federal agencies to address the issue of 
reducing health disparities. Part of our consortium included 
HRSA, CDC, other NIH institutes, the Office of Research on 
Minority Health, the Office of Research on Women's Health, and 
the Office of Behavioral and Social Sciences. All pulled 
together to look at the issues of access, training for a 
diverse workforce, and doing research; with the focal point 
being children and their caregivers. It is our number one 
priority in our request for fiscal year 2001.
    Our strategy is that we are going around the country 
holding town meetings in major cities that have very 
significant under-served, historically under-represented 
populations. We have been to Atlanta, Boston, Chicago, Dallas, 
the West Coast, and Washington, D.C. We believe that this will 
be significant, maybe as significant as fluoridation was 
historically, to begin to reduce the burden of disease.

              GENE DISCOVERIES--THE RAPID RATE OF PROGRESS

    Now let me switch gears. On the next chart in front of you 
is an idea from the shared time we have had together, Mr. 
Porter, from 1995 to the present. We have gone from 80 genes 
linked with craniofacial, oral, dental inherited diseases to 
360, and that number is growing.
    In terms of head and neck cancer, we have gone from 20 
genes identified with oral, pharyngeal, laryngeal, and tonsilar 
cancer to well over 600, in partnership with NCI and the 
National Institute on Deafness and other Communication 
Disorders.
    In terms of taking on the interesting problem of why 
normally benign microbes that live in our mouths, in some 
individuals become virulent, pathogenic, and cause serious 
infections, we are doing microbial genomics. We started at zero 
in 1995. We are completing six microbial genomics, and we have 
seven microbial genomes scheduled for the near future.

               ORAL INFECTION AND LOW-BIRTH-WEIGHT BABIES

    Here is an example of where the payoff could be. One of the 
most significant problems of newborn infants is the problem of 
low-birth-weight, premature babies. These are babies that are 
born and weigh less than 2,500 grams. It costs a quarter of a 
million dollars per child to take care of them, and the 
consequences of taking care of them are often neurological 
diseases, mental retardation, eye deficiencies, and other 
problems.
    A very interesting association has been found between oral 
infection and low-birth-weight babies. It is a risk factor that 
is seven-fold higher in individuals who have spontaneous 
premature babies.
    We are currently doing a demonstration, so-called 
``intervention study,'' to test the hypothesis: if you control 
oral infection, to the tune of spending about $100, can you 
reduce the burden of low-birth-weight, premature babies--which 
costs a quarter of a million dollars per child?
    On this graphic, it shows the mechanism and the emerging 
data. We are very excited about the possibilities that may come 
out of this research.

        GENES OF INFLAMMATION, TOOTH LOSS AND TOOTH DEVELOPMENT

    On the next graphic is a very counter-intuitive study. This 
is a very rare disease called ``Papillon-Lefevre Syndrome,'' in 
which children, when they are 4 years old, lose all of their 
baby teeth, and when they are 14 years old lose all of their 
permanent teeth. The gene responsible has been identified, 
cloned, and sequenced. It is called cathepsin-C. We supported 
that research, and we now have a significant clue for a 
mechanism--immune response genes--that may be involved in 
management of oral infection that leads to these devastating 
conditions.
    On the next and last graphic is something that, to all of 
you on the Committee, might be obvious, but, living in this 
genomic era, our scientists have taken apart all of the genes 
involved in making a tooth. How do you position it? How do you 
develop it? How do you form it? That gene network, those 
genetic circuits, are now amenable for biomimetics, tissue 
engineering and biomaterials, efforts to develop biological 
solutions to congenital missing teeth or teeth that are lost 
over a lifetime.
    Here, a gene called pax-9, which was published in January 
of this year, last month, and another gene called MSX-1, are 
causal. These are loss-of-function mutations that are causal to 
these deformities.
    In conclusion, I would like to thank Mr. Porter and the 
Members of the Committee for the opportunity to serve at the 
NIH and, in particular, at the National Institute of Dental and 
Craniofacial Research. I have been in Washington for 5 years. 
It has been one of the most incredible times in biomedical 
history because of your efforts. Working with Harold Varmus and 
the other Institute Directors has been enormously gratifying.
    In July my wife and I will return to four children and six 
grandchildren who say it is time to come home, and I will also 
return to the University of Southern California to continue an 
academic career.
    If you have any questions, I would love to entertain them. 
Thank you so much.
    Mr. Porter. Thank you, Dr. Slavkin.
    [The prepared statement follows:]



    Mr. Porter. Wait a minute. This is what I am doing.
    [Laughter.]
    Dr. Slavkin. You are a pacesetter.
    Mr. Porter. You arrived just at the time I became Chairman.
    Dr. Slavkin. Yes. Exactly.
    Mr. Porter. You could at least stay through the end of my 
term.
    Well, you have done just a marvelous job. I think the way 
people come from the private sector into Government to provide 
that service and then return is one of the great things about 
our country. We benefit both ways, and you have done just a 
wonderful job there, and the presentations that you have given 
us all these years to understand the rapid increase in the 
knowledge base in your areas just have been amazing to me.
    Dr. Slavkin. Thank you.

                        LOW-BIRTH-WEIGHT BABIES

    Mr. Porter. I have some irrelevant questions to begin with.
    This is not your area directly, but I wonder, are other 
countries in the world doing as much as we do to keep low-
birth-weight, premature babies alive? It seems to me this 
country goes out of its way to do something that other 
countries may not do. What is the situation in Europe and Japan 
and others? Do they do this, or not?
    Dr. Slavkin. Places that I am familiar with, which are in 
western Europe and in Japan and in Taiwan, industrialized 
nations, the patterns are very similar to ours.
    Mr. Porter. They are?
    Dr. Slavkin. But I do not know in eastern Europe or other 
parts of the world what the value systems and what the 
decisions are.
    Mr. Porter. Well, and the resources, too.
    Dr. Slavkin. And the resources. Right.
    Mr. Porter. So other countries are doing the same effort 
that we are.
    Dr. Slavkin. Yes.

                  CRANIOFACIAL, ORAL AND DENTAL GENES

    Mr. Porter. When you talk about--I think it was 360 genes 
that have been identified.
    Dr. Slavkin. Yes.
    Mr. Porter. When you say ``identified,'' is that simply 
that they are identified with some part of the mouth, the 
teeth, or others, or are they identified in a way that is 
specific to possible diseases of the mouth?
    Dr. Slavkin. Right. The latter.
    The 360 genes, which are all detailed in the National 
Library of Medicine and available to patients and health 
professionals with direct access, have been confirmed in at 
least two different laboratories and are currently being used 
for diagnosis of inherited genetic diseases that include the 
face, the mouth, and the teeth.
    Many of these are syndromes that also involve limb 
deformities or heart deformities or kidney or liver 
deformities, as well, but they are diagnostically being used 
today.
    Mr. Porter. So there are a number of other genes that 
relate to the same areas that are not suspect as being involved 
in problems or disease?
    Dr. Slavkin. Yes. As this rapid expansion of genetic 
knowledge is moving along, we are beginning to understand that 
there are biological mechanisms needed to make a brain, to make 
a face, to make a limb, to make many parts of the body, that 
are common.
    In certain kinds of loss-of-function mutations where the 
gene cannot be expressed, it often clinically presents itself 
as a syndrome, with different parts of the body being affected.

                           GENETIC TECHNOLOGY

    Mr. Porter. I asked Dr. Battey this question yesterday, but 
I want to ask you, as well. It seems to me, for example, in 
this Papillon-Lefevre Syndrome, where you have identified the 
specific gene involved, that the chance of developing a therapy 
that can change this result is probably quite good, but you are 
not there yet. You have identified where you need to put your 
efforts.
    Is it more likely that in your area or Dr. Battey's area, 
that you might be the ones to develop the first successful gene 
therapy, because you can identify the exact place where you 
need to work?
    Dr. Slavkin. I think, in deference to my colleagues, I 
think everyone has an equal opportunity in this area.
    Mr. Porter. Yes, but this involves a single gene.
    Dr. Slavkin. Yes.
    Mr. Porter. It is not a combination, where you have to work 
in a number of different places.
    Dr. Slavkin. Yes. When the candidate is just an individual 
gene, it does raise the likelihood. And one of the ways we are 
pursuing this is we started a forum at the NIH where we have 
FDA, private industry, academic scientists coming to the NIH, 
looking at emerging scientific discoveries, and trying to 
foster some of those, translating into new companies and new 
industries. There is a space between the discovery that takes 
place at the NIH and translation into a readily-accessible 
technology that all Americans can have access to.
    There is a meeting in March, next month, called ``Bio 
2000.'' We have a symposium presenting some of these new 
breakthroughs to try to entice biotech companies to get 
interested in moving some of this technology and testing some 
of those ideas.
    Mr. Porter. Is it likely that, when we discover the way of 
providing successful gene therapy in one instance, that that 
pathway, whatever it may turn out to be, will likely be applied 
to others? In other words, is there a key that will unlock many 
of these things?
    I know we do not know the answer yet.
    Dr. Slavkin. Yes. In the car coming over this morning we 
were talking about a new paper that just came out in the 
journal ``Cell'' from a group that we support and NIAMS 
supports at Southwestern Medical Center in Texas. It is a 
correlation of a gene called leptin with obesity and 
osteoporosis.
    Every once in a while, the intuitive approach is 
challenged, when you realize that unlocking that door opens up 
avenues that no one would have dreamt of. And the idea that 
genes are controlled in the central nervous system that affect 
obesity and also affect bone resorption and bone formation 
would not have been considered just a few years ago.
    There is a certain attitude you need to chase the 
opportunities as they bubble up and not miss them.
    Mr. Porter. Yes. Thank you, Dr. Slavkin.
    Mr. Hoyer.

                  ORAL INFECTION AND SYSTEMIC DISEASE

    Mr. Hoyer. Dr. Slavkin, I think this is probably a related 
question, but last year you and I discussed the relationship of 
dental care to overall health, which is some of what you have 
obviously been discussing.
    Last year also the National Academy of Science issued a 
report on medically necessary dental care.
    It is my premise that dental care is much more likely to be 
ignored than is physical health, or even perhaps mental health, 
because of the lack of compensation, third-party payers for 
such health.
    That report indicated that providing dental care to 
specific disease groups would be beneficial and would, as you 
pointed out, have multiple cost savings.
    You then indicated, in response, your collaborative efforts 
with various other institutes--NIAID; Heart, Lung, and Blood; 
and, in particular, Child Health and Human Development.
    Can you tell me what progress you have had there and how 
those collaborative efforts are going?
    Dr. Slavkin. Yes. As you heard earlier this morning from 
Dr. Lenfant, the Heart Institute has a very exciting heart 
study in Mississippi, and we have been able to add an oral 
component because, next to tobacco use, the second most 
significant risk factor is periodontal disease--severe 
periodontal disease. So in that relationship Claude and his 
colleagues made it possible for us to piggyback and take a look 
at those relationships.
    In a different context, Dr. Duane Alexander and the people 
in NICHD made it possible for us to team up with a neonatal 
intensive care unit in Alabama that they support, and, by 
augmenting the resources and focusing them, we are looking at 
oral infection and low-birth-weight babies. This also is being 
done in North Carolina by another group independently. A third 
group in Tennessee is trying to position itself between Meharry 
and Vanderbilt to also look at that problem, because the 
prevalence of low-birth-weight, premature babies is 
significantly higher in African American women than in the 
general population.
    So the way a small institute at the NIH can be effective is 
through partnering, leveraging, piggy-backing with some of the 
other studies so that these things do not just remain good 
ideas but we get into the field and we test them, and those are 
in progress.
    Mr. Hoyer. So would I be correct in concluding that we have 
drawn a substantially greater correlation between the lack of 
oral health and other diseases?
    Dr. Slavkin. Yes. A study was published earlier this month 
in the ``American Journal of Epidemiology'' revisiting the oral 
infection/cardiovascular link, and it held up beautifully.

                         DENTAL CARE IN AMERICA

    Mr. Hoyer. If that is the case, then do you have any 
observations or has your institute had any discussions or NIH-
wide discussions with respect to recommendations as to how we 
can heighten the interface of individuals, the American public, 
with dental care?
    Dr. Slavkin. Yes.
    Mr. Hoyer. You may have heard me say this--I know others 
have. My wife found it ironic--you may have heard me say this--
that in the HeadStart program, as you know, there is a dental 
component.
    Dr. Slavkin. Right.
    Mr. Hoyer. The HeadStart program, of course, deals with 
baby teeth--primary teeth, as opposed to permanent teeth.
    There is no, as far as I know, specific program that deals 
with teeth once they are going to be with us for our lives. We 
only treat them when we are going to have them for a short 
period of time.
    That is certainly not to derogate in any way the treatment 
of the primary teeth.
    Dr. Slavkin. Right.

                SURGEON GENERAL'S REPORT ON ORAL HEALTH

    Mr. Hoyer. But it is to say, have you done anything with 
respect to what we ought to be doing, perhaps, both through the 
private sector insurance programs and with respect to maybe 
public health services, with respect to children in grades 
above the second or third, fourth grades?
    Dr. Slavkin. Yes. Under the leadership of the Secretary, 
Donna Shalala, and the Surgeon General, David Satcher, our 
Institute was asked to be the lead Institute in a Government-
wide study for the first time on the Surgeon General's Report 
on Oral Health. A number of papers that have been solicited, 
reviewed, edited, all of those sorts of things, are going to be 
in that document.
    We are hosting a meeting March 19th, 20th, and 21st. The 
report comes out in the spring. We are having a major 
conference on children and their caregivers where it is all 
about access and reimbursement and education and diffusion of 
knowledge and all of the issues so that oral health does not 
become an out-of-pocket luxury item but it becomes naturally 
integrated into the well-being of people.
    We hope the Surgeon General's Report will bring the 
attention of the whole country to these issues. The Healthy 
People 2010 oral health goals are extremely compelling, and we 
support those completely, as does the American Dental 
Association and the American Medical Association.
    I believe we are going to get it right this time, and maybe 
those gaps will be closed.

                     ORAL HEALTH OF SENIOR CITIZENS

    Mr. Hoyer. Doctor, if I can follow up just briefly, I asked 
the question in the context of young people, but, as you know, 
I am also focused on the oral health of seniors and the lack of 
availability of third-party payer--Medicare, etc.--coverage for 
seniors.
    To the extent that we find an increasing relationship 
between oral health and other diseases, would you comment 
briefly on the necessity to deal with senior oral health?
    Dr. Slavkin. Right. We are exploring this. There is a small 
sub-set of the senior population 65 and older, with complete 
healthy mouths, complete dentition, but, for a variety of 
medical conditions, are being warehoused in facilities that 
provide no oral health whatsoever.
    It is a tragedy in a civilized country to do that. We need 
to address that issue.
    I know that you and your staff are thinking about that, and 
trying to develop some strategy to address it. There is no 
reimbursement for that population, and it seems criminal to 
allow, in our country, that to happen.
    Mr. Hoyer. Thank you, Doctor.
    Thank you, Mr. Chairman.
    Mr. Porter. Thank you, Mr. Hoyer.
    Mr. Jackson.

         CENTERS FOR RESEARCH TO REDUCE ORAL HEALTH DISPARITIES

    Mr. Jackson. Thank you, Mr. Chairman.
    Thank you for your commitment, Dr. Slavkin, and also let me 
indicate to you that your leaving NIH is quite a loss to our 
subcommittee.
    I have a number of questions for you, Dr. Slavkin, but I 
also have a number of questions for the record, because I do 
not want your successor to come before this committee and 
propose what I always hear from directors and heads of offices, 
a new beginning, or ``we have to do more,'' or ``my attitude 
about this is a little bit different than my predecessor's''--
which I think, quite frankly, is really a slap in the face to 
the predecessor when they say that their attitude about it is 
fundamentally different than the person who was there before 
them.
    The President's fiscal year 2001 budget for NIDCR is $263.1 
million, an increase of $14.1 million and 5.7 percent above 
fiscal year 2000 level. Included in this total is $12.2 million 
for the following NIH--here we go again--areas of special 
interest, which I prefer to call ``NIH priorities'': new 
avenues for the development of therapeutics, $1.750 thousand; 
genetic medicine, $2 million; bioengineering, computers, and 
advanced instrumentation, $1,500 thousand; and there it is 
again, health disparities, $7 million.
    Now, of course, if Congress does not see fit to make this 
increase or decides to fund your program or your institute at 
level funding, these priorities may not be addressed. So when I 
ask these questions, I am not necessarily talking about health 
disparities in the increase, but also the fair share of $263 
million, assuming that Congress does not follow the increase.
    I noticed also in your budget request--this very lengthy 
document that we have for the institutes that are before us 
today--the Centers for Research to Reduce Oral Health 
Disparities. ``In response to oral health disparities and the 
growing literature showing the importance of craniofacial, 
oral, and dental health in overall health, the NIDCR recently 
issued a request for applications.''
    My first question is this: are you aware of whether or not 
NIDCR has contacted the National Dental Association?
    Dr. Slavkin. Yes.
    Mr. Jackson. They have contacted them?
    Dr. Slavkin. Yes.
    Mr. Jackson. And they are aware of the----
    Dr. Slavkin. And the National Hispanic Association and a 
host of other organizations--American Indian organizations, 
Pacific Islander organizations, Appalachian-based 
organizations, because the initiative is to be inclusive for 
people who lack access, who are under-served, and people who 
have been historically under-represented.
    Mr. Jackson. Great. That was actually a trick question, but 
I am glad you answered it because it is no longer a trick 
question. I very much appreciate knowing that your office has 
actually reached out to the heads of the associations for which 
these dentists who are pursuing this type of research might be 
able to take advantage of the RFA.
    Let me ask another couple of questions, if you do not mind.
    Dr. Slavkin. Mr. Jackson, although I think we are doing the 
right thing, other Institutes, as well, are opening up those 
lines of communication. I do not think it is unique to the 
dental community. Other Institutes are also finding that 
working closely with the Hispanic and African American medical 
and dental associations is very useful as an entre into the 
kinds of populations that must be addressed.
    Mr. Jackson. Okay. I trust that you are speaking about 
other institutes other than those at NIH, because I am going to 
reserve the opportunity later to question them about their 
commitment in these areas.
    But I gather, in your general profession, they are now 
opening up.
    Dr. Slavkin. We have an oral health initiative with HRSA, 
CDC, HCFA, who are all engaged in this kind of networking to 
try to make a more effective inroad into the problem.

                          MINORITY RESEARCHERS

    Mr. Jackson. Okay. Let me ask you another question, Dr. 
Slavkin. Can you give us some ball park figure--and I know that 
reporting on this data is questionable, since information 
regarding race on grant applications are optional--can you give 
us some idea about grants awarded in fiscal year 1999 and 
fiscal year 2000, those given to minority researchers and/or 
minority-serving institutions? And when I say ``minority,'' 
obviously I do not just necessarily mean African American. I do 
mean Hispanic, Native American, women-related research grants, 
as well.
    Dr. Slavkin. Right. While being at the NIH, I have had an 
opportunity in several different roles to look at the principal 
investigators according to ethnicity on various grant 
mechanisms.
    Putting aside Asians, who are overrepresented in terms of 
their percentage of the population, the numbers in our 
Institute and most of the NIH is a couple of a percent, maybe a 
little over two percent, combining African American, Hispanic, 
Pacific Islanders, and so forth.
    This is painful evidence that if we are going to live in a 
culturally-diverse society and we do not have a workforce that 
even begins to represent the society, we are making a major 
mistake. The NIH is positioning itself, and many other parts of 
Government to find how to increase diversity in the workforce. 
These numbers are terrible.

                        ORAL HEALTH DISPARITIES

    Mr. Jackson. I want to say that I just added ``painful 
evidence'' to my litany of things that are normally said when 
it comes to addressing these disparities in terms of grants.
    I do have one other question. I am wondering if you can 
tell us what health disparities issues NIDCR is concerned with 
and what initiatives you have been undertaking to address some 
of these problems.
    Dr. Slavkin. In the current year we are spending a little 
over $22 million towards these issues. The oral infection and 
low-birth-weight, premature babies initiative is targeting 
African American women. Our issues in oral and pharyngeal 
cancer are targeting African American men. The dental caries 
issues are found in the Hispanic, Appalachian, Pacific 
Islander, American Indian populations. There is literally a 
tight correlation between education, accumulated wealth, so-
called the ``SES formula,'' and the extent of rampant tooth 
decay. Poor children in inner cities have 80 percent of the 
disease. We have documented it, and this initiative of Centers 
for Research to Reduce Oral Health Disparities--since the 
problem is multi-factorial--is about training a diverse 
workforce, it is about research, and it is about access to 
care. We need to build an approach that uses those different 
strategies to reduce the burden.
    So I believe that people are realizing that you need a 
different strategy than the way we would do genomic research, 
the mouse genome, or some of those other issues. This is a very 
different kind of problem and it takes a different approach.
    Mr. Jackson. Let me thank you once again, Dr. Slavkin.
    Thank you, Mr. Chairman.

                        SALIVA-BASED DIAGNOSTICS

    Mr. Porter. Thank you, Mr. Jackson.
    We do have about eight or nine minutes left, so additional 
questions are in order.
    Dr. Slavkin, saliva and blood are very close in the sense 
that saliva carries the same things that blood carries, and if 
you can use blood in your analysis you can presumably also use 
saliva; is that correct?
    Dr. Slavkin. Yes.
    Mr. Porter. How quickly are we going to get to the place 
where we can use saliva for a lot of the tests that we do with 
blood today?
    Dr. Slavkin. With modest resources, we are trying to push 
that as overtly as possible. The New York Academy of Sciences 
published a treatise on everything that you want to know about 
what is in saliva that is useful for diagnosis or as biomarkers 
to follow various studies.
    About five institutes at the NIH use saliva as part of 
their strategies in clinical trials. We had a conference this 
past September, brought together experts from around the world 
to focus on the opportunities. This is nanotechnology, 
biosensors, saliva, where saliva is basically a mirror to many 
things that are going on in an individual.
    We are also using that approach as an example to present to 
the private sector as an opportunity for new advances, and our 
intent is that this will go from an interesting idea to 
mainstream medicine and dentistry, diagnostics, and for 
following progression of disease or following progression of 
treatments.
    Mr. Porter. Would that apply to something as common as 
doing a blood test for cholesterol or something like that?
    Dr. Slavkin. Yes. In the State of California, the highway 
patrol uses saliva as a test for alcohol consumption. It is the 
State standard at the moment, and several other States in the 
Union are moving in that direction.
    For testing drug abuse, over-consumption of steroids, 
Olympic athletes, saliva is being used. In horse racing, saliva 
is being used routinely in the thoroughbred racing arena.
    There are many, many applications. It means, though, that 
we would change the curriculum in medical and dental schools to 
be able to use it as one body fluid that can be very 
informative.
    Mr. Porter. I am willing to recognize anybody else that has 
a question, if they would like to ask it. Mr. Jackson, do you 
have anything?
    Mr. Jackson. Thank you.

        LINKAGES WITH THE OFFICE OF RESEARCH ON MINORITY HEALTH

    If you could, Dr. Slavkin, can you characterize for me your 
relationship or your office's relationship with the Office of 
Research on Minority Health?
    Dr. Slavkin. I came to the NIH in July of 1995, and one of 
the first offices that I became aware of and connected with was 
with John Ruffin.
    At that time, we were involved in doing majority/minority 
matching of institutions to look at oral health, and John was 
extremely helpful, provided some co-funding with us, oriented 
me to a lot of issues that I was not aware of, and so I have 
used that access to John for advice in all of the things that 
we have done.
    We have served together on committees. I consider him a 
close colleague.
    Mr. Jackson. May I follow up, Mr. Chairman?
    Mr. Porter. Yes.

                  DIVERSITY IN THE RESEARCH WORKFORCE

    Mr. Jackson. So, in light of that personal relationship and 
the interaction between your institution and the Office of 
Research on Minority Health, when Dr. Ruffin approached you 
about this painful evidence of the absence of grants to 
minority researchers in the oral health area, as the Director 
of your Institute, what is it that you could have done to help 
address some of those disparities?
    Dr. Slavkin. We excel in the use of minority supplements. 
At the NIH, we go out and pay special attention to Puerto Rico, 
to Meharry, to Morehouse, to Xavier, which we have done. We go 
out and work with American Indian tribal communities to try to 
make connections, because that is a very dramatic area.
    We had a blue ribbon panel on the future of training in 
this country, to look at the needed competencies. We made sure 
that cultural competencies were clearly involved. We are doing 
a nationwide blitz, which we believe starts in K-12 education 
carries on to college and beyond, to try to identify, support, 
and sustain those young men and women who would be interested 
in careers in clinical medicine, clinical dentistry, patient-
oriented clinical biomedical research.
    There is no quick fix. Five years is not enough time. But I 
think we have leaned heavily in the right direction relative to 
our resources. Both in the Institute and with our other 
Institutes I believe we have been very proactive and positive 
about making this part of the NIH agenda, and it is part of the 
NIH agenda.
    Mr. Jackson. Thank you, Dr. Slavkin.

                          HEAD AND NECK CANCER

    Mr. Porter. Dr. Slavkin, all oral cancers are not 
necessarily genetic, or are they? And what about the use of 
smokeless tobacco? Would you be the lead institute in those 
kinds of cancers, or would that be NCI?
    Dr. Slavkin. Thank you for that question.
    Of the many things he did very well, one of the things that 
Harold Varmus did exceptionally well was invite the cancer 
advocacy community to come to the NIH and realize that there 
are many Institutes involved in reducing cancer. It is not 
exclusively in NCI.
    It turns out that all cancers are genetic in the sense that 
they are all the manifestation of a neoplastic process due to 
acquired mutations in a number of different genes that lead to 
the disease called ``cancer.'' It may be 10 or 12 or 20 genes, 
but it is at the genetic level that the lesions are taking 
place, and then clinically the cancer manifests.
    We are, along with NCI and the Environmental Health 
Sciences Institute in Chapel Hill, North Carolina, very 
interested in reducing tobacco cessation, and in children, 
smokeless tobacco or chewing tobacco, is a major item.
    Mr. Porter. It is a major item right here in Congress with 
some Members.
    Dr. Slavkin. Yes. Just a few hours drive from here, in 
Morgantown, West Virginia, we recently learned that half of the 
ninth graders in the State of West Virginia daily use chewing 
tobacco.
    Coming from Los Angeles, I had never seen that in children 
before in my clinical experiences. So there are pockets, 
especially in Appalachia, but also in the ``wannabe'' baseball, 
``wannabe'' football, ``wannabe'' sports people, where some 
people seem to think that athletic prowess is linked with 
tobacco.
    It is a major problem, and we need the coaches--and we are 
doing this with NCI--at the professional baseball level, at the 
minor league level, at the community level, to try to get the 
models to speak out against this.
    Mark McGwire is our poster child. His father is a dentist 
in Oakland and made a nice baseball card for us, ``If you want 
to hit home runs, do not use smokeless chewing tobacco.''
    Mr. Porter. As we have seen tobacco use come down in our 
country, we seem to see more use of other products, like cigars 
instead of cigarettes, and oral tobacco of some type. Is that 
true and what can we do about this?
    Dr. Slavkin. Yes. NCI did an excellent study that was 
published last year on cigars and the carcinogenicity in terms 
of oral, pharyngeal, tonsilar, and laryngeal cancer. I mean, it 
is motivation. It is not just the cognitive part of the brain, 
because many women feel it is very campy to smoke a cigar in a 
club or a cafe or something like that.
    There are a lot of behavioral studies that we need to do to 
try to figure out what age group, what culture, what is the 
right message, and how to be consistent, and we are still 
grappling at that.
    Mr. Porter. I, personally, would give FDA authority to 
regulate it and eliminate it, very frankly, and I would stop 
the sale of all tobacco products in our country. I think it is 
crazy. Sure, there is a balance between freedom and 
responsibility here, but it seems to me that the evidence is so 
overwhelming that this is toxic to practically everybody who 
uses it long enough, that there is no place in a smart society 
for something like this, in my judgment.
    Dr. Slavkin. Many of us at NIH enthusiastically and 
unconditionally agree with you.

                   CHAIRMAN'S TRIBUTE TO DR. SLAVKIN

    Mr. Porter. Dr. Slavkin, I used to think--and this is no 
reflection on anyone else, but I used to think that your area 
was kind of the least interesting of all the areas, but since 
you have been there it has become among the most interesting.
    Dr. Slavkin. Thank you.
    Mr. Porter. You have always provided us with tremendous 
insights and we have always been awed by the progress that has 
been made in respect to the mouth and face and the knowledge 
base that has grown so greatly. You have contributed 
tremendously to our country, and your service is so much 
appreciated. I know that you are going to stay involved.
    Dr. Slavkin. Yes.
    Mr. Porter. We wish you well in your retirement.
    Dr. Slavkin. Thank you.
    Mr. Porter. Thank you for your service.
    Mr. Hoyer.

              RETURN ON INVESTMENT IN ORAL HEALTH RESEARCH

    Mr. Hoyer. I feel constrained to observe--Dr. Loe, one of 
your predecessors, I suppose it was the mid 1980s that he was 
the director. I was amazed when he made the observation that 
you have again reiterated today, that all the money that we 
have spent since the very inception of your Institute is less 
than the savings we experience, I think, in a year. Is that 
what you said?
    Dr. Slavkin. In 1 year. Yes.
    Mr. Hoyer. In 1 year, because of the progress we have made 
in dental health among the American public.
    Dr. Loe was the one--and I am sure other institute 
directors may have said that, but he was the first one that I 
remember having said that, and it made a real impact on me in 
terms of the correlation between what appears to be a large 
number for us.
    You were not here when we had an extraordinary chairman 
that Mr. Porter and I served under named William Natcher, who 
came from a rural District in Kentucky but had as sound a sense 
of the worth of the investments we were making in this 
committee in terms of the education of our children and the 
health of our people, which is how he referred to it, and his 
observation that if we doubled--and I am sure that John would 
repeat that today--if we doubled the investment in NIH, it 
would not be too much.
    I think the example that you reiterate today is very 
compelling evidence of the truth of that statement.
    Thank you, Mr. Chairman.
    Dr. Slavkin. Thank you.
    Mr. Porter. Thank you very much, Mr. Hoyer.
    The subcommittee stands in recess until 2:00 p.m.



                                        Tuesday, February 29, 2000.

                      NATIONAL LIBRARY OF MEDICINE

                               WITNESSES

DR. DONALD A.B. LINDBERG, DIRECTOR, NATIONAL LIBRARY OF MEDICINE
KENT A. SMITH, DEPUTY DIRECTOR, NATIONAL LIBRARY OF MEDICINE
DR. DAVID J. LIPMAN, DIRECTOR, NATIONAL CENTER FOR BIOTECHNOLOGY 
    INFORMATION
SUSAN U. LEVINE, CHIEF, FINANCIAL MANAGEMENT OFFICE, NATIONAL LIBRARY 
    OF MEDICINE
DR. RUTH L. KIRSCHSTEIN, ACTING DIRECTOR, NATIONAL INSTITUTES OF HEALTH
DENNIS P. WILLIAMS, DEPUTY ASSISTANT SECRETARY FOR BUDGET, DEPARTMENT 
    OF HEALTH AND HUMAN SERVICES
    Mr. Porter. The subcommittee will come to order.
    We continue our hearings on NIH's budget with the National 
Library of Medicine. We are pleased to welcome Dr. Donald 
Lindberg.
    Dr. Lindberg, it is always good to see you. You always have 
fascinating things to tell us. Please proceed with your 
statement. We have run way beyond the time I had hoped we would 
be able to finish with NIDDK's hearing. We will go as fast as 
we can here.

                       Introduction of Witnesses

    Dr. Lindberg. Thank you very much, Mr. Chairman, members of 
the committee.
    I would first like to introduce, on my far left, Susan 
Levine, our Budget Officer; Mr. Kent Smith, our Deputy 
Director; David Lipman, Director of National Center for 
Biotechnology Information. And you know the others.

