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



 
                 DEPARTMENTS OF LABOR, HEALTH AND HUMAN
               SERVICES, EDUCATION, AND RELATED AGENCIES
                        APPROPRIATIONS FOR 1999

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

                                HEARINGS

                                BEFORE A

                           SUBCOMMITTEE OF THE

                       COMMITTEE ON APPROPRIATIONS

                         HOUSE OF REPRESENTATIVES

                       ONE HUNDRED FIFTH 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             LOUIS STOKES, Ohio
ERNEST J. ISTOOK, Jr., Oklahoma  STENY H. HOYER, Maryland
DAN MILLER, Florida              NANCY PELOSI, California
JAY DICKEY, Arkansas             NITA M. LOWEY, New York
ROGER F. WICKER, Mississippi     ROSA L. DeLAURO, Connecticut
ANNE M. NORTHUP, Kentucky        

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

  S. Anthony McCann, Robert L. Knisely, Carol Murphy, Michael K. Myers,
                and Francine Salvador, Subcommittee Staff
                                ________

                                 PART 4B
                            (Pages 1683-3189)

                      NATIONAL INSTITUTES OF HEALTH

                              

                                ________

         Printed for the use of the Committee on Appropriations
                                ________

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                       COMMITTEE ON APPROPRIATIONS                      

                   BOB LIVINGSTON, Louisiana, Chairman                  

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

                 James W. Dyer, Clerk and Staff Director













                            C O N T E N T S

                              ----------                              

                     NATIONAL INSTITUTES OF HEALTH

                           VOLUMES 4A AND 4B

                                                                   Page

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

National Cancer Institute........................................   333

National Eye Institute...........................................   627

National Human Genome Research Institute.........................   695

National Institute of Allergy and Infectious Diseases............   801

National Institute of Environmental Health Sciences..............   947

National Institute on Deafness and Other Communication Disorders.  1053

National Heart, Lung, and Blood Institute........................  1131

National Institute on Drug Abuse.................................  1277

National Institute on Alcohol Abuse and Alcoholism...............  1377

National Institute of Diabetes, Digestive and Kidney Diseases....  1481

National Library of Medicine.....................................  1619

National Institute of Nursing Research...........................  1683

Fogarty International Center.....................................  1753

National Institute of Arthritis and Musculoskeletal and Skin 
  Diseases.......................................................  1807

National Center for Research Resources...........................  1913

National Institute of Child Health and Human Development.........  1975

National Institute of Dental Research............................  2151

National Institute Mental Health.................................  2235

National Institute on Aging......................................  2355

National Institute of Neurological Disorders and Strokes.........  2445

National Institute of General Medical Sciences...................  2549

Office of the Director and National Institutes of Health 
  Buildings and Facilities.......................................  2619

Office of AIDS Research..........................................  2855

Noble Prize Recipients...........................................  2943

Child Health Hearing.............................................  3019




















DEPARTMENTS OF LABOR, HEALTH AND HUMAN SERVICES, EDUCATION, AND RELATED 
                    AGENCIES APPROPRIATIONS FOR 1999

                              ----------                              

                                         Wednesday, March 18, 1998.

                 NATIONAL INSTITUTE OF NURSING RESEARCH

                               WITNESSES

PATRICIA A. GRADY, DIRECTOR, NATIONAL INSTITUTE OF NURSING RESEARCH
MARY LEVECK, ACTING DIRECTOR, DIVISION OF EXTRAMURAL ACTIVITIES
MARY CUSHING, EXECUTIVE OFFICER
DR. HAROLD E. VARMUS, M.D., 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 this morning on the National 
Institutes of Health with the National Institute of Nursing 
Research. We're pleased to welcome Dr. Patricia Grady, the 
Director of the Institute. Dr. Grady, I apologize for being 
slightly late. We understand that Dr. Lindberg had the same 
problem I had, and we appreciate your being here and being able 
to start. So if you would introduce the people that are at the 
table with you and proceed with your statement, please.

                       Introduction of Witnesses

    Dr. Grady. Thank you, Mr. Chairman.
    Of course, Dr. Varmus is on my right, as he has been all 
week for you and for the staff. And Dennis Williams from the 
Department. On my left is Mary Cushing, the Executive Officer 
of NINR. And next to her is Dr. Leveck, who's the Acting 
Director of Extramural Activities.

                           Opening Statement

    We are pleased to appear before you this morning and have 
an opportunity to discuss the research that the National 
Institute of Nursing Research is doing. This morning, the 
President's budget for us is indicated at $68.3 million. That 
is including the approximate appropriation from the Office of 
AIDS Research, which is separate.
    I would like to say this morning that nursing research is 
currently at the frontiers of science. We are helping to build 
the foundation of knowledge for the Nation's providers of 
health care. The research that we do encompasses health 
promotion and disease treatment issues. It covers multiple age 
groups across the age span, and also population groups of all 
types, and people in a variety of settings, as well as acute 
hospital settings.
    Therefore, the research that we do is broad based. And you 
will find us in nearly every avenue into which you venture.

                       nursing research questions

    The questions that nurse researchers ask address the core 
of patients' and families' personal encounters with illness, 
and they also ask a number of questions that are very central 
to these issues.
    Examples of these questions, do men and women respond 
differently to therapeutic regimens used for relief of pain? 
We're finding out the answer is yes.
    What information is necessary and useful to help people 
reach decisions about genetic testing? We are funding that 
research. Also studies to determine what approaches will help 
to ease the symptoms of terminal illness. This is a central 
focus, studies that help patients maintain quality of life, 
dignity and sense of control throughout illness or at the end 
of life.
    Moreover, the research that we do involves multi-
disciplinary teams engaged in answering these questions, and 
basic and clinical research in health care. We say nurses bring 
life to research and bring research to life. This is in fact 
quite true.

                       arthritis self-management

    Let me give you some examples of how nursing research is 
making a difference. We funded a Spanish arthritis education 
and teaching self-management program which was translated into 
Spanish and tested for that population in California. The 
National Arthritis Foundation has adopted that program that was 
developed by the nurse researcher in Northern California, and 
is attempting to get the program adopted across the country. 
This researcher is also working with a local HMO to try to 
incorporate these principles into the care of arthritis 
patients. She is developing similar programs in Spanish for 
patients with other health problems such as cardiovascular and 
respiratory disorders.

                        pain and gender effects

    Our research has shown that gender does make a difference 
in pain relief. Researchers in California have been testing out 
certain compounds of drugs which were thought to be previously 
ineffective. The population in which they were tested was all 
male. In testing in a population that was predominantly female, 
these drugs do provide relief, and gender does make a 
difference.
    These have important implications for intervention and drug 
therapy in the future.
    Another example, a third example is one in which a 
nurseresearcher developed a scale to predict, within several days of 
admission of patients in nursing homes, which of that population would 
develop pressure ulcers. As you know, this is a very costly and serious 
complication for patients in nursing homes. The results of that 
research were translated into national guidelines, and those guidelines 
are now being used to inform care. So this is an example of the study 
that has made a difference in care and implementation.

                        early hospital discharge

    Another very important study that we funded and that is 
having impact is one that is a model for early hospital 
discharge. This model has been used in patient populations, 
including women with unexpected Caesarean deliveries, 
hysterectomies, and pregnant women with complications of 
diabetes. As a result of this program, which was nurse-run, 
patients have been able to be discharged earlier at a reduced 
cost in hospitalization and time spent.
    Moreover, and I think even more importantly, is that these 
patients report an increase in satisfaction in their quality of 
care and have stayed out of the hospital with a reduced number 
of unexpected re-hospitalizations and a reduced infection rate. 
This particular investigator is working with several HMOs to 
try to facilitate incorporating this model into their systems.

                          end of life research

    Let me move on to an issue which is very central to the 
Institute, and that is end of life research. NINR has been 
named the lead Institute in this issue. It is one that is very 
central to all of us, and particularly important to the 
National Institute of Nursing Research. Advances in biomedical 
and behavioral research have greatly improved the length of our 
lives, and in many cases the quality of life.
    However, all disorders cannot be cured. And at some point, 
we do need to address the needs of patients who have reached 
that phase of the end of life.
    Last year, the NINR, in cooperation with several other 
institutes, convened a workshop to address issues of symptom 
management in end of life. As a result of this, a program 
announcement has been issued with the National Cancer 
Institute, the National Institute of Allergy and Infectious 
Diseases, and also the National Institute of Mental Health to 
encourage research in this important area. We hope to report 
back to you on the progress of that in the coming year.

                              tele-health

    In closing, I would like to mention two ongoing studies 
which cover the gamut of some of the unusual areas that nursing 
has been moving into, and also address the 21st century. One of 
these is that of tele-health. We've been hearing a great deal 
about how technology can improve health and also health care 
delivery. We are funding a home monitoring project, the 
population of which is lung transplant patients. With the use 
of telemetry, home monitoring and computerized systems, these 
patients have enrolled and are able to monitor their 
symptomatology after they go home, post-transplant.
    As you know, the danger for rejection of such transplants 
is within the first year. So if patients can be monitored 
relatively non-invasively and safely at home, this could work 
toward positive outcomes and also decrease the cost of frequent 
visits to the hospital. So far, 100 patients have enrolled in 
the study and the compliance with this monitoring program is 82 
percent. We think that's very good.

                        pain relief and surgery

    Another study which is an unusual one, but is a result of 
an observation made clinically, is that typically, compounds of 
drugs called benzodiazapine, commonly known as Valium, are 
given to patients prior to surgery for their tranquilizing and 
beneficial effects. As it turns out, post-operatively, these 
interfere with the effects of morphine, which is used for pain 
relief.
    In one of the studies that we're funding relative to timing 
and management of pain medications post-operatively, the study 
is testing using a compound which neutralizes the effects of 
the Valium post-operatively, so that patients are able to be 
maintained more effectively on doses of morphine that are lower 
and also more effective.
    So this has an implication for adding to our basic 
knowledge for timing of medications and self-management by 
patients post-operatively.
    In conclusion, I would like to say that as we arrive at the 
21st century, health research, health care and health choices 
are increasingly interdependent, and nursing research will play 
a vital role in all of these areas. Scientifically validated 
methodologies, communications strategies and effective 
interventions, coupled with a basic understanding of human 
nature and our Nation's diverse populations, will make a 
positive difference to the health and the quality of the 
American people.
    Thank you, Mr. Chairman, and I would be happy to answer any 
questions that you may have.
    [The prepared statement follows:]


[Pages 1687 - 1692--The official Committee record contains additional material here.]



    Mr. Porter. Thank you, Dr. Grady.

                              aids funding

    My first question is for Dr. Varmus and it has to do with 
money. I notice that about 10 percent of the NINR budget is the 
OAR transfer and I wonder, is that the highest among all 
Institutes? I assume not, but it's got to be fairly high.
    Dr. Varmus. No, NIAID has the highest.
    Mr. Porter. Yes. But isn't 10 percent fairly high?
    Dr. Varmus. It's probably----
    Mr. Porter. As a percentage of the non-AIDS budget?
    Dr. Varmus. Probably close to average, since the AIDS 
budget is close to 10 percent of NIH. There are several others, 
including NIDA and NIAID that are higher.
    Mr. Porter. Let me ask Dr. Grady, then, what does the AIDS 
portion represent in your research portfolio? That is, what are 
you doing with that particular money?
    Dr. Grady. We have a very active program in HIV/AIDS 
research. It covers research with young adolescents in inner 
cities across the country to discuss prevention of transmission 
of HIV/AIDS, particularly young males in the Philadelphia and 
New Jersey area, as well as in California.
    It also is a program which works with young mothers who are 
HIV infected to try to prevent transmission of that disease. We 
are working with a number of teaching and education 
dissemination programs as well.
    We're also working with the babies of infected mothers and 
helping them to care for them, and to observe for signs of the 
disease, and to deal with that young population who is 
infected.

                          health care delivery

    Mr. Porter. This is a policy question, I guess, or at least 
an observation question. We've had tremendous changes in our 
health care delivery system over the last five or six years. 
Can you describe how this has affected the profession of 
nursing, and are you supporting any research that affects how 
this change in our health care system is affecting nurses?
    Dr. Grady. There are many ways in which these changes are 
affecting nursing. You will hear negative reports and positive 
reports. We see this as a time of great opportunity for nurses 
and for nursing. The opportunity is now available for nurses to 
assume more independent roles, and they are preparing to do 
that.
    Some of the examples I gave you in terms of nurse managed 
clinics and programs where nurses will deal with patients in a 
variety of other settings, not just the acute hospital, but in 
nursing homes and extended health care settings, they're making 
a major impact.
    There are also studies where nurses are training nurse 
practitioners and also nursing assistants in nursing homes 
caring for the elderly. In particular, one study where the 
population of patients are patients with Alzheimer's disease. 
Previously restraints have been used heavily. It was almost 
incarceration in terms of trying to limit the motion or the 
movement of this patient population.
    We have a number of studies which are attempting to deal 
with the problems of agitation, problems of delirium and the 
problems of wandering and aggressive behaviors in these 
patients. And these are nurse-run programs with nurse 
practitioners or nursing assistants helping to implement these 
programs.
    So we think this is an example of many things that can be 
done across the country.

                     nursing responsibility growing

    Mr. Porter. It seems that nurses have increasingly assumed 
more and more of the responsibilities that used to be exclusive 
to the physician and are therefore getting much greater 
training. Some of the mundane tasks that nurses used to do are 
being done by assistants of one type or another. Do you see 
this expansion of responsibility and professionalism extending 
into the next 40 or 50 years ahead and what are you doing 
within the Institute to anticipate those greater 
responsibilities?
    Dr. Grady. Yes, we do see these changes going into the 21st 
century and beyond. We're doing a number of things to try to 
prepare for the 21st century in this regard. First of all, more 
nurses are going into programs of higher education now than 
before. Many of those are nurse practitioner programs, but many 
of those are also research programs. We are supporting the 
research projects that will indicate which way the nursing role 
will go.
    Basically, we see nurses taking more responsibility for 
running programs in outpatient settings. We see them at the 
forefront at the variety of changes that are taking place.
    Recently in NIH, we had a bioengineering symposium that was 
very widely attended. There were two nurses on the program 
there describing their tele-health and informatics systems that 
they're using to help to deliver patient care. That's an area 
in which nurses are getting very involved.

                          genetics counseling

    Another area that we anticipate a great deal of activity in 
and that nurses are preparing for and we are supporting that is 
in the area of genetics. Genetics counseling is a very 
important area. But in addition, we've talked about promotion 
and research in that area being very important.
    As you, I know, have heard Francis Collins say many times, 
in the misspellings in the genes that are discovered early on, 
we're looking at one gene, one disease. But approximately 95 
percent of disorders are complex trait disorders. So a 
misspelling in a gene may put someone at a predisposition to 
risk of developing the disease. But that will be only one 
factor. The other risk factors will be factors such as 
environmental factors, dietary factors, exercise, etc., the 
kinds of risk factors that have been identified in other 
disorders, such as cardiovascular disease, stroke, cancer to 
some extent.
    These are areas in which nursing has always been active. 
And these are areas which involve behavior modification and 
teaching and issues that nurses deal with in other areas. I 
think that particular role will become even more important. And 
that is an area that physicians have not been as involved in, 
because they're doing other things. Nurses have been involved, 
and the responsibility will simply grow.
    There are many other examples I can give you, but I can 
give you those for the record.

               support for research in clinical practice

    Mr. Porter. We hear that physicians are finding it 
difficult to continue their clinical research because they're 
being pressed within the academic health centers to generate 
more practice revenues. Is this problem also one for nurse 
researchers?
    Dr. Grady. It is to some extent, Mr. Porter. There are 
nurses across the country in most university settings. A fair 
percentage of those nurses do have practices that they are 
running collaboratively or independently in limited practice. 
So those constraints, fiscal constraints, are also impacting on 
them as well.
    There are some very creative solutions that are being 
developed to try to deal with this. But it is a concern.
    More than 88 percent of what we fund in our institute is 
clinical research. So we do hear a great deal about the 
constraints in the clinical setting. We, in combination with 
other institutes at NIH, are supporting the new mechanisms to 
encourage people into clinical research and encourage them to 
maintain those clinical research careers throughout their 
trajectory.

                  pressure sores in spinal cord injury

    Mr. Porter. In your budget justification, it states that 
you're planning a protocol to study the skin of patients with 
spinal cord injury. Can you tell us more about this?
    Dr. Grady. Yes. One of the programs that we've had almost 
since the inception of the institute that has been an important 
program is that of wound healing. This is a cross-cutting 
issue. In fact, our intramural program's scientific director, 
Dr. Annette Wysocki, who is in our audience, is an expert in 
the area of wound healing.
    One of the studies she conducted when she was in the 
extramural program looked at the wound fluids of a variety of 
patient populations, to determine what would be a factor in 
either promoting healing or in retarding healing.
    One of the areas of particular interest is that of patients 
with spinal cord injury. Because as you know, these patients 
can be very active in many ways, but their skin integrity is an 
area that once breached can cause long-term complications. So 
we are looking at those factors.
    That is a basic science study, but it is an observation 
that was made from a clinical setting that has then been taken 
into the laboratory and hopefully will go back into the 
clinical setting when the factors are identified. This is also 
an interesting problem in patients with diabetes, it's a 
complication of that. And it's also a problem in the elderly 
population, as well as anyone who's not very mobile. But in 
particular, those populations are very vulnerable.
    So we have started a wound healing clinic on campus, and 
would hope to deal with some of those issues, both intramurally 
as well as extramurally.

                        collaborations with hrsa

    Mr. Porter. HRSA operates a number of nurse health 
professions programs. Can you tell us about your interface with 
HRSA? What do you do, how often do you talk with them? What's 
the relationship?
    Dr. Grady. The Division of Nursing is housed within HRSA.In 
fact, the early National Institute of Nursing Research, then a center, 
was formed with some of the staff and some of the research proposals 
that they had then been funding. The way things currently operate, we 
do meet on a fairly frequent basis, and our staffs meet. We are on a 
number of joint committees to deal with nursing issues. In fact, just 
last week I was at a meeting with the acting director of the Division 
of Nursing.
    They primarily fund programs related to manpower and early 
training issues. Our training, where we dovetail, is that we do 
fund a fair amount of training. Our training budget is for pre-
doctoral and post-doctoral trainees, whereas they target the 
undergraduate and special programs.

                          behavioral research

    Mr. Porter. Do you conduct any behavioral research, and if 
so, can you tell us more about that?
    Dr. Grady. Yes. We have a large program in behavioral 
research, and most of these programs are directed toward 
symptom management or in behaviors which are targeted toward 
modifying risk factors.
    We have two major programs in this area that I would like 
to mention. In the first case, in the Baltimore area, a program 
is directed at hypertensive inner city African-American youths, 
and consists of dietary modification, exercise program and 
healthy lifestyle types of approaches to try to change 
behaviors to decrease risk for developing heart disease and 
stroke.
    It's a fairly large program, and the early results are very 
encouraging.
    Another program of this sort is directed to younger 
children in the rural areas of North Carolina. That is a 
program which is really for young school children, pre-
adolescent, and it is a program which has been very successful 
in early preliminary findings. The school system down there 
wishes to enlarge this program and take it to a larger 
population and an older group in the school.
    The investigator has also been invited to Japan to try to 
incorporate some of this program into that population to see if 
it is internationally transferrable. Hypertension and risk 
factors for heart disease are very much a problem over there as 
well.

                          aids risk reduction

    So again, these are two programs which are directed toward 
behavior modification. Another one is in the area of HIV/AIDS, 
and this is directed at an inner city population in 
Philadelphia. It has been very successful. It's unusual in that 
it has a very high return rate of this population of young 
African-American adults. The males are harder to get into the 
studies, and the return rate is not so good. But this 
particular investigator has a very good record with that. And 
so we're seeing some signs of behavior change there.
    The program that she has started with a co-investigator is 
being adopted by CDC and used nationally for education of this 
group.
    Mr. Porter. This question is for you or Dr. Varmus. NIH did 
a recent study on needle exchange. Is that correct?
    Dr. Varmus. It wasn't a study, Mr. Porter, we had a 
conference.
    Mr. Porter. A conference.
    Dr. Varmus. It was actually not directed solely to needle 
exchange, it was a conference on behavior in risk modification, 
especially for HIV/AIDS.
    Mr. Porter. Within the Department, wasn't there a study 
done recently for the Secretary on this subject?
    Dr. Varmus. There was an evaluation of where we are. It was 
not a scientific study. It was a compilation of evidence that 
has been accumulated. And of course, the NIH consensus 
conference on behavior and HIV risk assessment was incorporated 
into that evaluation. We discussed that here last year.
    Mr. Porter. So the evaluation is over a year old?
    Dr. Varmus. That's correct.

                             aging research

    Mr. Porter. Dr. Grady, there's increasing evidence that a 
decline in brain power is not an inevitable part of growing 
older. In fact, given the proper environment, the brain can 
continue to function and adapt to environmental and 
psychological challenges. Your institute is sponsoring the 
first test outside the laboratory of the ability to train older 
people to maintain underlying mental skills needed to perform 
every day tasks involved in remaining independent.
    When can we expect the results of this study? Do you think 
we will be able to keep more older people out of nursing homes 
and hospitals in the future? It seems to me this will become 
extremely important in a few years when the baby boomers start 
to reach older age.
    Dr. Grady. Yes, Mr. Chairman, this is an area of particular 
interest for us. In fact, in Alzheimer's populations where 
there is a physiological reason for mental decline, we have 
studies that a simple series of mental exercises performed two 
to three times a day. The family members are trained to do this 
with the patient population. This intervention was able to hold 
off the decline in mental capacity for up to nine months in the 
test population.
    And so this is now being taken into the ``normal elderly 
population'' that does not show signs of impairment. We have 
every reason to believe that the results of that will be 
positive. I can't promise you, because of course research 
always has its surprises, but we would expect to be able to 
report back to you on that within approximately two years.

                         cognitive stimulation

    Mr. Porter. There's also some evidence that therapies such 
as art or music have an effect on patients. Can you tell us 
what's going on in that area, and whether those are also 
applicable to this kind of maintaining independence?
    Dr. Grady. There is a study that is being carried out in 
the midwest that has just recently started, a little over a 
year ago. It has several arms of testing the population. 
Besides the control population, it has a cognitive stimulation 
set of exercises for one arm of the population.
    And also, art therapy and music therapy for the other arm 
of the population. What is being tested here is mental 
alertness, mental capacity. Also the scales for depression are 
also being used. It is an elderly population, and the incidence 
of depression, we are finding out, is higher than previously 
thought.
    So they are looking at both of these, mental performance 
and also mood affected by this study.
    Mr. Porter. So this is the same study that we will hear 
about in a couple of years?
    Dr. Grady. It's another study, but it has several arms. The 
first one I mentioned is a separate study, but you will also be 
hearing about these at about the same time.

                           diabetes research

    Mr. Porter. Proper blood sugar control for persons with 
diabetes may help prevent the onset and/or progression of the 
complications associated with the disease. However, control of 
the disease is very difficult to manage in children. Is your 
Institute conducting research in the area of family-centered 
care to promote better outcomes for diabetes?
    Dr. Grady. Yes, we are. We have several studies in this 
area. And it's an area which is of growing interest and 
particular concern in young people. Because with an early onset 
of diabetes, they have a long time to develop these very 
difficult and perplexing complications, very disabling 
complications.
    We have one study that is directed to young adults and 
teenagers in the New England area which is addressing 
behavioral modification and has been very successful so far in 
adherence to diet and also in blood sugar control. So it's a 
small study which is now going to be enlarged to a larger 
group, but so far has been very encouraging.
    We have another study which is addressing the Native 
American population in the northern midwest. As you know, the 
Native American population has among the highest complication 
rate or the highest diabetes rate, even higher than our 
Hispanic population. That group is being followed for 
behavioral modification and dietary modification.
    An interesting part of that study is that they are using a 
Native American cookbook to develop the recipes which will then 
help to alter the diet. So it is culturally sensitive. And we 
expect that it will be much more effective than trying to get a 
group to learn to eat and enjoy new foods that seem quite 
unpleasant or odd, at best.
    Mr. Porter. Dr. Grady, thank you for your excellent 
statement. You've answered all of our questions very directly 
and efficiently. And thank you for the fine job you're doing at 
NINR.
    Dr. Grady. Thank you very much, Mr. Chairman. We really 
appreciate the opportunity to come up and tell you about what 
we're doing.
    [The following questions were submitted to be answered for 
the record:]


[Pages 1700 - 1751--The official Committee record contains additional material here.]



                                         Wednesday, March 18, 1998.