                           Opening Statement

    Mr. Chairman and members of the committee, the National 
Library of Medicine continues to make good progress in our 
efforts to make scientific information available to doctors, 
scientists and to the public.
    First, we have made MEDLINE, our major scientific database 
of millions of references and abstracts, easier to use by all. 
MEDLINE continues to climb amazingly, from 7 million in 1997 to 
250 million searches this year. Surprisingly, the public now 
constitutes about one-third of our MEDLINE searches. Even 
though MEDLINE content is highly technical and a bit difficult 
to read, frequently I hear of patients who consult the medical 
literature before they consult their doctors. I believe that, 
by doing this, these well-informed patients probably increase 
their chances to benefit from their visits to the doctor or to 
the hospital.
    Hence, we created MEDLINEplus, an information service 
really designed for the public. MEDLINEplus now has extensive 
information on 350 diseases and conditions. These include key 
links to information prepared and maintained by NIH institutes 
and centers, HHS agencies, and by selected special services and 
voluntary health associations.
    MEDLINEplus differs from other Internet health information 
services in two critical ways. We do not require registration 
by the users, so people's questions are truly anonymous; and, 
of course, we do not display advertising or offer items for 
sale, nor sell users' identities to those who do. It is our 
goal that consumers find at MEDLINEplus accurate and up-to-date 
medical information that has been selected solely on its health 
merits.
    As you might expect, NLM must frequently check the accuracy 
of all links to maintain a useful information resource. Web 
pages obviously change rapidly, and we frequently find it 
necessary to update or delete links if the sources become out 
of date or out of bounds. Thus, as usual, it is a lot easier to 
start such a service than to maintain it.
    There is a third new development I would like to report. 
Today, the NIH and NLM announced a new database, 
ClinicalTrials.gov. NLM developed this on behalf of NIH 
institutes and centers at the request of the NIH director and 
in response to congressional legislation for the FDA. 
ClinicalTrials.gov provides patients, families, members of the 
public and their health care providers with easy access to 
extensive information on over 4,000 clinical research trials in 
47,000 places sponsored or conducted by NIH.
    There are links, where appropriate, to even more detailed 
information when this exists on the NIH web and links to 
explanatory information in MEDLINEplus. Thus, a member of the 
public can move back and forth I think relatively easily 
between lay explanations of medical conditions, descriptions of 
clinical trials, and even preformed or completely customized 
MEDLINE searches of up-to-the-minute scientific literature.
    Today's worldwide web and Internet reach only about half of 
U.S. households. So, building upon our previous pilot project 
with 39 public libraries, we have recently made 49 new outreach 
awards. The purpose of these awards is to encourage 
partnerships between medical libraries and community 
institutions, including public libraries, schools, faith-base 
organizations, senior centers, and really all those who help to 
make electronic information widely available. We hope in this 
way to extend the reach of MEDLINE, MEDLINEplus, 
ClinicalTrials.gov and other valuable services beyond those 
with home computers and Internet access of their own.
    A key component of our outreach program is the work of 
medical librarians and the National Network of Libraries of 
Medicine. For this reason, Mr. Chairman, I would like to point 
out that we at NLM help train future leaders in the profession 
through our highly regarded NLM associate's program; and indeed 
five of the seven current associates are here in the room 
today.
    Minority disadvantaged populations continue to get our 
attention. The NLM toxicology and environmental health 
initiative has made special efforts in collaboration with the 
Historically Black Colleges and Universities to introduce NLM 
information resources to professional and community leaders who 
must deal with pollution and hazardous waste in disadvantaged 
areas.
    There is a similar program in HIV/AIDS-related databases 
and communities concerned with that disease. Further, NLM has 
also targeted grants and contracts to support health 
information programs specifically serving minority populations 
in other parts of the country.
    History may judge NLM's most important work in this decade 
to be its support of the molecular biology and human genome 
revolution. The National Center for Biotechnology Information 
at NLM provides worldwide on-line access night and day to this 
vast, growing store of knowledge. GenBank now contains over 5 
million DNA sequences made up of nearly 5 billion nucleotide 
base pairs. This genetic data is from laboratories in the U.S., 
Europe, and Japan. Consequently, GenBank receives thousands of 
queries each day from scientists all over the world.
    NCBI and its collaborators also have produced two on-line 
human gene maps that now picture over half of all human genes. 
In my view, without question, this work greatly facilitates and 
accelerates discoveries of new genes, gene actions and 
understanding of developmental and evolutionary biology.
    Our grants for medical work in the administration's Next 
Generation Internet program are also successful and 
interesting. These include telemedicine and networking projects 
and also the Visible Human program.
    Although NLM is very much involved in the latest computer 
communications developments, the institution at heart remains 
the biggest medical library in the world. We continue to 
acquire, organize and preserve this great collection of medical 
books, journals, prints, and photos.
    NLM must find ways and space to preserve the increasing 
amount of both electronic and physical literature for future 
generations. This must be our highest priority. Growth of our 
physical storage needs, the new digital preservation 
requirements and the need to house research personnel 
increasingly important to biotechnology and human genome are 
exceeding the physical buildings of NLM. The NIH has kindly 
allowed an expansion of NCBI into the nearby Natcher Building. 
NIH will consider NLM buildings needs within the revisions of 
the master plan. In the meantime, NLM has obtained a 
feasibility study, as directed by the committee, for possible 
future facilities expansion.
    Mr. Chairman and members, I thank the committee for this 
and all its help in the past. The President's request for NLM 
in total is $230,135,000. I would be happy to discuss anything 
further that you wish.
    [The written statement of Dr. Lindberg follows:]



                           SPACE REQUIREMENTS

    Mr. Porter. Dr. Lindberg, it seems to me you said about the 
same thing last year on your space needs as you are saying now. 
I recall that you had raised the issue and you had hired some 
consultants, I believe, to look into it; and basically what you 
are saying is they have put you on the general list for 
expansion as NIH expands. Is that what you said ?
    Dr. Lindberg. Well, we actually, as I indicated a year ago, 
had a preliminary feasibility study in hand; and we are now 
proceeding to do what I think the committee asked for which is 
a phase one A&E study; and this is being done through the NIH 
Division of Engineering Services and their contractors. I 
gather from what they tell me it should be done within 6 to 8 
months, and that would be sort of the next logical step toward 
the decision for or against a building. The complete A&E study 
would take a little bit more time and a little bit more money. 
NIH is helping us to do it.
    Mr. Porter. So you are satisfied with the progress you are 
making in addressing this problem at this point?
    Dr. Lindberg. I am delighted.
    Mr. Porter. If you are delighted, I am delighted.

                          INTERNET INFORMATION

    NIH, through the National Library of Medicine, puts out a 
great deal of information on medical research and medicine 
generally, but on the Internet there is a lot of other 
information about things, including medicine and products, that 
I think probably confuse a lot of people and lead them to maybe 
make wrong decisions. Do you see--first of all, do you see this 
as a problem? Second, does NIH have a role in addressing that? 
And, third, should NIH have a kind of a ratings system where 
you say what is good and what is untested--not necessarily bad 
but untested--so that people have some guidance when they begin 
tapping into this vast store of information, a large part of 
which is National Library of Medicine but a great deal of which 
isn't?
    Dr. Lindberg. Well, we really struggle with that problem on 
a daily basis to try to know exactly the right thing to do. We 
are certain there is an appropriate role for a government 
agency like ours and no doubt appropriate roles for industry in 
competition and money-making organizations.
    I am sure that we are right in not requiring people to log 
on and identify themselves. We have had many, many contacts 
with people who say they simply wouldn't ask the questions if 
they could be traced down--it's a privacy issue.
    We know, too, that there is a major debate in the Congress 
and elsewhere as to whether regulations ought to be established 
governing essentially the selling of identities for commercial 
purposes. Somebody has a disease, therefore, they might be a 
candidate to buy a certain set of equipment or insurance, for 
example. I think that is probably a very bad thing, but there 
is no law that prohibits it right at the moment.
    As to, then, the quality, I think what you said is 
absolutely true. You can certainly find silly stuff advertised 
on the web, just as you can in newspapers and magazines. But I 
find very good information there, too. That is what bothers me. 
I definitely wouldn't want to tell a patient not to use the 
web. Quite the reverse. You can get wonderful explanations and 
help your children write term papers and everything else right 
at your desk.
    I guess I mostly would want to know--if I were looking up 
medical information and I am worried about myself and a family 
member and I came across something interesting, I would like to 
know that somebody put it there to help me rather than to 
extract my identity to sell it for a commercial purpose. Or if 
it were put up there by, let's say, a company that manufactured 
a product or a drug or whatever, that would be perfectly okay, 
too. I hurry down and read the Chrysler advertising every year. 
I don't always get a new car, but it is fun to know. And I 
certainly wouldn't expect anybody else to speak out in favor of 
their product, but it is nice if they would identify 
themselves.

                      CONSUMER HEALTH INFORMATION

    The MEDLINEplus is our attempt to deal directly with 
consumers. We are not sure exactly what advisory structure to 
adopt. We have medical advisors. We have done extensive reviews 
with the medical librarians as they observe users. I think we 
are getting closer to an answer to your question, Mr. Porter, 
but I am hesitant to give it right at this moment.
    Mr. Porter. The reason I am asking the question is that not 
long ago--and I think I have got the right issue, but I am not 
sure I do--there was a rumor floating around that was put on 
the web that Congress was going to enact legislation that would 
tax the use of Internet services. I think all of us got flooded 
with letters saying, don't do this nobody had even thought of 
doing it. We can answer those letters and head that off and no 
damage is done, but what if there is the same kind of thing put 
out on medical procedure or something of the like that is 
simply bad information that you know is bad information? Do you 
have any responsibility to then alert people that this is wrong 
and should people have to come to NIH and get a stamp of 
approval for something before it is allowed to be put out there 
and believed?
    Dr. Lindberg. In a lot of respects, we have dodged the 
issue of stepping up and saying something is terrible because 
we have always emphasized the positive. And I would say that 
the essence of MEDLINE, this great file of the literature, the 
essence of that is selection. I mean, the library subscribes to 
something like 27,000 periodicals. Of those, only 4,000 are in 
MEDLINE.
    Actually, where I get any heat at all in my correspondence, 
it is publishers wanting to get their journal included in 
MEDLINE. I don't hesitate to point out it is commercially 
advantageous to them. But that is not why we put it there. We 
put it there because we think it is a good journal. The 
articles that go into those journals are almost always peer 
reviewed. So, again, it is a winnowing system.
    Mr. Porter. Yes, sir, but at least we have a very high 
degree of confidence in the things that NLM puts out. But there 
are things that are put out by others that maybe we don't have 
a degree of confidence in.
    Dr. Lindberg. I don't know how to do that.
    Mr. Porter. I am not sure there is a way to do it. I was 
just wondering whether there could be damage done by that.
    Dr. Lindberg. I think there can. I think it is very 
important on the website, which is really equivalent now to 
newspapers, that somebody announce himself or herself as the 
owner and proprietor of that publication with an address and 
affiliation and that we know who is behind the site and the 
ads. Then I think that is the best--then, of course, you have 
to make a judgment for yourself as a consumer.
    Mr. Porter. Thank you.
    Mr. Hoyer.

                          INTERNET INFORMATION

    Mr. Hoyer. It seems to be a widespread problem like 
Citizens Against Government Waste. Who are they? You and I 
agree that the Americans have the right to publish information 
under the first amendment, but all of us have a right to know 
who is saying what because that impacts on our judgment. Now, 
we are grappling with that issue in the campaign finance area 
and the campaign advertisement area. But FDA, of course, does 
control, does it not, medical advertising?
    Dr. Lindberg. It does.
    Mr. Hoyer. This is sort of a truth-in-labeling issue where 
I think the chairman is right, this could be very dangerous to 
get some bad information on the web that hundreds or thousands 
or millions of people access, utilize, and with dire 
consequences. It is a tough issue.
    Dr. Lindberg. If I understand correctly, the FDA has the 
problem whether something is truly a drug, a prescription drug, 
or an over-the-counter drug or a food supplement or a cosmetic 
is entirely different regulations.

                              MEDLINEPLUS

    Mr. Hoyer. Doctor, I had talked about this years ago--golly 
gee, I must be getting older--back in the early '80s on the 
committee. I think the first time that Francis Howard told me I 
ought to be interested in this issue, of course, I obeyed. 
Obviously, I have raised the issue about having access to the 
information we obtained at NIH on the most rural isolated 
doctor's desk in America but indeed the world. MEDLINE, I 
suppose, is there. Now, MEDLINE II is the non-medical? Which 
one is the layperson?
    Dr. Lindberg. MEDLINEplus.
    Mr. Hoyer. That is a great name. How many people does it 
take to keep your web page current?
    Dr. Lindberg. How many people are working on MEDLINEplus?
    Mr. Hoyer. Yes.
    Dr. Lindberg. I would say probably 20 to 25 at the outside.
    Mr. Hoyer. How can they possibly keep up with that?
    Dr. Lindberg. They get a lot of help from the national 
network of libraries of medicine. That is about all I can 
budget for. I think it probably would be worthy to have more, 
but I don't have more.
    Mr. Hoyer. I understand that, but the wealth of information 
produced every day in America, let alone on a monthly basis, 
which most of your periodicals are probably a monthly basis, is 
such that keeping timely data must be a real challenge.
    Dr. Lindberg. We are a nest happily in the middle of NIH. 
Many times we are quoting or citing or linking to, if you will, 
data that are created and maintained by NIH institutes.
    Mr. Hoyer. Am I correct that there is an absorption from 
the data put in and created by other NIH institutes so that 
none of your people--all we are doing is, in effect, putting it 
from one computer to the other computer and then accessing it 
to the web page?
    Dr. Lindberg. Well, we are going after the best information 
we can find. And we will first look at NLM; next look at NIH 
institutes; next look at, let's say, other HHS agencies like 
CDC; and then we will look at special services. I mean, there 
are some private hospitals that have very good explanatory 
information. We might link to the explanatory information.
    We have had a very good experience with the voluntary 
health associations like the American Heart Association, for 
example. In fact, in these clinical trials databases, which Dr. 
Alexa McCray is the major author of, she spent 6 months getting 
that tested out by the National Health Council which is about 
40 voluntary health agencies. So we work with them, in other 
words, to make sure the searches made sense and they were given 
the information you wanted.

                      CLINICAL TRIALS INFORMATION

    Mr. Hoyer. In your judgment, would the clinical trials 
information now be available to almost all medical 
practitioners in America today?
    Dr. Lindberg. Almost all medical practitioners. Of course, 
we want it to be available to all persons; but only half of the 
households actually have any kind of an Internet connection. So 
that is really why we have done the experiments with the public 
libraries. And that is why we are giving the outreach grants to 
try to pair up medical libraries and these community 
organizations. We think that is the essential thing.
    One of the experiments--we operated for 18 months with 39 
libraries in something like 217 locations in the U.S., five 
States, and we are looking--I think I mentioned it last year--
we are looking first at the question, does the public bring 
medical questions to public libraries, yes or no. It turns out 
it is yes. Not always and probably more in big cities than 
little towns, but yes. And can the librarians handle the 
questions, and the answer again is yes.
    Although in every case we found out the first thing they 
wanted really wasn't money. It was training in how to do 
MEDLINE searches, and they wanted a hand from the medical 
libraries.
    What really worried us mostly in doing those experiments is 
supposing it turns out that everything else is fine and what 
they really want is $10 interlibrary loans. In other words, 
they want a copy of these articles out of MEDLINE. Then we 
would blush to come to the Congress for that kind of money. But 
it isn't. A lot of it can be dealt with electronically much, 
much cheaper. And, anyway, we are learning how to do this 
through community organizations; and the community 
organizations will do the outreach, I think, to accomplish what 
you just suggested.
    Mr. Hoyer. Let me ask another question. In your clinical 
trials, how do you select--I presume all clinical trials do not 
go on the website; is that correct?
    Dr. Lindberg. At the moment we definitely want all NIH 
conducted or supported clinical trials, for sure.
    Mr. Hoyer. So there is no judgment made on which go on 
because all of them go on?
    Dr. Lindberg. No. The FDA modernization act requires us 
actually to go ahead and do, let's say all--in quotes--clinical 
trials. We are doing it in logical sequence first, so to speak, 
cleaning up our own backyard, doing NIH first. There are at 
least 400 trials Alexa tells me in the database right now that 
are supported by private drug houses. But the next step will be 
trials supported by other HHS agencies like CDC and then the 
private drug houses in the U.S. and then perhaps overseas.
    So our hope is that, if we do a really fine job, that 
people will want to participate and comply with the law, and we 
won't need to confront them with Federal marshals or anything. 
We believe that Alexa has done a very good job, and we believe 
it will be a good example and the drug houses will I think see 
it is to everyone's advantage to participate and give us the 
data.
    As is often the case, it is easier to start things than 
keep them running. The key thing is to know when a trial stops. 
We don't want to be enticing people to think they can get help 
and apply on the phone only to be told, heck, it ended 6 months 
ago. We are most careful to keep those data very, very current. 
And those are the systems we worked out, I would say very 
happily, with the NIH institutes that support the trials.
    Mr. Hoyer. Thank you, doctor. This is an exciting time for 
information dissemination and the impact it will have on 
delivery of health care in even the most rural areas of the 
world.
    Dr. Lindberg. I am confident that will help.
    Mr. Hoyer. Thank you, doctor.
    Thank you, Mr. Chairman.
    Mr. Porter. Does the gentleman from Maryland have 
additional questions?
    Mr. Hoyer. No.
    Mr. Porter. I have two.

                          SMARTCARD TECHNOLOGY

    In the budget justifications of the NLM it indicates that 
you plan to provide technical consultation on the use of 
smartcard technology to improve both diabetes care and 
adherence to preventive measures. What is smartcard technology?
    Dr. Lindberg. Well, it is a fun thing. Smartcard is a 
credit card sort of a thing that has a computer processor or 
chip in the middle of it. The advantage of all this is that it 
can, first of all, store information, but it also can store a 
kind of a digital signature that allows one to identify 
himself. And we are just tremendously enthusiastic about it 
because, potentially, it puts the patient--I would say jumping 
ahead a little bit, it puts the computer-based record in the 
hands--literally in the hands of the patient, which is where I 
think it belongs.
    The technology is pretty mature and in pretty full flower 
in Europe which, in this case, is way, way ahead of the U.S. 
Usually that is not the case in technology. But in France, 
Germany, and Italy there is a G-\7/8\ project to create 
interoperable smartcard records in those three countries. They 
are concerned mostly, of course, about EUs and dollars and 
cents and francs and commerce.
    But the French plan is to use the system to provide for a 
patient to derive access to the patient's record in the 
presence of the doctor the patient has selected. So again this 
is cutting edge--this is several steps ahead of where we are in 
the U.S. It is something I have learned as the department's G-7 
health representative.
    So with the French system, if the patient's smartcard is in 
a reader and the doctor's smartcard is in the reader, you don't 
need any further authentication or validation. You have access 
to that entire record. Voila, as they say. Whereas we in the 
U.S. still are debating legally how to obtain access and how to 
guarantee medical data privacy.

                           SMARTCARD STUDIES

    In order for there to be U.S. participation in this G-7 
project, which the Secretary and the Department and the 
administration wanted us to participate in, NLM went out and 
funded three projects so there would be some use of smartcards 
for medicine in the U.S., however small.
    I might say the first big one we funded is the Western 
Governors Association. This will have 22,000 smartcards in the 
hands of mothers and babies, mostly poor mothers and babies. 
This contrasts with 70 million in France, so it is a little bit 
of a smaller trial. The cards in the Western Governors 
Association are in three western cities, and it is just 
starting up. It is called the Health Passport, but it will also 
contain immunization data, which is kind of an interesting 
thing.
    We also fund a study in which the smartcard will be used as 
a token, I guess you would say, by diabetes patients; and this 
is in a disadvantaged area of Los Angeles and includes the Los 
Angeles County Health Department and Latino and African 
American patients. But there, too, they are enthusiastic about 
it for the same reason that the Western Governors are, that 
there is a certain empowerment with the card. It is like a 
credit card, and you can get stuff with it. You can get medical 
care, and you can get drugs, and you can get some food, and you 
can have your own medical record. It has been very, very well 
received. It is not viewed as sort of a bureaucratic extra 
thing.
    And in both of those experiments the idea that, you can't 
trust patients, particularly poor patients because they will 
lose every darn thing and show up without their card turns up 
to be not true at all. The card really is a valuable thing and 
people don't forget to bring what they value. So the experiment 
is very good.
    It is also in use in a telemedicine project that NLM has 
been funding in West Virginia where it is used more on a 
Statewide basis but as a means of identifying both patients and 
doctors to the information system for the purpose of doing some 
medical treatment or diagnosis.
    I am enthusiastic about smartcards.
    Mr. Porter. When will you get the results of the study?
    Dr. Lindberg. The Western Governors reported that they are 
about 9 months behind, so I think the answer is in about a 
year.
    In the West Virginia project, they have already reported to 
us, and it has worked swimmingly. They are going to try to fund 
giving the cards to everybody in their system of health care. 
They find it a success already.
    The Western Governors we will have to find out about, and 
the L.A. Diabetes project has just started.
    Mr. Porter. When you say ``in their system of health 
care'', what do you mean? I assume France has a central system 
of health care where they can do their entire population with 
this. We don't have that kind of system.
    Dr. Lindberg. That is the difference. The French government 
can make a single decision. But in West Virginia, we are 
working with a university and some managed health care 
organizations whose domain stretches across the entire State. I 
am sure it doesn't include everybody in the State but hundreds 
of thousands of persons. They have issued about 10,000 of these 
cards, and they find that it technically works pretty well. Of 
course, it is a big State in miles; and so if you can avoid 
travel by telemedicine then you have avoided a real expense.
    Mr. Porter. Dr. Lindberg, before Harold Varmus left NIH, he 
proposed a thing called E-biomed. What has become of that 
concept?

                             PUBMED CENTRAL

    Dr. Lindberg. E-biomed. Well, actually, it took root, and 
it is growing a little bit less widely and as fast as he 
thought, but it is a big success. Actually, the individual--it 
got renamed PubMed Central; and the individual on my right, Dr. 
Lipman, is a man who knows the very most about it. I refer your 
question to Dr. Lipman.
    Mr. Porter. Sir.
    Dr. Lipman. Thank you. The status of the project is that we 
have two sample issues up from the first two societies that 
wanted to participate, the National Academy of Sciences and 
American Society for Cell Biology. Over the next couple of 
weeks we will be putting the back issues--back to 1990, 
actually--for the proceedings of the National Academy of 
Sciences and for several years back for Molecular Biology of 
the Cell, which is the journal for the American Society for 
Cell Biology. We are making the system more stable. We want to 
make sure it works well for the early participants.
    There have been a number of additional groups that have 
committed to participate including the Canadian Medical 
Association with their journals and the British Medical Journal 
just contacted me the other day to say that we have gotten the 
last issues resolved in terms of them participating. The 
American Society for Plant Physiology is another group that has 
decided to participate. There is a commercial publisher in the 
U.K., a current science group, which will be putting all of the 
primary research articles from all of its journals in; and it 
is starting some new journals that will be participating.
    Mr. Porter. This is, Dr. Lipman, a little different than 
what was originally proposed because, as I understand it, the 
first proposal was that all the publications would be through 
E-biomed. Then you wouldn't need the journals any longer. You 
are not doing that?
    Dr. Lipman. Well, Harold is always very articulate, but I 
think that, on this particular issue, the first thing that went 
out on the Internet for people to look at was somewhat 
misleading. I don't think he ever intended that this would be 
the demise of existing journals but rather that there be 
another mechanism for them to get out, access without barriers.
    But, in fact, there was a lot of feedback initially, and we 
did modify the plan based on what we heard. And primarily what 
is moving this forward is the voluntary and actually very 
enthusiastic participation by a number of groups. I would say 
we are in the second phase.
    I am surprised by the number of groups that have come 
forward to try to work out how they are going to participate 
when there hasn't really been much of a presence on the net. 
Over the next couple of months, there will be more of a 
presence on the net. There will be more content there. There 
will be more access to it. I think we will be hearing from a 
number of additional societies and publishers.
    Mr. Porter. Do I understand in its present iteration that 
you are putting on the net through this site something that has 
already been published after it has been published?
    Dr. Lipman. In some cases, it is at the time of acceptance. 
In some cases, there is a delay; and this is up to the 
publishers.
    Mr. Porter. This obviates the need for them to have their 
own site or do they have their own site, too?
    Dr. Lipman. It is going to vary. In some cases, probably--
for example, the commercial publisher will be having all the 
primary research articles in PubMed Central and only put the 
sort of news and views and commentaries on their site; and they 
will point to the PubMed Central site. In the case of the 
British Medical Journal, they will be giving all the primary 
research articles, all the clinical research articles to PubMed 
Central. They will also have it on their own site.
    This actually bears on a point that you were making 
initially, I think, which is, with all of the information that 
is on the Internet, how do we ensure that there is good 
information up there as well? And clearly what PubMed Central 
bears on is that NIH supports a lot of very good research but 
up until now, other than the abstract which might be available 
in MEDLINE, the full text of the articles have not been 
available. And this in a growing way, I think, will provide 
very high quality information to the community.
    So while I think being able to grade all the possible sites 
out there would be a tremendous challenge and possibly 
controversial, at least ensuring that the very best information 
is completely available is a positive thing to do. So we are 
very excited about this, and actually we are working very hard 
on it now.
    Mr. Porter. Thank you, Dr. Lipman.
    Dr. Lindberg, you continue to do a wonderful job there. We 
can't tell you how much we appreciate the work that you are 
doing. It is fascinating to see all of the developments in 
information technology that are occurring in medical research, 
and obviously we want to continue to give you the kind of 
resources you need to do your work well. So I thank you for 
appearing today.
    The subcommittee will stand in recess until 10:00 a.m. 
tomorrow.
    [The following guestions were submitted to be answered for 
the record:]



                                      Wednesday, February 16, 2000.

        NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

                               WITNESSES

DR. DUANE ALEXANDER, DIRECTOR, NATIONAL INSTITUTE OF CHILD HEALTH AND 
    HUMAN DEVELOPMENT
THOMAS E. HOOVEN, ASSOCIATE DIRECTOR FOR ADMINISTRATION, NATIONAL 
    INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
JUDITH M. WHALEN, ASSOCIATE DIRECTOR FOR SCIENCE POLICY, ANALYSIS AND 
    COMMUNICATION, NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN 
    DEVELOPMENT
ARTHUR D. FRIED, BUDGET OFFICER, NATIONAL INSTITUTE OF CHILD HEALTH AND 
    HUMAN DEVELOPMENT
DR. RUTH L. KIRSCHSTEIN, ACTING DIRECTOR, NATIONAL INSTITUTES OF HEALTH
DENNIS P. WILLIAMS, DEPUTY ASSISTANT SECRETARY, BUDGET, DEPARTMENT OF 
    HEALTH AND HUMAN SERVICES
    Mr. Porter. The subcommittee will come to order. We 
continue our hearings on the budget for the National Institutes 
of Health with the National Institute of Child Health and Human 
Development. We are pleased to welcome Dr. Duane Alexander, the 
Director.
    Dr. Alexander, I apologize. We had one vote and in 15 
minutes or so we are going to have two more. I think you should 
proceed with your statement, and we will try to give you as 
much time as we possibly can.

                       Introduction of Witnesses

    Dr. Alexander. Mr. Chairman and Members of the Committee, 
let me introduce the staff that is with me today. On my left is 
Judy Whalen, Associate Director for Science Policy, Analysis 
and Communication. Next to her is Mr. Tom Hooven, Associate 
Director for Administration; Mr. Arthur Fried, our Budget 
Officer; and you know Dr. Kirschstein and Mr. Williams.

                           Opening Statement

    The NICHD seeks to assure that every individual is born 
healthy and wanted, that women suffer no adverse consequence 
from the reproductive process, and that all children reach 
adulthood able to fulfill their potential for a healthy and 
productive life unhampered by disease or disability.

                           MENTAL RETARDATION

    Since this institute was established 37 years ago, a major 
portion of our research has been devoted to better 
understanding the causes, treatments, and prevention of mental 
retardation. One by one, in large part as a result of the 
support for research from this committee, causes of mental 
retardation are being eliminated. PKU, congenital 
hypothyroidism, and Hib meningitis are gone and measles 
encephalitis and congenital rubella syndrome and bilirubin 
encephalopathy have nearly disappeared as causes of mental 
retardation.
    This progress has continued during the last year. In one 
highly significant advance, Dr. Huda Zoghbi, an NICHD grantee 
in our mental retardation research center at Baylor, identified 
the gene responsible for Rett Syndrome, a mysterious condition 
that causes severe mental retardation in girls. After years of 
exploration, encouraged by this committee and Mr. Hoyer in 
particular, researchers discovered the genetic difference 
between girls with Rett Syndrome and unaffected children. The 
gene that is abnormal in Rett Syndrome controls the function of 
several other genes, so when it is defective, multiple other 
genes, including some that are essential for brain development 
and function, operate improperly. Based on this discovery, the 
NICHD is encouraging investigators to try to find pharmacologic 
agents that can substitute for this control mechanism and 
thereby reverse or prevent the progression of Rett Syndrome.
    In another significant finding we reported this year, our 
research demonstrated that children born to mothers who have 
untreated hypothyroidism during pregnancy score lower on IQ 
tests than children of healthy mothers, with 19 percent in the 
retarded range. However, when mothers with hypothyroidism are 
treated for the condition, their children's IQ scores are 
normal. This study suggests that screening women with 
hypothyroidism before or early in pregnancy may provide another 
way to prevent mental retardation. A protocol is in preparation 
to test this possibility in the NICHD maternal-fetal medicine 
network. This network is also studying ways to reduce the 
incidence of low birth weight, another significant cause of 
mental retardation.

                                 AUTISM

    NICHD has also provided important testing for a proposed 
new treatment of autism. After several anecdotal reports 
suggested a potential benefit to using secretin in the 
treatment of autistic children, many parents began providing it 
without evidence of effectiveness. NICHD launched a series of 
placebo-controlled studies to investigate potential benefits 
and risks of secretin. In results from the first of these 
studies, NICHD researchers found that treatment with the 
synthetic version of secretin offered no more benefit for 
children with autism than did treatment with placebo.

                           HEALTH DISPARITIES

    Another area in which the NICHD has a deep commitment is 
the elimination of health disparities among minority 
populations. One effort to address this concern, to be funded 
in fiscal year 2001, will be a new program of specialized 
centers for research in reproductive medicine in minority 
institutions. The goal of this program is to increase the 
capacity of minority institutions and investigators to conduct 
research in the field of obstetrics and gynecology, focusing on 
problems particularly prevalent among minorities.
    Another component will build on the success of the 
Institute's national Back to Sleep campaign that has reduced 
deaths due to Sudden Infant Death Syndrome, SIDS, by 38 
percent. Despite this overall success, both the SIDS rate and 
the rate of stomach sleeping among African Americans remain 
more than double that of white infants. To address this marked 
disparity, the NICHD invited the leaders from a number of 
national African-American organizations to join us in 
developing and implementing strategies for reducing SIDS.
    As a first step, NICHD is developing more effective ways to 
communicate the Back to Sleep message to minority communities. 
One component is a transit ad, shown on the easel, which will 
be used first in the D.C. Metro system and eventually in other 
cities around the country. The Institute's goal is to eliminate 
the racial disparity in infant back sleeping position within 3 
years and hopefully thereby markedly reduce the racial 
disparity in SIDS rates.
    We are also exploring ways to improve reading skills in 
populations of culturally and linguistically diverse students. 
Three years ago, we began a reading instruction research 
program with nine D.C. public schools. Preliminary data from 
this project show a pattern of remarkable improvements in 
reading ability. For instance, reading scores in schools that 
have historically been at the 10th to 15th percentile have 
improved to better than the 50th percentile, and the entire 
class in intervention schools is now performing at the national 
average. In a related area, the NICHD and the Department of 
Education this year are jointly soliciting research proposals 
for systematically studying the most effective ways to teach 
reading English to children whose primary language is Spanish.

                       PEDIATRIC TRAUMA RESEARCH

    We also plan to expand research for children and teens in 
the area of trauma. Many clinical treatments for trauma in 
children are just extrapolated from adult regimens. The NICHD 
is planning a multi-disciplinary collaborative program to 
develop and assess therapies specifically targeted to children. 
As part of this program, we will start a collaborative 
pediatric injury and trauma clinical trials network with a 
special emphasis on traumatic brain injury.

                           ADOLESCENT HEALTH

    Since 1994, the Institute has supported the National 
Longitudinal Study of Adolescent Health. The study has provided 
new insights into the ways that peers, families, schools and 
neighborhoods influence health outcomes, such as violent 
behavior, smoking, drinking, illegal drug use, and sexual 
behavior. With the increased funding provided by this committee 
in fiscal year 2000, the Add Health study will collect 
additional data from the full original cohort. This study will 
help identify the major determinants of health and health 
behaviors during the transition from adolescence to early 
adulthood.
    Mr. Chairman, the support from this committee for the 
research of the NICHD has contributed to the elimination and 
near elimination of some of the major causes of childhood 
diseases and lifelong disabilities. We are proud of this 
progress, but we still face many research challenges. In the 
years ahead, with your continued support, I am confident that 
we will return to this room and report that we have eliminated 
some of the causes of learning disabilities, other health 
problems of women and children, and that we have contributed in 
a significant way to eliminating the health disparities that 
separate racial and ethnic communities.
    The President's request for NICHD for fiscal year 2001 is 
$904.7 million, including AIDS. I will be pleased to answer any 
questions you have at this time.
    [The written statement of Dr. Alexander follows:]



    Mr. Porter. Dr. Alexander, thank you for your good 
statement.

                    PUBLICATIONS OF RESEARCH RESULTS

    As you gave the opening part of your statement, I was 
thinking, did we and maybe this is a question for Dr. 
Kirschstein, do we ever list the progress that has been made in 
terms of discovery and elimination of disease in such a way 
that the layman can say, oh look, that money got some results? 
Do we list the results. I know that we are not in the results 
business directly, but do we ever do that?
    Dr. Kirschstein. Yes, we do. We have much of that put 
together in publications that we put out and many other things. 
I am not sure we always say that we have done this and 
eliminated that and it was our money in those stark terms. But 
we do it, yes. We will try to put some material together and 
send it to you.
    [Clerk's note.--The publication will be submitted under 
separate cover at a later date.]
    Mr. Porter. I recall seeing it before, but I have not seen 
it lately. I think people need to know that we have made this 
progress and there is a lot of hope that we will make further 
progress.
    Dr. Kirschstein. Yes.