                      FOGARTY INTERNATIONAL CENTER

                               WITNESSES

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

                           Opening Statement

    Mr. Wicker [assuming chair]. The subcommittee will come to 
order.
    Our next witness is Dr. Philip E. Schambra, Director of the 
Fogarty International Center. Dr. Schambra, we're delighted to 
have you, and we ask you to proceed in your own fashion.
    Dr. Schambra. Delighted to be here, Mr. Wicker.
    And thank you very much. Perhaps I can begin by introducing 
the other individuals at the table with me. Starting at my far 
left, Mr. Richard Miller, Executive Officer of the Fogarty 
Center. To my immediate left, Ms. Stephanie Bursenos, the 
Deputy Director of the Fogarty Center. To my right, Dr. Harold 
Varmus, Director of NIH, and to his right, Mr. Dennis Williams, 
Deputy Assistant Secretary for Budget for this Department.
    Mr. Chairman, I'm very pleased to appear before you once 
again to present the President's non-AIDS budget request for 
the Fogarty International Center for Fiscal Year 1999, the sum 
of $19.1 million. This reflects an increase of $1.4 million 
over the comparable Fiscal Year 1998 appropriation. Including 
the estimated allocation for AIDS, total support requested for 
the FIC is $30.4 million, an increase of $2.1 million over the 
Fiscal Year 1998 appropriation. Funds for the FIC efforts in 
AIDS research are included within the Office of AIDS Research 
budget request, as is the case with the other components of NIH 
this year.
    This year, the Fogarty Center enters its 30th year as a 
focus of NIH international activities. Our mission is to assist 
this Nation to deal with health problems that transcend 
national boundaries, that can be combatted most effectively 
through international cooperation. Through training and 
research support, the Fogarty International Center enables 
American universities and research institutes to cooperate in 
regions of the world that, due to disease burdens, provide 
unique opportunities to advance international health.
    Why international health? May I direct your attention to 
the chart on my far left, which pictorially displays why 
international health is important. First, to protect Americans 
against global health threats. With frequent international 
travel, vast movement of populations of refugees, and potential 
changes in our climate affecting health, global trends are of 
increasing importance for us all. One has only to consider the 
emergence and spread of AIDS to recognize the necessity of 
confronting health needs in a global context. Moreover, 
international commerce presents new risks for the transfer of 
infectious agents for both humans and livestock, as well as 
toxic substances such as pesticides and pollutants, and even 
biologic and chemical agents.
    Second, we pursue international health to fulfill a 
longstanding American humanitarian tradition. The Global Burden 
of Disease Study commissioned by the World Bank indicates that 
developing nations suffer over 90 percent of the burden of 
premature mortality as measured in lost years of life. These 
countries, constituting three-quarters of the world's 
population, now share a triple burden--the persistence of 
infectious diseases and malnutrition responsible for 16 million 
deaths each year, mainly children; a growing incidence of 
chronic disease and disability due to increased life spans and 
new risk exposures; and environmental and occupational health 
hazards which accompany industrialization.
    Third, we pursue international health to advance America's 
global interests. The United States is at the vanguard of 
scientific progress and produces more knowledge, publications 
and medical interventions than any country in the world. 
Because of our leadership, we share an opportunity and an 
obligation to influence the international community, 
international organizations, and developing and industrialized 
countries alike, to address the health problems of those most 
in need. Further, international cooperation in biomedical 
science not only enables the United States to share skills and 
knowledge, but cultural and societal values intrinsic to 
scientific progress as well.
    This Nation's investment in research on global disease 
prevention produces significant economic returns. For example, 
the Institute of Medicine of the National Academy of Sciences 
reports that the United States saves $450 million every year by 
not having to vaccinate our citizens against smallpox. The 
World Health Organization predicts that our efforts to 
eradicate polio will result in global savings of $500 million 
by the end of this decade. However, despite U.S. prominence in 
the creation of new drugs and medical devices as measured by 
percentage of world patents, our global share of exports to a 
market that exceeds $40 billion annually, namely developing 
nations, is a mere 15 percent. International cooperation in 
health is one pathway to emerging markets enabling millions of 
citizens of these countries access to more modern drugs.
    Now, how does the Fogarty Center meet these critical 
challenges? If you would, please turn once again to our chart, 
now with an overlay, which describes our major efforts. In the 
progress of biomedical science, one critical limiting factor is 
human talent. FIC's investment is in human capital, with a 
particular focus on developing nations. Scientific partnerships 
with these nations are of strategic importance. What follows 
describes our efforts to improve America's scientific capacity 
to conduct international research on global health priorities 
in collaboration with our sister institutes at NIH and the 
scientific community at large.
    With the support of this committee, the Fogarty Center's 
International Training and Research Program in Emerging 
Infectious Diseases was initiated this past year to improve our 
capacity to understand the fundamental biology and epidemiology 
of new or resurgent infectious diseases. Launched in 
collaboration with the National Institute of Allergy and 
Infectious Diseases, the program explores the changing patterns 
of infectious diseases due to microbial evolution, human 
behavior, and economic development and land use.
    The model for this new program is the Fogarty Center's AIDS 
International Training and Research Program. To date, under 
this program, over 1,300 foreign scientists from over 80 
countries in Africa, Asia, Latin America and Central and 
Eastern Europe have received long-term HIV research training in 
the United States. Many former trainees are now co-
investigators on NIH-supported research projects in developing 
countries where HIV/AIDS is epidemic. In addition, more than 
41,500 physicians, scientists, nurses and laboratory 
technicians have gained new skills throughin-country training 
courses. The emerging infectious diseases and AIDS programs, in tandem, 
represent investments in training and infrastructure that will assist 
the United States to develop vaccines and other interventions for 
diseases that require international trials. These include HIV, 
tuberculosis, diarrheal and parasitic diseases, and acute respiratory 
infections.
    HIV and other pandemics demonstrate that disease is not 
confined to national borders. In some cases, disadvantaged 
groups in the United States exhibit similar health risks with 
populations in resource-poor nations, risks due to 
micronutrient deficiencies and perinatal infections and other 
conditions. There are lessons to be learned domestically from 
research conducted abroad. For example, studies in Tanzania 
demonstrated that unless treatment regimens are supervised 
closely, TB rapidly becomes resistant to available drugs. That 
finding now has been applied to community health programs in 
New York City and other urban centers.
    Another FIC global priority is to prevent adverse health 
effects of industrial and chemical pollutants. The FIC 
International Training and Research Program in Environmental 
and Occupational Health enables U.S. institutions to train 
scientists from regions of the world with high levels of 
contaminants in the environment and work place, such as Eastern 
Europe, Russia and the new republics. The program is co-funded 
with the National Institute of Environmental Health Sciences 
and CDC's National Institute for Occupational Safety and 
Health, and National Center for Environmental Health. Current 
studies in Ukraine and Belarus undertaken after the accident at 
Chernobyl include the effects of radiation on growth and 
development, incidence of thyroid cancer, and reproductive 
health disorders.
    One of the chief casualties of environmental decay is 
biologic diversity. There is a tendency to assume that our 
increasing technological sophistication moves us further from 
dependence on the natural world. However, it is likely that 
ecosystems maintained by diverse species are a part of our 
protection against diseases. For example, deforestation has 
introduced new infectious agents into human populations; the 
depletion of ozone in the stratosphere erodes protection 
against the damaging effects of ultraviolet radiation.
    The Earth's biota also is a continuing resource for new 
therapeutics. The FIC leads an interagency effort to discover 
new drugs from the earth's biological diversity. The 
International Cooperative Biodiversity Groups Program is funded 
in partnership with several NIH institutes, the National 
Science Foundation and U.S. industries. This program consists 
of academic-industry consortia, examining genetic resources 
from terrestrial and marine environments worldwide. The program 
is now in its fifth year, and together these groups have 
examined over 3,000 species for activity in 13 therapeutic 
areas. At this early stage in the drug development process, 
there are approximately 25 high priority leads, including 
several to treat malaria, viral diseases, and cancer. Of equal 
importance, by demonstrating the economic and humanitarian 
potential of new drugs derived from biodiversity, this program 
has influenced governmental efforts to sustain ecological 
balance in Argentina, Peru, Chile, Suriname and Mexico.
    A root source of global health problems is demographic 
pressure. The world's population is now expanding at the 
unprecedented rate of nearly 1 billion per decade. Demographers 
at the United Nations estimate that virtually all of this 
growth will occur in the developing nations of Africa, Asia and 
Latin America. There is broad consensus that more stable 
population growth will enhance the prospects for improved 
living conditions for billions in the decades ahead. Yet this 
will require new medical technologies and social adaptations 
generated through research. Through our International Training 
and Research Program in Population and Health, the Fogarty 
Center increases the capacity to conduct research on 
reproductive and neonatal health care and improves demographic 
capabilities in countries where population growth impedes 
economic development. The program is co-funded with the 
National Institute of Child Health and Human Development. 
Already, several collaborative projects have yielded 
discoveries. Scientists at the University of Virginia and the 
National Institute of Immunology in New Delhi, India, have 
identified a specific antigen on spermatozoa in primates that 
could serve as the basis of a male contraceptive vaccine. If 
ultimately developed, this vaccine would be a major 
breakthrough in the field of contraceptive development.
    Finally, in partnership with the National Library of 
Medicine, the FIC conceived an International Training Program 
in Medical Informatics to increase research capacity and health 
care through information technology. A pilot program with 
Africa will be initiated this fiscal year. The fundamental goal 
is to develop collaborative teams of U.S. and African 
researchers and information specialists who apply state-of-the-
art telecommunications and computer technologies to challenges 
in biomedical science and medical care.
    Mr. Chairman, as we come to the conclusion of this century, 
it's worth noting an important historical symmetry. NIH began 
as a small laboratory on Staten Island, tending to the needs of 
merchant marine sailors at the turn of the last century. The 
Laboratory of Hygiene proved its worth after diagnosing cases 
of cholera among immigrant passengers on the steamship Alesia--
the first diagnosis of cholera in the western hemisphere.
    That landmark discovery was made possible through 
collaborations with the laboratory of Robert Koch in Berlin, 
who pioneered methods to isolate bacteria, and the laboratory 
of Louis Pasteur in Paris. This early discovery presaged the 
very practical benefits of public investments in basic 
research. It also signaled our reliance on international 
cooperation to accelerate the pace of discovery in medical 
science. This is our historic tradition, our public trust, and 
our mission at the Fogarty International Center.
    Mr. Chairman, my colleagues and I would be very happy to 
respond to any questions you may have.
    [The prepared statement follows:]


[Pages 1758 - 1761--The official Committee record contains additional material here.]



    Mr. Wicker. Thank you, Dr. Schambra, for your very fine 
testimony.
    As Chairman Porter may have explained before he had to 
leave the room, there are a number of other meetings and 
hearings going on, as well as a very important Floor debate 
right now. I know that the absence of other members of the 
subcommittee does not indicate a lack of interest in the very 
fascinating subject matter.
    Dr. Schambra. We look forward to the questions that they 
may wish to submit for the record and would be delighted to 
respond to them.

                                 polio

    Mr. Wicker. Indeed. Well, I was in China last year and 
received a briefing about our international efforts with regard 
to polio. Can you tell us how the effort to eradicate worldwide 
poliomyelitis is going, and what other agencies besides yours 
are involved in this project?
    Dr. Schambra. Mr. Wicker, polio will probably be the second 
human disease to be eradicated from the face of the earth, 
after smallpox. Currently, North America is free of polio, and 
has been for a number of years. Latin America has become free 
of polio just within the past year or so. Other countries 
around the world have massive programs of immunization against 
polio.
    There is the exceptation that by the turn of the century or 
soon thereafter, the world will be free of polio. It willbe 
another great achievement for humankind in biomedical science.
    Mr. Wicker. All right, but you mentioned in your testimony 
the benefits of this global savings of $500 million. What is 
your agency doing in this connection, and what other agencies 
are participating?
    Dr. Schambra. Since this is principally a problem of 
delivery of a vaccine which has been well tested and well 
proven in other environments, this is not a typical first line 
endeavor of the National Institutes of Health. We've done our 
job some years ago in helping to develop that vaccine, by 
supporting early research that enabled us to cultivate the 
virus in tissue culture.
    The Centers for Disease Control, and Prevention, in the 
United States, has primary responsibility for vaccination 
programs at the Federal level. Around the world, the World 
Health Organization, of course, plays a prominent, and in fact, 
the leading role in the fight against polio.
    Mr. Wicker. So you mentioned polio in your testimony not 
to----
    Dr. Schambra. Take credit for it, no.
    Mr. Wicker [continuing]. Indicate that you're involved in 
it, but just to demonstrate the importance of a global 
approach?
    Dr. Schambra. That's correct. And to support the argument 
that current efforts that are aimed at developing vaccines 
against a number of other diseases, including HIV, malaria, and 
tuberculosis, are worthwhile pursuing, considering the economic 
benefit alone that we will obtain from finding effective 
preventive measures.

                      emerging infectious diseases

    Mr. Wicker. I see. And you just mentioned a list of other 
diseases. Do you, are you referring to them as emerging 
infectious diseases?
    Dr. Schambra. There is a whole range of existing diseases 
that have not gone away that we have to deal with, such as 
tuberculosis, which was very close to being conquered on a 
global basis, until multiple drug resistant forms began to 
emerge. That is certainly a high priority.
    Then there are other reemerging diseases such as malaria 
that had also come very close to being controlled in many 
regions of the world. Because we didn't develop an effective 
vaccine and slacked off on various control measures, we are now 
faced with a resurgence of that disease, oftentimes in drug 
resistant forms, particularly in the developing regions of the 
world and most prominently, sub-Saharan Africa.
    Mr. Wicker. So we have existing diseases, reemerging 
diseases. Are there any emerging diseases?
    Dr. Schambra. Probably the best example of an emerging 
disease in the last decade or so, of course, would be AIDS. We 
have also become more aware of some of the rarer forms of fatal 
diseases, viral transmitted such as the Ebola virus, which was 
first encountered about 10 years ago. Disappeared from human 
knowledge until recently, two or three years ago, it came back.
    So whether this is a new disease or a reemerging disease is 
probably more of a semantical issue than a scientific one.

                               chernobyl

    Mr. Wicker. Tell us what we have learned about, you 
mentioned Ukraine and Belarus and the Chernobyl accident. Tell 
us what your agency, what involvement your agency has had and 
what we've learned in the history that we now have since that 
incident.
    Dr. Schambra. Our role has been to work with, and through 
various formal and informal agreements with the government 
authorities in Russia, Ukraine and Belarus to bring together 
the scientific talent and resources to bear to better 
understand, and measure what is going on, and then to 
understand what the consequences are.
    To date, I think the most profound or disturbing finding is 
the high degree of thyroid cancer among children who have been 
affected by the large scale release of iodine-131, a 
radioactive compound of iodine causing thyroid cancers. We are 
as well, of course, looking at other matters, and when I say 
we, I'm speaking of the Nuclear Regulatory Commission and the 
National Cancer Institute, the Department of Energy and other 
universities and academic and scientific institutions in the 
United States and around the world, looking at what the longer 
term health effects that the terrible accident at Chernobyl 
resulted in.
    Mr. Wicker. How old are these children now?
    Dr. Schambra. Well, let's see, when did the accident occur? 
It occurred about 10 years ago, about 1986. So the children 
probably were in utero at that time, or a little more than that 
age, or within six months of birth.
    Mr. Wicker. You're looking at the results, according to 
your testimony. Do you have an opinion as to whether there are 
other potential Chernobyls out there right now?
    Dr. Schambra. Well, there are certainly potential 
Chernobyls, whether there is another Chernobyl only time will 
tell. The particular reactor at Chernobyl, it was a reactor 
built by the Russians, had as it turned out some inherent 
instabilities in its operation, especially at low power levels. 
And it was in the course of running experiments, unauthorized, 
it's my understanding, on that particular type of reactor, that 
led to the runaway nuclear excursion, and the massive, 
essentially chemical and heat explosion.

                             aids in africa

    Mr. Wicker. I appreciate your trying to answer the 
question, and I'm mindful that you're not in the nuclear 
regulatory business.
    Tell us about the effect in Africa on the demographic 
pressure that you mentioned of the AIDS epidemic. You hear some 
people say that that is a continent that may be depopulated 
unless we do something to stem the spread of AIDS. And yet, in 
your testimony, you mentioned that you expect the unprecedented 
rate of growth to continue there. Do you have an opinion about 
that?
    Dr. Schambra. Yes, sir, I can share some of my thoughts 
with you. Certainly on a global scale, Africa was the region 
most early affected by the epidemic of HIV. It continues to be 
the most affected region of the world, with current estimates 
of the rate of the degree of infection, the number of 
infections, being probably understated by a factor of five to 
ten.
    Mr. Wicker. Understated?
    Dr. Schambra. Understated. This is just part of the problem 
in the developing world, where the basic capabilities of doing 
epidemiology and careful health statistics just do not exist. 
So one has to rely on extrapolation from smaller numbers and 
smaller samples to make those sorts of estimates.
    We do know that there have been communities within certain 
countries in Africa that have essentially been depopulated of 
those in their most productive years of life, leaving only 
elderly grandparents and orphans behind. I can provide some 
more details for the record, Mr. Wicker.
    Mr. Wicker. I would appreciate that.
    [The information follows:]

                  Demographic Impact of HIV in Africa

    The demographic impact of HIV in Sub-Saharan Africa is 
sobering. During 1985-1995 the epidemic killed 4.2 million 
people in Africa. This represents 90% of all deaths due to AIDS 
in the developing world. In Africa, AIDS mortality is projected 
to reach its peak in 1995-2005 when the number of AIDS-related 
deaths will reach 9.4 million. Because of the pandemic, life 
expectancy has stagnated and even declined in several African 
countries. This trend is projected to continue through the year 
2000.
    Botswana, Malawi, Uganda, Zambia and Zimbabwe are most 
affected by the epidemic. Currently, more than 10 percent of 
the adult population in these countries is infected with HIV; 
the HIV-related death toll in this region for the period 1985-
1995 is estimated at 1.5 million deaths and life expectancy at 
birth has decreased from 48 to 44 years. The pandemic also has 
reduced rates of child survival, reversing gains achieved over 
several decades. For example, by 2010 Zimbabwe's infant 
mortality rate is expected to rise by 139 percent because of 
HIV and its under-five mortality rate by 109 percent. Although 
the AIDS epidemic increases the number of deaths in each age 
category, its largest mortality affects age-groups in otherwise 
productive years of life. It is estimated that in these five 
most affected countries, mortality during 1985-2005 will 
increase by 160 percent in the 35-49 age group, compared with 
33 percent for the population in general.
    However, under most scenarios population growth rates in 
African countries will remain strongly positive within a 25 
year projection period. With no behavioral change, and HIV 
epidemic such as that in present-day Kampala, Uganda (perhaps 
the most affected metropolitan area in Africa) might reduce 
population growth by 1 percent. As yet, no country-wide 
epidemic of such proportions has occurred. Negative growth 
would result only with a country-wide epidemic two to three 
times as severe as the worst urban situation in Africa today.

                       international cooperation

    Mr. Wicker. Dr. Varmus, certainly there appears to be an 
impressive 30 year history of international cooperation with 
the Fogarty Center. Do other institutes partner internationally 
now in a similar way, and would it therefore be better for the 
subcommittee to increase other institutes' budgets at the 
expense of the Fogarty Center?
    Dr. Varmus. As you know, Mr. Wicker, there has been 
extensive involvement abroad by virtually all the institutes. 
And the Fogarty International Center has always been intended 
to be a focal point for international activity, to stimulate 
and coordinate, facilitate the international efforts made by 
the institutes.
    NIH overall has an investment of nearly $200 million each 
year in various kinds of international activities, training 
here and abroad, center development and collaborative research. 
The Fogarty International Center's budget has always been a 
fairly small fraction of that.
    As you've heard me say before, we are interested in 
expanding our efforts to combat disease in other parts of the 
world. We think that is an effort that is very much in the 
national interest. But I see that expanded effort going on in 
the institutes primarily, with coordination from the Fogarty.
    Fogarty's resources are important to sustain the 
coordinated efforts and to provide seed money for new projects, 
to help with a number of training programs, to help coordinate 
our international training programs on the NIH campus. We 
certainly don't think there's a need to reduce the Fogarty 
support to expand the others.
    We are currently seeking someone to serve as the associate 
director for international research in my office. That will be 
a further means to strengthen the way in which the 
international effort that the NIH is hoping to sustain and 
indeed expand will be benefitted by direction from my office.

                            accomplishments

    Mr. Wicker. If we had to list five top accomplishments over 
the past 30 years, for the Fogarty Center, what would we list? 
What are you most proud of?
    Dr. Schambra. Going back over the 30 years of the existence 
of the Fogarty Center and its precursor organization, the 
Office of International Research, in the Director's office at 
NIH, I think the first accomplishment we could point to and 
take a great deal of credit for is the role that the NIH and 
the American biomedical community has played in the post-war, 
post World War II era in which large parts of Europe and Asia 
were devastated in all aspects of their economy and society.
    Through the generous actions of the institutes at NIH and 
the Fogarty International Center, the support economically from 
the Congress and programmatically as well, we were ableto 
provide training opportunities for more than 20,000 foreign scientists 
since the late 1950s. I'd say that this was a major factor in the 
reconstruction and restoration of European science and Japanese science 
and technology in the biomedical field, and other fields of science as 
well. But certainly, emphatically and constructively in the field of 
biomedical science. So that would be the first one that comes to mind 
in response to your question.
    I'd say a second accomplishment has to do with the efforts 
that we, largely in the Fogarty Center, but also working with 
the institutes, put into developing formal relations with 
countries behind the Iron Curtain, Russia, Eastern European 
nations, China, and other countries denied free access to the 
outside world. So we were a window for them into not only 
modern science, but contemporary western culture. For us, it 
was a window into their closed societies, not only to 
understand them better, but to take advantage of sharing of 
scientific information that would advance a common humanitarian 
goal, which is health for all people around the world.
    A third highlight, I would say, has come up in more recent 
years. And I think Dr. Varmus touched on it in a way in 
discussing our role in the Fogarty Center in stimulating the 
institutes to deal with what we've termed global health threats 
or global health issues, looking at new and emerging infectious 
diseases such as AIDS in conjunction with the Allergy and 
Infectious Diseases Institute and CDC. Our biodiversity program 
that Mr. Porter played a very important role early on in 
encouraging us to undertake involving the National Science 
Foundation, the U.S. Agency for International Development, and 
other NIH institutes. I could mention the population program 
and the environmental and occupational health programs as well.
    So we have started along a path of getting the institutes 
and other components of the public health service, as far as 
that goes, more directly involved in the current time frame, 
but also hopefully in the future, involved in addressing health 
problems from a basis of American scientific expertise, but 
extended in a humanitarian tradition abroad, particularly in 
developing countries.
    I could probably name a few more.

                          biodiversity program

    Mr. Wicker. Let me just back up and I'll end with this. 
Would you expand on your testimony about the biodiversity 
program, give us an update on the program. That's one of the 
questions Chairman Porter wanted to make sure we asked.
    Dr. Schambra. Indeed. And I'm very pleased to do so. The 
program has just completed its fifth year. We have had an 
outside evaluation of the program, which turned out to be very 
favorable and encouraging us to continue and expand.
    Mr. Wicker. Who conducted that? Was that conducted 
internally?
    Dr. Schambra. I think it was the Battelle Institute. 
Correct. It's the Battelle Institute. And if I could just 
summarize briefly their principal conclusions, they found that 
the program represented ``a daring and well thought out 
concept, secondly, the group activities were already making a 
difference in most of their host countries, third, that at the 
rate of $2 million to $2.5 million a year, the program was an 
incredible value, fourth, that the program be renewed with the 
participation of all three agencies, that is, NIH, NSF and 
USAID, if at all possible, with sufficient funds to support the 
current five groups as well as two new groups.
    And finally, that the product research target areas be 
broadened to include herbal remedies already used traditionally 
in host countries as well as agricultural chemicals and 
veterinary agents. We have enlisted the participation of the 
Department of Agriculture in a renewal of that program as well.
    I think that in spite of it being a relatively young 
program and one trying out new ways of doing business, that the 
discovery of about 300 active species, pharmaceutically active 
species, strikes me as a signal accomplishment, particularly 
when 10 percent of that number show promising pharmaceutical 
value, and one or two are well on their way toward being 
patented, a sign that the scientists and companies see likely 
products emerging.
    Mr. Wicker. So tell a taxpayer what they're going to get 
out of this program.
    Dr. Schambra. Well, we hope that we'll get a number of new 
drugs and therapeutics that will protect their health. I think 
if you judge the future by the past, something like 57 percent, 
if I recall the figure, 57 percent of the most prescribed 
pharmaceuticals in the United States today come from natural 
products.
    Aspirin came from a natural product, quinine to treat 
malaria came from a natural product. Two of the most effective 
compounds against certain kinds of cancer, vinblastine and 
vincristine, came from the rosy periwinkle plant discovered in 
Madagascar. And I could go on, and on, penicillin, of course, 
comes from a natural product.
    So if we look at the past and have that as a guide to the 
future, I think we can be very confident, confident, I repeat, 
that we will discover useful products from natural sources. 
Taxol is another well-known chemotherapeutic that recently has 
become widely known with of its origin from the Pacific yew 
tree.
    Mr. Wicker. Dr. Schambra, I want to thank you and the other 
panel members for being willing to stay well after the noon 
hour. I know I've enjoyed the hearing. I'm sure other questions 
will be submitted for the record.
    Mr. Wicker. And we want to wish you well.
    Mr. Schambra. Thank you very much, Mr. Wicker.
    Mr. Wicker. This concludes this morning's hearing.
    [The following questions were submitted to be answered for 
the record:]


[Pages 1768 - 1806--The official Committee record contains additional material here.]



                                           Tuesday, March 17, 1998.

 NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

                               WITNESSES

DR. STEPHEN I. KATZ, DIRECTOR
DR. STEVEN J. HAUSMAN, DEPUTY DIRECTOR
MARGARET S. KERZA-KWIATECKI, EXECUTIVE OFFICER
ROBYN J. STRACHAN, BUDGET OFFICER
DR. HAROLD VARMUS, DIRECTOR; 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 National Institutes of Health and 
welcome Dr. Steven I. Katz, Director of the National Institute 
of Arthritis and Musculoskeletal and Skin Diseases. Dr. Katz, 
it is nice to see you. Please introduce the people who are with 
you and then proceed with your statement, please.
    Dr. Katz. Thank you very much. To my far left is Margaret 
Kerza-Kwiatecki who is our Executive Officer, and Robyn 
Strachan who is our Budget Officer, and Steve Hausman who is 
our Deputy Director.
    Also you know Mr. Williams, and I assume Dr. Varmus will be 
along momentarily.
    I am delighted and honored to appear before the committee 
as the Director of the National Institute of Arthritis and 
Musculoskeletal and Skin Diseases.