                                 AUTISM

    Mr. Porter. Dr. Alexander, I want to ask you about autism, 
and I don't need to express the concern of many Members of the 
Congress, but what I would like you--and there are probably 
representatives in this room from the community that is 
concerned about this terrible--I guess I will call it a 
disease. I want you to give us a feel, if you will about how 
this translates in other words, for a long time people feel 
autism has been, rightly or wrongly, that it has not been given 
sufficient attention. In the last 2 or 3 or 4 years, the 
parents whose children suffer from autism have organized 
themselves and impacted certainly the Congress, but I think 
also NICHD and others in NIH.
    How do we get from where we were to where we are today? How 
has this process gone in terms of your own attention to autism 
and further research on it? I would like to get a feel for how 
it translates in terms of any change in direction?
    Dr. Alexander. Autism is one of the most frustrating 
conditions in pediatrics for parents, for pediatricians, and 
for researchers. It has been a very difficult condition to 
understand and appreciate. It is frustrating for parents 
because the children seem to function almost normally in some 
areas and sometimes have islands of excellent performance, but 
overall they have difficulty with communication, speech in 
particular. They have perseverative movements and they withdraw 
socially.
    It is frustrating because of the islands of normal 
performance. A parent feels if the rest of this child could 
function as well as they do in this particular area, I would 
have a child who is really a normal child. It has been 
frustrating for pediatricians because we have had no effective 
treatment. And it has been frustrating for researchers because 
we have not had good tools to approach it.
    In the last few years, we have developed markedly improved 
tools for approaching autism, particularly in the neurosciences 
and genetics arenas. In 1997, we formed a coalition of the four 
institutes at NIH that deal with autism: in addition to NICHD, 
the National Institute on Deafness and other Communication 
Disorders that you will hear from next, the National Institute 
of Mental Health and the National Institute of Neurological 
Disorders and Stroke. We formed an autism coordinating 
committee and since then have added three other NIH institutes 
to this.
    We have made a commitment to markedly expanding the NIH 
research on autism. And, in fact, the NIH research contribution 
has quadrupled in just the last 4 years. We have established a 
network of 10 different sites, funded by NIDCD and NICHD, of 
Programs of Excellence in Autism for Collaborative Studies 
focusing on neurobiology and genetics, trying to recruit a 
thousand families who have more than one individual affected 
with autism, and using the newest techniques of modern genetics 
to try to get a handle on the genetic causes of this disorder. 
This is a complex multiple gene disorder.
    Mr. Porter. Dr. Alexander, I am going to have to interrupt 
you and call a recess because I am going to have to vote. Let 
us finish this when I get back. We will stand briefly in 
recess.
    [Recess.]
    Mr. Porter. The subcommittee will come to order. Dr. 
Alexander, you were in the midst of talking about autism. What 
I want to know is how you have been motivated to do what you 
are doing? Did our direction have something to do with this, 
did the community? Did you find a discovery that led you into 
other areas?
    Dr. Alexander. The initial impetus for an expanded effort 
came from the Congress asking us to hold a scientific 
conference on autism. It was very timely. We wanted to do this 
anyway. We put together a state-of-the-science conference on 
autism, and it was an excellent conference.
    This was back in 1995. From that came the real belief from 
the scientific community that there were opportunities for 
progress, particularly in neurobiology and genetics, and this 
was deserving of a special research emphasis. We put together 
this expanded program in autism research, funded 10 different 
sites with program project grants collecting a thousand 
families with more than one affected family member and doing 
genetic analyses, trying to identify the several genes that are 
probably responsible for autism and doing biologic and other 
assessments at the same time.
    This is probably going to take us about 5 years to 
accomplish to gather that many families. At the same time, we 
met with the parent groups and the advocacy organizations for 
autism. One of the things that they emphasized to us most 
strongly was that by the time their children got diagnosed with 
autism, they felt that valuable time had been lost for 
intervention attempts and that the medical community was not 
sufficiently versed in how to diagnose, look for, work up a 
patient with autistic symptoms, and could we help them with 
that?
    That is something that we can assist with but not do 
ourselves, so what we did was get the professional 
organizations, the American Academy of Pediatrics, child 
psychology and neurology societies, and other organizations to 
come and meet with us and researchers, getting information 
about what research showed about predictive features for autism 
and essential features for making a diagnosis, and then to 
translate that into guidelines for the profession to use in the 
early identification and diagnostic work up and evaluation of a 
child with autistic symptoms.
    That has been accomplished. About a dozen different 
professional societies have signed onto these guidelines. They 
are being published in neurology journals, in autism journals, 
and other journals as guidelines to the society, to the 
profession to use for earlier diagnosis of these kids. This is 
a major contribution that we have made and again it has been in 
response not just to emphasis on research but to what the 
parents and family members have been saying we need help with 
to help our children. So I think we have tried to be responsive 
in all aspects of this, from the research side, from the 
services side, from the diagnostic side, and helping the 
families as well as the physicians and medical community with 
this problem.
    Mr. Porter. Well, I think you have been also. I think 
people in this country don't know how responsive people want to 
be to others who have problems. So many people in America say 
well, I don't matter, nobody listens to me, but there are so 
many people that do listen if you do make the effort to bring 
it to their attention, and I am not just talking about Members 
of Congress, but members of NIH, they are there to help and 
respond. When people cry for help, they always do respond.
    I think it is wonderful what you are doing. I think this is 
one of the best things that I can think of because you are 
going to put it where it will reach the broadest audience of 
people who need to hear this message. I have been using your 
name, Dr. Alexander, you haven't heard me but----
    Dr. Kirschstein. I told him.

                        CHILDREN'S HEALTH HABITS

    Mr. Porter. Thank you. I think this is a perfect example of 
what I think we need to do in respect to children's health 
habits; and I want, if you will join me, I would like to have 
you and Dr. Koplan over at CDC, Dr. Chavez at SAMHSA and Dr. 
Fox at HRSA, all get together and try to find a way to get 
these kinds of messages on things we know that work into the 
mainstream of consciousness of the average child and parents of 
children and see if we can change the habits. In other words, 
the knowledge has to be translated into something concrete in 
terms of better health habits; and if we start with children, I 
think we are doing the best we possibly can to change the 
future.
    This is a prime example of exactly--this is a message of 
course for parents, but it affects the health of the children 
obviously. It is the kind of thing that I want to focus on, 
whether it is putting up messages in a metropolitan transit 
system or using TV or radio, whatever it is that reaches the 
audience that we want to reach. I think we need to put some 
real resources into getting this translated into messages that 
can make a difference in people's lives.
    Dr. Alexander. We will be glad to do that, Mr. Porter.

                          READING DEVELOPMENT

    Mr. Porter. My final question is, and I listened carefully 
to what you said about reading. Did we know the things some 
time ago that you tell me that you have translated into real 
progress in the D.C. schools? When I sit here, reading has been 
a part of the needs of every child from the beginning of time; 
and yet we have sort of watched as our public schools have 
deteriorated and kids have not gotten the skills that they 
need. And reading is at the heart of it. Now we are doing some 
things that one would say, gee, why didn't we do that 10 or 15 
years ago when we saw the system going down.
    Dr. Alexander. Reading is something that prior to maybe 15, 
20 years ago was not a major topic of research. It was 
something that people just thought kids learned automatically, 
and you give them phonics and put books in front of them and 
most kids would pick it up. We had not done formal studies of 
how kids learn, specifically how to read, and what the 
processes are, the neurocognitive processes that are involved 
in learning to read.
    As a consequence of NICHD's research in learning 
disabilities, part of that program focused on the normal 
process of learning; and a substantial effort was made on 
learning to read normally and how this process works. We gained 
a substantial amount of information about how that process 
works and discovered that it was often not being taught and 
applied in the schools.
    We took this then to the next step with what I called 
clinical trials in the classroom. We used a medical clinical 
trial approach and applied it with randomized-controlled 
studies where we randomized classrooms, not kids, to different 
types of interventions and assessed whether we could apply in a 
classroom setting what we had learned in the laboratory about 
how kids learned to read and the essential neurocognitive 
processes that are involved in teaching that skill. And we 
demonstrated pretty clearly that you could apply this in the 
classroom with LD kids, with special kids.
    The next question was whether you can apply this in the 
regular classroom to most kids and have children learn better 
than they are just with whatever is being done at the present 
time. We have done this on a small scale in Texas, in New York, 
in California, and in a number of other States; and the results 
have been pretty consistent. We then said let's try this on a 
large scale in the classrooms in D.C. where there are very 
clearly problems with kids learning, where we are close to the 
Federal Government and we can demonstrate right here in D.C. 
the effectiveness of this approach.
    The University of Houston investigators put in an 
application to us to do this in D.C. They are doing clinical 
trials in the classrooms. We have nine schools that are 
intervention schools and three control schools, and we have 
clear evidence that using the techniques that we developed in 
the laboratory, kids learn effectively when we teach the 
teachers how to teach using these techniques in the classroom.
    The results are phenomenal. Some of the committee Members 
have been out to our schools in D.C. and seen this in progress. 
Mr. Cunningham has been there, Ms. Northup has been there and 
seen it in operation. It is really gratifying to see real-life 
documentation of payoffs from the investments that you have 
made in research.
    Mr. Porter. Thank you. I will ask more on that later. Ms. 
DeLauro.

                                 AUTISM

    Ms. DeLauro. Thank you, Mr. Chairman. Thank you, Dr. 
Alexander. Just a follow-up question on the autism and your 
testimony talked about the testing of secretin?
    Dr. Alexander. Yes.
    Ms. DeLauro. There are a lot of parents out there who are 
seeking treatment methods and medications for treatment to help 
their kids. Oftentimes, I mean, they may be looking at stuff 
that is very expensive, it is unsafe, ineffective. What kind of 
plans do you have to expand the research on effective treatment 
options in the area of medications particularly? You hit on 
some other things but in terms of the issue of medications?
    Dr. Alexander. We have additional trials of secretin for 
autism underway. The trial that I mentioned in the opening 
statement was one dose, one time, of secretin, which is what 
had been reported in anecdotal accounts to be effective in 
improving long term the function of children with autism. That 
didn't work.
    One reason that we got into this was as you say, parents 
had been investing large amounts of money in trying to get 
secretin for this use for their children, and it became very 
scarce. There became a black market, and there became instances 
reported where things were being sold as secretin which were 
essentially saline. And parents with these kids with autism are 
so desperate and eager to help them that they will do almost 
anything to try and help their children.
    We felt that it was essential for us to make an investment 
very quickly to try and determine first if there were some 
benefit here we ought to know about it and be able to spread 
that information more widely. But we suspected, that this 
probably was not effective treatment; and if it wasn't 
effective, parents ought to know that so they could stop 
investing in it and try something else that would help their 
kids.
    The other trials are looking at multiple administrations, 
and different doses to see whether there may be some benefit. 
Personally, my suspicion is that there will not be; but we need 
to settle this and resolve it. If this doesn't work, we need to 
look for other things that may, in fact, have benefit. Your 
constituents at Yale are at the forefront, both in the child 
study center and in one of our collaborative Programs of 
Excellence in Autism that is at Yale, and they are some of the 
major players in this whole arena.

                                 ASTHMA

    Ms. DeLauro. Let me ask you about asthma. I have read and 
know about the concern and the commitment to eliminate the 
health disparities among minority populations, and I think this 
is one of the areas in pediatric asthma where you will see 
great disparity. Asthma in children is on the rise everywhere, 
and as I mentioned in the last couple of days at these 
hearings, there has been a particularly high increase in my 
community. And the rates for all ethnic groups, especially for 
African American and Hispanic children are rising tremendously.
    What kind of plans do you have to expand the research on 
pediatric asthma, looking at causes, looking at treatments, I 
read somewhere today about children that do have asthma are 
much--there is much more fear that they live with than other 
children do, and it makes sense given that it is very serious 
and what kinds of problems that they could have and life-
threatening problems that they can have so this whole area of 
increase in asthma is something that I am very concerned and 
trying to be involved in my own community.
    Dr. Alexander. Ms. DeLauro, asthma is not one of the 
primary assignments for NICHD. The asthma research at NIH is at 
NIAID and the Heart, Lung, and Blood Institute and in 
environmental health sciences. We are more of a side player in 
asthma.
    There has been a major Departmental interest in asthma, a 
special Secretarial initiative in childhood asthma with 
involvement of all three of these institutes and other 
components of the Department as well because of this very 
specific concern that you cite. Of all the pediatric 
conditions, there are very few on the increase. Fortunately 
most are on the decrease.
    But asthma is going up in terms of its incidence, 
prevalence, and death in kids that should not be dying. Also it 
is one of the areas of health disparity that is more severe in 
African American populations and Hispanics. So the Department 
has been paying special attention to asthma research. These 
other three institutes all have made expanded commitments for 
their research, but this is not something that NICHD has been a 
major player with.
    Ms. DeLauro. I have done some work with the American Lung 
Association and had a meeting in my own district several weeks 
ago to talk with the Lung Association about their truly 
empowering children, a program where they work with the 
youngsters. And this is not in every school, but in my view it 
ought to be in every school with the school nurses and the 
clinics that help youngsters cope with the illness when at 
first signs and using the inhalers, of writing down their 
percentages every day, of what kind of exercises to be involved 
in to, one, lessen the fear, and again as I said to empower so 
there are some good pieces of trying to work with this illness.
    Let me ask a question on tobacco.
    The Add Health study and those kinds of insights that you 
are looking into on why teens in a variety of areas may choose 
to smoke, how are the insights and the data being put into 
practice on the prevention front?

                        ADOLESCENTS AND SMOKING

    Dr. Alexander. The Add Health study is the largest ever 
done on adolescence and health behavior, and the factors that 
contribute to adverse health behaviors in particular such as 
smoking. There has been 1 year of follow-up data from this 
longitudinal study.
    This year, fiscal year 2000, we are back 5 years later 
surveying again the whole cohort looking at their health 
behaviors 5 years down the pike. We have much greater data now 
about whether these kids who we surveyed 5 years ago and 6 
years ago have taken up smoking or not and then can make 
correlations with all of the data that we originally gathered 
about their health behaviors, their peer influences, school 
influences, community influences, whatever, and its 
relationship to whether they began smoking, as well as 
associated alcohol abuse, other drug abuse, and many other 
health behaviors. So that data is currently being collected in 
the wave this year.
    The investigators have made a commitment to make that data 
available not only to the investigators participating in the 
study who get the first crack at analyzing and presenting it, 
but making that raw data available to the full scientific 
community. That was done with the original data set and more 
than 200 scientists are now using that data set to do 
subsidiary studies. The same will happen with this wave of data 
collection from Add Health that I think is really going to be 
the most valuable component of it. A 1-year longitudinal study 
is not very longitudinal. This 6-year follow-up is going to be 
the gold mine.
    Ms. DeLauro. Thank you. A final comment, Mr. Chairman, I 
want to applaud your outreach, if you will, to Dr. Alexander 
and to CDC and HRSA because I think it is absolutely right, 
this kind of an effort or anything that can provide a way for 
families, for teachers, for whomever to understand what the 
health implications are and what they can do in a graphic way, 
in a way that really grabs them, if you will, that is the kind 
of thing that we need to do with the work that you all are 
doing and making sure that it is getting to the people who need 
it the most and need to understand some of these things. Thank 
you very much.
    Mr. Porter. Thank you, Ms. DeLauro.
    Mr. Wicker.

                           ADOLESCENT HEALTH

    Mr. Wicker. With regard to the Add Health study, who are 
the people whom you hope to get the information to?
    Dr. Alexander. Investigators doing the study which is based 
at the University of North Carolina and about six other 
institutions around the country will have first access to the 
data for analysis. That data set will also be made available to 
investigators on request by the study coordinators for their 
use.
    Mr. Wicker. Who are investigators?
    Dr. Alexander. Scientists with grants from the NIH 
primarily to use that data set for secondary analyses that they 
are interested in conducting.
    Mr. Wicker. Okay. Let me explore this a little more. Your 
testimony since 1994, the Institute has supported this Add 
Health study. But do I take it that you have not been involved 
each year in such a study?
    Dr. Alexander. We have been involved each year, yes. Our 
funding provided several things. It provided for refinement of 
design of the original study, the collection of data from a 
hundred thousand initial subjects and then more detailed data 
from about 20,000 subjects and their families.
    Mr. Wicker. A subject would be a child.
    Dr. Alexander. A child between the 7th and the 12th grade.
    Mr. Wicker. A hundred thousand and then a subset of that 
100,000?
    Dr. Alexander. Yes, a subset of that 100,000.
    Mr. Wicker. So like answering the long form.
    Dr. Alexander. That is right. The short form goes to a 
hundred thousand and the long form is a detailed face-to-face 
interview of 20,000 teenagers in the home, and then a 1-year 
follow-up after that of the same 20,000. Now we are going back 
5 years later and surveying them again with follow-up questions 
about health behaviors and being able to relate that to the 
information originally gathered with full privacy protections 
so that there are no names associated with this. The name 
disappears as soon as the survey instrument is completed on the 
computer by the subject.
    Mr. Wicker. How much money have we spent since 1994 on this 
project?
    Dr. Alexander. The cost for the first 5 years was 
approximately $24,000,000 and the cost last year was about a 
million and this year will be about $8,500,000. The heavy years 
are the data collection. The lighter years are the data 
analysis times.
    Mr. Wicker. UNC Chapel Hill has been in charge of this?
    Dr. Alexander. That is correct.
    Mr. Wicker. Who has helped them out? Is that nationwide, 
all 50 states?
    Dr. Alexander. It has been a national probability 
representative sample. It has not been every State, but it has 
been a sample selected by middle school and high school to be 
representative of the U.S. population.
    Mr. Wicker. And you say that the study has provided new 
insights into the way that peers, families, schools, and 
neighborhoods can influence positive health outcomes as well as 
negative outcomes.
    How about churches and faith-based institutions?
    Dr. Alexander. They have been a part of this as well. Part 
of the information that has been collected about community has 
been related to churches' influence in the community and 
church-related activities participation by the families and by 
the subjects themselves. Information has been gathered about 
church participation, about what we generally term as 
religiosity, and that is one of the factors that is being 
analyzed in the data and one of the factors in the initial wave 
of data collection that proved to be a positive association 
with good health outcomes and good overall outcomes.
    Ms. DeLauro. Would the gentleman yield?
    Mr. Wicker. I would be delighted to yield.
    Ms. DeLauro. When does this information get to the 
communities?
    Mr. Wicker. I have that question, too. These insights, I 
just wonder how much of a new insight that is. You are learning 
the same things over and over.
    Dr. Alexander. The original data analysis was put together 
about 2\1/2\ years ago. We have done a number of congressional 
briefings by the investigators who have been here on the Hill 
presenting the data from the study. I have a nice summary 
brochure of the data from the study that I would be glad to 
supply you.
    [Clerk note.--The information is retained in Committee 
files.]
    Mr. Wicker. Wonderful. I am sure Ms. DeLauro and I would be 
glad to see that.
    Dr. Alexander. In about 2 years, a year and a half, we will 
have a follow-up on that that will be an analysis of the 5-year 
follow-up data.
    Mr. Wicker. What strikes you as new from this--from these 
insights as something that we didn't already know? Good peer 
groups and family involvement in a child's life and things like 
that we sort of already intuitively feel like we know?
    Dr. Alexander. Just as one example, one of the claims that 
had been made in recent years, is that when a child gets to be 
a teenager, family does not matter any more, it is all peers.
    This study provides clear refutation of that claim. Family 
involvement, a feeling of closeness, of relation to school and 
to family clearly is associated with better outcomes. Kids 
clearly want that to continue during their teen years and 
parents do still matter in terms of influencing positive or 
negative outcomes in the teen years, and it is not all peers. 
That is contrary to what the general thinking was before this 
study was done.
    Mr. Wicker. I don't know if it is contrary to what my 
thinking might have been. Let me just say that I think the 
Chairman made a statement at another hearing last week that 
part of our job is to be skeptical, but I sort of do wonder are 
we spending millions of dollars learning something that we 
already know. So I really am interested in whether this is 
getting us somewhere. If it is, then I am all for it. Thank you 
very much, Mr. Chairman.
    Mr. Porter. Thank you, Mr. Wicker. Mrs. Northup.

                          READING DEVELOPMENT

    Mrs. Northup. Thank you. Welcome. I have certainly 
appreciated NICHD and you and others who have answered my 
questions along the way.
    I want to ask you again about reading. I noticed in your 
report that you continue to talk about the astounding results 
that you have been experiencing in some of the D.C. public 
schools that had the poorest reading records, whole classes of 
kids that averaged about 10 percentile in achievement that are 
now at the Nation's average.
    I have been there. The not only success rate but the 
excitement, the sense of being engaged in school is just very 
phenomenal. I continue to be very discouraged by the fact that 
we know what works and that it is not going on in every school 
in this country. I just wondered what sort of response that 
NICHD gets from whether it is the Department of Education, 
Federal, whether it is schools that--universities that teach 
our teachers, whether they are picking up the information that 
is so clearly available, and what your thoughts are that we 
might need to do if they are not.
    Dr. Alexander. Our interaction with the Department of 
Education is extremely positive. That has not always been the 
case; but in recent years, our interaction with both 
individuals and organizations within the Department of 
Education has been extremely positive. They are highly 
interested in our research and how they can get it applied into 
the schools.
    Mrs. Northup. Am I correct in saying that you are working 
very closely with OERI and that is a partnership now?
    Dr. Alexander. That is correct. OERI is our closest link, 
and they are the ones that are most interested in our research, 
and we
are co-funding some studies with them. The Spanish to English 
reading initiative that I mentioned in the opening statement is 
a joint effort, $4.5 million from NICHD, $4.5 million from OERI 
this year. We have 55 applications in response to that RFA. 
They are excellent in quality.
    We are going to get some very good research done out of 
this; and 4 or 5 years from now when that research is done, we 
are going to have some clear indications of how you take a 
child whose primary language is Spanish and teach them to read 
in English. We are going to learn that, just as we have been 
able to learn how you take a kid that doesn't know how to read 
and teach him to read when English is his primary language.
    Now there is a method that we have in progress that is 
specifically targeted to translating the information from 
research to practice, and that is at the direction of the 
Congress. Two years ago, I established in consultation with the 
Secretary of Education, a national reading panel. This is a 
group of 14 individuals, scientists, researchers, teachers, 
school principals, parents, and other educators who have been 
charged to review the scientific literature in reading research 
and determine what that literature shows about what we know 
about how children learn to read, what is required for them to 
learn to read, what are the most effective techniques for 
teaching reading in the classroom to these kids, and what is 
ready for implementation in the classroom, and what needs more 
study.
    That panel has now completed its work. It has reviewed 
literature of more than 25,000 articles, selected those that 
have experimental designs that meet rigorous scientific 
criteria for analysis, done meta-analyses when that was 
possible, and reached conclusions that clearly demonstrate 
those factors that are essential for kids to learn to read, 
what is a successful way of teaching that particular skill, 
what has not been demonstrated to be an effective way of 
teaching, what is ready for application in the classroom, and 
what needs more research. That report is going to be pretty 
clear cut. We plan to have that ready about the end of March. 
We are running behind schedule, but it has been important 
enough that I have given the panel additional time to complete 
their work.
    We are trying to have this information boiled down to as 
small a volume of words as we can so that its message is clear, 
coherent but doesn't take forever to read. And that message 
then we will try to get out not just to the Congress and to the 
Secretaries to whom we are directed to report, but to teacher-
preparation colleges and universities, to boards of education, 
to teachers in the classroom and to parents about what works, 
what is effective.
    We plan an unusual step with this report. Accompanying this 
report of 30 pages will be a videotape that takes the 
conclusions and recommendations about what works and then 
provides examples in the classroom setting of how you implement 
this particular finding in the classroom. We hope that this 
method of outreach, if you will, using the latest in 
information-transfer technology, will be more effective than 
anything we might do otherwise in translating this information-
collection effort and research-analysis effort into application 
in the classroom so that people learn to read.
    Mrs. Northup. Well, I hope you are right. The resistance is 
pretty amazing. Let me start by listing areas that I would like 
to know about the resistance. For example, you have 12 public 
schools here in Washington, D.C. that had the lowest scores 
that have experienced enormous, astounding change. So have all 
of the rest of the schools adopted this method?
    The second thing is that we have whole school reform that 
we funded. Some of those programs fall under the definitions of 
what works. Many of them do not. Are you going to recommend and 
do you expect the Department of Education to conclude saying 
that it has to be one of the methods that works?
    Mr. Chairman, I would just say again, I am sure in my 
letter to you before the committee marks up the bill is a 
reiteration by this committee that it is unacceptable that we 
know how to teach kids how to read and who are the children 
that are most likely to fall into the cannot-read category, 
children from disadvantaged backgrounds, minority children 
because of the disadvantaged background and children with 
learning disabilities and the success rate is astounding. And 
we as the appropriators ought to use every bit of the effort we 
can to try to break through a bureaucracy that exists at many 
of the universities that are training our teachers that are 
just frankly resistant to it.
    Dr. Alexander. I think you have put your finger on the 
major challenge: to teach the universities teacher preparation. 
There is a lot of resistance to this information. There are a 
lot of people who have built their reputations and their 
stature on different approaches.
    Mrs. Northup. On publications.
    Dr. Alexander. Who will have difficulty in accepting this 
and changing. Someone once said the only thing harder than 
moving a graveyard is changing education and there is a lot of 
truth to that.
    So we are going to make the try. We made a commitment on 
our own behalf, and I have gotten the panel members to commit 
to spreading their report. This is not an NICHD or HHS report 
or Department of Education report, it is a report of a national 
reading panel established by the Congress. So it is not 
Washington, the Department of Education, telling local 
education agencies or universities what works from research. 
This is the panel members, and we intend to use them and they 
have agreed to be messengers, ambassadors of this report and 
the information that it contains to universities, to boards of 
education, to school systems, teachers, whatever to try to get 
this information out.
    Mrs. Northup. Mr. Chairman, just a final comment. I would 
challenge every Member, especially Members that have schools 
that are underachieving, to go visit a couple of their under-
achieving schools in their districts and go to one of the 12 
schools in Washington, D.C. where the entire class is 
performing at national averages or above, the entire class, and 
see not only the difference in a successful school but the way 
all of those children feel about school, how excited they are, 
how confident they are that they are going to be high achievers 
in school and tell me that you don't feel every day that the 6-
year-old in your district who will only get to be 6 years old 
one time, and what we know is that you can't recapture at 9 
years old what you missed when you were 6. You never get that 
stage in development again. Tell me that they can sleep at 
night without trying to push this forward.
    Mr. Porter. Thank you, Mrs. Northup. Mr. Hoyer.
    Mr. Hoyer. Thank you very much. I am sorry I wasn't here at 
the beginning of your questioning. I will do that.
    Mrs. Northup. Very impressive. It is astounding.

                             RETT SYNDROME

    Mr. Hoyer. Thank you.
    Dr. Alexander, I have been absent for a lot of this 
hearing, but thank you for your observations with reference to 
Rett Syndrome. Only Mr. Porter has been on the committee long 
enough--and Mr. Obey, long enough to remember when I first 
brought up the issue of Rett Syndrome, and it was because of a 
personal experience that I had with Christy Smith who suffers 
from Rett Syndrome. But you and NIH have been extraordinary in 
following up on a relatively, less than a million dollars 
usually and then not earmarked but simply referenced in the 
report, request. I very much appreciate the fact that because 
of your tenaciousness and NIH's tenaciousness and your 
willingness to take a chance on an extraordinary researcher, 
that we have had this breakthrough and identified the gene 
which may now lead to preventing other baby girls from 
suffering with Rett Syndrome, but also perhaps reversing the 
consequences of the onset of Rett Syndrome.
    I know that Mr. Porter has been very supportive of that 
through the years; and John, I thank you for that. I know that 
you mentioned that at the beginning of the hearing, and I was 
voting during that time.
    On a less happy note, Eleanor Holmes Norton has asked me to 
ask you a question about the perinatology research project. As 
you know, I guess back 10 years ago, 1990, NICHD was given the 
direction to establish such a center here in light of the high 
infant mortality and morbidity rate in the District of 
Columbia. It is Ms. Norton's understanding, which she has told 
me and Senator Sarbanes, and the rest of us who represent this 
region, that we should be concerned about the young people in 
the District of Columbia. My understanding is that we have now 
decided, or you have made a determination not to proceed with 
that here in the District of Columbia and are looking at a 
national, I guess, prospective grantee. Obviously that is of 
concern to Ms. Norton. Can you comment?

                         PERINATOLOGY RESEARCH

    Dr. Alexander. Sure. First, the directives that we had from 
this committee really focused on encouragement to establish an 
intramural program in obstetrics and gynecology and 
perinatology that looked at reducing infant mortality 
particularly with regard to inner cities such as D.C.
    We also got directive language to focus research on infant 
mortality in D.C., specifically, but not necessarily, the 
perinatology research branch. We have made a major effort over 
the last 7 years to target research on infant mortality in the 
District of Columbia. With the assistance of the Office of 
Research on Minority Health, we have directed $34,000,000 over 
the last 7 years in the D.C. infant mortality initiative.
    These have been grants, cooperative agreement awards to the 
three D.C. medical schools, the D.C. Health Department, the 
University of the District of Columbia, and several other 
agencies focused very specifically on developing and testing 
interventions to reduce infant mortality in the District of 
Columbia. For the first time in their history, these 
institutions have worked together around the same table 
cooperatively to design, develop and implement protocols 
focused on problems associated with infant mortality in D.C., 
with injuries, with immunization, with prenatal care, with teen 
pregnancy, early sexual activity, and repeat pregnancies at 
short intervals.
    These have been implemented. They have been tested; studies 
have been completed; results published. Practices changed as a 
consequence of this intervention. The second phase of this 
study, which is two 5-year programs, is now 2 years into 
action, and we are continuing these efforts again with the 
three D.C. medical schools, Children's Hospital, and other 
organizations working with us in a very targeted effort to 
infant mortality in D.C. During the time this has been in 
operation, the D.C. infant mortality rate has dropped from 23 
to 13, not all as a result of this project, but that is what 
has happened.
    Now, separately from that has been our establishment of a 
perinatology research branch. To do this, we recruited the best 
OB-GYN researcher in the country, Dr. Roberto Romero, generally 
acknowledged as such. He agreed to come here and head this 
branch. We then sought a site for him to operate because we 
cannot do that at the clinical center at the NIH where we would 
ordinarily operate such a program. We have tried twice 
unsuccessfully in the past to set up a perinatal unit 
delivering babies at the clinical center. It isn't going to 
work.
    So we sought a site in D.C. D.C. would be terrific. It is 
convenient. Our program could work with the rest of our 
intramural program, it has a high-risk population; and at the 
time we started soliciting initially, had hospitals with a 
substantial number of deliveries at a given site. That is a 
requirement to operate a clinical research program in 
obstetrics. Adverse outcomes of specific types are rare enough 
on their own that you need a large number of deliveries under 
your control and observation to get a significant number of 
problem deliveries for study.
    When we first started this, we tried to establish a program 
in D.C. We actually awarded a contract to Georgetown 
University, and put the perinatology research branch there. 
After about a year and a half, for a variety of reasons, that 
was not working. We cancelled the contract, and withdrew the 
program. It has been operating since at Wayne State University 
at Detroit where Dr. Romero was recruited from and he went back 
there.
    Meanwhile, we have been trying to find a site for this 
perinatology research branch to do its work. The requirement 
had been for about 4 to 5,000 deliveries at a single site. When 
we first operated, we had that in D.C. Because of changes in 
obstetrics in general across the country, including D.C., many 
managed care organizations are contracting not with university 
hospitals but with private hospitals to deliver babies because 
it is cheaper. And so universities everywhere in the country 
have had their delivery rates go down, and the hospitals in 
D.C. have been a part of this national phenomenon, so that no 
D.C. university hospital has more than 1200-1400 deliveries a 
year. That is too small for a high-risk obstetrics research 
program. It would take years to get enough patients with the 
problems that we are interested in researching to get answers, 
and by then the field has moved on.
    So we made every effort, even though we were not 
technically required to, to locate this perinatology branch in 
D.C. It would have been advantageous to us for a number of 
reasons to have it in D.C., but it proved impossible. So what 
we wound up doing was when no offeror in D.C. or in the 
surrounding area that was eligible in the original solicitation 
proved capable of meeting our requirements, we cancelled the 
solicitation back in January.
    We have now put out a sources sought notice nationwide for 
an institution that can meet the clinical space and academic 
requirements of having a maternal-fetal medicine training 
program (which also disappeared from D.C.) to serve as a 
location for this branch. That sources sought will be followed 
by a request for proposals, for a support contract to provide 
the space, patients and support services for this branch. It 
will now be competed on a nationwide basis. There are a number 
of medical institutions around the country that still have the 
sufficiently large patient base of high-risk patients that can 
meet these requirements, and we will locate this perinatology 
research branch at the place that can best meet our 
requirements for delivering a patient base, maternal-fetal 
medicine training program, academic support, and space for us 
to operate.
    Mr. Hoyer. I am sorry that I surprised you with this 
question, and you didn't have an answer. My time is up.
    Mr. Porter. Dr. Alexander, you are doing, as you always 
have, a wonderful job at NICHD; and we very much appreciate 
your service there. You always answer our questions 
beautifully. A good example was the last answer.
    Mr. Wicker. Mr. Chairman, what about one more minute.
    Mr. Porter. All right. Everybody gets one more question.

                       MATERNAL HIV TRANSMISSION

    Mr. Wicker. Thank you. Would you comment on the reduction 
in the rate of maternal HIV transmission. What percentage of 
AIDS in the United States is attributed to maternal HIV 
transmission, and what is that percentage worldwide?
    Dr. Alexander. It has decreased dramatically in the United 
States. Virtually all pediatric AIDS in the United States, once 
the blood supply was cleaned up, have been as a result of 
maternal to fetal transmission. This occurs primarily during 
pregnancy, labor, and delivery, and to a lesser extent, from 
breast feeding, until we discovered breast transmission and 
made a general recommendation that women with HIV bottle feed 
their infants. Essentially, all pediatric AIDS, which was 
1,000-2,000 cases a year, was due to maternal to fetal 
transmission. The rate of transmission was about 25 percent. 
With the protocol on AZT treatment which was reported about 5 
years ago, that rate of transmission was reduced by two-thirds, 
to about 7 percent.
    With further research on adding other antiretro viral 
agents and protease inhibitors, we are able with drug treatment 
alone to reduce the transmission rate in the United States to 2 
to 3 percent. If you add Cesarean delivery to that, it goes 
down to 1 to 2 percent. There has been an incredible reduction 
through research on reducing perinatal and pediatric AIDS in 
the United States.
    This does not apply in developing countries, and we have 
been looking for regimens that could be applied, because of 
cost and because of logistics, in developing countries. What is 
included in the opening statement is progress reported from 
NIAID and NICHD on a study in Africa that provides us for the 
first time with a cheap, logistically feasible two-dose 
regimen, one dose of nevirapine to mother during labor and one 
dose to baby after birth, for trying to reduce this 
transmission; and it cuts it in about half.
    Mr. Wicker. What I want to know is of all of the cases of 
AIDS in the United States, what percentage of it is infant?
    Dr. Alexander. Now?
    Mr. Wicker. Yes.
    Dr. Alexander. Probably 1 to 2 percent. I will give you 
that figure for the record.
    Mr. Wicker. Great. And also that figure for the entire 
planet.
    Dr. Alexander. Will do.
    Mr. Wicker. Thank you.
    [The information follows:]

            Pediatric AIDS Cases in the USA and in the World

    In the U.S., as in other countries, most children become 
infected by mother-to-child tranmission. As of June 1999, 8,461 
AIDS cases were reported in children under 13 years old, 
accounting for 1.2% of the 711,344 total reported AIDS cases. 
Additionally, 3,564 AIDS cases were reported in adolescents 13-
19 years old and an additional 25,210 in young adults aged 20-
24 years who were likely infected as adolescents, together 
accounting for an additional 4% of cases. In the developing 
world, where a greater proportion of childbearing aged women 
are infected, pediatric AIDS accounts for 15-20% of AIDS cases.
    However, AIDS survelliance does not accurately reflect the 
incidence and prevalence of HIV infection in children, as it 
represents only chidren with severe, end-stage infection. Based 
on seroprevalence data, it is estimated that more than 16,000 
HIV-infected children under 13 years old were born through 
1995, approximately 3,800 of whom had died. An estimated 6,000 
HIV-infected women give birth every year. Using optimistic 
estimates that all infected women know their HIV infection 
status and receive AZT during pregnancy (likely an 
overestimate), approximately 300 infected children have 
continued to be born each year. Thus, as of 2000, a minimum 
estimated 14,000 HIV-infected children are alive in the U.S., 
and need to receive appropriate treatment. Additionally, long-
term follow-up is needed for the large number of children who 
are uninfected but were exposed to antiretroviral drugs that 
their mothers took during pregnancy (currently this would 
include AZT in combination with other antiretovirals). HIV 
infection among adolescents also continues; it is estimated 
that 12,000 to 38,000 infected adolescents aged 13 to 19 years 
and 62,000 to 185,000 infected youth aged 20-24 years are 
currently alive in the U.S.
    On a global basis, it is estimated that 33 million people 
were living with HIV infection at the end of 1999, including 
12.2 million women and 1.2 million children. During 1999 alone, 
an estimated 600,000 children became infected with HIV. An 
estimated 1,600 infected children are born each day, with most 
of these infected children living in developing countries, 
particularly sub-Saharan Africa. An additional 11 milion 
infected individuals are youth between 15 and 24 years old, and 
half of the global 5.8 million new infections each year are in 
youth. It is estimated that 5 new infections occur in youth per 
minute on a global basis.