                         tribute to Mr. Stokes

    I consider it a privilege to tell you about the exciting 
science and plans in our research areas. I would like to begin 
by acknowledging the significant contributions of Congressman 
Stokes to the NIH and to the American people. He has been a 
tireless advocate for improved public health for all Americans, 
and an ardent supporter of the NIH in its quest to accomplish 
this goal.
    We at the NIAMS have within our research mandate many 
diseases that affect minorities and women disproportionately, 
diseases like systemic lupus erythematosus, and we are actively 
addressing various issues raised by Mr. Stokes for the past 
many years, and we are very grateful for all of his 
contributions.
    You have heard my past testimony, that virtually every 
household in America is affected by some disease of bones, 
joints, skin or muscle, and that these diseases have an 
enormous impact on one's quality of life.
    I would like to spend a few minutes focusing on my outlook 
for the future, where we seize upon unfolding scientific 
opportunities and invest in the unprecedented tools of medical 
research and on the bright minds that are being recruited to do 
this research.
    I believe that we can make an enormous difference in 
people's lives, if we wisely invest the funds proposed in the 
1999 budget.

                             bone diseases

    Let us start with our aging population. Imagine a future 
where quality of life is not compromised by pain and suffering 
brought on by bone fractures and arthritis--where people are 
productive and independent well into their senior years. We 
have learned an enormous amount about how bones become strong, 
and how they are constantly being built up and broken down.
    This past year, in an important series of discoveries, 
researchers supported by NIAMS, and the National Institute of 
Dental Research, identified a gene essential for the build-up 
of bone, thereby opening up exciting opportunities for the 
development of potential new bone strengthening interventions 
to prevent bone fractures, and also perhaps to repair them more 
expeditiously. This finding has clear implications for 
osteoporosis, Paget's disease, osteogenesis imperfecta, and 
many other bone diseases.

                           building bone mass

    Move now to the younger years, to the schools. We are 
heartened to see children and adolescents benefiting from 
programs targeting their strong bones and reducing sports 
injuries. We know that calcium is critical for maintaining the 
integrity of bones and that people build up their bone ``bank 
account'' during the first three decades of life.
    During the past year, in studies in Mexican-American girls, 
we learned how the vitamin D receptor gene is related to bone 
mineral density, and why some girls are much more susceptible 
to low bone mineral density than others. We are supporting 
studies that will identify factors that may alter or reverse 
this susceptibility.

                             osteoarthritis

    In arthritis, we know much more about the changes that 
occur in cells of the joints in people with osteoarthritis, and 
we are focusing increased emphasis on identifying appropriate 
markers to determine diagnosis, prognosis, and severity of 
osteoarthritis, the most common of the over 100 forms of 
arthritis.
    During the past year, we have learned how certain genes are 
turned on and produce products that cause cartilage cells to 
die. Until recently, it was very difficult to cultivate and 
propagate these cells in a test tube, but during the past year 
certain growth factors have been identified that enhance 
cartilage cell growth. These findings provide important 
scientific opportunities for increasing our knowledge of 
osteoarthritis.
    We are also continuing to increase our identification of 
risk factors such as obesity and knee and thigh muscle weakness 
in osteoarthritis, and we are supporting studies to identify 
preventive measures in this disease. Even small increments of 
knowledge may have an impact on this important and very 
prevalent public health problem.

                          autoimmune diseases

    Move now to diseases that occur disproportionately in 
women. A major overarching category of diseases under study in 
our institute is autoimmune diseases, those in which the 
bodies' own cells turn against the body and cause diseases such 
as rheumatoid arthritis, lupus, Sjogren's syndrome, as well as 
alopecia areata, scleroderma, and many others. We are making 
progress in all of these, and advances in understanding one of 
these diseases has implications for all of them.

                          rheumatoid arthritis

    Studies in tumor suppressor genes, long an integral 
component of cancer research, have revealed new insights into 
rheumatoid arthritis. Investigators have reported this year 
that synovial tissue from the joints of patients with severe 
chronic rheumatoid arthritis contain a mutated tumor suppressor 
gene that controls the growth of normal cells. This may, in 
part, account for the chronic overgrowth of joint-lining cells 
in rheumatoid arthritis and may suggest new approaches to 
treatment.

                      familial mediterranean fever

    Another important discovery was made by researchers in our 
NIAMS Intramural Research Program. These investigators 
identified the gene responsible for the disease called Familial 
Mediterranean Fever or FMF. Attacks of this disease are 
characterized by widespread inflammation as manifested by 
arthritis, chest pain, abdominal pain, recurring bouts of 
fever, as well as skin rashes.
    This discovery will provide important insights into causes 
of inflammation in FMF and many other inflammatory diseases and 
provide for new and improved treatment for this and perhaps 
many other diseases that are characterized by inflammation. 
Funds provided in Fiscal Year 1999 budget will facilitate the 
development of animal models, diagnostic tests, andfurther 
identification of some of the mutated genes in this disease.

                              skin cancer

    Move now to the beach, and other recreational sites. Here 
we see people of all ages enjoying time outdoors while taking 
informed and proven precautions to avoid the complications of 
skin cancer caused by sunlight exposure.
    During the past year, we have learned more about how 
certain mutated genes cause cancer of the skin, the most common 
form of human cancer, and we are now trying to understand how 
these effects might be reversed or altered.
    These brief highlights provide a glimpse of the hope that 
research offers for the many people suffering from the common, 
costly, crippling, and chronic diseases within the mandate of 
the NIAMS.

                         future research plans

    What are the challenges to reaching the future that I 
described earlier, and how do we plan to invest the budget to 
address these challenges?
    The increased budget will allow the NIAMS to support more 
research grants in key areas of opportunity and need, and we 
will expand our research portfolio in a number of priority 
emphasis areas such as skeletal morphogenesis and growth, 
mechanisms of central nervous system damage and cardiovascular 
disease in lupus, blood and immune system effects on bone 
physiology, gene therapy in arthritis and skin disease, and 
structural biology of muscle membrane proteins.
    Also as a result of discussions that occurred during four 
clinical research working group sessions this year in 
arthritis, bone, orthopaedics and skin, we will expand our 
focus into more support of clinical research training and 
development and of patient oriented research in general.
    In closing, I want to express my thanks to the Members of 
this subcommittee for their strong and unwavering support of 
medical research.
    The budget request for the NIAMS for fiscal year 1999 is 
$295,576,000. I will be happy to respond to any questions you 
may have.
    [The prepared statement follows:]


[Pages 1811 - 1817--The official Committee record contains additional material here.]



                           building bone mass

    Mr. Porter. Thank you for your excellent statement, Dr. 
Katz.
    I think you said, and if you didn't, it was said earlier--
that we form our bone structure early and it can be only 
strengthened up to a certain age, early to mid-20's, something 
like that. Is that true?
    Dr. Katz. There have been many studies that we have 
supported over the years, that have demonstrated that once you 
build bone mass, which I call the bone ``bank account,'' that 
is a major factor in what happens subsequently.
    So it is really during that time, those first three 
decades, with a peak, perhaps, between the ages of 20 and 30, 
that once you hit your peak bone mass, it is all downhill from 
there. So the higher you start, the better off you are.
    You are constantly building up and breaking down bone, 
beyond the third decade. But the major mass of bone is built 
between the second and the third decade.
    Mr. Porter. So taking calcium supplements is not going to 
get you beyond your peak, but it may help you hold your peak 
longer?
    Dr. Katz. Exactly; exactly. If one looks at all of the 
interventions--and now there are many interventions we have, 
for example, to prevent osteoporosis, whether it is calcium and 
vitamin D, whether it is estrogen as hormone replacement 
therapy, whether it is one of the bisphosphonates, whether it 
is some of these new selected estrogen receptor modulators--all 
of them are used to block that downfall of bone that occurs in 
the older ages.
    Mr. Porter. Is an individual limited in how strong their 
bones can be by their genetic makeup, or can one do something 
in the first three decades to go beyond that? In other words, 
is there a way to reach a higher peak by what you do? Or is the 
peak limited by your genetics?
    Dr. Katz. In studies that were reported this year, for 
example, in the study that I quoted from Los Angeles in 
Mexican-American girls, it has been shown that the vitamin D 
receptor gene will correlate with bone mass.
    However, there are things that one can do to enhance bone 
mass. Calcium intake is one. There are many recommendations in 
terms of how much calcium one takes in, whether it is in the 
very early years, whether it is in the teenage years. There are 
other recommendations for exercise, for example. Exercise is an 
important factor in how much bone one builds up early in life 
and later in life.
    Mr. Porter. So you have control over that and can go to 
whatever limit that you choose?
    Dr. Katz. You have no control over your genes. But you can 
modify the amount of bone that you have by certain activities, 
and these are the activities that we try to educate the public 
about.
    Mr. Porter. Okay. Now vitamin D is necessary for calcium to 
be assimilated and used to build bone mass, is that correct?
    Dr. Katz. Right.
    Mr. Porter. Is it true that most people get enough vitamin 
D from their food, and from sunlight, that they do not need to 
take a supplement? I guess I am asking some medical advice 
here. [Laughter.]
    Dr. Katz. Many people get sufficient vitamin D in their 
diet, and by virtue of being exposed to sunlight, minimal 
sunlight, minimal outdoor light. There are studies that show 
that 15 minutes of exposure to the back of the hands is enough 
to develop your vitamin D for a one-day period.
    However, there are recommendations for vitamin D to be 
taken in individuals who do not get that minimal amount of 
exposure and there are large parts of our population that are 
not exposed. People who are homebound, for example, are not 
exposed to the ultraviolet radiation, and they may not get the 
vitamin D in their diets. As a consequence they are recommended 
to take vitamin D supplements.
    Mr. Porter. What part of the diet gets you vitamin D?What 
foods is it found in?
    Dr. Katz. Basically vegetables. It is also fortified in 
dairy products.

                          rheumatoid arthritis

    Mr. Porter. What is the therapy of choice today for 
rheumatoid arthritis?
    Dr. Katz. There are many therapies, depending on the extent 
and severity of rheumatoid arthritis. There has been a change 
in the philosophy about the treatment of rheumatoid arthritis 
in the last several years, and that is it is currently thought 
that early, aggressive treatment is probably better than just a 
palliative treatment that coincides with how severe the 
rheumatoid arthritis is.
    So there are many studies, now, that are actually looking 
at early intervention with much more potent medications.
    Conventionally, one would start with non-steroidal anti-
inflammatory drugs, and then go on in patients who are not 
responding to more potent drugs like----
    Mr. Porter. Like steroids of some type?
    Dr. Katz. Of course, also steroids. Methotrexate is 
currently being used extensively. Methotrexate, which was 
developed as an anti-cancer drug, is being used extensively in 
rheumatoid arthritis, not only in adults but also in children. 
There are certain patients who do not respond to methotrexate, 
and as a consequence more potent drugs are used, like 
cyclosporin.
    And then there are developmental drugs that are being 
looked at right now, experimental drugs, to look at reversing 
some of the inflammatory effects.
    These are drugs that are being developed by pharmaceutical 
and genetic engineering companies.
    Mr. Porter. Cyclosporin. What is that?
    Dr. Katz. Cyclosporin is an agent which is called an 
immunosuppressive agent. It is formed from a fungus, but now, 
it is synthesized. It is used mainly as an immunosuppressive 
for transplantation biology. It was the major change that we 
saw in improvement of transplantation of organs--the advent of 
cyclosporin.
    Now there are other drugs like that which suppress the 
immune system by actually interfering with the internal 
workings of T-cells, which are very important in causing 
transplant rejection. That same type of inflammation is thought 
to be very important in the genesis of rheumatoid arthritis.

                             calcium intake

    Mr. Porter. Studies have led to an increase in the 
recommended daily dietary allowances for calcium for all ages. 
It seems especially important for children, through their 
teenage years, to have an adequate supply of calcium in their 
systems daily.
    The new recommendation for children ages 9 to 18 is 1,300 
milligrams per day.
    What do they have to eat, or drink, to get to this level of 
calcium intake?
    Dr. Katz. Well, a glass of milk is 300 milligrams of 
calcium. One glass of milk. So basically, they can get there 
with four glasses of milk. If they do not get there with four 
glasses of milk, they can get there with certain vegetables. 
Calcium is also contained in bread. Or many of them will take 
vitamins.
    Many multi-vitamins, for example, contain about 150 or 165 
milligrams of calcium per vitamin tablet.
    Mr. Porter. Do calcium tablets have the same effect as food 
intake? In other words, can you supplement your diet with the 
pills? I guess you are saying yes, you can.
    Dr. Katz. Yes.
    Mr. Porter. And is this recommended for children?
    Dr. Katz. Generally not. Generally, it is recommended that 
they have a good diet, a good balanced diet that contains milk 
and milk products. As you have seen, our Secretary of HHS Dr. 
Shalala, has demonstrated with her milk mustache, promotion of 
the low fat or nonfat milk. Several glasses a day will provide 
the nourishment that one needs in terms of calcium and in terms 
of the required amount of calcium for young people.

                              osteoprosis

    Mr. Porter. Some nutritionists believe that fat-free diets 
and the adherence to them has contributed to a rise in 
osteoporosis. Do you agree with that statement?
    Dr. Katz. I just do not know enough about it to make that 
correlation, but I can certainly provide that information to 
you.
    [The information follows:]

                    Fat-Free Diets and Osteoporosis

    In trying to reduce dietary fat, individuals may 
potentially remove dietary sources of calcium and vitamin D. An 
inadequate intake of calcium and vitamin D in the diet many 
contribute to osteoporosis. Since diary products are the major 
source of both calcium and vitamin D in the American diet, the 
best way to promote skeletal health is to include fat-free or 
low fat dairy products in any fat-reducing diet. Although dairy 
products provide the most concentrated source of calcium and 
are fortified with vitamin D, other foods that are components 
of a low fat diet--broccoli, beans, kale, calcium-set tofu, 
fortified cereals, and orange juice--also provide sources of 
calcium. Exposure to the sun--15 minutes, both hands--can 
provide sufficient active vitamin D through conversion of a 
skin precursor, but this may be limited during the winter 
months at some northern latitudes.
    If an individual cannot take in adequate dietary calcium 
and has no sun exposure, calcium and vitamin D supplements may 
be indicated. Currently, at least 1,000 mg. of calcium (more in 
adolescents and people over 50) and 400 IU of vitamin D are 
recommended for optimal skeletal health.

                            public education

    Mr. Porter. Let us talk for a minute about how you get the 
message out. We talked about it this morning. How do you get 
the message out to young people especially, that taking in 
adequate amounts of calcium is something that is going to help 
them later in life, or is that a message that never resonates 
with young people?
    Dr. Katz. Well, it is a message that we are trying to get 
out. Certainly, the milk moustache message is a good one. We 
have funded for the last 4 years, and have a request for 
applications for the next 5 years, an information source for 
getting out the message with regard to osteoporosis and related 
bone diseases. This has been carried out through the National 
Osteoporosis Foundation, through our Osteoporosis and Related 
Bone Diseases Resource Center, which we have funded in the 
amount of about $500,000 for the last 4 years.
    This is one of the ways that we have been able to get that 
message out. There is a particular focus that the Department, 
in general, has tried to make with regard to young people, not 
only with regard to calcium but also with regard to exercise.

                         epidermolysis bullosa

    Mr. Porter. You state a couple of times in the budget 
justification that epidermolysis----
    Dr. Katz. Epidermolysis bullosa.
    Mr. Porter. EB--EB is what I should have said--that EB is a 
prime candidate for gene therapy. How do you know which 
diseases are more receptive to gene therapy than others?
    Dr. Katz. Well, epidermolysis bullosa is a true success 
story in terms of investment of our Government funds. About 10 
years ago, there was an investment in an epidermolysis bullosa 
registry as well as a repository of material. As a consequence 
of that repository, a tremendous amount of information was 
gained about the basic function of the area of skin that is 
affected in epidermolysis bullosa.
    There are actually about 18 different forms of 
epidermolysis bullosa, so we expect at least 18 different 
mutations, and in the last 7 years, or 8 years, a tremendous 
amount has been learned about what those mutations are, and 
those mutations are in genes that encode for various parts of 
this basement membrane zone. In fact, the success of that 
repository was so great that we have maintained just a part of 
the repository, but not the registry, because we have 
tremendous amounts of material there.
    So these gene mutations have been identified, and those 
that are most susceptible to gene therapy are currently being 
looked at in not only epidermolysis bullosa, but also in 
certain forms of ichthyosis which is a widespread fish-skin-
like picture. Many of the genes have been demonstrated to be 
mutated in those diseases as well.
    There has been some correction of these defects. For 
example, in the last year, in a form of ichthyosis where it is 
known where the mutation is, one can now grow what we call 
keratinocytes, which are the main skin cells, epidermal cells, 
and one can insert genes that will then provide the integrity 
that the skin needs.
    So at least in culture this has been done in certain areas 
of the skin.
    Mr. Porter. Let us see if Mr. Hoyer can do better with the 
medical lexicon than I did.
    Mr. Hoyer.
    Mr. Hoyer. I have got a couple of questions to test me on 
that, and I was not sure, after your efforts, that I was going 
to try mine.
    Dr. Katz, I want to welcome you to the committee.
    Dr. Katz. Thank you.

                               psoriasis

    Mr. Hoyer. Thank you very much for your leadership and what 
you do. It is very important work.
    Let me first ask, and Mr. Chairman, it is my understanding 
that the word I am going to use is not a word but a P-U-V-A as 
opposed to PUVA or PUVA.
    Mr. Porter. Good; you got it.
    Mr. Hoyer. But in any event psoriasis, obviously a pretty 
widespread disease, with 2 percent of the public suffering from 
it.
    Your institute has played an important role in developing 
an effective treatment, to which I have just referred. P-U-V-A. 
But there is also now, as I understand it, an article in the 
journal which says there may well be some relationship between 
the use of this therapy and the advent on the skin of a skin 
cancer, a melanoma.
    What are you doing about that to both educate users of this 
therapy and/or seeing whether or not there is a direct 
correlation, and if that correlation relates to particular skin 
types or users?
    Dr. Katz. Well, that is a very important issue that we are 
dealing with, and in fact we have been dealing with it for 
about 20 years.
    With the advent of the treatment, that is, where one takes, 
orally, a medication called Psoralen, and then exposes the skin 
to long ultraviolet, which is the UVA--that is why it is called 
PUVA--we anticipated, 20 years ago, that there would be 
problems on the skin in terms of long-term adverse effects of 
sunlight, which it is actually accentuated.
    So about 20 years ago, the institute developed a registry 
of all patients who were being treated with Psoralen and 
ultraviolet radiation. That registry is being handled at the 
Beth Israel Hospital in Boston by Robert Stern, and he has 
followed a cohort of individuals who have received this 
treatment. There are about 1,400 individuals who he has 
followed for close to 20 years now, to try to determine whether 
we would or would not see these adverse effects, these skin 
cancers.
    At about 15 years, he and the group started noticing, 
statistically, and through epidemiological studies, that there 
was an increase in the number of squamous cell cancers that 
were formed on the skin.
    As you may know, there are three main forms of cancer of 
the skin. Basal cell is the most common, and it is relatively 
easily treated.
    Squamous cell carcinoma is less common, but certainly can 
produce severe morbidity and mortality. It can spread to other 
parts of the body, and we have shown that this type of cancer 
does occur in these patients. So as a consequence, those 
patients are followed that much more closely.
    Now, the third type of skin cancer is a melanoma, which I 
think most people know can be an absolutely devastating 
disease, if not detected early. But if detected early, it is 
totally curable. Well, in this prospective study of 1,400 
patients, Stern and his co-workers demonstrated that there is 
an increased frequency of melanoma in these patients who have 
had long-term PUVA therapy.
    Now, there are certain correlates that they have learned 
from this study. The correlate is the more therapy you have 
had, the more likely you are to get this type of melanoma.
    So immediately, one becomes rather cautious in the amount 
of PUVA that one gives these patients. Furthermore, patients 
who have had these large doses of PUVA are now more closely 
scrutinized to try to identify these lesions. If they are 
identified early, as I said, they are totally curable.
    So we continue to support this registry in order to try to 
identify what risks are really associated with PUVA therapy.
    The Europeans have done a very similar thing. This therapy 
started in the United States. The Europeans have used it 
extensively. They use a lower dose of UVA and have not found 
the association with melanoma. However, I do not know that they 
are following their patients as closely as Rob Stern is in 
Boston.
    Mr. Hoyer. Thank you, Doctor.
    I presume, in addition to that, that you are following 
patients more closely who use these therapies, not just the 
UVA, but the others as well, and warn them to be on the lookout 
for certain symptoms.
    Dr. Katz. It is an important balance here because one might 
say why would you expose any patients to the potential 
devastating effects of skin cancer, whether it is squamous cell 
cancer or melanoma? But these patients have severe, widespread 
disease. The alternative treatments carry risks in and of 
themselves, and it is a balance that is reached by the 
physician and the patient.

                              osteoporosis

    Mr. Hoyer. Let me move on to a different subject, which the 
Chairman mentioned. I came in late, and I apologize if this 
question has been asked.
    Osteoporosis, obviously, is a very significant concern. I 
am told that it affects 709,000 men and women in Maryland. That 
would be somewhere in the neighborhood of about, I guess, 17 or 
18 percent of our population.
    I do not know whether in answer to the Chairman's question 
you gave us an update on where we are on that. Perhaps it is in 
your statement, but could you tell me where we generally are on 
osteoporosis, other than having the milk ads, which I think are 
terrific ads, personally. But other than that what are we 
doing?
    Dr. Katz. I should say that across the NIH there are many 
Institutes that are investing in obtaining knowledge about 
osteoporosis. Actually, 14 different Institutes invest in 
various aspects of osteoporosis.
    The NIAMS, as the lead Institute, has invested in a broad 
spectrum, in a multi-pronged approach, from the very 
fundamental studies of learning about how cells lay down bone 
and break down bone.
    As I said in my opening statement, bone is no longer 
thought of as being just a stone that withers away. It is 
constantly being built up and broken down, and there are 
various cellular elements that are involved in the build-up and 
breakdown of this bone.
    This year, and I have outlined it in my opening statement, 
a very important series of discoveries were made from groups 
around the world. Some were supported by the NIAMS program, and 
they have demonstrated that there is a certain gene that is 
involved in the cells that actually buildup bone.
    So, once one knows that this gene exists, many 
investigators are now looking at the function of that gene to 
determine how one can produce more of what we call 
mineralization of bone to build up the bone more strongly.
    There are also animal models of osteoporosis and 
osteopetrosis that are being funded. Osteopetrosis is a human 
disease where there is too much bone being made, and there is 
certain information that one can learn from that as well.
    Last year the Chairman, Mr. Porter, asked me the question 
about the fibrodysplasia ossificans progressiva. You remember 
that question that you asked me. [Laughter.]
    Mr. Hoyer. I am sorry, but I did the very best with that 
question. [Laughter.]
    Dr. Katz. He did ask that question, and we continue to 
invest in our understanding of this disease. This is a really 
unfortunate disease that has been studied extensively, because 
what happens in these patients, usually young people, is that 
there is a deposition of bone throughout the soft tissues of 
the body.
    One might say, obviously, that this is terribly 
unfortunate, but is there something one can learn from that? 
And we have learned a lot from some of the studies that Dr. 
Kaplan has done in Philadelphia to try to understand what 
produces bone in the soft tissues, because perhaps we could 
utilize that knowledge for producing bone in the right place.
    We also support many studies of calcium metabolism in young 
people. We support studies that Connie Weaver in Indiana does 
every summer called ``Camp Calcium.'' She brings groups of 
teenage girls together, not only to educate them, but also to 
do metabolic studies, where their precise intake and output of 
calcium are studied very carefully.
    We are also, supporting clinical studies in these areas, so 
we cover the spectrum in terms of support.

                          resurging enthusiasm

    Mr. Hoyer. Mr. Chairman, I know my time is up. Can I ask 
one more question?
    This is a general question, Doctor. I should have asked 
this of all the directors, and Dr. Varmus, of course, spoke to 
it in his initial presentation.
    How long have you been the Director of your Institute?
    Dr. Katz. 2.5 years. As director, 2.5 years.
    Mr. Hoyer. You have been at NIH for how long?
    Dr. Katz. At NIH for about 24 years.
    Mr. Hoyer. There was an extraordinary member of this 
committee, who knew more about NIH than almost all of the rest 
of us put together. It is unfortunate that he is no longer in 
the Congress because he was an extraordinary member. He hid it 
very well, but Joe Early was somebody who really cared about 
what we were doing.
    In that context, this is sort of a Joe Early question. He 
was very concerned as he saw the reducing pay lines in all of 
the Institutes and particularly concerned about are we giving 
encouragement to young people in medicine who would go into 
basic biomedical research, but as they see the pay lines 
withering and they see the opportunities decreasing, are 
discouraged from going into basic research.
    Frankly, I should have asked all of the research directors. 
What is your observation of the impact in terms of the 
extramural, grants over which you have sort of perspective of 
any adverse impact that is occurring as a result of reducing 
pay lines?
    We are trying to reverse that, I know, which is good.
    Dr. Katz. Well, you all have done a lot to really reverse 
that in recent years. Very clearly what you have done, what 
this subcommittee has done has created an air of enthusiasm for 
young people.
    Mr. Hoyer. Good.
    Dr. Katz. Before that----
    Mr. Hoyer. The Chairman is due a lot of that credit. He has 
been a real giant in terms of this, I might add.
    Dr. Katz. We still see the results of the despair that some 
of the young people had in terms of the pay lines going down. 
These are really smart people, and they are thinking, ``Well, 
gee, why should I have to suffer in terms of worrying about 
whether I can actually do research, if even highly meritorious 
research is not being funded?''
    So there was a lot of despair. I think a lot of that is 
being reversed in the last several years. There was despair in 
the clinical research community for a while, because clinical 
research was thought to be funded to a lesser extent than more 
fundamental research.
    I think with some of the activities that Dr. Varmus talked 
about--new incentives for clinical research, support of 
clinical research training and development, support of 
institutions for development of curricula that address patient-
oriented research, and in talking about this to our 
professional societies--I feel that there is a resurgence of 
hope and enthusiasm.
    So I think that you all are really the cause of that 
resurgence of hope.
    Mr. Hoyer. Thank you, Doctor.
    Thank you, Mr. Chairman.
    Mr. Porter. Thank you, Mr. Hoyer.
    Mr. Stokes.
    Mr. Stokes. Thank you, Mr. Chairman.