    Mr. Porter. Mrs. Northup do you have any further questions?
    Mrs. Northup. I have tons, but I will submit them.
    Mr. Porter. Submit tons for the record.
    Mr. Hoyer. I will submit them for the record also. I have 
some questions on bone development and infants, the impact of 
adolescent pregnancy on bone development and also the use of 
oral contraceptives by children and how that manifests itself 
in later life in osteoporosis, and I will submit those for the 
record. Thank you for your other answers.
    Mr. Porter. Ms. Pelosi has not had a chance at all.
    Ms. Pelosi. Thank you, Mr. Chairman. My conflicting 
responsibility in the intelligence committee as we prepare for 
our Colombia foray kept me from attending the hearing until 
now.
    I am sorry I could not be here for Dr. Alexander's 
presentation. I too will submit my questions for the record. As 
I have said to him he must have the best job in America to be 
thinking every day about America's children and doing such 
excellent work. I look forward to reading your testimony. Thank 
you.
    Mr. Porter. I always thought I had the best job in America. 
Thank you, Dr. Alexander. Thank you all.
    We stand briefly in recess.
    [The following questions were submitted to be answered for 
the record:]



                                        Tuesday, February 29, 2000.

            NATIONAL INSTITUTES OF GENERAL MEDICAL SCIENCES

                               WITNESSES

DR. MARVIN CASSMAN, DIRECTOR, NATIONAL INSTITUTE OF GENERAL MEDICAL 
    SCIENCES (NIGMS)
DR. NORKA RUIZ BRAVO, ACTING ASSOCIATE DIRECTOR FOR EXTRAMURAL 
    ACTIVITIES, NIGMS
MARTHA PINE, ASSOCIATE DIRECTOR FOR ADMINISTRATION AND OPERATIONS, 
    NIGMS
G. EARL HODGKINS, FINANCIAL MANAGEMENT OFFICER, NIGMS
DR. RUTH KIRSCHSTEIN, ACTING DIRECTOR, NATIONAL INSTITUTES OF HEALTH
WILLIAM A. BELDON, DIVISION DIRECTOR, OFFICE OF BUDGET, DHHS
     Mr. Porter. The subcommittee will come to order.
    We continue our hearings on the budget for the National 
Institutes of Health with the National Institute of General 
Medical Sciences. We are pleased to welcome Dr. Marvin Cassman, 
the Director.
    Dr. Cassman, it is good to see you again. You are doing a 
wonderful job there. Because we are not in session until 6:00 
p.m. tonight for votes, it is probable that this is not going 
to be a very well attended, but I am very interested in hearing 
what you have to tell us, and our staff has prepared some tough 
questions for you.

                           Opening Statement

    Dr. Cassman. I hope that I can answer them.
    Thank you, Mr. Porter, and good morning.
    Before I begin, let me introduce the other people at the 
table with me. To my far left, Dr. Norka Ruiz Bravo, the Acting 
Associate Director for Extramural Activities. Next to her is 
Mr. Earl Hodgkins, who is our budget officer. To my immediate 
left is Martha Pine, the Associate Director for Administration 
and Operations. I don't think that I have to introduce Dr. 
Kirschstein to you, but I will: Dr. Kirschstein, the Acting 
Director of NIH. To the far right is Mr. Bill Beldon from the 
department.
    It is always a pleasure to present the programs of the 
National Institute of General Medical Sciences to this 
committee, but it is with considerable regret that I do so 
today realizing that this is the last time that you will be 
presiding as chair. It has been a privilege to have the 
opportunity to testify before you, Mr. Porter, and I wish you 
well.
    Each year there are a number of outstanding new 
developments emerging from the research we support, and this 
year is no exception. But probably the most remarkable 
accomplishment is the determination of the structure of the 
ribosome.
    The ribosome is the particle in the cell where proteins are 
synthesized. It is found in much the same form in bacteria. It 
is a veritable factory where the elements of the protein chain 
are brought in, assembled, and then released into the cell. 
This has to be done through a mass production process with a 
good mechanism for checking for errors.
    Understandably, this process is complex, and so is the 
ribosome. You can see it in the picture to my left. It is a 
giant, by cellular standards. It is composed of 54 individual 
proteins, three strands of nucleic acids. Since the 
determination of a single protein is not easy, for many years 
the understanding of the ribosome was thought impossible.
    Although the structure you see looks like a wad of bubble 
gum, and I understand there is not a lot of definition there, 
there is sufficient information to begin to understand how it 
works, and we anticipate considerable improvement in 
understanding more details in the future. It is a result of a 
dogged effort over many years and contributions from many 
sectors of science.
    As you can see from this next poster--I know the details 
are not clear there, and I certainly won't go through them--
they are more evident on the illustration on your desk--the 
main point is that the contributions came from many areas of 
science, from physics, structural biology, from biochemistry 
and from genetics over a period that began in the '50s and 
continued into the '70s with accelerated progress in recent 
years. NIGMS has made contributions in all of these areas as 
outlined in yellow. Those are the areas--the discoveries--in 
which we had a direct hand.
    Since the ribosome is a primary target for antibiotics, the 
structure, even in its present form, should be helpful in 
developing an understanding of new approaches to antibiotic 
design and the mechanism of antibiotic resistance. But I will 
say that the primary accomplishment and the primary value of 
this is that it gives some insight into one of the key 
mechanisms by which cells operate and ultimately will allow us 
to understand an integrated sense of cellular function.
    Now this is the result of ongoing research that was carried 
out over many years, as is indicated, mostly through 
investigator-initiated research which is the basis of all of 
the progress--or most of it--of the research that we support. 
Now, with the resources that we have been provided, we have 
also been able to begin some new initiatives.
    The first I am going to mention is pharmacogenetics, the 
second is structural genomics, and the third is a collaborative 
program which we term the ``glue grants.'' All of these are 
characterized by large-scale collaborative interactions.
    Pharmacogenetics is the effect of inheritance on drug 
action. Over 100,000 deaths and many more poor therapeutic 
outcomes are the result of individual responses to drugs that 
are not anticipated based on the norm for the population.
    We have passed out a brochure at your desk. It is small--
right in front of you. Yes, that is it, right there.
    It is a public information effort designed to deal with the 
concerns and questions that the participants in this study and 
general public may have about the programs that we are 
planning. This brochure is the result of an advisory group that 
we have established with lay members reflecting various ethnic 
and racial groups, as well as a number of focus groups also 
targeted to a variety of segments of the population. The focus 
groups were designed to find out what people were concerned 
about and what they felt the benefits would be for such an 
effort. We intend to keep contact with public concerns through 
continued meetings with our advisory group and through any 
other approaches that may be necessary.
    Our program, which we are initiating this year, will 
systematically collect and interpret information about the 
inherited variations in humans that result in a poor response 
to drugs. This will be closely coordinated so all of the 
research teams interact, with the results placed in a shared 
and publicly available depository. We are collaborating on this 
with a number of other institutes at NIH, including the 
National Heart, Lung and Blood Institute; the National Human 
Genome Research Institute; the National Institute of 
Environmental Health Sciences; the National Institute of Mental 
Health; and the National Institute on Alcohol Abuse and 
Alcoholism.
    Now, a second major effort is an initiative to determine 
the structures of all of the proteins in nature. This is the 
structural genomics initiative. By selecting appropriate 
members of protein families for direct structural 
determination, scientists can use these to model the rest. 
Since structure is closely linked to function and to our 
ability to modulate functions through drugs and other 
approaches, a repository containing a complete set of protein 
structures is much anticipated by both academia and industry.
    We are beginning a number of pilot programs this year which 
will be integrated with other such programs in the U.S. such as 
those sponsored by DOE, and which will also be integrated with 
international efforts. There will be a meeting in Great Britain 
in April to discuss the overall goals of the structural 
genomics effort and to provide the ground rules for 
international collaboration.
    The third program I would like to mention attempts to 
provide the resources for collaboration for large groups of 
investigators. This initiative emerged from workshops we held 
about 2 years ago with many of our investigators, perhaps 200 
in all, who clearly indicated that for a number of problems the 
material and intellectual resources that were to be found in a 
single laboratory were not sufficient to carry out some of the 
more ambitious programs and concepts that we need to understand 
modern biology.
    All of the investigators in the collaborations that we 
proposed, or that our funding will permit to be established 
will already have independent support for their own projects. 
What we will provide is the glue in the form of core support, 
data bases, travel, communication, whatever else is needed to 
facilitate the interactions.
    In addition to further developing these programs, we plan 
next year to provide more support to data bases and data base 
development. These will be major tools for biologists in the 
future and will be used to develop new programs in 
computational biology and to develop initiatives in other 
emerging areas such as new approaches to drug development.
    Finally, we continue to focus on training generally and our 
attempt to bring more underrepresented minorities into 
biomedical research. We significantly expanded our minority 
programs in the last few years and developed new initiatives 
over the past 4 or 5 years, including one that I would like to 
specifically point out. This is called the Bridges to the 
Future Program. This attempts to facilitate the transition of 
underrepresented minorities from 2 year to 4 year colleges, 
that is from community college to baccalaureate granting 
institutions and from universities offering the terminal 
Masters Degree to a Ph.D. granting institution.
    This program grew out of a study carried out by the Office 
of Research on Minority Health, and we are cofunding this 
program with that office. We have tracked the students since 
the initiation of this program, and all of the evidence on 
transfer rates, retention, final attainment of degree, et 
cetera, suggests that it has been highly successful. We will be 
significantly expanding the program this year.
    In addition, we are planning a number of initiatives for 
next year, including a collaboration with the Indian Health 
Service focused on using some of the Indian Health Service 
programs to bring Native Americans into research. The National 
Institute of General Medical Sciences' proposed budget is 
$1,389,492,000.
    I will be happy to answer any questions that you may have.
    Mr. Porter. Thank you, Dr. Cassman.
    The written statement of Dr. Cassman follows:]



                         X-RAY CRYSTALLOGRAPHY

    Mr. Porter. Going back to the ribosomes--and maybe I 
shouldn't even attempt to ask this question--but what means 
have been used to get as far as you have in understanding them? 
In other words, is this a microscope that allows you to look 
farther than you could look before? How have we learned what we 
have learned?
    Dr. Cassman. It is a combination of two techniques. First 
of all, electron microscopy helped provide the overall 
organization. But the details that you see here come almost 
entirely from X-ray crystallography--in fact, from X-ray 
crystallography performed by synchrotrons, another research 
tool in which we have a significant interest and investment. 
There are four groups that were primarily involved in this 
finding. We are either now supporting or have supported all 
four of them. But it is actually X-ray crystallography which 
can do this level of detail for a particle of this size.
    Mr. Porter. Does the possibility then exist that you can go 
beyond this in determining down to the smallest----
    Dr. Cassman. Yes. We hope eventually to get to atomic 
structure, the atomic level of definition which we are not yet 
at. That will be a complicated process, but it will still 
involve X-ray crystallography. It just requires further 
refinement of the existing technique.
    Mr. Porter. Is the synchrotron involved with that or is 
that part of that?
    Dr. Cassman. Synchrotrons are part of that technique, yes. 
All of the data is collected at the synchrotrons. As I think I 
have testified before, there are five synchrotrons in this 
country. This research has been done at several of the 
locations.
    Mr. Porter. One being near Chicago?
    Dr. Cassman. Yes, the Argonne Laboratory's Advanced Photon 
Source.

               INDUSTRY SUPPORT FOR FUNDAMENTAL RESEARCH

    Mr. Porter. Because you are the Institute of General 
Medical Sciences, these may be questions for Dr. Kirschstein, 
but let me ask them to you. I think you could probably 
enlighten us on them. Is this kind of research the kind of 
research that industry might do? Or is this something that is 
so basic that they probably wouldn't want to put resources into 
it?
    Dr. Cassman. I don't think they would have wanted to put 
resources into it. This was a very chancy kind of research. For 
a long time nobody thought it could be done at all. Indeed, we 
had to rescue one of the grant applications, because the review 
groups thought it was interesting and exciting but didn't think 
it would work. I don't think industry is interested in that 
level of risk when the benefits or the outcomes are not 
immediately apparent in terms of economic gains. Although, 
ultimately, there certainly may be lots of economic benefits 
that will emerge from this, at the moment it is a basic 
research effort.

                      COLLABORATION WITH INDUSTRY

    Mr. Porter. I see this also in Congress itself, but there 
is a lot of thought that what NIH does is simply discover how 
to cure disease and that you come up with the pharmaceuticals 
that somebody else produces. Can you describe for us the 
collaboration, if any, and the mechanisms by which basic 
science is then transformed into applied science and the actual 
products that do this?
    What I really want to know--I think I understand that, but 
what I really want to know is there a greater collaboration 
with industry at certain points? Is there greater collaboration 
with foundations and patient advocacy groups that now have 
substantial money to invest in research? How much is done 
together with NIH in basic science in seeing the process 
through?
    Dr. Cassman. This is a complex interaction. I will be happy 
to give you my perspective on it.
    Currently in biology right now, more than any other 
science, the distinction between basic and applied research has 
almost been completely broken down. Consider some of the 
programs we support. We have been supporting now for over 10 
years a program on structure-based drug design against AIDS. 
This requires determining these kinds of structures, not this 
complex, but certainly structures of the AIDS HIV virus. If you 
ask one of the investigators, are they doing basic research or 
applied research, I think their answer would depend on the time 
of day you ask.
    On the one hand, it is a fundamental study of--let's say 
the specific enzymatic mechanism that the virus uses to 
replicate itself. On the other hand, it is an opportunity to 
develop a structure that can then be used for targeted drug 
design. That is clearly an applied effort. So the two intermesh 
at a lot of different levels.
    There are certainly areas that are so basic that their 
immediate application is not obvious. These take awhile to 
filter into the industrial arena, but there are many other 
areas that get translated almost immediately through patent 
rights and a variety of other processes. There are times I 
think any college with an organic chemist in the basement 
probably has a patent lawyer on retainer.
    The rate of translation is very rapid. We interact a good 
deal with industry at different levels. We support some 
industrial efforts, and we have done so in the past.
    We talk quite a bit to various foundations--Howard Hughes, 
the Keck Foundation. I recently had a series of discussions 
with the Sloan Foundation on a number of issues.
    It is a very complex and articulated process. But the 
points of contact between basic and applied research and then 
on to developmental, which is almost exclusively industrial, 
are many. They go on all the time.
    Mr. Porter. Are they increasing over what they used to be?
    Dr. Cassman. Greatly. No question about that at all. Of 
course, this has caused some problems as well because of the 
many ties that our researchers have to biotech companies, 
pharmaceutical companies, and so on. Conflict of interest 
issues come up as well.

              SHORTAGE OF INVESTIGATORS IN SPECIAL FIELDS

    Mr. Porter. Are there times when you lose a key researcher 
to an industry, a company?
    Dr. Cassman. Often. In some areas more than others. For 
example, bioinformatics, which is an effort we are going to be 
pushing this next year, there is an incredible shortage in 
academia of people in that area. They are just getting pulled 
away by industry all of the time.
    Mr. Porter. That is interesting, because the first question 
the staff prepared is, is there a shortage? Why don't you give 
us an update on the shortages that you just mentioned? This is 
something that we talked about last year. You are telling me 
that the situation is worse than it was a year ago?
    Dr. Cassman. I think it probably is worse. I haven't 
quantitated it so I don't know exactly how bad it is--just what 
I hear from colleagues in academia and even NIH itself. What is 
happening is that biology is moving from a data poor to a data 
rich environment. We are getting masses of data being generated 
by the human genome project, and by other genome projects. 
Structural genomics will generate enormous amounts of data. 
There are a variety of techniques that are just pouring out 
information.
    This data has to be assembled in some way and understood. 
You need people who can design approaches to looking at large 
aggregates of data, who can generate and create data bases and 
then query the data bases so researchers can extract the 
information they want. This was not a problem, let's say, a 
decade ago. But it is certainly an issue now. Industry in 
particular has moved over to high-throughput approaches. There 
are a variety of different kinds of high-throughput mechanisms. 
They need computational people to do the analysis, but, of 
course, so do the academicians, and there aren't enough of 
them.
    Mr. Porter. So there are opportunities there?
    Dr. Cassman. There are lots of opportunities there and a 
shortage.
    Mr. Porter. Thank you, Dr. Cassman.
    Mr. Jackson.
    Mr. Jackson. Mr. Chairman, Dr. Cassman has done a great job 
at the National Institute of General Medical Sciences; and 
probably the best way for me to honor him is to give him a pass 
today. I have no questions for the doctor, Mr. Chairman.
    Dr. Cassman. Thank you, Mr. Jackson.

                INDUSTRY INVOLVEMENT IN PHARMACOGENETICS

    Mr. Porter. You talked about pharmacogenetics and showed us 
what is being done here. My question there is, would industry 
do this?
    Dr. Cassman. They are using a variety of different 
approaches toward somewhat similar goals. But I don't believe 
they were going to do this.
    What we are trying to do is link the variants in individual 
humans and populations to the expressed disorder, the so-
called, phenotype, the description of how people respond to 
drugs well or badly and then try to link it to all of the 
mechanisms in the cell that create that disorder. This is a 
very fundamental study of drug response and drug interactions. 
It seems unlikely to me that industry would be interested in 
generating this level of fundamental biological detail. On the 
other hand, I have no doubt they will find the results of great 
interest and importance.

               TIMELINE FOR DISCOVERING GENETIC FUNCTIONS

    Mr. Porter. With the human genome project comes not only 
the ability to unravel the very basic building blocks of 
humans, but also the ability to discover what gene or genes 
triggers the onset of disease. In many diseases, a single gene 
is not responsible for a single event. For example, researchers 
studying the fruit fly discovered that cocaine sensation is 
linked to genes that control the body's biological clock. As we 
dig deep into gene functions, do you think we will ever solve 
the whole picture, that we will ever find all of the genes or 
combination of genes responsible for diseases?
    Dr. Cassman. Yes, I think ultimately we will. I don't think 
it is around the corner by any means. In fact, one of the 
things that we found in our focus groups on pharmacogenetics is 
that people in general have a very inflated idea of how rapidly 
some of these fundamental responses are going to be translated 
into practical benefits. This is both good for us and not so 
good. I think that we can raise expectations that we can't meet 
in the immediate future.
    However, there is no question in my mind that we will be 
able, perhaps not too long from now, to identify the functions 
of all of the genes in the human body. These are the 
biochemical functions, that is, their specific reactions that 
they carry out or the structures in which they are built. 
Understanding how genes interact is an entirely different 
matter and will take a great deal longer than just identifying 
each individual gene. Many diseases, as you have stated, are 
not the consequence of a single gene defect but the consequence 
of a failure, partial or complete, of the system of genes 
actually--systemic failure. We don't really understand how 
biological systems operate in space and time. That is one of 
our major efforts in the next few years. We have already begun 
these efforts to develop an approach to what we call complex 
systems analysis, understanding how interactions and 
consequences evolve.
    Mr. Porter. How long is not too long? You said we would 
understand--not too long from now--we would understand the 
basic functions.
    Dr. Cassman. I would have said 10 years. But since I am 
always off on these things at least by a factor of two that 
means probably 5 years. Things happen so much faster than one 
can expect. I do think probably 5 years is right. So that means 
2\1/2\ years. We can go on forever with this.

                       RESISTANCE TO ANTIBIOTICS

    Mr. Porter. Bacteria have an innate ability to develop 
resistance, and we are beginning to see resistance to many 
commonly prescribed antibiotics. Part of the problem with 
development of resistance is the use of antibiotics in 
livestock. Antibiotics are given to animals in low enough doses 
to promote growth, but not kill any bacteria present which in 
turn could contribute to the problem of resistance development. 
What is being done on the agricultural front to address this 
problem? I know agriculture is not your realm of research, but 
is this something that NIH is pursuing alone or along with the 
Department of Agriculture?
    Dr. Cassman. There is, of course, general concern about the 
overuse of antibiotics in both humans and in livestock. I 
really am not sure if NIH is doing anything with the Department 
of Agriculture.
    Dr. Kirschstein. I suspect that Dr. Fauci will be able to 
address that issue.

                      OPPORTUNITIES FOR MINORITIES

    Mr. Porter. All right. You talked earlier about the 
opportunities for minorities and some of the things that you 
are doing to address that. We provide the Federal funding of 
the portion of the budget for Howard University, for example; 
and I have had a lot of discussions over recent years with Dr. 
Patrick Swygert, the president of Howard, in the problem of how 
minorities--actually in recent years having fewer minorities go 
into advanced degrees. That has begun to turn around now, but 
for a long time it was going in the wrong direction. A 
significant part of that problem apparently is a lack of 
funding. In other words, people who have the ability to go on 
to advanced degrees don't have the resources to do that. Does 
NIH have anything going that addresses that kind of problem, or 
is that something that you would say is your problem, which 
is--really is ours? Do you have fellowships or grants or 
graduate student assistance?
    Dr. Cassman. We offer all of those things, fellowships, 
graduate student assistance, and even undergraduate assistance 
in junior and senior honors level programs at many institutions 
through one of our programs. The Bridges Program is another 
assistance mechanism that begins at an even more junior level 
than that, that is starting with the community colleges and 
going on up. We are doing what we can to provide assistance at 
that level. We support roughly half the applications that we 
get in those areas.
    Mr. Porter. It seems to me that--and, of course, Mr. 
Jackson has focused on this very heavily and correctly so. It 
seems to me that here is a whole field of opportunity for 
people to get involved. You are saying in so many areas we need 
people, and what people need it seems to me is the opportunity 
to get the education that qualifies them for this.
    Obviously, Mr. Jackson is not saying and no one would 
support making research grants to people who aren't qualified 
to do the research. But what we are all saying is we need to 
make certain that people have the opportunities in all ways to 
get the skills that they need to be competitive for those.
    It seems to me that this is a whole area where the 
opportunities are huge, and we have to make certain that we 
begin at the youngest age, if we can. Mr. Jackson knows all 
about this, but there is a program in the Chicago public 
schools to encourage young people to pursue a science 
education, to get them excited about science at a young age. 
Bill Curtis, a prominent Chicago newsman, has been the leader 
in this and apparently has done very well to begin that 
process.
    But if you hit a point where you have excited the interest 
but you don't have the resources to pursue it, it seems to me 
the door kind of slams in your face. What we have to do is to 
take young people and assure that they have a way of getting 
into the system and having the opportunities to get the 
training and the abilities that are needed to be competitive.
    Dr. Cassman. I entirely agree, Mr. Porter. We have one 
program in particular that addresses that at a level more 
junior than we are normally accustomed to, that is the minority 
supplement program where researchers can bring students into 
the laboratory. We give them specific supplements for that. 
That could be even high school students, college students, all 
of the way up the ladder. These supplements are available to 
all of them. It is very important to start early, however. 
There is just no question of that at all.
    Mr. Porter. Now, Mr. Jackson, have I stimulated any 
questions?
    Mr. Jackson. Mr. Chairman, you have stimulated a number of 
them, but I do believe genuinely that they are doing a great 
job at this particular institute and everything that we can do 
to encourage them and try our best to honor their budgetary 
request and increases should be supported.
    Thank you, Mr. Chairman.
    Dr. Cassman. Thank you, Mr. Jackson.

             TRACKING STUDENTS SUPPORTED ON TRAINING GRANTS

    Mr. Porter. What do you do to track students? Maybe this is 
a question for Dr. Kirschstein, but you have these programs. 
How do you track whether the students are graduating with a 
science degree, whether the goal of increasing minority 
scientists is being met? How do we judge whether we are doing 
anything that produces a result?
    Dr. Cassman. In the Bridges Program we have a mechanism for 
tracking the students from the time they enter the program. We 
have a central computerized data base, populated through the 
Internet, where the institutions deposit the information. We 
collect it; we track it. That is how we know at this point how 
well those students are doing. That program is about 6 or 7 
years old. It began in 1993, so it is 7 years old. Of course, 
we are just beginning to get enough information for useful 
analysis. That is a tracking mechanism that we began at the 
start.
    We also have done an analysis of a variety of other 
programs, the Medical Sciences Training Program, the MARC 
program. Recently completed was a very extensive analysis of 
all of the institutional training programs that NIH has, both 
pre- and post-doctoral, as I recall. It tracks the outcomes of 
these students. So we do have a reasonable amount of knowledge, 
more in some areas than others, but a degree of knowledge that 
does support what happens to people whom we support through 
these mechanisms.

                ENCOURAGEMENT TO PURSUE RESEARCH CAREERS

    Mr. Porter. One of the things that I think we have learned 
is that many young people don't have an adult that they look up 
to or that looks to them and encourages them. Is there any kind 
of program that gets the scientists together with a young 
person and kind of says, hey, you are doing wonderful things 
and keep doing it, and gives them encouragement to pursue that 
kind of career? I don't say that science should support a 
substitute for family, but in many cases you need some kind of 
substitute. The family is broken; the child doesn't have an 
adult that cares.
    Dr. Cassman. There has been a program at NIH.
    Dr. Kirschstein. I think most of those are on a voluntary 
basis rather than a formalized basis. But when an individual 
brings a high school student, for example, into his or her 
laboratory, it is usually with the idea of becoming a mentor. 
Now the mentorship is very often on a scientific basis, but I 
have seen, time and again, a development of a relationship 
between the senior mentor and the high school student that 
becomes not quite parental but that of an older friend or older 
brother. Those work extremely well.
    I wanted to add a little bit to what Dr. Cassman was saying 
because there are two other things that we do that I think are 
important. One of them is in the intramural program. We bring 
high school science teachers in for the summer to learn the new 
nuances and the new things about science that they really never 
learned when they were going to either normal school or to 
college to learn how to be teachers. This is very important 
because if the high school science teacher is not excited about 
the science that he or she is teaching or really doesn't know 
it very well, they won't be able to inspire students.
    The second thing in this whole continuum of support is the 
program that we have been talking about for some time, and it 
was mentioned to Mr. Jackson and that is the loan repayment 
program. What we find is that even if the students had a 
certain amount of resources to start, by the time they finish a 
fairly extensive educational process, either through medical 
school or graduate school, they are mostly in debt. Now, in our 
intramural program we have had a loan forgiveness or loan 
repayment program for some time. We have not had the ability 
through authorization legislation, to provide that to the 
academic institutions that we support. We are asking for that, 
and it is part of this appropriation bill this year.
    Mr. Jackson. Mr. Chairman, I don't have a question so much 
as to participate in the dialogue that is taking place.
    I have always seen research fundamentally as passion 
driven. If I have less than 600 books on the Civil War because 
it is one of my passions in my office, I would be 
underestimating what I believe is an enormous library on the 
subject matter. It is one of my passions. I am driven by it. I 
like to look at the dynamics the war created for our Nation and 
what it has done, its implications for our future.
    I happen to think--I remember watching a movie called 
``Gross Anatomy.'' There was a teacher, I believe, in the movie 
who had lupus. Part of her research was driven by trying to 
find answers and cures for lupus. One of her students who 
lacked a certain amount of motivation, she was trying to pull 
some passion out of him, and before the semester had ended she 
had expired. But clearly the passion for her research was 
driven not only with her family's history of the disease but 
her present and current circumstances.
    So I want to say that I think there is a fundamental 
difference when we encourage students--and I do encourage them, 
I think it is a wonderful program--to encourage students to 
come into libraries and--to come into laboratories, I mean, and 
to study alongside of scientists and to have some exposure to 
the idea of research.
    Oftentimes as a student, particularly a young student or a 
high school student, the passion and the drive is to get a good 
grade and to get out of science class as quickly as possible 
and go onto the next subject matter, while we appreciate the 
exposure. But the passion for a lifetime of research is really 
found, Mr. Chairman, at the level that people find themselves 
in advanced education or in graduate school pursuing the kind 
of passion necessary to dedicate one's life to or a significant 
part of one's life to this kind of passion.
    So I think that the universe of students that we are 
looking for who might be driven by a particular passion will be 
found fundamentally at that level, while at the same time we 
need to expose younger Americans to the opportunities that 
laboratories present. I think nothing, Mr. Chairman, can do 
that more systemically than the idea that Dr. Kirschstein has 
mentioned about this whole idea of loan forgiveness programs. 
If we can take that financial burden off of future researchers, 
we might unlock enormous passions for research amongst millions 
of Americans--well, let's just say thousands of Americans who 
hopefully one day may choose to enter the research field and 
address some of the fundamental disparities that I have been 
probing.
    Thank you, Mr. Chairman.

                      INTEREST IN RESEARCH CAREERS

    Mr. Porter. Well, I was going to say, Mr. Jackson, that I 
think we are talking about the same thing. At a younger age it 
seems to me you have to see that it is possible. And if you 
don't see that it is possible, then you are never going to get 
to the stage of having the passion to pursue it. So opening the 
door early and letting a young person know that, by God, they 
can do it if they set their mind to it and the doors will be 
open along the way, it seems to me that all of these help to 
get to the end where you have gotten an accomplished 
researcher.
    Mr. Jackson. Mr. Chairman, I couldn't agree more. I could 
only add that when I mentioned passion at the level of 
competent researchers that have the advanced education, 
certainly opening the doors is very important.
    For example, we talked to the National Institute of Alcohol 
Abuse and Alcoholism last week. I asked for information about 
RFPs on the study of 40 ounces of malt liquor on, let's say, 
hypothalamus or the medulla oblongata or the thalamus itself. I 
don't know what region of the brain reminds us that we are 
married, but 40 ounces of malt liquor on that region of the 
brain it is quite possible that someone can forget that they 
are married. When the National Institute of Alcohol Abuse and 
Alcoholism sat here and indicated to us that the liquor 
industry now begun selling to certain communities in our 
country 64 ounces of malt liquor--I know if there are no RFPs 
on 40 ounces, there are clearly no RFPs on 64 ounces, and the 
impact that those studies could have for a generation of people 
entering into research, particularly brain research, I imagine 
would be fascinating.
    But if malt liquor is not sold--let's say it is only bought 
or sold in the Hispanic and African American communities, the 
passion for that research will never be generated unless we in 
fact recognize that there is a disparity in terms of how 
corporate America, particularly the liquor industry, is 
targeting certain communities. That is the context, Mr. 
Chairman.
    Mr. Porter. I suspect, Mr. Jackson, that you already have 
excited the passion for this research, and the NIH is listening 
very carefully.
    Mr. Jackson. I am just having problem finding the 
researchers. Thank you, sir.

                    RAISING PUBLIC AWARENESS OF NIH

    Mr. Porter. Well, the two of us have raised a number of 
questions that actually aren't specific to your Institute, but 
when you have ``general'' in your name you are expected to know 
everything.
    Dr. Cassman. Well, I try, Mr. Chairman.
    Mr. Porter. And you actually do. So we very much appreciate 
the excellent work that you are doing there, Dr. Cassman. It is 
always inspiring to listen to the developments that are 
occurring. I think this discussion, which was off the subject 
perhaps a bit, still was a very important discussion.
    The final thing I would say, and it is to Dr. Kirschstein, 
primarily, and that is that I doubt that many Members of 
Congress, besides a few in this room, now know anything about 
all of the programs that you have to outreach to young people, 
whether it is minorities or others. I just think that there 
isn't enough information here, and if it isn't here it isn't 
out there across the country either. There are so many 
wonderful things that NIH is doing in so many ways that affect 
society that people don't know about.
    Ruth, I told Harold Varmus this when he first came on the 
job. We have to do more to let people know the good things that 
are occurring somehow. I know that we tried a pilot on Maryland 
Public Television on medical research that apparently for one 
reason or another didn't get very far. We somehow need to get 
this information into people's minds. People need to be 
uplifted and understand the progress that has been made. There 
just isn't enough out there. The science page on Monday isn't 
sufficient to reach people's consciousness nor even to reach 
the consciousness of the Members of Congress. So my final 
question is, what are we doing in this area, Dr. Cassman or Dr. 
Kirschstein, either one of you?
    Dr. Cassman. Not enough is probably the short answer. It is 
a little difficult to know how to let people know about NIH.
    One of the things that we have tried to do, for example, is 
when an institution issues a press release about some great 
discovery that has been made at Hopkins or wherever, they also 
should say that this research was supported by the National 
Institutes of Health. That is neither their main interest nor 
the interest of the media that is reporting it. Sometimes NIH 
support gets mentioned, and sometimes it doesn't. We have urged 
people to do this. I think it has improved somewhat but not 
enough.
    We do try to have other kinds of outreach activities to 
various segments of the population, usually linked to some 
specific efforts such as pharmacogenetics. But that is still 
fairly limited. I am quite sure we should do more.
    Dr. Kirschstein. I would agree that we don't do enough. 
Having been at NIH for many years I think that we are doing 
more than we used to, and we will continue to do so. That is 
why I and Dr. Varmus before me both were very excited about 
this Council of Public Representatives that we have put 
together because we now have a group of people who are 
empowered, if you will, to go out and tell the public what we 
are doing. And they are doing it very broadly. They have added 
to the ranks a group of associates of the Council of Public 
Representatives. These are people who were not chosen for one 
reason or another, and they are now having meetings and sharing 
newsletters.
    When you over the last 5 or 7 years read the newspapers, as 
we have for many years, I have seen, an enormous increase in 
the number of articles that are about biological sciences. I am 
not sure the public necessarily realizes how much of that work 
is supported by NIH. We have to do what Marvin has said. But, 
nevertheless, I think there is an awareness in the public about 
health and biology in a way that 15 or 20 years ago there was 
not.
    Mr. Porter. I don't mean to suggest that we ought to put 
$100 million into buying publicists all over America to say how 
great NIH is, not at all. But I think people need to understand 
what you do and the fact that you are involved in a lot of 
results that are achieved. Is there a particular office within 
NIH that does this?
    Dr. Kirschstein. There is not only one office but, in 
addition, an office in every one of the institutes, the Office 
of Communications and Public Liaison. These people are working 
very hard at this. We probably don't have sufficient staff to 
do all of the things that you and I would like them to do, but 
we are working very hard at it, and we will continue to try 
very hard.
    Mr. Porter. Is there any kind of effort to do what I had 
hoped we could do 6 years ago and that is popularize biomedical 
research in the same way that Carl Sagan popularized space 
exploration? I mean this. I think it is important for people to 
be inspired by it.
    Dr. Kirschstein. I think so. We will have to continue to 
work even harder.
    Mr. Porter. It may be too complex and difficult for people 
to understand, and therefore you get a very narrow listener or 
viewership but----
    Dr. Kirschstein. I think we need to work at it.
    That brings us to the point Mr. Jackson was talking about. 
What we want to do, particularly at a young age, is to make 
sure that the students don't turn off, which is what you say, 
all they want to do is get a good grade and get out of that 
science. We want to get them excited so they will go on. But we 
do need to do much more, and we will work at it.
    Mr. Porter. Dr. Cassman, thank you.
    The subcommittee will stand briefly in recess.
    [The following questions were submitted to be answered for 
the record:]



                                          Wednesday, March 1, 2000.

                      FOGARTY INTERNATIONAL CENTER

                               WITNESSES

GERALD T. KEUSCH, M.D., DIRECTOR, FIC
SHARON HRYNKOW, PH.D., ACTING ASSOCIATE DIRECTOR FOR PROGRAM 
    COORDINATION, FIC
RICHARD MILLER, EXECUTIVE OFFICER, FIC
KATHRYN CHANTRY, BUDGET OFFICER, FIC
RUTH L. KIRSCHSTEIN, M.D., ACTING DIRECTOR, NIH
DENNIS P. WILLIAMS, DEPUTY ASSISTANT SECRETARY FOR BUDGET, DHHS

                       Introduction of Witnesses

    Mr. Porter. The Subcommittee will come to order.
    We continue our hearings on the NIH budget with the Fogarty 
International Center. We are pleased to welcome Dr. Gerald T. 
Keusch, the Director. Dr. Keusch, it is good to see you again.
    We will, with your permission, give you as full an amount 
of time as we can. I recognize that we started late this 
morning. So, why don't you introduce the people who are with 
you and then proceed with your statement.
    Dr. Keusch. Thank you, Mr. Porter.
    At the table with me, on my far left, is Richard Miller, 
who is the Executive Officer of Fogarty; Ms. Kathryn Chantry, 
who is our Budget Officer; Dr. Sharon Hrynkow, who is the 
Acting Deputy Director; and, of course, those on my right, need 
no introduction.

                           Opening Statement

    At the outset, Mr. Porter, I would like to echo what Dr. 
Fauci (Director, NIAID) said at the beginning of his remarks, 
and I will personalize it. I am fortunate that Dr. Varmus 
recruited me to the NIH 16 months ago so that I have had the 
opportunity to present the Fogarty plans to this Committee 
during your chairmanship. You have truly done extraordinary 
things for biomedical science, and I wish you well in your 
future undertakings.
    I am also grateful for the increase in the funding that 
Fogarty has received during your tenure and I can assure you 
that we have used every single taxpayer dollar both wisely and 
productively.

                         LEADERSHIP ROLE OF FIC

    Last year you asked Fogarty to take a more visible 
leadership role on behalf of the NIH and for the nation in the 
international arena of biomedical research. And I would like to 
begin with that and to tell you what we have been doing.
    As I have travelled abroad this past year, I am continually 
reminded of how much the Fogarty International Center is 
recognized as a symbol of the international commitments of the 
NIH and of the United States in biomedical research. The 
Fogarty today is much changed from the Fogarty of yesterday and 
many things have happened in the past year that allow us to 
better apply our resources but to the same goal as before and 
that is science for global health and its impact on the 
American population and on the world's population.

                        RESEARCH ACCOMPLISHMENTS

    I think we have been very innovative. We have applied 
ourselves to the ethics and the health and economic development 
agendas I described to you last year. In bioethics, the Fogarty 
International Center conceived of and secured international 
support for a global forum on bioethics in research. The first 
such global meeting was held in Bethesda in November 1999, 
which included over 120 participants, over half of whom were 
from the developing world. We were joined in support of this 
critical global forum for the discussion of ethical issues by 
the WHO, the Pan American Health Organization and, more 
recently, by the British equivalent of the NIH, the Medical 
Research Council.
    Forums for the next two years are already sponsored and in 
the planning stage, one in Asia, one in Africa, and discussions 
about the continuation of these forums are ongoing.
    We are about to issue a bioethics training program 
announcement to build the ethics review capacity in resource-
poor countries, to address some of the issues that Dr. Fauci 
talked about. And this is particularly important because 
international public--and, importantly, industry-sponsored 
research is increasing, and our goal is to ensure the equity 
and the ethics in the conduct of this research.
    In the economics and health area, in November this past 
year, Fogarty organized an international meeting to examine the 
relationships between health and economic growth at the 
national, local and household levels. We were joined in this 
effort by the Economics Advisory Service at the World Health 
Organization and colleagues at the World Bank. On the basis of 
this input, we have developed a new research and training 
program that will be cosponsored by the Global Development 
Network at the World Bank, and which we expect will be issued 
within the next 6 weeks.

                          RESEARCH INITIATIVES

    We have promoted new research as well. An example is the 
program announcement for research to better understand the 
relationships between ecology, environment and emerging 
infectious diseases. We are joined in this effort by 3 NIH 
institutes and centers (ICs), including NIAID, NIEHS and NIGMS, 
and the National Science Foundation. The goal of this research 
program, which has been spearheaded by Fogarty and NSF, is to 
better understand the rules of nature within the breeding 
ground for emerging infections: The environment, including 
habitat fragmentation, species loss, alien species invasions, 
ecological relationships among pathogens, vectors, reservoir 
hosts and human populations.
    And what we hope is that moving beyond the current efforts 
to improve surveillance and rapid response in emerging 
infectious disease, we will develop predictive rules to prevent 
emergence. In other words, we aim to keep the horse in the barn 
whenever possible and not always need to react to the horse's 
escape because some are harmed in the process. The response 
from the scientific community to this program announcement has 
been enormous and laudatory for the effort.

                           GLOBAL PARTNERSHIP

    In addition, Fogarty is representing NIH in many new 
consultation roles to the World Health Organization, UNAIDS, 
other Government research agencies, the major foundations, the 
Institute of Medicine, the World Bank and many others. We have 
been asked to lead the Multilateral Initiative on Malaria, a 
global effort to coordinate and support research and research 
capacity development in malaria, particularly in Africa. We are 
serving on two working groups for the Commission on 
Macroeconomics and Health at WHO, and we are deeply involved 
now in issues related to public/private partnerships.
    As globalization proceeds and we continue to address 
disparities in health among our own and the rest of the world's 
population, the biomedical research frontier will increasingly 
become international and NIH will need to be there. Fogarty is 
the window on the world for the NIH, and I am most pleased to 
say that the spirit of cooperation and collaboration among the 
ICs at NIH, with which we have worked closely over the past 
year, has fostered this programmatic development.
    We enjoy the respect and support of our colleagues at NIH 
and, I might add, other U.S. agencies involved in health, 
including CDC and USAID.

                          GLOBAL HEALTH EQUITY

    Your Committee has demonstrated its clear understanding of 
the importance of carrying the NIH research program 
internationally. This agenda reflects our nation's enduring 
commitment to global health equity. At the same time it allows 
research on problems that either do not exist in this country 
but may impact on the health of our population or that can be 
most cost-effectively studied under conditions of high disease 
burden which exists elsewhere.
    Dr. Fauci's discussion of the Nevirapine trial, which was 
enabled by Fogarty's training programs in HIV-AIDS which 
trained the foreign scientists who participated in that 
collaborative study, could not have been done in the United 
States because maternal-to-infant transmission is so low. We 
are unable to develop new strategies in this country unless we 
work internationally, and the only way we can do that is with 
equity, with mutual priorities and with ethics.

                        GLOBAL BURDEN OF DISEASE

    In the first display (Figure 1), I am showing the global 
burden of disease for those under 4, in the pie chart on the 
right-hand side. This is another representation of some of the 
data that Dr. Fauci presented. The upper panel represents the 
burden of disease in children under 4, in which infection and 
malnutrition account for two-thirds of the deaths per year in 
children. That, astoundingly, is 40,000 deaths per day in 
Africa, Asia and Latin America. In fact, most of the deaths due 
to infectious disease are also conditioned by malnutrition. So, 
the problem of nutrition is of much greater importance than the 
3 percent that is attributed as the cause of death in this 
particular depiction.
    The child in the photo on the left (Figure 2) has bacterial 
dysentery which has precipitated severe malnutrition, which we 
call protein and energy malnutrition but also includes multiple 
micronutrient malnutrition. His body is swollen with fluids as 
a result. He has survived the acute infection, but now, because 
of this severe malnutrition, he has a high likelihood of dying 
of another infection within the next 6 months unless his 
nutrition can be restored. Nutrition is probably the largest 
cause of an acquired immunodeficiency syndrome in the world 
because of malnutrition's impact on the immune system.
    The bottom pie chart (Figure 1) looks at disease burden 
from birth to age 44. And what this reveals is that although 
infections remain a major problem throughout the world, there 
is an increasing toll of chronic, noncommunicable diseases, 
problems that are typically conditioned by poor diet, as well 
as other risk factors such as disease susceptibility genes.

                           CAPACITY BUILDING

    You know of Fogarty's efforts to train investigators in 
developing countries, those most affected by AIDS, to address 
AIDS prevention science and vaccine development. This AIDS 
program is now in its 12th year. It has trained the majority of 
researchers in the hardest-hit countries in Sub-Saharan Africa, 
in Asia, and Latin America, who now work closely with the 
United States and with other collaborators to try to halt the 
spread of this deadly epidemic.
    As I mentioned, the study on Nevirapine could not have been 
done without the support of both the Institutes on the research 
side and the Fogarty International Center on building the 
research capacity on the developing country side. Just this 
morning, Mr. Porter, and Mr. Jackson, you may have heard on NPR 
the report of another study carried out in Kenya, in which the 
impact of breast feeding on transmission of HIV was described. 
And in that study a simple change from breast feeding to 
formula feeding over a 6-month period reduced the transmission 
by 50 percent. The African investigators were trained by the 
Fogarty; the study was supported by NICHD; and it has important 
implications for strategies to deal with HIV in developing 
countries.

                                MALARIA

    May I have the next two displays (Figures 3 and 4), please. 
Malaria is another problem. Dr. Fauci talked about it. We think 
there are perhaps one billion episodes of malaria per year and 
something on the order of 2 million deaths, as Dr. Fauci said, 
mostly in children, as shown on the right panel and the right 
graph on that panel (Figure 3). But the overall impact of this 
disease burden on productivity, economic growth and stability 
is enormous. In the left-hand graph (Figure 3), productivity is 
measured by the amount of crops harvested by a family. And when 
the family has malaria in the household, the harvesting of 
crops is reduced by about 50 percent. One can imagine not only 
the household but also the national impact of that loss of 
productivity.
    On the left-hand graphics (Figure 4), you see a child with 
malaria affecting the brain, a condition we call cerebral 
malaria with high mortality and severe sequelae for those who 
survive. Fogarty is not only leading the Secretariat for the 
Multilateral Initiative on Malaria, engaging new global 
partners to work effectively in close collaboration in Africa, 
but intends to extend the activities to other malaria areas of 
the world in Asia and Latin America where tremendous morbidity 
and impact is sustained on a yearly basis. And we have just 
issued a new research training program announcement for malaria 
which will help create the human capacity for collaborations 
for the necessary drug and vaccine trials to reduce this 
threat, which is actually increasing due to drug resistance of 
the parasite, habitat and climate changes that favor mosquito 
breeding, and enhanced exposure due to migration of populations 
and U.S. citizens travelling to malaria-endemic zones. We are 
close partners with our colleagues at NIH in these efforts.

                         FOUNDATION DISCIPLINES

    To turn to the future. We have reoriented our strategies 
for capacity development to emphasize four foundation 
disciplines of modern science which is shown in the next 
display (Figure 5). This includes information technology, 
clinical research, human genetics and genomics and bioethics in 
research. Our efforts in information technology, support and 
training began two years ago. Our initiatives in bioethics are 
beginning within this fiscal year and our budget for the 
subsequent year includes our efforts in genetics and clinical 
research being developed with our colleagues at the rest of the 
institutes at the NIH, including the Clinical Center. 
Establishing these foundation disciplines in international 
collaborating institutions will allow U.S. investigators, in 
virtually any area of biomedical research interest supported by 
any of the ICs at the NIH, to work together on health problems 
of mutual priority on the basis of equity and the highest of 
ethical principles.

                     GLOBAL EFFORTS AGAINST SMOKING

    Time does not permit me a more thorough review of our plans 
which are presented in the justification for our budget, but I 
would touch on one issue which is succinctly captured in the 
next display on the left (Figure 6--young Latin American child 
smoking a cigarette). We now know how much of an impact tobacco 
has on health especially when begun early in life. 
Globalization of marketing for tobacco has initiated an 
epidemic of smoking that is predicted to be the single most 
significant factor causing disease and death in developing 
countries in the next two decades. The toll is unimaginable.
    Fogarty has taken leadership at NIH to organize a working 
group composed of 8 ICs, coordinated with the global 
surveillance efforts at CDC, and a major effort at WHO to 
address the legal issues in tobacco. It is our intent and we 
are working towards the development of a coordinated research 
and training program for fiscal year 2001. There are so many 
other things I would like to tell you about but time does not 
permit.
    Thank you very much for the opportunity to address you.
    [The written statement of Dr. Keusch and figures 1 through 
6 follow:]



                            THE ROLE OF FIC

    Mr. Porter. Dr. Keusch, I think you really are changing the 
way Fogarty has operated in reaching out across the world and 
it is very impressive to hear you describe all the new 
initiatives that you are engaged in. It is a little difficult 
to understand the differing roles that Fogarty plays, that CDC 
plays, that the Secretary plays in terms of how we interact and 
interface with health officials in other countries. Can you 
give us a greater insight on this? Does Secretary Shalala do a 
lot of contact or are you the ``Secretary of State'' for the 
Department? CDC, of course, does public health and you work 
closely with them in many instances, but where do you work 
without them? In other words, is all your work without them 
strictly on research or are you doing some things that have 
broader implications where they are not involved?
    Dr. Keusch. I certainly will not speak for the Secretary. I 
have learned in my two testimonies to stick to what I know.
    Mr. Porter. You can speak about the Secretary. [Laughter.]
    Dr. Keusch. The tactic we have taken, Mr. Porter, is that 
the research capacities of the NIH can be focused in the 
context of global health priorities. And these priorities are 
important as Tony Fauci said, not only because it allows us to 
express our humanitarian instincts and our responsibilities as 
a wealthy nation but also to carry out a research agenda that 
impacts on our own population. And not the least because many 
of our minority populations have not so recently emigrated from 
parts of the world where disease burden is high and they share 
the genetic susceptibility and the background of their 
experiences in their nation's of birth. We can better address 
their health issues through international collaborative 
research.
    We have increasingly been trying to identify the areas in 
which NIH can exert the kind of leadership that you had talked 
about last year. And that means working with Ministers of 
Health. NIH is visited by many of the ministers of health from 
the developed and developing countries, and by the directors of 
medical research councils. And in Dr. Varmus's tenure, which 
has certainly continued into Dr. Kirschstein's tenure, Fogarty 
is involved with the NIH director and the institutes in meeting 
with those Ministers.
    But we also realize that if the goal is to apply research 
to changing health for all of the reasons that Tony Fauci has 
already mentioned this morning, that the Ministry of Health is 
probably the poorest part of the Government in a developing 
country to address the needs. And that is why we have taken on 
the issue of economics and health as such an important 
component of what we do. And in this area, Fogarty is clearly 
taking a leadership role at the NIH, which our colleagues at 
the other institutes have applauded and have joined in support.
    And, so, we are actually planning to work with the Bank, 
the World Bank that is, in being able to get to the Finance 
Ministers who do control the budget for disbursements and 
development within the countries, as well as with the Bank and 
its loan policies, to further the research and the public 
health agenda.
    Now, how do we differ in our approach from that of CDC? 
Well, NIH is a research institution. We generate new knowledge 
that can be applied in the public health arena. And we do not 
intend to duplicate what the CDC does, but I think in areas of 
basic research, of translational research, which includes 
epidemiology and extends into public health, NIH is right there 
and increasingly a part of our activities internationally.

                 ACCESS TO TREATMENTS AND INTERVENTIONS

    Mr. Porter. I know you were here when we were talking to 
Dr. Fauci, so, I want to go back to something that Dr. Fauci 
said and try to understand it a little better. I think it bears 
also perhaps on what you told us a moment ago about 
understanding that if you can go from breastfeeding to formula 
you can head off some of the effects of HIV.
    Why would the Minister of Health in Uganda, in effect, put 
barriers in the way of bringing Nevirapine's use into their 
country, even if someone else is going to pay for it? In other 
words, why do you think there is that resistance to doing it? 
Secondly, is there not--I may be asking three or four questions 
together here--but are there not cultural problems for example, 
when you say, oh, we know the answer, all we have to do is go 
away from breastfeeding to formula? People in those societies 
have been breastfeeding forever and they may not know formula. 
I may be making an assumption here, but how do you change those 
kinds of habits? You know how to get the result, but how do you 
get from where you are, culturally, to where you want to go?
    Finally, we are talking about human genetics and genomics. 
The body of science in our society and societies like ours is 
increasing exponentially in an understanding of these matters. 
And then we are thinking, we are going to apply these in 
countries that do not have a program to vaccinate against some 
basic diseases that we vaccinated against 60 or 70 years ago. 
How do we leap from one place to another to get the kinds of 
results for people that we are seeking even with all of this 
knowledge that we are gaining?
    That is sort of where you are. That is your job. I mean 
really that, you know, sort of states the difficulty of it, I 
think.
    Dr. Keusch. And I, personally, and I think the rest of my 
colleagues at the NIH welcome the opportunity to try to address 
those sorts of issues. With respect to the barriers for 
Nevirapine, in fact, I think the barriers are lower than the 
attempt at therapy of already infected individuals. The target 
can be identified at the time of birth. This particular regimen 
is at least within the reach of international organizations to 
help support it, and it is one-two-hundredth of the cost of 
prior regimens.
    Some of the barriers to the initiation of it remain. The 
fact that many of the developing countries still do not talk 
frankly about their HIV problem. And I can understand----

                         CULTURAL IMPLICATIONS

    Mr. Porter. But Uganda is not one of them.
    Dr. Keusch. And Uganda has----
    Mr. Porter. They have an active program of prevention where 
they have hit it head-on, as I understand it.
    Dr. Keusch. Uganda has made significant strides forward, in 
fact, in attempting to control the progression of the epidemic. 
But we have to recall that even $4 is a significant part of the 
total health budget within a country. So, without external 
resources, which are now in the process of being mobilized, 
truly for the first time, to address this effectively, it would 
not be possible for the countries, themselves, to take that on.
    There are ethical issues of whether or not you impact on 
mother-to-infant transmission and do not treat the already 
infected individuals. And, so, there are a whole set of issues 
that need to be addressed and it requires systematic and 
continual collaboration and support.
    And it relates to the second question you asked about 
cultural issues and how we address those. Well, the first way 
that we address them, Mr. Chairman, I think is to understand 
them and not to project a cultural imperialism from our own 
nation. And I think that we are learning how to be much more 
sensitive to that.
    Behavioral change is very difficult, if we look at 
ourselves as individuals and our nation, and particularly 
behavioral change with respect to sexual practices is extremely 
difficult, extremely difficult to talk about because of 
stigmatization in many of the developing countries. And, so, we 
have initiated close collaborations with colleagues at NIMH to 
begin to develop the resources towards better understanding of 
issues in changing behavior.
    This picture (Figure 6) of a young Latin American child 
smoking is another example of where we are looking to 
understand cultural issues. I use this as an example of risk 
behavior. And particularly with young children and adolescents, 
the understanding of their risk behavior, the consequences of 
that is poor in our country and poorer still in the rest of the 
world. We need to understand it better in totality so we can 
have better impact on our nation's youth and their risk-taking 
behaviors.
    And, finally, your question about genetics. I do agree with 
you that we could do a significant amount to reduce morbidity, 
mortality through the implementation of strategies already 
developed. The use of hepatitis B vaccine, of hemophilus 
influenza B conjugate vaccine, for example. Mr. Gates and his 
foundation have really jump-started the international efforts 
now to bring these vaccines to actual use.
    But our interest in genetics is because we are also 
interested in the progression of science. We do not intend to 
support genomics or sequencing in the developing world. But you 
might be surprised to know that 99 percent of the clinical 
geneticists in the world are in a handful of developed 
countries. It is not a science in the developing world. We need 
to have that capacity because I submit that in terms of public 
health, understanding the genetic basis of health and disease 
susceptibility will permit us to apply other kinds of public 
health strategies that will affect the regulation of those 
genes. It may be diet, it may be environment, but if we could 
understand the factors that influence gene expression, it would 
have an enormous impact on public health in the developing 
world, I guarantee you this knowledge would also affect how we 
address our public health priorities in this country.

                      GLOBAL DISPARITIES IN HEALTH

    Mr. Porter. Just one further comment. If you sit here and 
think about it, it seems to me that we can look 30 years down 
the line and we can see that we have done a great deal to 
conquer disease and have the infrastructure to apply it to 
every American and our life expectancy has gone up 
substantially and, yet, the rest of the world or at least those 
most in poverty are left so far behind and are dying of AIDS as 
they are right now in huge numbers that the spread of not only 
the economics of the world but the spread out of the health 
opportunities or lack of opportunities of the world could be 
huge.
    It seems to me that that is in the interest of no one and 
that is why Fogarty has got to go up, in terms of its reach and 
impact because we simply cannot, as a wealthy nation enjoying 
all these benefits for ourselves, say, goodbye to the rest of 
the world and not care about their problems.
    That is why it is so encouraging to hear the Vice President 
talk about our doing something which we should have done 15 or 
20 years ago about AIDS in Africa and other health problems 
that, obviously, are just as severe. In fact, as Dr. Fauci said 
people are dying of a lot of other diseases that we have not 
done enough about for a long time now.
    That is just a statement.
    Dr. Keusch. Fogarty, in my view, is clearly poised to 
address those issues that you describe. To the extent of our 
resources, we can move forward. The more resources, the more we 
can do. I am sure you hear that from everybody and every 
direction. [Laughter.]
    Mr. Porter. Mr. Jackson.
    Mr. Jackson. Thank you, Mr. Chairman.
    Sir, how do you pronounce your name?
    Dr. Keusch. As if there were an ``R'', Mr. Jackson.
    Mr. Jackson. ``Dr. Keursch?''
    Dr. Keusch. Yes, that pronunciation is correct.

                         FIC MISSION AND BUDGET

    Mr. Jackson. I guess you guys touched upon--let me first 
associate myself with the Chairman's remarks and with his last 
statements. My question does concern the budget. The 
President's fiscal year 2001 budget for Fogarty is $32,532,000, 
an increase of $3,620,000 and 12.5 percent above your fiscal 
year 2000 level. My question in light of what I understand the 
three objectives of Fogarty are is objective number one, to 
accelerate the pace of discovery and its application by special 
projects enabling scientists worldwide to share conceptual 
insights, analytic methods, data sets, patient cohorts, and 
special environments; objective number two being to engage and 
assist young as well as more established U.S. investigators to 
address scientific challenges related to global health; and 
objective three being to help to develop a cadre of highly 
capable, young foreign investigators positioned to cooperate 
with U.S. scientists in areas of the world that, due to 
geography, genetics and disease burdens provide unique 
opportunities to understand disease pathogenesis, anticipate 
disease trends and develop interventions, that a budget of 
$32,500,000 does not even approximate the scope of your 
objectives.
    What does, from your perspective after having served there 
for 16 months, what does a very effective Fogarty budget look 
like?
    Dr. Keusch. Thank you for the opportunity, Mr. Jackson. 
First of all, let me say that you are absolutely right in the 
context of the objectives and the budget for the Fogarty they 
do not exactly match. And as I said, we are limited only by 
resources in carrying out this agenda. However, if you look at 
the NIH expenditures in international research, which represent 
approximately one-and-a-half to 2 percent of the total NIH 
appropriation, consistently, over the last 20 or 25 years, that 
amounts to approximately $220,000,000, in the last year (1998) 
for which we have data, and approximately half of that was 
expended on the training programs at the NIH, the visiting 
scientists programs. Which means that the support expended in 
research and training activities abroad is somewhere in the 
order of $100,000,000.
    When you look at it in that sense, Mr. Jackson, Fogarty's 
contribution is significant in the context of the whole of the 
NIH. Dr. Varmus and Dr. Kirschstein have been extremely 
supportive in understanding where NIH needs to go in 
international research and it is for that reason that my second 
job--and this is an indication of cost effectiveness in 
Government, one salary-two jobs--I am in the director's office 
as the Associate Director for International Research. And in 
that context my job is to encourage and enhance the 
international research activities from the other institutes. 
And I think you will see in the present year and even more in 
the coming year that the resources devoted to international 
research are going to be increasing.
    But what we can do with relatively small budgets is to 
effectively leverage and, so, in the example of the Nevirapine 
trial, Fogarty's investments in the AIDS training program 
created a cadre of scientists who were there to collaborate 
with investigators supported by NIAID and the study that 
appears in this week's ``JAMA'' supported by NICHD, Fogarty 
investments in the local investigators in Kenya allowed that 
collaboration to happen. The larger institutes with the larger 
budgets have contributed proportionally. And that kind of 
collaboration is exciting.
    In the Ecology of Infectious Diseases initiative that we 
have undertaken, Fogarty is investing $750,000, but we have 
brought in other institutes in collaboration with the NSF and, 
so, that the first year budget is well over $4,000,000.
    If we could leverage every dollar in our budget in that 
manner with our colleagues, the impact, I think, you will 
agree, will be far beyond our resources and we continue to do 
that in every area in which we are becoming involved.

                       RESEARCH CAPACITY BUILDING

    Mr. Jackson. Thank you, Dr. Keusch. It just strikes me that 
considering the nature of the global epidemic, if I am using 
the word correctly, that your efforts for increasing the amount 
of researchers on these trials in various parts of the world, 
particularly in the underdeveloped world and particularly in 
geographies that are extremely difficult to reach, that, Mr. 
Chairman, we should do whatever we can, at least from my 
perspective, to support their budget and if we can, improve 
upon it.
    Thank you very much, Dr. Keusch.
    Thank you, Mr. Chairman.

              INFECTIOUS DISEASES IN DEVELOPING COUNTRIES

    Mr. Porter. Thank you, Mr. Jackson.
    We will have time for a second round.
    We talked with Dr. Fauci about influenza, malaria, HIV-
AIDS, and tuberculosis. The problems of developing countries 
are mainly in infectious diseases, certainly more so than in 
developed countries; is that correct?
    Dr. Keusch. Yes.

                          ANTI-MALARIAL DRUGS

    Mr. Porter. I do not know the answer to this and I am 
curious about it. We have drugs to treat tuberculosis although 
there are problems with resistance to those drugs. We have 
vaccines for influenza and generally know what to do. What 
about malaria? Malaria is not just a public health problem, it 
is also a problem in that you cannot necessarily prevent the 
death of that young boy who has it go to his brain. What 
research do we do with respect to malaria in terms of having 
drugs to treat it? Am I correct in what I am saying, if 
somebody contracts malaria we do not necessarily have the 
ability to save that person, even if we spent all the money we 
had?
    Dr. Keusch. It is certainly true, Mr. Porter, if you are 
looking at the developing country populations in the endemic 
areas, where drug resistance to the cheap, safe, effective 
anti-malarial drugs has increased in prevalence so dramatically 
over the last several years.

                         DRUG-RESISTANT MALARIA

    Mr. Porter. So, we do have drugs but there are resistance 
to the drugs developed because of the prevalence?
    Dr. Keusch. Resistance develops rapidly and that is part of 
the problem. And the newer drugs are more costly and we do not 
have very many of them. I think the largest impact has been in 
the development of the Chinese herbal medication that has led 
to a series of compounds that are extremely effective. This is 
called artemisenin, and derivatives of artemisenin have been 
added to regimens now in combination to more effectively treat 
drug-resistant malaria and to prevent the emergence of 
resistance.
    We think there are more artemisenins out there to be 
discovered. In fact--I know that you are interested in issues 
of environment and biodiversity--one of the products of the 
biodiversity programs that Fogarty and NSF have been so active 
in has been the identification of three new malaria, effective 
compounds which originate from folk medicine traditions in 
various parts of the world. That is one kind of research that 
we can engage in.
    The other was intimated by Dr. Fauci and that is to do the 
basic science, the sequencing, and the immunology; to 
understand new targets and focus on the development of new 
drugs and potentially vaccines for those new targets. That 
requires a global collaboration and that is now beginning to 
happen, in fact.
    So, I think if we were not engaging in these forward-
thinking strategies to address a problem like malaria, I think 
the situation would be, in fact, dismal.
    Mr. Porter. Now, DDT the other part of that, of course, is 
the prevention part. There is now, I understand, a movement 
globally to ban DDT. We have banned it here, but there is a 
great deal of controversy about this because if you ban DDT, 
what do you do to prevent the malaria mosquito from surviving 
and infecting more people? What is the United States' position 
on that issue and what role does Fogarty play in addressing it?
    Dr. Keusch. I think the position is evolving. The role 
Fogarty has played in it is that I was on the delegation to the 
World Health Assembly in which malaria, DDT, came up as issues. 
And our position which, to our gratification, has been accepted 
by two of the leading advocacy groups, World Wildlife 
Federation and Physicians for Social Responsibility, is that, 
in fact, a targeted date ban on DDT is counterproductive to 
human health. The concern has been over the problems with DDT 
toxicity in the area of unrestricted agricultural use. There is 
very little evidence to suggest that the use of DDT targeted to 
mosquitos and malaria prevention would have that environmental 
impact. And World Wildlife and Physicians for Social 
Responsibility now agree with that position.
    What we need to do is continue to encourage in a positive 
way rather than a negative way the development of new 
strategies, new insecticides that, in fact, are safer, more 
targeted. In the area of DDT, the problems are how do you 
control the distribution of DDT within a country? How do you 
ensure that it, in fact, goes for the purpose for which it is 
intended in a safe manner? That extends again beyond the 
purview of the NIH but I can tell you that we, the NIH and the 
Fogarty, in particular, are taking the leadership role in this 
in trying to ensure that effective tools remain while we 
encourage the development of newer tools.

                        FIC BIODIVERSITY PROGRAM

    Mr. Porter. Just a quick final question. I have not learned 
the technique of asking all my questions upfront. [Laughter.]
    Can I take it from what you said about the biodiversity 
program that it is now in its third running cycle and that you 
are very pleased it is producing the kind of results you had 
hoped?
    Dr. Keusch. I am absolutely excited by the number of lead 
compounds, discoveries, several patents moving forward and 
being done in an extremely responsible and responsive manner. I 
think that we should not expect more than such a program can 
deliver. Now, the pharmaceutical industry has spent the last 40 
years trying to mine natural compounds for antibiotics. And 
there are no new classes of antibiotics, only modifications of 
previous antibiotics in the last two decades. And, some of the 
companies that have been involved in the bio-prospecting, not 
necessarily with the same ethical construct as the program that 
NIH and NSF are leading, have gone out of business in bio-
prospecting because the investors out there do not have the 
time frame to wait for a return on their investment.
    So, I think it is absolutely encouraging. I am surprised 
that we have as many leads as we do now. We need to be in this 
for the long haul and not forget that these investments 
ultimately will be useful. But it is not going to be a quick 
fix.
    Mr. Porter. Thank you very much.
    Mr. Jackson.
    Mr. Jackson. Mr. Chairman, I have no further questions.
    Thank you, Dr. Keusch.

                          NEW DIRECTION OF FIC

    Mr. Porter. Dr. Keusch, let me say how encouraged I am 
listening to you about the new reach and great understanding of 
the role that Fogarty can play for health worldwide and on 
behalf of our country. It seems to me, as I said before, that 
you are really on the lead edge of so much that has to be done 
to ensure that we do not become further spread in terms of 
lifespan and good health from our societies to others, that I 
think it is terribly, terribly important.
    We are glad you are there. Thank you for the fine job that 
you are doing.
    Dr. Keusch. Thank you very much, sir.
    Mr. Porter. The Committee will stand in recess until 2 p.m.
    [The following questions were submitted to be answered for 
the record:]



                                       Thursday, February 17, 2000.

                    NATIONAL INSTITUTE ON DRUG ABUSE

                               WITNESSES

ALAN I. LESHNER, DIRECTOR
DONNA JONES, BUDGET OFFICER
RUTH L. KIRSCHSTEIN, ACTING DIRECTOR, NATIONAL INSTITUTES OF HEALTH
DENNIS P. WILLIAMS, DEPUTY ASSISTANT SECRETARY FOR BUDGET, DHHS
    Mr. Porter. The subcommittee will come to order. We 
continue our hearings on the appropriations for the National 
Institutes of Health with the National Institute on Drug Abuse. 
We are pleased to welcome Dr. Alan Leshner, the Director.
    Dr. Leshner, you always give us fascinating updates on what 
is occurring regarding drug use and abuse. We look forward to 
your presentation.

                       Introduction of Witnesses

    Dr. Leshner. Thank you. I do very much appreciate the 
greeting. Let me introduce Donna Jones, who is my Budget 
Officer. You know Dr. Kirschstein, you know Mr. Williams.