                         tribute to mr. stokes

    Mr. Porter. Maybe Dr. Katz would like to repeat a portion 
of his initial testimony for your benefit now thatyou are here.
    Dr. Katz. Well, I was extolling your virtues and thanking 
you very much on behalf of not only the NIAMS Institute that 
you have interacted with for so many years, not only with me, 
but also with my predecessor, Dr. Shulman. Even before the 
Institute was established 12 years ago, for many years before 
that, you were not only raising issues with regard to diseases 
that we are particularly concerned with that disproportionately 
affect women and minorities, such as lupus and vitiligo, but 
also showing sensitivity in terms of the importance of bringing 
minority investigators to the bench, and to the laboratory, and 
to the clinic to do investigation on all diseases.
    So thank you very much.
    Mr. Stokes. Thank you. You make me want to yield back my 
time. [Laughter.]
    Mr. Porter. I was going to say we are not even going to 
charge you with that.
    Mr. Hoyer. My suggestion would be that you yield it to Dr. 
Katz. [Laughter.]
    Dr. Katz. I could go on. [Laughter.]

                                 lupus

    Mr. Stokes. Thank you so much, Dr. Katz. It has also been a 
pleasure to interact with you over the years that you have been 
with the Institute and, as you mentioned also, your 
predecessor, who I worked with for quite a while.
    Unfortunately, I am next door at another hearing, and I was 
not able to be here during your presentation, and I appreciate 
your taking the time to repeat what you said so eloquently.
    You may have mentioned lupus in your formal presentation or 
in the questioning here, but, as you have mentioned, this is 
one of the areas I am particularly interested in.
    Did you discuss at all the association between heart 
disease and lupus today at all?
    Dr. Katz. I did. Actually, it is virtually impossible for 
me to talk about what the Institute does without talking about 
lupus. Lupus is a disease that we are very concerned with. We 
support research in all areas, from the very fundamental to the 
clinical.
    I did mention in my opening statement that, with the 
increased funds in the Fiscal Year 1999 budget, we are going to 
emphasize two areas of lupus erythematosus; one is in the area 
of central nervous system lupus erythematosus, an initiative 
that we are going to take with the Neurology Institute, and the 
other is the issue of arteriosclerotic disease in patients with 
lupus.
    There are concerns, obviously, with any of the patients who 
are taking long-term corticosteroid therapy. But there seems to 
be a 40 to 50 times increase in the amount of cardiovascular 
disease in women with lupus from the age of 30 to 50. We are 
tremendously concerned about that.
    We have convened panels of investigators, rheumatologists, 
to discuss this issue and an initiative that we can take. 
Before we undertake that initiative, we will certainly be 
working with the Heart Institute and getting experts in that 
area to work together on this as a special emphasis area, and 
that is one of the emphasis areas that was submitted to Dr. 
Varmus as one of our initiatives for 1999.
    Mr. Stokes. Dr. Katz, what part or how much of your funding 
is devoted to investing in the study of lupus and in lupus 
public education and outreach?
    Dr. Katz. In lupus erythematosus, our funding for 1997 was 
in excess of $24,000,000. It is anticipated that in 1998 it 
will be in excess of $26,000,000.
    We have, through our clearinghouse, as well as through our 
Office of Science and Health Communications, created many 
publications for the public about lupus, including publications 
that are particularly geared towards vulnerable populations.
    Two years ago we put out a booklet about what black women 
should know about lupus. We put that out in regular form and 
also in large print, so that people who had difficulty reading 
would have more access to information on lupus.
    With regard to our outreach programs, in terms of minority 
health and assistance, we have made contributions to the 
National Institute of General Medical Sciences for the Minority 
Biomedical Research Supplement program. We contribute in excess 
of $500,000 a year, and our minority health and assistance 
program is in excess of, for 1997, $30,000,000.

                    lupus and vulnerable populations

    Mr. Stokes. I appreciate the data that you provided for us 
here in reference to minority women, in particular, because 
this is an area that you have concentrated on and which we are 
seeing some results.
    I noticed in your Congressional justification it discusses 
that recent research has found an association between lower 
socioeconomic status and higher morbidity and mortality in 
African Americans with lupus.
    What are the implications of this finding and the 
opportunity for further research advances.
    Dr. Katz. The study to which I referred and you referred 
just now is a study that came from one of our centers in Boston 
at the Brigham Hospital done by Matthew Liang and his 
coworkers.
    The implications of that study are that, number 1, 
vulnerable populations probably have less access to early 
diagnosis and early therapy for lupus erythematosus. As I told 
the Chairman, for treatment of rheumatoid arthritis, and lupus 
erythematosus, and many of these diseases, early diagnosis and 
treatment is very important in terms of curtailing some of the 
more devastating effects of these diseases.
    So, not only are we concerned with early diagnosis and 
treatment, we are also concerned with education. The 
educational programs that we have within the Institute, within 
our Office of Science and Health Communications, only represent 
one small part of our initiative in this area.
    Another part is supporting various centers that we have 
around in the country, in terms of their educational programs. 
For example, I have recently visited our Multi-purpose 
Arthritis and Musculoskeletal Disease Center in Michigan, where 
a particular focus is on how to educate people who do not have 
general access to the Web, for example, or access to fax lines, 
where they can utilize our resources on a regular basis.
    So this type of educational research is also ongoing, 
particularly in vulnerable populations.
    Mr. Stokes. Are the historically Black Colleges and 
Universities being utilized in the kinds of research in which 
you are involved, that particularly and uniquely impact the 
African American population?
    Dr. Katz. They are. I think all of the Institutes make 
contributions to the HBCUs through various programs. We do it 
through our supplement program and through some of our MBRS 
grants.
    The dean at Morehouse University is a rheumatologist and, 
before he went there, he was funded by the Institute in the 
area of lupus erythematosus.
    So there is an interaction. Should it be more? Yes, it 
probably should be more.

                            clinical trials

    Mr. Stokes. How about clinical trials in your type of work, 
your research, are there some major clinical trials underway 
currently?
    Dr. Katz. There are major clinical trials. If one starts 
with lupus, again, one of the major clinical trials that we 
have is what is called the SELENA trial, which is addressing 
the question of whether oral contraceptives or hormone 
replacement therapy in post-menopausal women are deleterious or 
provide a negative effect in lupus erythematosus.
    For years it was thought that patients with lupus could not 
take oral contraceptives, could not take any type of estrogen, 
because it worsened their disease. Well, estrogen provides an 
important form of treatment or preventive treatment for 
osteoporosis. So there is a large populationthat does not have 
access to this.
    Two years ago we initiated a study, which is a multi-center 
study, addressing the question of the safety of estrogens--that 
is the ``SE'' part, the S-E of the SELENA--the safety of 
estrogens in lupus erythematosus.
    Those studies are ongoing, and they are accruing patients 
around the country. A large percentage of those patients are 
African American, because they are more frequently affected by 
lupus, and we look forward to the results of those trials.
    We have many other trials in lupus. We have one that is 
being started within our intramural program looking at cytoxan 
and fludarabine, which is an adenosine compound, to try to 
improve patients who have lupus nephritis, for example. That 
study has just recently begun.
    There was another study that was just completed within our 
intramural program looking at DNase treatment for lupus 
erythematosus. In many patients with lupus, they have immune 
complexes, which are made up of an antibody, plus the antigen 
to which the antibody targets. The antigen, in many cases, is 
thought to be DNA. So with this treatment one injects DNase to 
try to get rid of that part of the complex, so that it no 
longer can deposit within the kidneys.
    So these are the types of studies that we are supporting, 
clinical studies that relate directly to patients and translate 
not only to the patients whom we are treating, but also to 
patients who are affected by these diseases nationally and 
internationally.
    Mr. Stokes. Thank you very much, Dr. Katz.
    Thank you, Mr. Chairman.
    Mr. Porter. Thank you, Mr. Stokes.
    We have time for a second round. Let me get an indication 
of who has questions for round two. Mr. Hoyer or Mr. Stokes do 
you have questions for a second round?
    Mr. Stokes. I have questions which I will submit for the 
record.

         collaborations with the office of alternative medicine

    Mr. Porter. Dr. Katz, it seems your Institute works more 
closely on research initiatives with the Office of Alternative 
Medicine than many of the other Institutes. Do the diseases 
associated with your Institute lend themselves better to 
alternative methods of treatment?
    Dr. Katz. Well, our interactions with that office are 
considerable. I think one of the reasons is because underlying 
many of the diseases that we are concerned with is the symptom 
of pain.
    As you know, there are many alternative approaches to pain 
control, and that is one of the reasons why there is so much 
interaction. That interaction includes our supporting or 
administering three of the ten centers--actually, now it is 
four of the 11 centers--that the Office for Alternative 
Medicine supports.
    Three of these have been supported for about three years. 
They deal with all aspects of pain; some widespread pain, some 
pain that is particularly associated with low back pain.
    The recent Consortium for Chiropractic Research has been 
funded in Iowa at the Palmer College of Chiropractic, and the 
purpose of that Center is to try to help the chiropractic 
community develop the critically and scientifically important 
questions and ways to go about answering those questions using 
the conventional scientific approach, and we certainly hope 
that that will be successful.
    Also, we are, with the Office of Alternative Medicine, 
looking into the question of supporting a study looking at 
glucosamine and chondroitin sulfate for the treatment of 
osteoarthritis.
    So there is considerable interaction between our staff--we 
have an orthopaedic surgeon on our staff who works very closely 
with the office, as well as the head of our Rheumatic Diseases 
Branch.
    Mr. Porter. NIDR is the lead Institute on chronic pain. Are 
they involved with you in these matters?
    Dr. Katz. Not when it comes to the specifics of the Office 
of Alternative Medicine. We are all a part of the pain 
consortium that was started last year. I think most of the 
Institutes at NIH are a part of that because most of us deal 
with some aspect of pain. We each come to the table with our 
particular areas of concern.
    Our particular areas of concern are the pain of arthritis, 
the pain of fractures, and low back pain. So that is where our 
interaction with the Office of Alternative Medicine comes in.
    Mr. Porter. On the chiropractic grant, how many 
applications did you receive for that?
    Dr. Katz. There was one application. What that application 
represented was a consortium of not only schools of 
chiropractic, but also medical schools.
    For example, one of our grantees from Iowa, Malcolm Pope, 
is a part of that Center, and it is really to focus and to help 
the chiropractic community compete more successfully for 
funding with regard to conventional scientific approaches to 
questions. Those questions should be able to be answered using 
the conventional double-blind studies when possible.
    Mr. Porter. Are you saying that the chiropractic community 
responded well to this or did they respond very sparingly?
    Dr. Katz. The NIAMS and the Office of Alternative Medicine 
worked with the community long before the RFA was even put out. 
I think they responded in a way that they thought could bring 
together the best of the resources to build up the field 
nationally.
    So the Center does not represent just one school of 
chiropractic, but many schools of chiropractic because there 
are many investigators who are involved in this consortium.