                           Opening Statement

    I am really pleased to report that NIDA-supported research 
continues to make extraordinary progress in clarifying the 
nature of drug abuse and addiction and what to do about them. I 
am especially pleased that we have made great progress toward 
meeting many of the challenges that members of this 
subcommittee put forward to us last year. Much of that success, 
of course, is a direct result of the substantial budget 
increases we have experienced over the past few years. Let me 
say here, Mr. Chairman, how very much we have enjoyed and 
benefitted from your leadership. I am saddened that this is the 
last year we will have you working with us in this role. I hope 
we will continue to work together.
    Last year, we promised to build a National Drug Abuse 
Treatment Clinical Trials Network to more rapidly and 
systematically bring new science-based addiction treatments 
into real life treatment settings. Well, since September, we 
have awarded the first six nodes and brought over thirty-five 
community treatment providers into this national treatment 
research infrastructure. We also plan to add at least five more 
nodes with another thirty-five providers this fiscal year. We 
will begin implementing the first three treatment research 
protocols within the next two months. So we have made 
tremendous progress in a short period of time.
    This Network will be particularly useful as we continue our 
work to eliminate the health disparities caused by drug abuse 
in different populations in the United States. For example, we 
know that members of some minority groups are 
disproportionately affected by the consequences of drug abuse. 
Given the diverse patient populations that we will reach 
through the Clinical Trials Network, we will be able to both 
enhance understanding of drug abuse as it affects these 
populations and use the Network as a vehicle to expand research 
into these communities.
    We are also making significant progress through our new 
vulnerability to addiction initiative in clarifying what makes 
some individuals more susceptible to addiction than others. As 
one example, this first poster, over to your right, illustrates 
how an individual's brain chemistry, before that individual has 
any drug exposure, how that chemistry may actually help 
determine their responses to drugs and therefore contribute to 
the likelihood that they will develop drug problems.
    This study shows that individuals who have lower pre-drug 
resting dopamine D2 receptor levels, like the one on the top 
that has less of a red color--red shows more D-2 receptors. The 
dull colors are fewer receptors. Those individuals who have 
lower pre-drug resting dopamine receptor levels, like the one 
on the top, find the mild stimulant methylphenidate quite 
pleasant. On the other hand, individuals who have higher 
resting dopamine receptor levels, that is the one on the bottom 
that has more intense red, report an unpleasant response to the 
stimulant. Those who find drugs less pleasant are less likely 
to continue to use them.
    So what you see here is actually a way that we might be 
able to predict who would find drugs more or less pleasant. We 
now understand more about the mechanisms that determine 
people's responses to drugs and, therefore, the probability of 
developing problems. That understanding, of course, is critical 
to developing the most effective prevention and treatment 
approaches.
    This past year we also gained great insight into how 
prolonged drug use can modify an individual's behavior in such 
long-lasting ways. Last year I showed that long-term use of 
drugs such as Ecstasy and methamphetamine lead to residual 
brain changes that can last up to three years after the 
individual stopped using the drug.
    Well, our researchers have now taken those discoveries the 
next step and have shown how these long-lasting brain changes 
can compromise cognitive and behavioral abilities. The 
researchers have found that the impaired memory that you see in 
former methamphetamine users is directly associated with the 
drug-induced long-lasting depletion of dopamine transporters 
that I showed you last year. So we are seeing now the next 
step, the mechanism being expressed in a change in behavior.
    As we gain an even greater understanding of the entire 
addiction process, many individuals and groups are using this 
science base to help frame how our Nation approaches the 
complex drug problem. One example is that NIDA-supported 
research is fueling a blending that is occurring between public 
health and public safety approaches to drug problems in States 
and communities throughout the United States.
    Our research has shown clearly that treating drug users 
while they are under criminal justice control dramatically 
reduces both their later drug use and their later recidivism to 
criminality by 50 to 70 percent. These findings then are the 
basis of the trend now gaining momentum throughout the country 
to make drug treatment much more commonplace in the criminal 
justice environment.
    As a second example, you may recall that last year members 
of this committee encouraged us to find better ways to take our 
state-of-the-art neurobiology to the public. In fact, Mr. 
Chairman, you suggested that we find ways to show young people 
what drugs can do to their brains. Well, we have just about met 
your challenge.
    What you see in this next poster over here is a portion of 
an almost complete story board for a public education campaign 
that we are mounting to inform the public about the potential 
long-term effects that drug use can have on the brain. Like 
you, we believe that scientific evidence is our best prevention 
message.
    We are also continuing to develop summaries of the results 
of NIDA-supported research for use by both practitioners and 
the lay public. In October, we published the first ever 
science-based guide to drug addiction treatment, which you have 
in front of you, called ``Principles of Drug Addiction 
Treatment: A Research-Based Guide.'' Since then, more than 
150,000 print copies have been disseminated. And I checked this 
morning, 50,000 copies have been accessed on our popular 
website.
    One final example of how we are disseminating research 
information is our recently bunched multimedia initiative on 
``club drugs,'' such as methamphetamine, ecstasy, and GHB. This 
initiative is a concerted effort to get in the path of an 
emerging epidemic. We have launched a special website called 
``clubdrugs.org'' that has been accessed by over 90,000 people 
in the past two months. We issued a community alert bulletin on 
club drugs to over 100,000 communities around the country, and 
we distributed 300,000 of these art cards in places where young 
people congregate. You will notice, this shows you your brain 
before and after using ecstasy.
    To conclude my formal statement, let me say that we believe 
that NIDA's comprehensive research portfolio, our efforts to 
share research findings, and a continued commitment from the 
Administration and the Congress to furthering the science will 
serve as this Nation's best defense against drugs of abuse and 
their consequences for all of society. I would of course be 
happy to answer any questions.
    [The written statement of Dr. Leshner follows:]



                                DRUG USE

    Mr. Porter. Thank you, Dr. Leshner. While I realize it may 
be too early, can you give us an overview of drug use 
particularly among young people in America today as opposed to 
four or five years ago.
    Dr. Leshner. We have gone through some very interesting 
cycles. In the late 1980s, of course, we had a peak in drug 
use, then it fell off, began to rise again in the early 1990s, 
and over the course of the last two or three years it has 
actually begun to move in a downward direction. As a scientist, 
I'm afraid to say it is moving in a downward direction, until I 
have one more datapoint. But the truth is, it has at least 
levelled off and we believe it is beginning to go down.
    That is important in many ways. First of all, we are 
pleased that, although the levels aren't as low as we would 
like them to be, they are not going up anymore. But what is 
also happening simultaneously is that attitudes about drug use 
are changing. That is, young people are beginning to show an 
increase in the perception of the harmfulness of drugs and an 
increase in their disapproval of drugs. So although use rates 
have not gone precipitously down, they are, in fact, stable and 
beginning to go down, and they seem to be tied to what usually 
drives changes in drug use, which are attitudes.
    Mr. Porter. Do you have a way of evaluating the efficacy of 
this or that; in other words, can you evaluate whether it 
actually is changing behavior?
    Dr. Leshner. We have a number of research grants that are 
looking at the efficacy of various media campaign approaches 
and different approaches to changing behavior. We use those, of 
course, to help drive any kind of educational campaign that we 
use. We have focus tested--that is about as well as we have 
been able to do so far--we have focus tested all of this 
material. Our testing indicates that our efforts have dramatic 
effects on gaining people's attention. We do not have to use 
inexact metaphors like eggs frying on the sidewalk to show 
young people their brain on drugs. But we do not know, of 
course, the ultimate efficacy.
    We are in the process of evaluating all of our science 
education activities to try to get a more concrete handle on 
what is actually having an effect. We certainly have gotten 
people's attention. Last year, we sent out our ``Mind Over 
Matter'' series to every middle school in the country. It 
features the young star Sarah Bellum and she takes young people 
through what drugs do in their bodies. We have given out over 
1.5 million copies and are continuing to get incredibly large 
requests. We know that at least these things are popular. 
Whether they are actually changing behavior, I think we will 
have a better idea within the next couple of years.

                          COLOMBIA INITIATIVE

    Mr. Porter. The President has proposed a major initiative 
in Colombia. If we take out the political aspects of that, 
which we needn't discuss here today, and talk about the roughly 
$1,000,000,000 the President proposes to spend there, wouldn't 
there be a better use for that $1,000,000,000 in terms of 
treatment or even research than it is to try to change what is 
being produced in one country where it can be produced in many 
other countries as well?
    Dr. Leshner. I am not really an expert on interdiction and 
I am not an expert on those approaches.
    Mr. Porter. Nor am I. But I am interested in your opinions.
    Dr. Leshner. I can only speak from the health perspective 
to say that we do have a treatment gap in this country. My 
Institute certainly could do with more funding. We have many 
things that we would like to be doing.
    I do believe that we need to have an approach that balances 
all of the different aspects. Unless we have a strategy for 
dealing with drug abuse that is as complex as the problem 
itself, I don't think we will ever get a handle on it.
    Mr. Porter. Mr. Hoyer, I apologize. I was told that you had 
another meeting and I meant to call on you first. So, please.
    Mr. Hoyer. Doctor, I want to ask you some questions about 
alcohol. Before I do that----
    Dr. Leshner. I do not do alcohol.
    Mr. Hoyer. Pardon?
    Dr. Leshner. I am the drug guy. [Laughter.]

                        COORDINATION WITH ONDCP

    Mr. Hoyer. Okay. Excuse me. You are right. Let me ask you 
about the coordination of your office with the Office of 
National Drug Control Policy, General McCaffrey's office.
    Dr. Leshner. We, of course, are part of the Department of 
Health and Human Service where we do have rather close 
relationships with ONDCP. My own view is we are their science 
advisors. General McCaffrey appears to value science 
tremendously; he has been very supportive of what we do and he 
asks for our advice all the time. So we have a very close 
relationship. In addition to that, they have been very helpful 
in helping us further the science by helping us establish 
facilities around the country for brain imaging and other kinds 
of activities.
    Mr. Hoyer. And is there a regular systemic coordination? Do 
you meet regularly? I don't mean you personally necessarily, 
but your staff?
    Dr. Leshner. Yes, sir. We have numerous committees that 
meet regularly. There are a number of coordinating committees 
that do work on the ``demand side,'' and there are a variety: 
on data, on media activities, on communication. In addition to 
that, I think it is well known that General McCaffrey and I 
meet regularly and talk about what the latest science is and 
what can be done with it.
    Mr. Hoyer. And from your perspective, how well is the 
coordinated effort that was envisioned by the Act that we 
adopted creating the Office of National Drug Control Policy 
working?
    Dr. Leshner. I have not been working in drug abuse all that 
long. My own view is that the Office of National Drug Control 
Policy appears to be about the best it has ever been. My 
experience is that they have been providing strong leadership 
and strong coordination. But I really do not know enough about 
the history to be able to give you a fuller answer than that.

                          SHARING INFORMATION

    Mr. Hoyer. Okay. The reason I asked those questions is 
because I am on the Treasury and Postal Committee that oversees 
the ONDCP and that effort is a critical one. The Chairman asked 
the question about how effective is interdiction or trying to 
eliminate the production in Columbia as opposed to some other 
uses. Obviously, I think the Chairman would agree there are 
multiple things that we need to do. But in any event, I 
personally think General McCaffrey is doing an excellent job.
    Let me go on to your field as opposed to alcohol. Last 
year, with the establishment of the National Drug Abuse 
Treatment Centers, you discussed that in your testimony, I 
understand the Clinical Trials Network will develop 
partnerships that you talked about. Can you elaborate on how 
you are going to share this information that are generated from 
the partnerships and through the Internet, publications, 
seminars? How are we going to get that information out?
    Dr. Leshner. The Network is set up into nodes. Each node 
has a regional research and training center at its core tied 
to, right now, between five and ten treatment programs, 
ultimately ten to fifteen treatment programs. Every one of them 
has to have an information dissemination component to it. We 
are also tied with the CSAT's addiction technology transfer 
centers so that the results will get disseminated. Of course, 
when the Network is finally completed, it will have 400 or more 
treatment programs as a part of it, and that by itself will be 
a tremendous national resource for information dissemination.
    Mr. Hoyer. Will that information be accessible on the 
Internet?
    Dr. Leshner. Absolutely. The public can actually access 
information on our Clinical Trials Network now. We don't have 
much to say, yet but we have it available.

                            HEROIN ADDICTION

    Mr. Hoyer. Right. Now let me ask you about heroin 
addiction. I understand there is some new research that NIDA 
has developed as an alternative to methadone treatment for 
heroin addiction. Can you tell me a little bit about the new 
anti-addiction medication.
    Dr. Leshner. Absolutely. We are expecting within the next 
couple of months approval from the Food and Drug Administration 
of Buprenorphene and Buprenorphene combined with naloxone. What 
is particularly important about this medication, which was 
developed through a CRADA between NIDA and Reckitt & Colman, a 
pharmaceutical company, this medication is likely to be the 
first medication, hopefully all things will fall together, to 
actually be delivered in physicians' offices.
    The addition of naloxone to the Buprenorphene makes it a 
near non-abusable substance. That means that it could be 
prescribed through normal pharmacy practice without concern 
that a heroin addict might abuse the substance. It is very well 
accepted by the patients who have been using it, and it appears 
to be extremely safe. So we are very hopeful.
    Mr. Hoyer. In layman's terms, why is that non-abusable?
    Dr. Leshner. Well, the compound itself Buprenorphene is an 
interesting compound. It is what is called a partial agonist; 
it partly acts at the opiate receptor where heroin acts. So it 
does some direct blocking or competing with heroin, if someone 
were to take heroin while on it, and it blocks craving. In that 
way, it has a ceiling effect, so the odds of overdose are 
extremely low. Then the addition of naloxone, which is an 
antagonist, means that if you take Buprenorphene in the normal 
way, or this buprenex in the normal way, sublingually, the 
Buprenorphene is absorbed and has its anti-craving, anti-
addiction effect, the naloxone is not absorbed, because 
sublingually it is not absorbed. However, if you were to grind 
up the tablet and try to inject it and you are a heroin addict, 
you will go into withdrawal immediately because of the 
naloxone.
    So, if I said that clearly, basically what you have is a 
preparation that if you take it properly it does its job fine, 
you will not need heroin; and if you try to abuse it, if you 
try to inject it and you are an addict, you will go immediately 
into withdrawal. So that, obviously, makes it non-abusable. I 
hope that was clear.
    Mr. Hoyer. I think so. Reasonably clear. [Laughter.]

                      DRUG PREVENTION COORDINATION

    As clear as you could be discussing it with a layperson 
like us or like me.
    Obviously, the research in drug abuse needs to be applied 
to drug prevention, which is a little bit of what you were 
talking about having an antidote, if I can say that in layman's 
terms, that cannot be abused because it does not work properly 
if not used correctly. How are your efforts on drug prevention 
coordinated with those various programs of drug prevention that 
we have?
    Dr. Leshner. In a couple of ways. One, we work quite 
closely with the Center for Substance Abuse Prevention, we work 
closely with the Department of Education and their activities. 
You may recall that two years ago we released the first ever 
science-based guide to drug abuse prevention, which has now 
gone out to over 250,000 communities around the country.
    We are now moving to what we call the next generation of 
prevention research, trying to figure out how to tailor 
prevention approaches to different localities, different kinds 
of drug contexts, different kinds of patient populations, 
different kinds of prevention programming approaches, how to 
work with communities. We work very closely with the Community 
Anti-Drug Coalitions of America. So we actually have a great 
deal of direct interaction with people who deliver prevention 
programming and, again, trying to bring a science-based 
approach to what they do.

                         SUCCESS IN PREVENTION

    Mr. Hoyer. Lastly, let me ask you to give me an assessment 
on your feeling of how successful we are being in terms of the 
objective of preventing drug abuse or the uses of drugs through 
education, and then in rehabilitation. Obviously, one of the 
great problems in drug abuse is recidivism and the difficulty 
of getting somebody off drugs once they are on drugs. We know 
that recidivist, and I suppose that is applied to the criminal, 
addicts who cannot get off drugs are the largest purchasers and 
problems that we have in this society. What is your judgment on 
the success rate we are having?
    Mr. Leshner. Let me start by saying I really know the 
scientific aspects of it of course the best, and I can tell you 
that we have made truly extraordinary advances in both 
understanding the nature of drug abuse and addiction and what 
we ought to be doing about it from a scientific point of view. 
A large problem of course is always going to be moving that 
science-based knowledge into actual practice in real-life 
settings.
    The statistics suggest that we have actually made quite a 
bit of progress; that is to say, cocaine use is at the lowest 
it has been in a decade. A variety of indicators suggest that 
we have as a Nation made some substantial progress. I have to 
say that from where I sit I see new drug problems emerging 
constantly. And so I would be nervous if anybody got too 
sanguine. For example, methamphetamine a couple of years ago 
became a major national crisis particularly from the midwest 
westward. Right now, we are seeing a rather rapid rise in 
``club drugs'' and that is why we mounted this club drug 
initiative recently to try to get ahead of it, to try to get in 
the path of what I think of as an infectious disease plague 
that is going on. So as we are making progress, I think that 
realistically there are new problems emerging constantly.
    I do feel very sanguine about the progress that we are 
making in advancing both prevention technology and treatment 
technology. We have in the last ten years brought on line 
probably ten or fifteen new science-based behavioral treatments 
that are ready to be tested in our Clinical Trials Network and 
to be moved into real-life practice. So from where I sit, I 
feel like we are making tremendous progress. It is a complex 
problem, we are obviously not going to solve it very rapidly, 
but I do feel as if we are beginning to use the science to get 
a better handle on what we are doing.
    Mr. Hoyer. Thank you, Doctor.
    Thank you, Mr. Chairman.

                        COORDINATION WITH NIAAA

    Mr. Porter. Thank you, Mr. Hoyer.
    I will complete my questions and then call on Ms. Pelosi 
and Mr. Jackson.
    Your colleague Dr. Gordis is in the room, and I would like 
to ask the degree of coordination and cooperation between your 
Institute and his, since both deal with addictive behavior and 
many people think that alcohol is a gateway to the use of 
harder drugs. What do you do in terms of coordination with Dr. 
Gordis?
    Dr. Leshner. We actually do a lot together. There are both 
similarities and differences among these substances. We 
certainly have many researchers who are supported by both 
Institutes and we have many projects that we both support. So 
that there is a significant amount of collaboration on what we 
do.

                     FUNDING FOR ALCOHOL AND DRUGS

    Mr. Porter. I asked this question of Dr. Gordis last year 
so I will ask it of you this year. Given the effects on society 
of alcohol and drugs, is there a fair balance between the 
funding for your Institute and his Institute? I know it is a 
difficult question.
    Dr. Leshner. I am not going to answer it. [Laughter.]
    I can do that short or long, sir. In the same way that I do 
not compare the addictiveness of various abusable substances 
because I do not think it is a comparison that is easy to make, 
I am not sure I could make this kind of a comparison. I can 
only speak for my own Institute and say we have many problems 
we still have not solved.
    Mr. Porter. My take is that both of you need more funding 
to get at the heart of these things and we should continue 
along the path that we have chosen and try to really ramp up 
funding for research in both areas.
    Dr. Leshner. Thank you, sir.
    Mr. Porter. Bidis. Are you doing any research on them? That 
has become the latest kind of pull for our young kids, nine, 
ten, eleven years old let's say, and it seems to have a great 
appeal. We have legislation I am cosponsoring that has been 
introduced to simply forbid the importation of these 
cigarettes. But what do you think?
    Dr. Leshner. We have not done anything on Bidis per se 
because they are another vehicle for administering nicotine. 
But we have a very large nicotine program and we have a very 
large anti-smoking program. We spend a couple hundred million 
dollars a year on smoking-related activities.
    One of the things that we have done jointly with the 
National Cancer Institute, as you may know, has been to mount 
this very large transdisciplinary tobacco use research centers 
program, some of which, at least two of the first five awards 
are geared toward prevention in young people. So we are trying 
to get to younger smokers and trying to develop not only better 
prevention modalities, but better treatment modalities 
directed, in the treatment case, at adolescents particularly.

                            NICOTINE VACCINE

    Mr. Porter. Are we working on the development of a vaccine 
against nicotine?
    Dr. Leshner. We do have a grant that you may have read 
about recently in the newspaper of a vaccine against nicotine, 
not dissimilar from the one that I think I mentioned last year 
that we have developed for methamphetamine and one for PCP. The 
notion is basically to prevent whichever abusable substance 
from reaching the brain and therefore having its psychoactive 
effect.
    I am a bit skeptical personally about a vaccine approach 
only because I am concerned that it might not be able to bind 
all of the substance, and therefore an individual might try to 
override the vaccine. But having said that, we are pursuing 
that approach for nicotine, methamphetamine, cocaine, and it 
has had very good preliminary results. So in spite of the 
skepticism, it does appear to have an effect.
    Mr. Porter. Thank you, Dr. Leshner.
    Ms. Pelosi.

                        DEMAND REDUCTION FUNDING

    Ms. Pelosi. Thank you very much, Mr. Chairman.
    Dr. Leshner, welcome. Thank you, as always, for your great 
leadership and your hard work.
    Dr. Kirschstein, once again welcome to you. Thank you also 
for your contributions to our society and your leadership.
    Dr. Leshner, I want to follow up on Chairman Porter's first 
question earlier about better use of the $1,000,000,000 that is 
proposed for Colombia, or words to that effect. Forgive me for 
missing the beginning, but my Chairman's cowhand and I are 
going very early tomorrow morning to Colombia and all week we 
have been briefed, et cetera, on that subject because we are 
going to have to try to sell that program, once it is sold to 
us that is, to our colleagues. I believe that the rationale 
that we are sending $1,600,000,000 or $1,300,000,000 
supplemental emergency spending to Colombia with the rational 
that it is to fight the war on drugs is really not justified 
until we spend at least a commensurate amount to recognize the 
need for demand reduction and prevention in that same war. 
There will always be a source as long as there is a demand.
    I would like to propose an amendment to the supplemental 
that would say for the $1,300,000,000, which is additional to 
aid that we would be giving anyway, that we have a 
corresponding $1,300,000,000 for prevention demand reduction 
capacity expansion domestically. This money is all under 
SAMHSA. I know that you were sort of diplomatic in your 
response to the Chairman. But from your perspective, do you 
think that would be money that could be spent in the next 
couple of years?
    Dr. Leshner. I really do not want to comment on any 
potential trade-off amongst different domains because I am not 
really qualified to make that calculus. But I can tell you--
    Ms. Pelosi. There were two options I have. One is to offer 
this as a substitute to the package. But I am presenting it to 
you as an amendment to the package. So to say, we are granting 
them the $1,300,000,000 for the moment and just saying if there 
were $1,300,000,000 that we could spend in the next two or 
three years on demand reduction in the U.S. Could you comment 
on that?
    Dr. Leshner. I think it is widely recognized that there is 
a very large treatment gap in this country between those who 
need treatment and those who have access to treatment.
    Ms. Pelosi. Can you quantify that?
    Dr. Leshner. It is hard to know exactly what the number is. 
We believe there are about 4,200,000 hardcore addicts, no more 
than 2,000,000 of those individuals have ever been in drug 
treatment. That leaves you about a 50 percent treatment gap. It 
is not clear to me that we could get all those people into 
treatment, so I would be careful with that number.
    Ms. Pelosi. That's right.
    Dr. Leshner. But there is a large treatment gap. There is a 
tremendous need for increased prevention programming in this 
country. Now that we have a better and better science base, I 
think we can do a better job of that. I do need to say there 
are many, many research opportunities that we are unable to 
pursue. So are there opportunities? There are opportunities. 
But, again, I do not feel qualified to comment on the balance 
issue.
    Mr. Porter. Would the gentlelady yield?
    Ms. Pelosi. I am pleased to yield to the Chairman.
    Mr. Porter. I specifically, in my question, took out the 
political equation because there is a lot of thought that, 
apart from the drug problem, this country is in deep trouble 
and may end up with total anarchy, which sounds to me 
farfetched, but I think I have to learn more about that before 
I can make any judgment as to whether this money is wisely 
spent.
    Assuming that that is not the problem and this money is 
intended simply for additional interdiction and an attempt to 
restrict the supply, then I would like to offer an amendment to 
your amendment to put this money where I think it can do a lot 
more good. I believe, like you do, that you really have to get 
the demand under control. The supply will be there whether it 
comes from Colombia or somewhere else; it is going to be there 
always. It seems to me it is up to us to choose priorities and 
to make judgments as to where the money can best be spent. So I 
would like to amend your amendment.
    Ms. Pelosi. I am very interested in that, because your name 
on any amendment is going to carry a tremendous amount of 
weight in full committee. I think that is the arena for this to 
be. So thank you, Mr. Chairman, for that opportunity to 
cooperate on this.
    What I heard you say, Dr. Leshner, is you are not going to 
comment on the Colombian side of it, and I appreciate that. But 
if there is a $1,300,000,000 on the domestic side, in addition 
to what I had mentioned, that SAMHSA substance abuse block 
grant targeted capacity expansion, knowledge development and 
application, that there might be some research opportunities as 
well, scientific opportunity in prevention in your Institute as 
well.
    Dr. Leshner. Sure.
    Ms. Pelosi. I appreciate that.
    The numbers are very compelling about this. And don't take 
my word for it. I mentioned these when we talked with SAMHSA as 
well. Substance abuse treatment is the most effective use of 
drug control investments. This is after prevention of course; 
prevention first and foremost so that we do not get into the 
problem. But a Rand Corporation study on reducing cocaine 
consumption found funds spent on drug treatment were 23 times 
more effective than source country control, 11 times more 
effective than interdiction, and 7 times more effective than 
law enforcement. Now, of course, we have to do all of those 
things. It is just important to know what works best.
    A 1996 National Institute of Justice report found that 
providing treatment to all addicts in the United States would 
cost $21,000,000,000 and save more than $150,000,000,000 in 
social cost over the next 15 years. So if we average that out 
to $10,000,000,000 a year over 15 years, and it cost us 
$21,000,000,000 in the first 2 years, we would after that make 
$130,000,000,000. So strictly from a financial standpoint we 
are missing so many opportunities in what it cost to our 
society and our economy, even putting aside the personal 
aspects of it. That is the Rand Corporation figures on that 
subject.
    Do I have any more time, Mr. Chairman, on this round?
    Mr. Porter. Yes, you do. Also, I am not going to be very 
strict on time because we have enough time.

                       PREVENTION AND TECHNOLOGY

    Ms. Pelosi. Thank you. Last year, you said you were looking 
at a geometric acceleration in the pace of discovery and you 
never fancied that you could put out science-based principles 
of drug prevention in nearly as rapid pace as you have done. 
Congratulations. What does the future hold in that regard? Is 
this improved instrumentality? How have you been able to move 
so rapidly?
    Dr. Leshner. Well, overall, we have, like most of 
biomedical science, profited tremendously from three converging 
areas of technology advance. One is the ability to look into 
the brain of living, breathing, awake individuals as they are 
having drug experiences. As I mentioned earlier, it is allowing 
us to begin to predict how people will ultimately react to 
drugs when they get them. That, of course, would be a 
tremendous prevention advance as well as a treatment advance. 
So one area is neuroimaging. The second is the molecular 
genetic revolution which has allowed us to gain a phenomenal 
understanding about the mechanisms that underlie both drug 
abuse and addiction. The third is the information technology 
revolution. We have been very fortunate to have a large cadre 
of researchers who are bringing those three together.
    In addition to that, there is a tremendous amount of 
behavioral science and understanding of behavioral change 
technology that has gone on. That has played directly into the 
prevention domain where we have made I think tremendous 
advances in understanding how to actually develop comprehensive 
prevention strategies that use all sectors of society in an 
integrated way to send the same messages and to get them into 
the hands particularly of young people.
    Ms. Pelosi. Thank you very much, Dr. Leshner.
    Thank you, Mr. Chairman.
    Mr. Porter. Thank you, Ms. Pelosi.
    Mr. Jackson.

                           HEALTH DISPARITIES

    Mr. Jackson. Thank you, Mr. Chairman.
    Thank you, Dr. Leshner, for your testimony and for your 
service at NIDA. The President's fiscal year 2001 budget for 
NIDA is $496,300,000, an increase of $27,100,000 or 5.8 percent 
above fiscal year 2000 level. Included in this amount is 
$4,900,000 for the following NIH areas of special interest: 
biology of brain disorders, $2,500,000; bioengineering 
computers advanced instrumentation, $400,000; health 
disparities, $2,000,000.
    I don't think it is a secret that the U.S. prison 
population is overrun with Americans who are addicted to some 
form of illegal substance, and increasingly the U.S. prison 
population is African-American, Hispanic, and others. Because 
of the absence of treatment at these penal institutions, many 
Americans are leaving these prisons still addicted to many of 
these illegal substances. This is known as the revolving door 
process in our prison system.
    The Office of Research on Minority Health (ORMH) must have 
shared this information with your office. I was just wondering, 
in light of these facts, when that information was brought to 
your attention what percentage of the $496,300,000 did you 
determine should be used to address this problem?
    Dr. Leshner. Just to be precise, sir, that $496,000,000 is 
the non-AIDS number. And it is easier for me to answer your 
question if I aggregate the entire $725,000,000.
    Mr. Jackson. Okay.
    Dr. Leshner. We estimate that we spend about $101,000,000 
on health disparities research in the course of a year. You may 
know that we have a large array of programs that have two 
purposes. One purpose is to gain a greater understanding of the 
health disparities that you just referred to, and secondly, to 
recruit additional minority researchers so that we can do a 
better job both of the research and of accelerating the 
progress of advance.
    Mr. Jackson. I am not so sure if the issue on this point is 
the recruitment of minority researchers as much as it is the 
study, which anyone can do the research on as far as I am 
concerned, on why, at least based upon the prison data, it 
appears that minorities are disproportionately addicted to some 
form of illegal substance that lands them in prison. That would 
tell me that since many of the substances that you study in 
your Institute are also criminalized under our penal code, that 
of all the budgets at NIH, your budget, in light of the way the 
prisons look today, disproportionately African-American, 
disproportionately Hispanic, that your budget of all the 
budgets at NIH would be the budget where we would see some 
significant increase in the awarding of grants to address 
domestic disparities that might exist in this particular area. 
Do you want to comment on that?
    Dr. Leshner. Yes, sir. I think you are right and I think it 
is true. The $2,000,000 number that you cited was above the 
normal increase that has to do with the way in which the budget 
is allocated across areas of emphasis. But in fact, over the 
course of the last six years, I have been tracking health 
disparities since 1993 when I became the NIDA Director, this 
area of emphasis has grown tremendously in our Institute for 
exactly the reasons that you mention. I think you are 
absolutely right.
    The reason I made the point about two fundamental 
strategies is that, of course, it is not only minority 
investigators who are studying these health disparities, but 
having said that, we find that, particularly because so much of 
the research needs to be done at the community level and in the 
community, it is very important that we have more minority 
investigators (a) who are interested in those areas, and (b) 
who work well in those areas.

                       ENVIRONMENT AND DRUG ABUSE

    Mr. Jackson. I want to make it clear, because I know the 
pattern is beginning to emerge here in my inquiry of various 
institutes, offices, and centers at NIH, that I am not just 
making an argument for more minority investigators. Quite 
frankly, when you look at some of the disparities that exist 
across the entire industry of emphasis, it is becoming 
increasingly clear to me that almost anyone can do the research 
if RFPs, Request For Proposals are introduced in the area that 
might generate a market of concern for someone to help us 
arrive at some data for which the rest of NIH might be able to 
make some progress. Then that takes me I guess to my next 
question.
    I am really wondering, according to your congressional 
justification, individuals whose lives happen to be marked by 
poverty, illiteracy, malnutrition, and other unhealthy 
environmental conditions are at risk for some form of drug 
abuse. Do you know why this is the case?
    Dr. Leshner. We do not, sir. One of the things that we have 
learned in the last few years is that many of these apparent 
disparities are quite complex and that they emerge at different 
times and with different substances. For example, in contrast 
to popular belief, the drug use rates for young people, that 
is, adolescents, is lower in both African-American and Hispanic 
communities than it is in caucasian communities. That lower 
drug use rate holds until people are well into their 20s. Then, 
if you look at all illicit drug use, of course, the overall use 
rates are similar, although with both heroin and crack cocaine 
use you see a higher representation.
    Having said that, there is also no question that there is 
disproportionate impact of the consequences of drug use to 
racial and ethnic minority groups. So that what we have learned 
is that it is not necessarily use rates per se that are the 
critical variables of course, but the impacts, some of which 
have to do with the issues that you mentioned.
    Mr. Porter. Will the gentleman from Illinois yield for just 
one quick question?
    Mr. Jackson. My time has expired, but I would be happy to, 
Mr. Chairman.
    Mr. Porter. Well I will grant you more.
    Mr. Jackson. I yield you the time that you have granted me, 
sir.

                         PRISON AND DRUG ABUSE

    Mr. Porter. You said that prisoners are coming out of 
prison still addicted to drugs.
    Mr. Jackson. Yes, sir.
    Mr. Porter. Am I missing something, or is that a 
confirmation that you can do all you want on the interdiction 
side but, if you cannot cut off the demand side, people are 
going to find a way to get them. Is that what is happening?
    Mr. Jackson. I don't think I can disagree with what the 
Chairman is saying. But I think it is very clear that the very 
fact that we are sitting in this hearing today and the fact 
that we are about to appropriate $500,000,000 for this 
Institute, there has been a determination at some point in time 
that we have got a disease here called drug abuse.
    They are telling us it is a disease. But then the Judiciary 
Committee is telling us it is a crime. Then there is some 
significant political problem between the acknowledgement that 
they are saying, doctors, professional people who are spending 
a significant amount of money studying the disease, and our 
desire when we get elected to say we are going to lock people 
up. So I don't know the answer to this very difficult question. 
If it is a disease, then we have to treat it like it is a 
disease and try and get people help. If we are saying that it 
is not a disease, that we just want to lock people up, at least 
if we lock people up with the disease, somehow there should be 
some relationship between what we try to do to get them better 
while locked up.
    Mr. Porter. That is what I am saying. What I hear you 
saying or what you are implying is that even when they are 
locked up, the drugs are getting into the prisons and they are 
remaining addicted.
    Mr. Jackson. A combination of all, yes, sir.
    Mr. Porter. It is clearly not legal for drugs to get into 
the prisons but they are getting through anyway.
    Mr. Jackson. Yes, sir.
    Mr. Porter. That seems to me to be a big part of the 
problem. If you are going to take people to treatment, 
presumably you have got to get them away from the source in 
order to treat them, otherwise they are going to remain 
addicted.
    Mr. Jackson. Mr. Chairman, from my own understanding, 
prison can also be, without the appropriate and adequate 
treatment while in prison, prison can also be just a period of 
enormous withdrawal that creates a tremendous desire at the 
time that the person who has been convicted returns to society. 
So that particular problem seems to be more in the majority 
than just the illegal presence of drugs within the penal 
institutions themselves.
    Mr. Porter. Thank you.
    Mr. Jackson. Thank you, Mr. Chairman.
    Mr. Porter. We have a little time, Ms. Pelosi. Do you have 
additional questions?
    Ms. Pelosi. I do.
    Mr. Porter. Please proceed.

                         PERCENTAGE OF DRUG USE

    Ms. Pelosi. Thank you, Mr. Chairman, for the additional 
time.
    Just to follow up on a couple of the comments that were 
made. It is always interesting to me to hear the statement made 
that young African-American males really do not engage in drug 
use until they suffer some other frustration in society and the 
rest, but it is a lower rate of addiction than the general 
population. That says something about generally what we need to 
do in the larger sense. I appreciate your making that point.
    I also am going to go back to this demand reduction that 
the Chairman mentioned. Indeed, some people pick up the 
addiction in prison. They not only continue, they pick up the 
addiction in prison. What percentage of drug use in the U.S. is 
cocaine, heroin, methamphetamines? My point being, if we got 
rid of every cocoa leaf in the world, we would still have a 
problem in the U.S.
    Dr. Leshner. We estimate that there are 810,000 hardcore 
heroin users in this country, somewhere on the order of 
3,000,000 cocaine addicts in this country, and I don't have an 
accurate number for methamphetamine addicts. But as you know 
well, on the West Coast of this country the methamphetamine 
addiction rates are comparable to those for cocaine and exceed 
the cocaine addiction rates in some cities on the West Coast. 
Having said that, we have a tremendous number and it is rather 
well distributed across the drugs, although cocaine I believe 
overall remains the largest sector of the addicted population.

                               NEEDS GAP

    Ms. Pelosi. That still remains the largest. Okay.
    I just wanted to make one other comment. Maybe you could 
tell me the needs gap. What is the magnitude of need for 
prevention programs and treatment services? I know you said 
earlier it was hard to quantify, there are 2,000,000 that are 
not served and we don't know how many of them that want to be 
involved in drug treatment programs. But can you give any 
ballpark figure from your own needs and your own agency what 
the gap is.
    Dr. Leshner. I can only speak to the research enterprise in 
any quantified way. I can say that in our own professional 
judgement it is substantially larger of course than anybody has 
been able to provide since we have many, many unapproached 
opportunities.
    Ms. Pelosi. Would you be willing to put a price tag on 
that?
    Dr. Leshner. Yes, ma'am. Our professional judgement budget 
for this year, after consultation with the National Advisory 
Drug Council on Abuse, was $838,000,000.
    Ms. Pelosi. As the equivalent of your non-AIDS.
    Dr. Leshner. No, no, our entire.
    Ms. Pelosi. Including. So about $100----
    Dr. Leshner. As against $725,000,000, which was the 
request. So a 22 percent increase over the FY 2000 estimate.

                            NEEDLE EXCHANGE

    Ms. Pelosi. Since you mentioned AIDS, you know how hard 
some of us have been fighting here for the needle exchange 
program, Dr. Leshner, in your work on substance abuse and drug 
abuse and AIDS, could you speak to the efficacy of needle 
exchange programs in reducing the transmittal of AIDS in 
heterosexuals, or any community for that matter.
    Dr. Leshner. Yes. I think the data continues to support the 
conclusion that Secretary Shalala made last year, one that Dr. 
Varmus and I have stated repeatedly. Needle Exchange Programs 
have to be viewed as a part of a comprehensive program not a 
stand alone activity. Needle exchange is effective in reducing 
the spread of blood-born infections, particularly HIV, and that 
it does not appear to increase drug use. We do not have data on 
whether it actually decreases drug use, but it does not appear 
to increase drug use.
    Ms. Pelosi. Thank you, Dr. Leshner.
    Thank you, Mr. Chairman.
    Mr. Porter. Mr. Jackson.

                 OFFICE OF RESEARCH ON MINORITY HEALTH

    Mr. Jackson. Mr. Chairman, I just have one general comment, 
and I would certainly appreciate the Chairman's inquiry. My 
very astute staff, under the leadership of Mr. Charles Dujon, 
prepared some wonderful memos for me which I find very 
difficult often times to get through before these hearings. I 
noticed that, because of my line of inquiry, he has now started 
including a little health disparity section, and the health 
disparity section appears to be included in almost all of the 
NIH increases in almost every department where I have been 
raising these inquiries. And while I feel, on the one hand, 
that this money is very necessary and certainly a step in the 
right direction in each of the agencies, I do want you to know 
that I kind of feel like I am being placated just a little bit 
because there is now this new category called health 
disparities which has a little money in it in just about every 
institute.
    That is not what I am talking about. I am still talking 
about our fair share, meaning in terms of priorities and 
research, of the big picture--the $500,000,000 that the 
President is requesting for this--in light of what I have 
objectively shared with you are some significant areas, for 
example, in NIDA. So, the way these memos are written, and 
maybe it is my fault over the course of my tenure on this 
committee, I am not going to be fighting every year for another 
$1,000,000 to be added to the health disparities account when I 
am talking about some priorities that exist in light of what we 
objectively know to be a significant problem at NIH.
    And I want to go one step further, which is my own 
criticism, if you will, Mr. Chairman, and critique of the 
institution of Congress itself. We cannot, on the one hand, 
spend $500,000,000 and acknowledge that this is a disease, and 
then another committee in the Congress turn around and tell us 
that it is a crime. If cancer, for example, is a disease, but 
then another committee in the Congress told us that cancer or 
the use of some form of alternative medicine for the cure for 
cancer is a crime, then we cannot say it is a disease and a 
crime at the same time.
    So while this is not limited or specific to Dr. Leshner, 
the fact that we are appropriating and considering 
appropriating the kind of money that we are because we are 
suggesting that millions of Americans are addicted and have a 
mental illness associated with this particular problem, and 
overwhelmingly those who are being penalized for this mental 
illness are people of color and people who economically are 
disadvantaged in the society, that we cannot punish them, one, 
for being sick, and we also cannot punish them for not being 
able to afford good legal counsel in another committee because 
of what is obviously, and what I think Dr. Leshner and others 
have indicated, an illness.
    And while I am not asking Dr. Leshner to comment on that 
very political statement, I do want to ask him just one final 
question about his relationship generally and his department's 
relationship with the NIH Office of Research on Minority 
Health.
    Thank you, Mr. Chairman.
    Mr. Porter. Thank you, Mr. Jackson.
    Mr. Jackson. That was a question.
    Mr. Porter. That was a question?
    Mr. Jackson. Yes. I asked him to comment on the 
relationship.
    Mr. Porter. I am sorry. I thought you were not going to ask 
him a question.
    Dr. Leshner. Yes, sir. We have had very strong 
relationships with the NIH Office of Research on Minority 
Health, in part because this issue of health disparities is not 
a new issue for us. If you look at the funding for minority 
health research in our Institute, it has gone up 68 percent 
over the last five years compared to a 58 percent total 
increase for NIDA, and I will not go through all the pieces of 
that. But I assure you that this has always been a priority 
area for us exactly for the reasons that you have articulated. 
And we are the source of the information about the 
effectiveness of treatment in prison and its long-term 
consequences.
    Having said that, we have very good relationships with the 
NIH Office of Research on Minority Health. We have our own 
Office of Special Populations that is well known for being 
tremendously effective, and they have worked very well with Dr. 
Ruffin and his colleagues for many years. So we have done very 
well.
    Mr. Jackson. Thank you, Dr. Leshner.
    Thank you, Mr. Chairman.
    Mr. Porter. Thank you.
    Ms. Pelosi. Mr. Chairman, may I just follow up for a half a 
second on Mr. Jackson's comment?
    Mr. Porter. Half a second.
    Ms. Pelosi. On top of all that Mr. Jackson said about 
addiction being a disease, et cetera, it is just curious that 
on top of all of that, the disease here and crime there, it 
just reminded me of how ridiculous it looked when we struck 
people with addiction from their SSI benefits. What could we 
have been thinking?
    Dr. Leshner. Don't ask me. [Laughter.]
    Ms. Pelosi. So you agree it wasn't a smart move.
    Dr. Leshner. Ma'am, with all respect, yes.

                 RESEARCH-BASED GUIDE TO DRUG ADDICTION

    Mr. Porter. Dr. Leshner, do you know Haymarket in Chicago, 
Father Mac and the program there?
    Dr. Leshner. Yes, sir.
    Mr. Porter. What would you say if I told you that we had 
one of our staff visit there in January and they have no 
knowledge of your research-based guide to drug addiction. 
Wouldn't they be on your list for distribution?
    Dr. Leshner. I hope so. To be honest, I am shocked.
    Mr. Porter. Yes. That is what I thought. So am I.
    Dr. Leshner. Because every treatment program in this 
country has asked for a dozen copies. But having said that, I 
will also tell you that, you will recall, two years ago I 
brought you the little ``NIDA Goes To School'' school box----
    Mr. Porter. I was going to ask you about that, too. So 
fine.
    Dr. Leshner. Yes, 1,300,000 copies, but who is counting. 
And just before I came to the hearing today, the new NIDA 
Clinical Toolbox has just been produced, into which will go the 
manuals that we have produced over the last few years, the 
various materials about effective drug abuse treatment, and it 
will be sent to every drug treatment program in the United 
States. I promise you that by next year they will have more 
than they ever wanted.
    Mr. Porter. It may be that there was some problem at the 
other end, but I would really appreciate your checking with 
them and seeing whether there is any broader problem.
    Dr. Leshner. Absolutely.
    Mr. Porter. Because from a Chicago standpoint, they are one 
of our leading drug treatment centers and do a great deal of 
wonderful work and they ought to have this.
    Dr. Leshner. I agree with you. You are absolutely right.
    Mr. Porter. You have done some wonderful work and it has 
got to be in the hands of people who are on the front lines.
    Dr. Leshner. Absolutely.
    Mr. Porter. We really appreciate the job you do.
    Dr. Leshner. Thank you.
    Mr. Porter. You do a wonderful job there at NIDA. 
Obviously, we want to provide all the resources we can. I think 
the President's budget, in respect to all the Institutes, is 
far from what we need to provide. While I might not agree with 
my colleague from Illinois on everything, I think he is correct 
that if you have people in prison who are addicts, what we 
ought to do is get them off the addiction before they are 
released from prison. There ought to be a way of accomplishing 
that, otherwise we are just going through a revolving door, or 
worse.
    Dr. Leshner. I agree with you.
    Mr. Porter. So thank you for the fine job you are doing.
    Dr. Leshner. Thank you.
    Mr. Porter. The subcommittee will stand in briefly in 
recess.
    [The following questions were submitted to be answered for 
the record:]



                                       Thursday, February 17, 2000.

           NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

                               WITNESSES

ENOCH GORDIS, DIRECTOR
MARY C. DUFOUR, DEPUTY DIRECTOR
FAYE CALHOUN, ASSOCIATE DIRECTOR, COLLABORATIVE RESEARCH
STEPHEN W. LONG, ACTING EXECUTIVE OFFICER
NANCY PARFITT HONDROS, BUDGET OFFICER, PLANNING AND FINANCIAL 
    MANAGEMENT BRANCH
RUTH L. KIRSCHSTEIN, ACTING DIRECTOR, NATIONAL INSTITUTES OF HEALTH
DENNIS P. WILLIAMS, DEPUTY ASSISTANT SECRETARY, BUDGET, DHHS
    Mr. Porter. The subcommittee will come to order. We are 
pleased to welcome Dr. Enoch Gordis, the Director of the 
National Institute on Alcohol Abuse and Alcoholism.
    Dr. Gordis, it is good to see you, as always. I am trying 
to get you proportionately more money because I think that 
alcohol affects more people and has more negative effects on 
our economy than even drug abuse. I do not think we invest 
enough in your area to stop or attempt to at least slow down 
the gateway from alcohol to drugs.
    So please proceed with your statement and then we will go 
to questions.
    Dr. Gordis. Thank you very much, Mr. Porter. I would like 
to begin by introducing my colleagues here. Mr. Stephen Long, 
the Acting Executive Officer; Ms. Nancy Parfitt Hondros, the 
Budget Officer, Dr. Mary Dufour, our Deputy Director and Dr. 
Faye Calhoun, Associate Director.
    I would like to begin by saying how sad we are that you are 
leaving us. We want to wish you good health, which is the 
prerequisite for everything else, and much happiness and 
success in whatever road you take. Thank you for the support of 
science at the NIH.
    Mr. Chairman and members of the committee, I am pleased to 
present the President's non-AIDS budget request for NIAAA for 
fiscal year 2001, a sum of $288,578,000, which reflects an 
increase of $14,587,000 over the comparable fiscal year 2000 
appropriation. Including the estimated allocation for AIDS, the 
total support requested is $308,661,000, an increase of 
$15,427,000 over the fiscal year 2000 appropriation. Funds for 
the NIAAA's efforts in AIDS research are included within the 
Office of AIDS Research budget request.
    Nearly 14,000,000 American adults meet diagnostic criteria 
for alcohol addiction or abuse, and 100,000 Americans die of 
alcohol-related causes each year, according to NIAAA 
epidemiological data. While death is the final consequence of 
alcohol-use disorders, the impact on the living, in sheer 
numbers, is even greater. Approximately 442,000 people occupy 
hospital beds each year as a result of these disorders. In 
fact, one out of every four adult beds in the urban hospitals 
in our country are occupied by people who are being treated for 
the consequences of drinking.
    The financial burden that alcohol misuse imposed on the 
Nation in 1998 was approximately $185,000,000,000 in direct and 
indirect costs. The sequelae of alcohol-use disorders include 
damage to the liver, brain, and other organs; cancer; fetal 
alcohol syndrome and the lifetime disabilities that follow 
that: trauma; property damage; crime; broken families and the 
loss of productivity that deprives the Nation of valuable 
resources. Important data that came out from our Institute this 
year was that one out of every four children in this country 
spends some or all of their childhood in a home where there is 
alcoholism.

                        WHO REPORT ON DISABILITY

    Two days ago, during the hearing that you held with Dr. 
Kirschstein, the WHO report on disability for mental health was 
mentioned. I would like to point out that alcohol is very high 
on that list. As far as disability goes, it is the fourth 
highest cause of disability in the whole world, and in male 
disability it is the number one cause of disability in all the 
developed countries.
    What I would like to do in the next few minutes of my 
introductory remarks is to highlight some of the progress that 
we have made in several of the areas that we research.
    Basically, we ask two kinds of questions in our Institute. 
There are questions that have to do with the development of 
addiction, why some people get into trouble from alcohol, some 
don't, and all the biological and social forces which lead to 
addiction, especially in the young. So the issue of alcoholism 
as a behavior and the acquirement of addiction is one point. 
Since alcoholism has an extensive list of organ damage, which I 
just alluded to, our understanding of that damage and our hope 
to be able to prevent or reverse the organ damage is really a 
second piece of the kind of work that we do.

                       THE GENETICS OF ALCOHOLISM

    Congress saw fit to support our Collaborative Study on the 
Genetics of Alcoholism starting about ten years ago, and, as I 
reported to you in previous years, the study has had major 
findings, with the identification of chromosomal locations 
where genes relating to the vulnerability to alcoholism are 
likely to lie. The COGA database, of course, is very extensive 
and it includes minorities populations. We are expanding this 
study and Howard University has just joined us as a grantee in 
the genetics study to over-represent the minority populations 
and make the statistical calculations more precise.
    We are happy to report that the whole database from this 
Collaborative Study on the Genetics of Alcoholism is now 
available to the qualified scientific community. The pedigree 
data, the family data, the clinical data, as well as the DNA 
now lies in the repositories. So with this, we hope that the 
chase to find the genes that lie in these identified areas will 
be accelerated.
    In our neuroscience work, we are increasingly understanding 
the brain with many of the high-tech approaches that you have 
heard about and will hear about in the future few weeks. Our 
neuroscience does two important things in relation to what I am 
going to speak about in a few minutes. First of all, it 
suggests avenues for developing new medications for treating 
alcoholism, and it also helps us on the gene chase because it 
suggests certain candidate genes that might be responsible for 
the vulnerability to alcoholism.

                        MEDICATIONS DEVELOPMENT

    You know from previous testimony here that we have had 
success in the medications area. The FDA approved naltrexone 
for the treatment of alcoholism a few years ago. This year our 
research has reported another opiate antagonist, nalmefene, as 
being potent for the treatment of alcoholism. A drug originally 
devised in Europe which has been extensively tested by NIAAA 
investigators, although we did not fund that study, the drug 
house did, called Acamprosate, is now under review by the FDA 
for approval. It works by a very different mechanism. So in the 
field of medication development, we have really made excellent 
progress.
    Of course, in our molecular biology and genetics work, we 
use all the tools you hear about repeatedly--arrays, knockouts, 
breeding of animal species to show certain effects. I want to 
show you one which I think is very dramatic that appeared this 
year.
    May I have the first poster, please. [See poster on page 
1300]

                             NEUROPEPTIDE Y

    The knockout technology refers to a technology by which it 
is possible to disable a gene at the time of the embryo's 
development and the embryo then spends the rest of its life 
without that gene. When you study the behavior which is 
abnormal you can be reasonably confident that the absence of 
that gene is related to that behavior. There is a substance in 
the brain called neuropeptide Y which has been associated with 
the control of appetite or eating, and associated with the 
relief of anxiety. It turns out that in these knockouts where 
NPY has been knocked out so the animal grows up without it, 
these animals drink a lot more than the wild-type liter mate, 
while in a very nice experiment where they double-dose the 
animals with the gene instead of taking it out, these animals 
drank less. This was somewhat counter-intuitive because in 
other experiments with food NPY increases food intake.
    This just shows that it is possible to do important work on 
alcohol with knockouts. And by the way, we have about 20 
knockouts, each one showing an effect on alcohol drinking, 
which is guiding us to where we will look in the human genome 
for vulnerability genes.

                        DAMAGE TO THE CEREBELLUM

    I mentioned that alcohol has a wide range of damaging 
effects on the body. I want to show you some recent evidence 
about the cerebellum. The cerebellum is the organ at the back 
of the brain which is largely responsible for the control of 
our equilibrium, gait, and balance. It has been known for a 
very long time from anatomical studies and clinical studies 
that the cerebellum is damaged by alcohol, especially the 
central part of it called the vermus.
    May I have the second poster please. [See poster on page 
1301]
    Here, with MRI it is possible to show--and if you look at 
the right-hand slide at the lower right-hand corner--that the 
dense texture of the cerebellum seen on the left side is absent 
on the right side because of a loss of a tremendous amount of 
the white matter. The fact that the cerebellum is damaged is 
not new. What is new here is that it is possible for us now to 
follow the course of this damage, its potential reversibility, 
either spontaneously or with the help of new medications, and 
also to address the very interesting question which has been 
raised in recent years that the cerebellum is not only a site 
of balance and gait control, but it may have a role in 
cognition as well because it has a major connection to the 
front part of the brain which we normally think of in those 
terms.
    May I have the next poster, please. [See poster on page 
1302]

                  CIRRHOSIS AND TUMOR NECROSIS FACTOR

    About 12,000 people a year die of alcoholic cirrhosis. 
Alcoholic cirrhosis is about half the cases of cirrhosis in 
this country. We have had spectacular progress in this area 
during the last few years because we now learn that the way 
this happens in the liver is that alcohol causes an increased 
absorption of bacterial toxins from the gut. These toxins 
arrive at the liver, turning on a whole mess of inflammatory 
cytokines, substances which evoke other cellular responses of 
an inflammatory and destructive nature.
    One of the substances that is turned on by alcohol when it 
is drunk is tumor necrosis factor alpha. In this study the 
investigators utilized a knockout for this cytokine. It turned 
out that, in the absence of this cytokine, the same dose of 
alcohol which produced an immense amount of fatty changes in 
the mouse on the left, those big white globular areas are the 
fat in the liver which is the first step of liver damage, they 
are totally absent in the mouse on the right which has its 
tumor necrosis factor alpha knocked out. Since there are other 
ways of getting at this substance besides knocking it out 
genetically, this holds great promise for us in the control and 
perhaps reversibility of alcoholic liver disease.

                       REDUCING MARITAL VIOLENCE

    In the area of prevention, we have made important progress 
as well. Americans are subject to domestic violence at a very 
great rate, maybe 30 percent of them. This is not our data, but 
data produced by the National Institute of Mental Health with 
some outside organizations. But what we have shown at the NIAAA 
is that effective marital therapy is able to bring the rate of 
domestic violence down to the level of the general population.
    Prevention is supported by science in two kinds of domains. 
One is the prevention efforts that deal with attending to 
individuals and their families. The other has to do with the 
prevention efforts that results in regulatory and legislative 
action, and hopefully, in an ideal situation, these would be 
governed by the findings of science. An area which has been 
very much in the public eye, of course, is the issue of the 
blood alcohol level and safety in various activities. A very 
interesting study this past year has to do with the ability to 
pilot maritime vessels in congested harbor areas.
    May I have the next poster, please. [See poster on page 
1303]

                         BAC LEVELS AND SAFETY

    This study was done with junior and senior members of a 
maritime training course in Maine. What you see on the left is 
not a platform of a commercial vessel, but a simulator of a 
vessel which has all the technology in it that a live maritime 
ship would have to use. It has steering, it has got 
communications, a radio, and all sorts of sensitive instruments 
for measuring various aspects of the weather, the waterflow and 
so on. What was done here, they took these young people and put 
them in this simulator with very demanding kinds of challenges 
of maneuvering and further challenged them with levels of 
alcohol on one day and placebo on the other. The blood alcohol 
levels were up to 0.04, which is the legal limit for maritime 
use, but is less than half the limit that many States have for 
driving, which is 0.1 in so many States. It turned out that 
these young people, who are already experienced in this 
simulator, had a 20 percent reduction in their ability to 
perform the very challenging kind of navigation which this 
simulator produced.

                     PLASTICITY OF THE YOUNG BRAIN

    Finally, I mention that we are very much interested in 
youth. One of the issues that comes up here is the issue of 
plasticity; this means that the young brain is not a finished 
product at birth. Even through adolescence new connections are 
being formed and new connections are being removed. That 
removal is called ``pruning.'' The final status of the brain, 
or what is close to it, is probably not achieved until the age 
of 18.
    This means that the adolescent brain is very susceptible to 
all sorts of potential toxins and potential stresses, including 
alcohol. For the sake of time, I will not go into too much 
detail right now. But in both animal studies and in human 
adolescent studies, we are now seeing that heavy drinking 
during adolescence is a major cause of cognitive impairment, 
problems with visuospatial attention, problems of retrieving 
memories in various situations. We can talk about that more 
later if you choose.
    I want to finish by highlighting an area which you have 
been interested in, Mr. Porter, and so has the committee, and 
that is the outreach that we extend to the general community in 
this country.

                     GOVERNORS' SPOUSES INITIATIVE

    As you mentioned before, the alcohol problem is more costly 
and more extensive in both human and financial terms than all 
the illegal drugs put together. And because of the lack of real 
serious national conscientiousness on this question, a new 
initiative has begun, with the collaboration of the Robert Wood 
Johnson Institute, called the Governors' Spouses Initiative, in 
which so far 13 governors' spouses are participating. One of 
the goals of this initiative, which will culminate in a meeting 
in March here, and I think I see in your hand some of the 
publications that we have prepared for this, is informational 
for activities that could be done within the States. We hope to 
enlarge the activities of the States under the leadership of 
these governors' spouses with many opportunities for education 
and policy discussions related to the prevention of drinking in 
the young, which is so important.
    One other point I did not mention with the young is that we 
know that the earlier the onset of drinking, the more likely 
the young person is going to become an alcoholic as an adult. 
We have met with the MADD, the Mothers Against Drunk Driving, 
with whom we cooperate in several ventures, and with a group of 
editors of teen magazines and women's magazines. Four of the 
governors' spouses were at that meeting with us in New York a 
couple of weeks ago to urge them to bring the issue of young 
people's drinking to national attention. We have a major effort 
on college drinking now, with the help of ten college 
presidents and ten major researchers in the area. The Kettering 
Foundation which I think I mentioned last year, is holding 
thousands of symposia across the country trying to bring 
alcohol issues to public attention.

                     NATIONAL ALCOHOL SCREENING DAY

    And finally, once again this year, like last year, we are 
going to be having Alcohol Screening Day. Last year it involved 
50,000 people across the country coming to 1,700 sites, of whom 
many finally went to some sort of treatment as a result of an 
anonymous and private interview with the people at these 
screening sites. Surprisingly enough, against our best 
intuition, the colleges were very successful sites. Out of the 
1,700 sites, almost 500 of them were college sites which were 
very, very well attended.

                          RESEARCH TO PRACTICE

    You spoke about the translation of research to practice, 
and I promise this is my very last point. I ran a treatment 
program for many years in New York before I came to NIAAA. I 
know how difficult it is to bring the innovations from science 
into treatment programs which, like all areas of health, have 
habits, a sense of inertia and a sense of ``we know how to do 
it.'' Plus, in the alcoholism field, which didn't come into 
science directly but started outside the mainstream of 
medicine, we have the extra obstacle of encouraging the 
treatment people to see science as the source of their future 
progress. [See poster on page 1304]
    It is not sufficient to put out good publications, I have 
found in my career. One really has to do hands-on help. We have 
been doing that with our Research-to-Practice program. On the 
next poster that is the two blue dots over there; one is in New 
York State and the other in North Carolina. It began with a 
conference of treatment program supervisors because they are 
the only ones that can make things happen. Together we had a 
very interesting meeting a year and a half ago where the 
supervisors and the researchers in the treatment world from our 
Institute came together. The researchers to tell about the 
innovations, the treatment folks to talk about how difficult it 
is for various reasons to get these innovations into the real-
world.
    We have just begun the next step. The researchers are going 
to be spending several days themselves directly visiting these 
treatment programs, six of them have volunteered in New York 
State, to see if we can bring the various innovations into 
treatment, such as new medications, such as manual directed 
behavior therapy, better data collection, and so on. This is an 
experiment to see whether under real conditions we can make 
these changes which even the best publications alone cannot do, 
in my opinion. North Carolina and other States are interested 
in doing this, too and it is already in progress.
    This completes my perhaps overlong statement. I would be 
delighted to answer any questions you have.
    [The written statement of Dr. Gordis follows:]



                      FUNDING FOR ALCOHOL RESEARCH

    Mr. Porter. Thank you, Dr. Gordis.
    This question is for Dr. Kirschstein. With one in four 
hospital beds, $185 billion, one in four families, the number 
one cause of disability, why do we keep underfunding alcohol 
research as opposed to hard drug research? Is it that it is a 
legal drug? Does the industry prevent us from putting more 
resources here? Is there not enough good science available? Is 
it because moderate use of alcohol has been said to have good 
health benefits? Why are we not giving this more effort? Do we 
think that we cannot do anything about it?
    Dr. Kirschstein. Mr. Chairman, that is a very complex 
issue. Dr. Gordis and I have had, since January 3rd, when I 
started in this position, numerous discussions about it. I 
think part of the answer comes from all of the issues that you 
have mentioned. I do not think there is not enough good 
science. I do not think it is purely a result of the fact that 
many people believe that there are some benefits to parts of 
the body, possibly the cardiovascular system, from moderate 
alcohol consumption. I do not think it is all of the other 
things that you have mentioned. I do not really know the answer 
and I am not sure anybody does.
    But when somebody gets to the point, where the crucial 
decisions have to be made, other priorities sometimes take 
over. Dr. Gordis and I have talked about how we, at NIH, can 
rectify this. I think we can only do it at the margins. 
Certainly, from the amount of discretionary funds that might be 
available from the $1,000,000,000 that the President has asked 
for, only small amounts can go to this Institute because there 
are demands from the science done by other Institutes also. The 
process has been a long-standing one, and it is going to be 
very difficult to make the kinds of corrections that this area 
demands under the current circumstances. I think it is a 
cumulative series of events.
    Mr. Porter. I guess I do not understand that answer, 
because it seems to me that we have been saying the same thing 
for a long time here, that this is a very serious area that has 
very deleterious effects on our society and affects every 
family in the United States. We keep saying we do not want to 
politically make the judgments as to where the money goes, but 
please look at this and do a better job of addressing these 
needs. I do not see a lot of progress being made. Congress 
obviously has the power to move or add $100,000,000 or 
$200,000,000 and say here it is, now go out and expand your 
outlook and see if we can't make greater progress in this area. 
Obviously, we do not want to do that. We shy away from doing 
that. In fact, we do everything we can to avoid doing that, but 
it is possible.
    I do not see a lot of progress being made in ramping up 
this Institute to the point where I think most Members of 
Congress who gave it some thought would think it ought to be in 
terms of its priority. I just despair sometimes at seeing our 
low level of funding relatively for an area that I think 
deserves a great deal more attention. That is not a question.
    Dr. Gordis, if we gave you substantially more money, is 
there enough good science out there for you to spend it wisely?

                        SCIENTIFIC OPPORTUNITIES

    Dr. Gordis. Well the short answer is, yes. The long answer 
I am not sure you want to hear. Yes, we have many plans which 
we can only touch on actually with the present budget and we 
will start on these to the best of our ability.
    Among the top ones we wish to do number one would be the 
application of many contemporary approaches using high 
technology to study the recovery process. As people recover and 
they are subject, in fluctuating ways, to the craving for 
alcohol which leads to relapse, many things are going on even 
in the abstinent phase which we really could understand now in 
a much bigger way. For example, we can use imaging to study the 
changes in the brain that occur from the time that a person is 
comfortable in sobriety to the time that the person feels this 
urge to drink again.

                    SLEEP AS A PREDICTOR OF RELAPSE

    We can study the abnormalities in sleep. It sounds like it 
is a remote and perhaps bizarre topic, but actually it is not. 
It turns out that the failure to restore normal sleep after 
recovering from being withdrawn from alcohol is predictive of 
relapse. And we know that alcohol has serious effects on the 
physiology of sleep and on the components of the sleep cycle, 
which you have probably heard about in other testimony. In 
fact, it may be related to the adolescent question we discussed 
before, because we know that the sleep needs and the sleep 
habits of adolescents change. Sleep may be a mirror into the 
brain in ways which I think we really ought to be tapping into.
    Another thing we should be doing in relation to recovery is 
the issue of cognition. We still do not know whether the 
cognitive impairment produced by alcohol itself is related to 
the propensity to relapse. I think with modern techniques we 
can determine that.
    And finally, the genetics of drug use and pharmacogenetics 
to see whether the reason why some people respond to naltrexone 
and others don't may be related to genes. That is only one 
project and I could tell you about a couple more.

                         INITIATION OF DRINKING

    Mr. Porter. Do you look at the other side of this, that is, 
the reason why people drink? Some say people drink to feel 
good. Others say people drink to not feel bad, in other words, 
to avoid depression, or the hard circumstances of their 
existence, or a bad relationship, or whatever it may be. Do we 
look at it from that side as well?
    Dr. Gordis. You have asked a very deep question which has 
answers at many levels. I think it is important to distinguish 
the forces which lead to the initiation of drinking from those 
which maintain addiction once it has been established. An 
example from smoking might be at the age of 40 you might try to 
recall why you took your first cigarette when you were 8, but 
that is not going to help you stop smoking two packs a day when 
you are 40 years old. So the issue of what starts the drinking 
is probably different from what sustains it.
    Now as far as what starts it, we have major longitudinal 
studies in which we study family relationships and we study 
qualities of young people such as shyness or aggressiveness 
which have been known to predict all sorts of aberrant 
behaviors ten years after kindergarten. And, of course, we 
study all sorts of social effects on drinking, such as 
advertising and so on.
    But what maintains the drinking once the addiction has 
begun may be quite independent of that. In fact, the best 
evidence now is that there is no genetic role at the time of 
onset of use, that onset is all an environmental, familial 
thing, but not genetic. But once the use begins, the various 
genetic factors kick in.
    You have raised a point about addiction itself, which is 
also a subject for study. You have heard a lot from both Dr. 
Leshner and me over the years about the reward circuits in the 
brain, and about dopamine being one of the central 
neurotransmitters. It is hardly the only one but it is 
certainly an important one. In people who are addicted somehow 
their reward circuit is either hungry for more alcohol or the 
alcohol is so rewarding they drink more, and one hears many 
explanations. We continue to study these issues.
    The other side of it, called the ``alcohol deprivation 
effect'' is what is being studied now. That is the opposite 
side of the coin. What is the nature of the discomfort that 
exists when chronic alcohol use is interrupted? That is really 
very different and it probably involves different circuits and 
different neurotransmitters. For example, I mentioned the 
European drug Acamprosate which is coming down the road and is 
now being reviewed by the FDA. This drug probably works on 
those circuits having to do with the relief of deprivation 
rather than the reward circuits affected by naltrexone, which 
has been approved already.
    So your question really is very wide-ranging and it applies 
in some ways to the initiation of drinking in one body of 
research, and to the maintenance of addiction as another body 
of research.
    Mr. Porter. Thank you, Dr. Gordis.
    Ms. Pelosi?

                      PROFESSIONAL JUDGMENT BUDGET

    Ms. Pelosi. Thank you, Mr. Chairman.
    Welcome, Dr. Gordis, and to all of you, thank you for your 
excellent work. Dr. Kirschstein, thank you for what you are 
doing at the NIH and what you have done over the years.
    Dr. Gordis, we were together in San Francisco at a 
convention of some kind and we talked, that was several years 
ago, we talked about the prospect of doubling the NIH budget in 
a short period of time. Our Chairman is doing his best to do 
that and we are all trying to help him. I would hope that with 
all of that increased funding that your Institute would 
benefit.
    What was your professional judgement request?
    Dr. Gordis. It was about $100,000,000, 40 percent.
    Ms. Pelosi. More?
    Dr. Gordis. Of an increase, yes.
    Ms. Pelosi. It was like $380,000,000----
    Dr. Gordis. Yes, for fiscal year 2001.
    Ms. Pelosi. So you wanted a 40 percent increase?
    Dr. Gordis. Yes. We are talking about compensation for, as 
Mr. Porter said, years in which the disparities in budgets have 
been growing.
    Ms. Pelosi. I associate myself with the concern expressed 
by our distinguished Chairman as to the size of the problem 
that is being defined and the resources that you are receiving. 
So your professional judgment request was 40 percent higher 
than last year. And how much higher than what is in the budget?
    Dr. Gordis. How much higher than what it would be now in 
the President's budget?
    Ms. Pelosi. Yes.
    Dr. Gordis. Probably about 30-35 percent.
    Ms. Pelosi. So you got, what, $288,578,000. I have got to 
check my notes here.
    Dr. Gordis. That's correct.
    Ms. Pelosi. The budget request is $288,578,000?
    Dr. Gordis. That is right.
    Ms. Pelosi. So you asked for what, $388,000,000?
    Dr. Gordis. Right. That was the professional judgement 
budget.
    Ms. Pelosi. I understand that, and I know what the process 
is from there on in. The litany that you presented to the 
Chairman's question about what other opportunities there were 
that if you had more funding was quite impressive.
    Do you think we are in a state of denial in our country 
about alcoholism and that is why we are not putting the 
resources to it?
    Dr. Gordis. I think your question hits on a good deal of 
the issue. Certainly, the war on drugs is so important and it 
has commanded public attention in a way which alcohol issues 
have not and yet alcohol costs more and kills more than all the 
illegal drugs together. The denial is probably a good deal of 
it. It is a legal substance. It has been made the butt of jokes 
in our media and it is part of culture for a long time. It also 
has a proper use and a use which people enjoy without any 
noxious effects at all. And there is a legal industry involved 
with it in this country as well.
    But what is disturbing is to hear a parent say ``at least 
he is not using drugs.'' Because the drug which is most likely 
to kill your kid is alcohol. So, you are quite right, I think 
denial is part of it and perhaps a lack of conscientiousness 
about it is the other.
    Ms. Pelosi. I always ask you this question, being a 
Californian, could you comment on any beneficial effect of a 
moderate consumption of alcohol and wine?
    Dr. Gordis. Yes, it is an area of research which we have 
invested I think over $2,000,000 this past year, if I am not 
mistaken. There is no question that an extensive series of 
studies, most of them consistent, not all, have shown an 
association between moderate drinking and a reduced rate of 
heart disease. I had better define moderate drinking for 
everybody, which is no more than two standard drinks for a man 
or one standard drink for a woman per day, and also the same 
one drink a day for the elderly, for reasons which we can talk 
about later if you want. There is no question that at that 
level, or even less, there has been an association between that 
level of drinking and a reduced death rate from heart disease, 
which is a major chunk of mortality in general in this country.
    What I am not persuaded of is that we have proven that this 
association is causal. And that is what we are working on. The 
reason why that is important is because if we are going to 
recommend drinking as a public health policy, which I do not 
think we ought to do, we better have our ducks in a row, and we 
don't. We are supporting research on the biologic mechanisms 
which could account for causality if causality were there, 
effects on lipoproteins, effect on blood clotting in various 
ways, platelets and tissue plasma, as an activator, and so on. 
But, as a matter of fact, we do not know that the association 
is causation because there are other surrogates which could be 
represented by the drinking affecting this reduction such as 
exercise, fat intake, social class, education, health care 
habits, and so on down the line.
    It is a complex issue in which our advice, to sum it up, 
would be if you are drinking moderately with no problems, enjoy 
it. Don't start drinking just for the health benefits because 
there are other ways to get them.
    Ms. Pelosi. And I think that in defining moderation, what 
you are talking about is just a little bit of intake.
    Dr. Gordis. Yes. It is one or two drinks a day. And a drink 
would be an ounce and a half of hard liquor, four or five 
ounces of wine, or a 12-ounce can of beer. They all have 
roughly the same amount of alcohol with roughly the same 
effects.
    Ms. Pelosi. Moderation is a relative thing and we have to 
make sure people understand it is a small amount that is what 
is considered moderation here.
    Again, thank you very much for all that you do.
    Dr. Gordis. I have been corrected, Ms. Pelosi. The 
$388,000,000 is non-AIDS. It would be $411,344,000 with the 
AIDS funds if the professional budget became a glorious 
reality.
    Ms. Pelosi. Does the $288,000,000 contain the AIDS money?
    Dr. Gordis. The $288,000,000 is non-AIDS.
    Ms. Pelosi. Non-AIDS. Okay. Thank you so much.
    Thanks, Mr. Chairman.
    Mr. Porter. Thank you, Ms. Pelosi.
    Mr. Jackson.
    Mr. Jackson. Thank you, Mr. Chairman.
    Dr. Gordis, thank you. Your reputation in this particular 
field of study is unparalleled. I want to congratulate you for 
the work that you have been doing in this area.
    Dr. Gordis. Thank you.

                     support for health disparities

    Mr. Jackson. The President's fiscal year 2001 budget for 
your Institute is $288,600,000, an increase of $14,600,000 and 
5.3 percent above fiscal year 2000. Included in this total is 
$5,000,000 for the following NIH areas of priority: biology of 
the brain, $2,000,000; new preventive strategies against 
disease, $2,000,000; and development of therapeutics and the 
genetics of medicine, $1,000,000.
    According to this budget request, minority research does 
not seem to have a problem in this area worthy of study. Do you 
want to comment on that?
    Dr. Gordis. I am sorry. I did not hear the last sentence, 
Mr. Jackson.
    Mr. Jackson. According to this budget, unlike the other 
Institutes that have been before me which have set aside some 
money for health disparities in this particular area, but in 
your budget there is no money set aside to look at the problem 
of disparities. So I wanted to hear what your response to that 
was.
    Dr. Gordis. We have had a long-standing and extensive 
commitment to research of minority issues and alcohol issues 
related to health disparities as well. In fact, anticipating 
the discussion that we would have with you today on this, we 
did try to make the most careful estimate, and we will even 
sharpen it up further for the record, where we stand on the 
issues that you raise.
    Minority health research funding, I am not talking about 
researchers but rather the content of the research material, 
has gone from 10 percent in 1993 to 16 percent of our budget in 
1999, a total of approximately $41,000,000. And if you will 
permit me, Mr. Jackson, may I describe some of the activities 
that go on in these areas.
    Mr. Jackson. Would you please.
    Dr. Gordis. Thank you. It is a very big area and I could 
subdivide it into several compartments I think for the sake of 
discussion. We are very much interested, for example, in ethnic 
differences in prevalence because these can have both social as 
well as biological reasons. For example, we know that in fetal 
alcohol syndrome the incidence of fetal alcohol syndrome in the 
African-American population is six times greater than in the 
white population, among Native Americans it is close to thirty 
times greater. We are very busy trying to determine the 
possible biological sources of this inasmuch as these 
differences seem to be present, at least in part, even when the 
intake of alcohol by the mothers is the same.
    Another area we are very interested in studying is why is 
the life trajectory of alcohol use in different ethnic 
populations disparate. And by the way, on every one of these 
topics we have ongoing research and planned research. I am not 
telling you topics where the work is not going on. It is. We 
know, for example that among adolescents, the young African-
Americans drink less than their white counterparts. And yet, 
later on in life, the alcohol problem seems to be very big and 
the cirrhosis death rate among middle-aged African-Americans is 
very high indeed. As you can see we are exploring health 
disparities in the issue of liver disease and fetal alcohol 
syndrome for both social and biological differences.
    Mr. Jackson. Dr. Gordis, let me ask that the remaining 
parts of this be submitted for the record, and I will explore 
the record, so that I can ask a couple of additional questions 
before my time expires.
    I was wondering if there are any studies at the National 
Institute on Alcohol Abuse and Alcoholism between malt liquor 
and beer, for example, that you are aware of.
    Dr. Gordis. No, I do not know of any studies on that, 
unless you are referring to concentration differences.
    Mr. Jackson. I think I am going to get to concentration 
differences in a moment. Where I am going with this is I am 
wondering if the Office on Research on Minority Health provided 
you with the demographic information on who is likely to 
consume malt liquor versus populations that are likely to be 
let's say beer consumers or wine consumers or hard liquor 
consumers. The reason I am going at this is because 
objectively, without having studied any research, and I am not 
a big beer drinker, but I do know that in my community, for 
example, malt liquor is marketed in 40-ounce containers. Not 
being a big beer drinker, I do know that if you open a beer it 
is just a matter of time before that beer goes flat and you 
throw it away because that beer doesn't mean anything. But 
marketing a highly concentrated form of malt liquor in a 40-
ounce container, there is a presupposition there that if you 
open a 40-ounce container that the consumer is to consume the 
entire 40 ounces, which could not possibly keep someone sober 
very long. Trust me, I know this one. [Laughter.]

                  MARKETING TO UNDERSERVED COMMUNITIES

    So I wonder if someone who opens a 40-ounce container and 
whether or not they are actually being encouraged to consume it 
before it goes flat is worthy of research at the National 
Institute on Alcohol Abuse and Alcoholism. And furthermore, the 
study of that type of liquor involved in domestic abuse and 
domestic violence cases particularly in underserved communities 
because specifically of corporate America's marketing of this 
container and this concentration of alcohol in those 
underserved populations, whether or not that is worthy of 
research in your department.
    Dr. Gordis. I am going to ask Dr. Calhoun to respond 
because she has this information at the tip of her fingers.
    Dr. Calhoun. Mr. Jackson, it gets worse. We were recently 
in Los Angeles and we saw a 64-ounce, not just a 40-ounce, a 
64-ounce.
    Mr. Jackson. A 64-ounce container?
    Dr. Calhoun. A 64-ounce container. We have been very 
successful in developing alcohol research at Drew University. 
The focus of that research effort at Drew is prevention and 
intervention in the African heritage and Hispanic communities 
in Los Angeles. We have been able to partner researchers and 
clinicians at Drew University with our very senior researchers 
at Berkeley and together they are developing research projects 
on just that and also on geomapping, in other words, 
determining where alcohol issues are occurring around the sale 
and distribution of alcohol in L.A.
    Mr. Jackson. Doctor, let me ask you a question since this 
appears to be your area of expertise. I am just wondering if 
you are aware of any test at the National Institute on Alcohol 
Abuse and Alcoholism of the neuropeptide Y tests that were done 
on--this is this thing that you showed earlier. I have no idea 
what half the terminologies are that come before me in this 
committee sometimes. But I saw a couple of rats which if in 
fact they consumed a certain amount of a certain kind of 
liquor, which remained unclear to me, that they behaved a 
certain way based upon the amount of liquor consumed. I am 
wondering if there has ever been a test on what 64-ounces of 
malt liquor would do to an neuropeptide Y rat and whether or 
not it would do what I think it probably do, and that is knock 
a rat out.
    Dr. Gordis. We have a lot of information which we have 
known for a long time, Mr. Jackson, on absorption of alcohol, 
how rapidly blood levels change, how much you need to have for 
intoxication at different levels. Certainly, a concentrated 
drink drunk in a short amount of time is going to get the blood 
level up much higher than a more dilute drink drunk over a 
longer period of time. Those distributions we know quite well. 
So there is nothing specific about malt liquor except the fact 
that it is concentrated and it comes in large volumes. We have 
ways of actually calculating given a certain person of a 
certain weight----
    Mr. Jackson. And who it is marketed to, would you not 
agree?
    Dr. Gordis. Pardon me?
    Mr. Jackson. And who it is marketed to.
    Dr. Gordis. I was just talking about the pharmacology. The 
whole issue of marketing, especially to minority communities, a 
very important question and it is somewhat distinct from the 
issue of the way alcohol is distributed in the body.
    Mr. Porter. Will the gentleman yield for a second?
    Mr. Jackson. I would be happy to yield.
    Mr. Porter. He raises an issue, and you probably know the 
answer to this, but it seems to me that some of our media 
groups like 60 Minutes or 20/20 ought to look into this whole 
subject. It seems to me that the industry is really morally 
guilty here of bringing people to alcohol abuse and alcoholism 
by that kind of an approach. I have been disturbed for a long 
time how the State lotteries, if you watch the advertising for 
State lotteries, put them in the poorest communities in hopes 
of selling more of the lottery tickets there instead of in 
other areas. There is obviously a targeting of poor people to 
get them to spend their money on lottery tickets, understanding 
that this is a way that they would see out of their poverty. It 
seems to me there is a moral element here that the national 
media ought to skewer industries that do things like that.
    Mr. Jackson. Mr. Chairman, I could not agree with you more. 
I really wish 60 Minutes would do something on it. But I do 
know that the President of the United States is requesting a 
little more than a quarter of a billion dollars for this 
Institute and maybe there are some studies that we can do on 
this subject. I am hoping at some point in time a 
recommendation will come from this Institute to the NIH 
Director, then on to the Secretary of Health and Human 
Services, and then to the President that we need to convene 
these manufacturers and these bottlers and say, hey, we have 
got you.
    Thank you, Mr. Chairman.
    Mr. Porter. Thank you, Mr. Jackson.
    Dr. Gordis, thank you for the fine job you are doing there. 
Again, I think the resources are not sufficient to match the 
magnitude of the problem that you are researching. I just think 
you have done a wonderful job there and we need to give you 
more resources to do it even better.
    Dr. Gordis. Thank you.
    Mr. Porter. Thank you, Dr. Gordis.
    The subcommittee stands in recess until 10:00 a.m., 
February 29th.
    [The following questions were submitted to be answered for 
the record:]
    Offset Folios 1871 to 1927/2200 Insert here





                           W I T N E S S E S

                              ----------                              
                                                                   Page
Alexander, Dr. Duane.............................................   875
Baldwin, Wendy...................................................     1
Battey, Dr. J.F., Jr.............................................   545
Beldon, W.A......................................................   997
Bravo, Dr. N.R...................................................   997
Burgess, E.S.....................................................   625
Calhoun, Faye....................................................  1219
Cassman, Dr. Marvin..............................................   997
Chantry, Kathryn.................................................  1069
Collins, F.S.....................................................   625
Coy, G.J.........................................................   737
du Buy, Yvonne...................................................   737
DuFour, M.C......................................................  1219
Fried, A.D.......................................................   875
Gordis, Enoch....................................................  1219
Gottesman, M.M...................................................     1
Hodgkins, G.E....................................................   997
Hondros, N.P.....................................................  1219
Hooven, T.E......................................................   875
Hrynkow, Sharon..................................................  1069
Hudson, K.L......................................................   625
Iteillag, Anthony................................................     1
Jones, Donna.....................................................  1139
Jordan, Elke.....................................................   625
Kerr, W.D........................................................   545
Keusch, G.T......................................................  1069
Kirschstein, Dr. 1, 221, 545, 625, 737, 819, 875, 997, 1069, 1139, 1219
Klausner, R.D....................................................   221
Kleinman, Dr. Dushanka...........................................   737
Leasure, C.E., Jr................................................   625
Leshner, A.I.....................................................  1139
Levine, S.U......................................................   819
Lindberg, Dr. D.A.B..............................................   819
Lipman, Dr. D.J..................................................   819
Long, S.W........................................................  1219
Luecke, D.D.H....................................................   545
Maddox, Yvonne...................................................     1
Miller, Richard..................................................  1069
Pine, Martha.....................................................   997
Quantius, S.E....................................................     1
Rabson, A.S......................................................   221
Slavkin, Dr. H.C.................................................   737
Smith, K.A.......................................................   819
Sparks, P.T......................................................   545
Whalen, J.M......................................................   875
Williams, D.P........ 1, 221, 545, 625, 737, 819, 875, 1069, 1139, 1219


                               I N D E X

                              ----------                              

                     National Institutes of Health

                                                                   Page
Administrative Costs.............................................    83
Advisory Committees..............................................    67
Allocation of Resources.....................................15, 41, 110
Allocations Among Institutes and Centers.........................   141
Applications for 1999 and 2001...................................    65
Applied Knowledge Practice.......................................    79
Assumptions and Priorities for Budget Increases..................    24
Bioinformatics...................................................   104
Biomedical Research and Development Price Index..................    67
Breakout of NIH Budget...........................................    71
Cancer Research..................................................    98
Children and Clinical Trials.....................................    94
Clinical Research................................................   123
Clinical Trials..................................................41, 48
Clinical Trials Program..........................................    73
Competing Grants.................................................   111
Complementary and Alternative Medicine...........................    72
Construction and Renovations.....................................    33
Cost for Electronic Grants Processing............................    72
CSR Reorganization...............................................    69
Culture of Research..............................................    91
Decrease in New Grants...........................................    85
Delayed Obligations.........................................20, 24, 112
FY 2001 Delayed Obligations......................................   112
Detailed Budget Breakout.........................................    57
Diabetes....................................................20, 33, 125
    Diabetes Research Working Group............................142, 152
    Resource Allocation..........................................   143
    Funding......................................................    37
    National Diabetes Education Program..........................   145
Direct Reimbursement.............................................    53
Director's Advisory Committee....................................    33
Director's Discretionary Funds...................................    60
Doubling of NIH Budget...........................................    82
Doubling of NIH Budget and Administration........................    83
Earmarks.........................................................    16
Electronic Grant Processing......................................    72
Estimated Spending by Disease....................................    65
Fiscal Responsibility and Accountability.........................44, 99
Food Safety Initiative...........................................    57
FSH Disease......................................................   105
Funding Allocations..............................................     3
Future of Medical Research.......................................    96
FY 1999 and 2000 Commitment Base.................................   115
Gene Therapy Research............................................   117
Gene Sequencing..................................................    87
General Clinical Research Centers................................   107
Genome Project...................................................    19
Grant Support....................................................   113
Health Disparities...........................................38, 70, 93
Hispanic Researchers.............................................   157
Human Genome Project.............................................    84
IdeA Program.....................................................    34
Imaging Research.................................................    22
Inclusion of Hispanics in NIH Clinical Trials....................   150
Increase for Competing Grants....................................   114
Indirect Costs...................................................   120
Innovative Clinical Trials Programs..............................    74
Investigators in Biomedical Research.............................    53
Managed Care and Clinical Research...............................    56
Measuring Success................................................    51
Mental Health Issues.............................................    50
Neuroscience Research............................................    33
New Investigators................................................    94
New and Competing Grants.........................................   114
NIH Allocation Process...........................................    46
NIH Budget Request...............................................    82
NIH Commitment to H.R. 2391......................................    39
NIH FTE Level....................................................    54
NIH FTE's........................................................    61
NIH Partnerships.................................................    67
Obesity Prevention...............................................    54
Opening Statement................................................  1, 5
Outreach.........................................................44, 87
Outreach to Community Advocates..................................    42
Oversight........................................................   118
Parkinson's......................................................   140
Peer Review Committees...........................................    37
Peer Review Process..............................................   121
President's Increase.............................................    89
Priorities.......................................................    90
Priority Setting.................................................   119
Privacy Regulations..............................................   116
Professional Judgement...........................................    17
Public Education Activities......................................    64
Quality of other Agencies' Research..............................    92
Reducing Regulatory Burden.......................................    86
Reducation of New Research Grants................................    97
Regulatory Burdens...............................................    70
Regulatory Reform and Paperwork Reduction........................    84
Research Accountability..........................................   102
Research Advances................................................     2
Research Breakthroughs...........................................    40
Research Funding Per Death.......................................23, 81
Research Grants..................................................    18
Review of NIH....................................................    20
RMS and Non-RMS Actuals and Estimates............................    63
Scientific Misconduct............................................    47
Scientific Resources.............................................    19
State Funding....................................................    46
Stem Cell.......................................................45, 126
Success Rates....................................................   109
Support for Clinical Research....................................   107

                       National Cancer Institute

Actual Number of Deaths Decreasing...............................   222
Alcohol Consumption and Cigar Smoking as Cancer Risks............   281
All Ireland Cancer Consortium....................................   252
Analyzing the Atlas Data.........................................   250
Angiogenesis.....................................................   268
Atlas of Cancer Mortality........................................   249
Basic Cancer Research............................................   272
Behavior and Nutrition Cancer....................................   264
Biotherapeutics in Cancer Therapy................................   287
Breast Cancer..................................................318, 322
Breast Implants..................................................   281
Burden of Cancer...............................................221, 226
Cancer:
    Cancer Cell Line Screens.....................................   296
    Cancer Cube..................................................   272
    Cancer Mortality Rate Falling................................   222
Cancer and Minorities:
    African-American Cancer Burden...............................   258
    Attracting Minority Researchers............................262, 263
    Funding for Research on Cancer in Minorities.................   258
    Minority Researchers.........................................   259
    Office of Research on Minority Health........................   257
Carcinogen Listings..............................................   302
Centers:
    Centers of Excellence......................................274, 286
    Centers of Excellence for Drug Development...................   282
    NCI Cancer Centers...........................................   297
Cervical Cancer................................................254, 320
Diagnosis of Cervical Cancer.....................................   280
Clinical Researches and Trials:
    Clinical Research Advances...................................   290
    Clinical Trials--A Cornerstone of Progress for Patients......   233
    Insurance Payment for Clinical Trials........................   286
Decline in Prostate Cancer Deaths................................   290
Drugs:
    Drugs and Natural Products Development.......................   249
    Laboratory of Drug Discovery Research and Development........   296
Earlier Research.................................................   309
Early Detection Research Network...............................248, 273
Enterprise Vocabulary System.....................................   276
Fiscal Responsibility and Accountability.........................   310
Funding and Grants:
    Number of New Grants.........................................   255
    Reduction of New Research Grants.............................   307
    Total Funding of Cancer Research.............................   247
Future of Medical Research.......................................   305
GIS..............................................................   283
Goals of Cancer Research.........................................   222
Health Disparities...............................................   297
High Dose Chemotherapy...........................................   265
Homeopathy Community.............................................   285
Human Papillomavirus.............................................   267
Imaging:
    Imaging Cancer...............................................   231
    Magnetic Imaging of Thermal Effects..........................   280
International Cancer Consortiums.................................   251
Justification of the FY 2001 Budget Estimates....................   326
Markers for Cancer...............................................   255
Microvascular Complications in Diabetes..........................   289
Middle East Cancer Consortium....................................   251
Molecular Targets--New Approaches to Prevention & Treatment......   232
Molecular Profiles Guide Clinical Decisions......................   223
Mortality Maps...................................................   319
Multidisciplinary Molecular Biology..............................   300
National Network for Causes of Cancer in Children................   279
National Prostate Cancer Tissue Resource.........................   271
New Approaches to Detection and Diagnosis........................   229
Other Cancer Research Sources....................................   301
Ovarian Cancer...................................................   322
    Ovarian Cancer Research......................................   252
    Ovarian Spore................................................   270
Pediatric Neuro-Oncology.........................................   278
Planning for Cancer Research.....................................   245
Prevention Research..............................................   246
Progress in Basic Research.......................................   229
Prostate Cancer Deaths...........................................   305
PSA and Reduction in Prostate Cancer Mortality...................   292
Quality Cancer Care--A Research Agenda...........................   234
Reduce Cancer Mortality by Half..................................   245
Refining Early Detection.........................................   250
Research:
    Accountability...............................................   312
    Career Path..................................................   261
    Consortia....................................................   246
Rural Poor.......................................................   264
Seer/Medicare Data...............................................   303
Solid Tumor Spore................................................   270
Specialized-Comprehensive Research Centers.......................   277
Statement of the Director........................................   225
Strategic Planning for Minority Health Research..................   260
Targeted Therapy.................................................   247
Tobacco:
    Cigar Use....................................................   304
    Smoking Trends...............................................   253
    Tobacco Initiatives..........................................   275
Understanding Molecular Profiles.................................   223

    National Institute on Deafness and Other Communication Disorders

Allocation of Funds..............................................   562
Americans with Disabilities Act..................................   561
Animal Models....................................................   559
CMV Infection and Newborn Testing Cost...........................   575
Cochlear Implant Research........................................   560
Computer Modeling in Research....................................   562
FY1999 Awards for Grants and Contracts by State..................   564
Gene Therapy.....................................................   559
Hearing Ability and Early Childhood Development..................   577
Intervention Strategies For Infants..............................   576
Introduction of Witnesses........................................   545
Justification....................................................   579
New Grant Guidelines.............................................   573
Newborn and Infant Hearing Screening and Intervention Act........   574
Opening Statement................................................   545
Selected Funding Levels..........................................   573
Specific Language Impairment.....................................   577
Statement by the Director........................................   550
Uses of Additional Funds.........................................   572

                National Human Genome Research Institute

Ahead of Schedule and Under Budget...............................   665
Alliance of Genetic Support Groups...............................   684
Availability of Genetic Tests....................................   658
Benefit to Human Health........................................636, 660
Benefits of the Human Genome Project.............................   694
Budget Mechanisms................................................   680
Chromosomes--Numbers, Sizes, Shapes..............................   669
Comparative Genomics.............................................   635
Computational Biology............................................   636
Consumer Day.....................................................   685
Curriculum Development for Primary Care Physicians...............   683
Curriculum Supplement for Genetics...............................   685
Diabetes Research................................................   668
Ethical, Legal and Social Implications....................636, 662, 682
Faster Completion of the Human Genome Project....................   686
Fruit Fly Genome...............................................641, 674
Francis Collins' Curriculum Vitae................................   643
Free Access to Fundamental Information...........................   633
Functional Genomics..............................................   635
Future of the HGP................................................   661
Gene Based Risk Behavior.........................................   667
Gene Patenting..................................647, 648, 687, 693, 694
Genetic Discrimination in the Workplace..........................   683
Genetic Links to Factors in Different Populations................   689
Genomes Being/To Be Sequenced..................................673, 678
Genomes of Differing Sizes.......................................   646
Glutaric Aciduria Type II C......................................   686
Greatest Intellectual Moment...................................637, 659
Guidelines for Cystic Fibrosis...................................   682
Health Outcomes in Developing Areas..............................   671
Health Disparities...............................................   690
Human Chromosome 22 Sequenced..................................633, 639
Human Genetic Variation........................................635, 640
Human Sequence Production............................628, 629, 638, 639
Increase in Sequence Rate........................................   645
Individualized Gene-Based Risk Information.....................684, 691
Justification of FY 2001 Budget Estimate.........................   697
Legislation Needed...............................................   663
Mammalian Gene Collection........................................   677
Mouse Sequencing Network.......................................640, 676
Opening Statement................................................   638
Oral Remarks.....................................................   625
Other Goals of the HGP...........................................   635
Pharmaco Genetics................................................   664
Private Sector Growth............................................   646
Professional Judgement Budget....................................   693
Protections from Genetic Discrimination..........................   692
Rett's Syndrome Gene Identified..................................   666
Safeguarding the Fair Use of Genetic Information.................   642
Secretary's Advisory Committee on Genetic Testing................   676
Sequencing Milestones..........................................625, 626
Short-Term and Long-Range Research...............................   689
Tools for Understanding the Human Genome.......................634, 641
Unclonable Gaps in Chromosomes...................................   677

         National Institute of Dental and Craniofacial Research

Biomimetics and Tissue Engineering...............................   780
Birth Defects....................................................   775
Bone Clinic......................................................   765
Bone Research....................................................   770
Burden of Diseases and Disorders.................................   738
Burden of Facial Deformities.....................................   773
Centers for Research to Reduce Oral Health Disparities...........   758
Centers of Discovery.............................................   765
Chairman's Tribute to Dr. Slavkin................................   763
Craniofacial Birth Defects.......................................   772
Craniofacial, Oral and Dental Genes..............................   754
Dental Care in America...........................................   757
Dental X-Rays....................................................   771
Diversity in the Research Workforce..............................   761
Funding Mechanism................................................   766
Genes Discoveries--Rapid Rate of Progress........................   739
Genes of Inflammation............................................   740
Genetic Technology...............................................   755
Head and Neck Cancer.............................................   762
Justification of FY 2001 Budget Estimate.........................   781
Linkages with the Office of Research on Minority Health..........   761
Low-Birth-Weight Babies..........................................   754
Minority Researchers.............................................   759
Opening Statement................................................   737
Oral Health of Senior Citizens...................................   757
Oral Health Disparities..........................................   760
Oral and Systemic Diseases.......................................   777
Oral Infection and Low-Birth-Weight Babies.......................   739
Oral Infection and Systemic Diseases...........................756, 779
Oral Remarks.....................................................   737
Periodontal Infections and Low-Birth-Weight......................   771
Return of Investment in Oral Health Research.....................   763
Saliva-Based Diagnostics.........................................   760
Surgeon General's Report on Oral Health..........................   757
Temporomandibular Joint Disorders................................   767
Tissue Engineering...............................................   767

                      National Library of Medicine

Biological Information Science Technology........................   840
Clinical Trials Information......................................   830
Consumer Health Information....................................828, 840
Exhibits.........................................................   841
Funding Mechanism................................................   839
High Performance Computing and Communications....................   837
Internet Connections.............................................   838
Internet Information...........................................827, 829
Introduction of Witnesses........................................   819
Isolated Areas and Information...................................   829
Justification of the FY 2001 Budget Estimate.....................   845
MedlinePlus......................................................   829
Opening Statement................................................   819
Outreach Program.................................................   843
Privacy Issues...................................................   837
PubMed Central...................................................   833
Smartcard Studies................................................   832
Smartcard Technology.............................................   831
Space Requirements...............................................   827
Telemedicine Projects..........................................836, 843
Training Programs................................................   841

        National Institute of Child Health and Human Development

Adolescent Health.........................................877, 894, 913
Adolescents and Smoking..........................................   893
Asthma...........................................................   892
Autism Research......................................876, 888, 892, 905
Behavioral Research............................................886, 918
Budget Including AIDS............................................   904
Child Neglect....................................................   924
Childhood Violence...............................................   910
Children in Clinical Trials......................................   908
Children's Health Habits.........................................   890
Curriculum Vitae.................................................   887
E. Coli..........................................................   909
Environmental Toxins.............................................   921
Funding for Selected Research Areas..............................   904
Glutaric Aciduria Type II C......................................   916
Health Disparities.............................................876, 883
HIV Research.....................................................   885
Introduction of Witnesses........................................   875
Justification of FY 2001 Budget Estimates........................   926
Juvenile Diabetes................................................   919
Mandated Research Programs.......................................   906
Maternal HIV Transmission........................................   901
Mathematics and Reading Skills...................................   912
Mental Retardation.............................................876, 881
Obesity Among Children...........................................   911
Pediatric AIDS Cases in the USA and in the World.................   902
Pediatric Trauma Research......................................877, 885
Pelvic Floor Dysfunction.........................................   922
Perinatology Research............................................   899
Publication of Research Results..................................   888
Reading Development............................................890, 896
Reading Disabilities.............................................   918
Rett Syndrome....................................................   899
Sodium Consumption...............................................   912
Statement of the Director......................................875, 879
Traumatic Brain Injury Clinical Trials Network...................   909
Vaccinations.....................................................   923

                      Fogarty International Center

Anti-Malarial Drugs..............................................  1097
Access to Treatments and Interventions...........................  1093
Budget Mechanism Table Including AIDS............................  1100
Capacity Building................................................  1072
Cultural Implications............................................  1093
Drug-Resistant Malaria...........................................  1097
Ecology of Infectious Diseases Program...........................  1101
FIC Biodiversity Program.........................................  1098
FIC Budget Mechanism Including AIDS..............................  1100
FIC Mission and Budget...........................................  1095
Foundation Disciplines...........................................  1073
Global Burden of Disease.........................................  1071
Global Disparities in Health.....................................  1095
Global Efforts Against Smoking...................................  1073
Global Health Equity.............................................  1071
Global Partnership...............................................  1071
HIV/AIDS International Programs..................................  1104
Infectious Diseases in Developing Countries......................  1097
Justification of the FY 2001 Budget Estimates....................  1106
Leadership Role of FIC...........................................  1069
Malaria..........................................................  1072
Minority International Research Training Program.................  1101
New Direction of FIC.............................................  1099
New Initiatives for FY 2001......................................  1102
Opening Statement................................................  1069
Research Accomplishments.........................................  1070
Research Capacity Building.......................................  1096
Research Initiatives.............................................  1070
The Role of FIC..................................................  1092
Tuberculosis International Training and Research Program.........  1101

                    National Institute on Drug Abuse

Blue Prints Program..............................................  1168
Budget Mechanisms................................................  1170
Clinical Trials Network and Dually-Diagnosed Individuals.........  1176
Cocaine Addiction Vaccine........................................  1168
Colombia Initiative..............................................  1152
Coordination with NIAAA..........................................  1156
Coordination with ONDCP..........................................  1153
Demand Reduction Funding.........................................  1157
Drug Abuse Treatment Clinical Trials Network.....................  1169
Drug Prevention Coordination.....................................  1155
Drug Use.........................................................  1152
Environment and Drug Abuse.......................................  1161
Funding for Alcohol and Drugs....................................  1156
Health Disparities...............................................  1160
Hepatitis C......................................................  1172
Heroin Addiction.................................................  1154
Integrated Treatment and Public Health Programs..................  1177
Introduction of Witnesses........................................  1139
Justification of the FY 2001 Budget Estimates....................  1180
Mental Illness and Drug Abuse....................................  1176
Message to Children..............................................  1178
Needle Exchange..................................................  1164
Needs Gap........................................................  1164
Nicotine Vaccine............................................ 1157, 1174
Office of Research on Minority Health............................  1164
Opening Statement................................................  1139
Percentage of Drug Use...........................................  1163
Prevention.......................................................  1172
Prevention and Technology........................................  1160
Prison and Drug Abuse............................................  1162
Research-Based Guide to Drug Addiction...........................  1166
Sharing Information..............................................  1154
Statement of the Director........................................  1142
Substance Abuse and Father and Child Relationship................  1173
Success in Prevention............................................  1155

           National Institute on Alcohol Abuse and Alcoholism

Adolescent Alcohol Abuse.....................................1231, 1247
Advances in Prevention and Treatment.............................  1230
Alcohol Laws for Youth...........................................  1251
Alcoholism Problems in an Aging Population.......................  1247
Alcoholism and Co-occurring Illness..............................  1248
BAC Levels and Safety............................................  1223
Budget Mechanisms for the NIAAA..................................  1245
Cirrhosis and Tumor Necrosis Factor..............................  1222
Collaborations on Co-occurring Disorders.........................  1249
Damage to the Cerebellum.........................................  1221
Driving under the Influence of Alcohol...........................  1243
Family Strategies to Prevent Under-age Drinking..................  1254
Funding for Alcohol Research.....................................  1234
Genetics.........................................................  1228
Governor's Spouses Initiative....................................  1223
Initiation of Drinking...........................................  1235
Justification of the FY 2001 Budget Estimates....................  1255
Marketing to Under-served Communities............................  1240
Medications Development..........................................  1221
Medications for Alcoholism Treatment.............................  1246
Mixed Messages about Alcohol Use.................................  1252
National Alcohol Screening Day...................................  1224
Neuroscience.....................................................  1227
Neuropeptide Y...................................................  1221
Opening Statement................................................  1226
Outreach.........................................................  1232
Parents' Role in Preventing Underage Drinking....................  1251
Plasticity of the Young Brain....................................  1223
Professional Judgment Budget.................................1236, 1238
Reducing Marital Violence........................................  1222
Research to Practice.............................................  1224
Review of the Centers Portfolio..................................  1244
Scientific Opportunities.........................................  1235
Sleep as a Predictor of Relapse..................................  1235
Source of Messages about Underage Drinking.......................  1253
Support for Health Disparities...................................  1238
Surgeon General's Report on Underage Drinking....................  1243
The Genetics of Alcoholism.......................................  1220
Toxicology.......................................................  1229
Treatment of Alcoholism and Co-occurring Disorders...............  1249
WHO Report on Disability.........................................  1220

             National Institute of General Medical Sciences

Budget Mechanism Table.......................................1023, 1024
Collaboration with Industry......................................  1012
Collaborations...................................................  1026
Encouragement to Pursue Research Careers.........................  1017
Industry Involvement in Pharmacogenetics.........................  1014
Industry Support for Fundamental Research........................  1012
Interest in Research Careers.....................................  1019
Justification of FY 2001 Budget Estimate.........................  1032
Minority Opportunities in Research...............................  1022
Opening Statement and Introduction of Witnesses..................   997
Opportunities for Minorities.....................................  1016
Pharmacogenetics Initiative......................................  1025
Raising Public Awareness of NIH..................................  1020
Research and Development Contracts...............................  1023
Research Centers.................................................  1022
Resistance to Antibiotics........................................  1015
Shortage of Investigators in Special Fields......................  1013
Synchrotron Support..............................................  1022
Timeline for Discovering Genetic Functions.......................  1015
Tracking Students Supported on Training Grants...................  1017
Training Programs................................................  1026
X-Ray Crystallography............................................  1012

                                
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