                        stress and low back pain

    Mr. Porter. You are aware that we had a briefing last fall 
on the role of the mind in health and healing and, as part of 
that, one of the persons who briefed us talked about the role 
of stress in respect to low back pain. Are any studies going on 
in that regard?
    Dr. Katz. We have many studies that we are supporting with 
regard to low back pain; none that deal very directly with the 
question of stress and low back pain.
    But one that I would like to cite is the study of Margareta 
Nordin, who is looking at workers at Con-Edison and the Transit 
Authority in New York. She is looking prospectively at 
individuals who have acute low back pain to try to identify 
those determinants that will result in chronic low back pain. 
Whether stress is one of those factors, we are yet to see the 
results of those studies.

      collaboration with the office of research on women's health

    Mr. Porter. Osteoarthritis is a major contributor to 
functional impairment and a major cause of disability. It also 
causes many individuals to undergo joint replacement surgery. 
Arthritis is more common in women and women receive a higher 
percentage of both hip and knee replacements than men. Do you 
plan to undertake any studies in conjunction with the Office of 
Research on Women's Health to better understand why arthritis 
is more common in women and why the incidence of joint 
replacements are higher in women?
    Dr. Katz. We do an enormous amount of collaboration with 
the Office of Research on Women's Health. As I said in my 
opening statement, there are so many diseases that we are 
concerned with that disproportionately affect women--all of the 
autoimmune diseases, as well as osteoporosis.
    We do co-fund grants with the Office of Research on Women's 
Health in all areas of arthritis, not only in osteoarthritis, 
but in rheumatoid arthritis and lupus erythematosus, et cetera.
    With regard to areas of osteoporosis, we will have some co-
funding with them on some of the grants that deal with 
information about what is called periprosthetic osteolysis. 
Periprosthetic osteolysis is what happens when an artificial 
joint no longer fits into the bone, and one of the reasons it 
does not fit into the bone too well is because particles are 
released from this artificial hip or knee and produces 
inflammation around the bone, and it causes loosening.
    The problem, fortunately, does not occur very often. It 
occurs in 10 to 15 percent of hip or knee replacements. But 
when it does occur, it makes putting back an artificial hip or 
an artificial knee that much more difficult.
    So those are some of the areas that we co-fund with 
theOffice of Research on Women's Health.
    Also, the SELENA trial, for example, the one that I spoke 
to Mr. Stokes about, was co-funded by the Office of Research on 
Women's Health and many others as well.

                        gender and autoimmunity

    Mr. Porter. Do we know why autoimmune disorders have a 
disproportional effect on women?
    Dr. Katz. No, but we are trying to find out. About a year 
and a half ago, we put out a request for applications along 
with the National Institute of Allergy and Infectious Disease, 
the National Institute of Diabetes and Digestive and Kidney 
Diseases, and other institutes that are concerned with 
autoimmunity. Many of these autoimmune diseases occur more 
frequently in women than men. We have put out a request for 
applications dealing with gender and autoimmunity. This year, 
we put out an RFA again with these other institutes on 
autoimmunity mechanisms, genetics and pathophysiology to 
address this question of gender.
    We have gotten applications. We now fund applications in 
gender and autoimmunity. NIAID got the bulk of those 
applications, and they now fund direct responses to that RFA. 
Excuse me; it might have been a program announcement. But we 
all fund applications in response to that announcement.

                         cartilage restoration

    Mr. Porter. It was reported in the Washington Post on 
January 28 that a new surgical procedure called biological 
resurfacing, developed at the Mayo Clinic, has successfully 
restored cartilage damaged by injuries to the knee and other 
joints, delaying or preventing the need for joint replacement. 
Are you familiar with this procedure, and can you describe it 
to us?
    Mr. Katz. There are several resurfacing techniques that 
have been popularized. The one that recently received FDA 
approval is when one has an injury to the knee or to any 
articular cartilage where there is a specific defect, one can 
take cartilage cells from that individual, grow up the 
cartilage and then return those cartilage cells to that 
particular defect.
    Now, that does not really correct osteoarthritis. It 
corrects a specific defect that is usually due to injury. Those 
studies were initially done in Sweden and now have been done 
extensively in the United States. Whether that is really 
extrapolatable to osteoarthritis is another question. There are 
many people who are trying to address the question of taking 
and growing cartilage cells or chondrocytes and then inserting 
certain genes into those chondrocytes to make them more likely 
to take in the joint.

                               hair loss

    Mr. Porter. This question is on hair loss. I remember 
reading somewhere that Americans spend $7 billion a year trying 
to fight baldness with drugs, cosmetic surgery, and wigs. An 
article published in Science this past January stated that the 
first human gene ever linked to hair loss has been identified 
in Pakistan. This gene causes a rare condition found only in a 
Pakistani village, not the more common types of baldness, but 
like all gene discoveries, you have to start somewhere. Do you 
have any studies planned to expand on this discovery? When do 
you think we will have a gene therapy for baldness?
    Dr. Katz. Well, I was taught that one never gives a time 
frame for these things. [Laughter.]
    And certainly, as a dermatologist, I would not venture a 
guess with regard to that.
    But I think it is important to identify that the study that 
was reported, really derives from many of the investments we 
have made in developing animal models, because that gene, that 
hair loss gene was first identified in a mutant mouse that was 
identified, I believe, at the Jackson Labs in Bar Harbor, 
Maine. And it is from those types of studies that Angela 
Christiano and her co-workers, who are supported by the NIAMS 
in an early career award, what we call an R-29, and now I think 
she has another award, a small grant, to support her work, they 
have demonstrated that this gene is defective in this 
particular family that has seven generations of individuals who 
are actually born with hair and then lose the hair shortly 
thereafter, and the hair does not regrow.
    Now, the title of that paper was unfortunate, because it 
talked about alopecia universalis. Alopecia universalis is a 
term that is usually used for acquired hair loss in children or 
adults. It can be a devastating disease, devastating, as you 
can imagine, psychologically. But the alopecia universalis that 
was identified by these investigators was the inherited form of 
alopecia universalis.
    Will this help us understand hair growth? It certainly 
will.
    Mr. Porter. I cannot imagine why the staff wanted me to ask 
that question.
    Mr. Hoyer?
    Dr. Katz. You cannot?
    Mr. Hoyer. Well, I cannot understand either, Mr. Chairman, 
but it is my understanding that if there is not a quick answer 
to that, the budget for this Institute is in trouble. 
[Laughter.]

                             success rates

    Mr. Hoyer. Doctor, let me go back to my pay line question, 
and Dr. Varmus may want to comment on this, too.
    First of all, can you remind me, because I do not know, 
where we are now on the pay line on your extramural grant and 
where that relates to, for instance, we were 5 years ago or 10 
years ago?
    Dr. Varmus. Do you want to know for the whole NIH?
    Mr. Hoyer. Well, either the whole of NIH or this institute, 
if we have it. I would like both, sure.
    Dr. Varmus. Well, the overall success rate for all of NIH 
this year is going to be roughly 28 or 29 percent. We are 
forecasting 31 percent in the coming year. I mentioned the 
other day the importance of an equitable success rate for new 
investigators. The success rate that we have been talking about 
includes people applying for a new grant, who may not be new 
investigators----
    Mr. Hoyer. Right.
    Dr. Varmus [continuing]. And those applying for their 
continuation grants, the competitive renewal. Of course, those 
who have achieved a grant before tend to do better. New 
investigators have success rates of around 22 to 24 percent at 
the moment. Five or 10 years ago, the success rates had 
declined overall at NIH to the low twenties. In some 
institutes, the success rate was as low as 10 or 13 percent. 
And when you disaggregated that further and looked at the R01 
specifically and excluded, for example, the health services 
research grants or the R03s, which are smaller awards, some 
categories, the success rate could be as low as 5 or 8 percent.
    So, we have come quite a long way, and we envision going 
further. We are especially pleased with the President's budget 
request for this year because it forecasts 5 years of continued 
increases, allowing us to maintain a very stable environment 
that gets us back to your earlier point about providing an 
inviting environment for doing science, one that allows 
innovation and encourages the best people to come into the 
field. I appreciate your bringing up this issue.
    Mr. Hoyer. Following up on that question, have we had 
enough experience or has there been sort of a lineal study done 
with reference to what level you become at risk of losing a 
flow of researchers into basic biomedical research? In other 
words, have we drawn any conclusions from this experience that 
if you are up in the forties as opposed to if you are down in 
the teens?
    Dr. Varmus. That is a very difficult question to try to 
answer. I think you would find that if you went to the very 
best training sites that very, very good young people have been 
entering the system even in those periods of relative drought, 
but that when you go to, perhaps, one peg down, you might find 
that the quality of new entries into medical research has 
declined.
    I think that the place we have seen the decline in interest 
most profoundly is in the clinical research arena, because the 
training program is less well developed; the risks to clinical 
investigators who have an alternativecareer as practitioners is 
greater; and the support that can be provided to clinical investigators 
through patient revenues has declined as a consequence of the incursion 
of managed care into the academic health centers.
    Mr. Hoyer. Doctor, let me ask you another question on that.
    Assuming unlimited resources, for the sake of argument, 
what would you speculate would be an appropriate pay line, 
unrelated to resource availability? In other words, what I am 
saying is----
    Dr. Varmus. I understand.
    Mr. Hoyer. Of the cohorts of applications, how many really 
good ones are there to do good science, and therefore, if it is 
60 percent or 70 percent, we have 30 percent out there if we 
are doing 40 or 35, that is really good science that we are not 
funding.
    Dr. Varmus. This really is a somewhat subjective judgment.
    Mr. Hoyer. Sure.
    Dr. Varmus. But most people that I have talked to feel that 
if we were funding in the range of 30 to 40 percent of the 
applications, that would be about right. In my view, there 
should be a basement level; that is, all institutes should be 
up to that kind of level, and we should be supporting new 
investigators at roughly 30 or 35 percent, because I am 
particularly concerned about investing in 10 years of training 
and then not letting at least a substantial portion--a third to 
a half of those trained people--have a chance at doing research 
with NIH grants.
    Mr. Hoyer. Given that, Doctor, and you said we are going to 
be at the 31 percent average----
    Dr. Varmus. That would be an average.
    Dr. Katz. An average, but it cuts across many institutes.
    Dr. Varmus. Yes, and not all institutes are at that level, 
and not all the new----
    Mr. Hoyer. My question, therefore, is what is the low, and 
what is the high, if you know? Do we know?
    Dr. Varmus. Oh, I believe we do have those numbers. The 
highest numbers are for competitive renewals, and that would 
probably be in the range of 55 percent or so. The lowest 
numbers would be for new investigators at certain institutes, 
and the number is probably about 20 percent or a little lower.
    Dr. Katz. Our level for success rate last year was about 24 
percent.
    Mr. Hoyer. For new competitive----
    Dr. Katz. For total.
    Mr. Hoyer. Total.
    Dr. Katz. Total; but that may not be the right way to 
actually look at it, because, as Dr. Varmus said, if one looks 
at new investigators, our new investigators, we have maintained 
our new investigators at that level. We would like to be 
higher, but we have maintained them at about the same rate as 
the established.
    Mr. Hoyer. It seems to me this is a pretty key question for 
this committee, to make sure that we do not fall below an at 
risk. Obviously, we will never be given all of the resources 
that we need, but we do need to have some sort of feel that we 
can go to the floor. The chairman can go into the 602(b) 
allocation discussion with the other subcommittee chairs, and 
say look, here is where we are, but we need to be is here.
    And, Doctor, that is particularly true in light of your 
comments in your statement, which I have now read while I have 
been sitting here. That it is, particularly for those of us 
that it has become more relevant to as time goes by, the kind 
of world which you express in your statements is a pain free or 
substantially less problems in the aging process than now exist 
and the amelioration of a lot of the quality defeating aspects 
of growing old.
    And you paint a picture which is certainly exciting. 
Certainly, I think, many of us believe that we are on the 
threshold because of the findings that have gone on to a major 
spurt, which you seem to indicate, in the next decade or two 
decades of a geometric increase in our knowledge and ability to 
cope with problems that confront the health of Americans and 
the people of the world.
    Dr. Katz. I am certainly enthusiastic that we can achieve 
those goals and attain that type of world.
    Mr. Hoyer. Well, it is exciting.
    Thank you.
    Mr. Porter. Thank you, Mr. Hoyer.
    Can I follow up on questions that Mr. Hoyer asked? Ten 
years ago we were in the low twenties, I think you said, Dr. 
Varmus.
    Dr. Varmus. That is about right. I would have to take a 
look at it.
    Mr. Porter. Now, we are almost to the low thirties.
    Dr. Varmus. Almost.
    Mr. Porter. Ten years ago, we were funding NIH very 
strongly. There has always been strong support for NIH. What 
made the difference?
    Dr. Varmus. Well, there was a time in about 1990 or 1991 
when the numbers of grants that came up for renewal was high, 
and I would have to look back exactly at the level of funding. 
There were a couple of years that were not so strong, and one 
of the lessons I took away from this experience was that even 
one or two years of a very low funding rate could have a really 
disastrous impact on the system, because it meant that many 
investigators were denied their renewals or failed to get a 
first grant. Of course, they submit a reapplication. Then the 
system backs up with a lot of high quality grant applications 
in the system that are not getting funded.
    The reviewers get very discouraged, because they are giving 
high marks to grants that do not get supported, and the impact 
on the mood in the scientific community is probably much larger 
than you might have expected from the moderate difference in 
the number of grants actually supported.
    Mr. Porter. I am not sure whether that means that 
scientists got discouraged because there were not as many being 
supported, and, therefore, we did not get as many proposals of 
good science or what it means.
    Dr. Varmus. No; the number of applications was high and, of 
course, stayed high because people were resubmitting 
applications. But we have talked before about the effect of 
discontinuation of a productive laboratory--it means that you 
lay people off and it is very hard to reconstruct a laboratory. 
Senator Hatfield used to make the analogy of the lumber mill. 
If you lose funding, and if you take the mill apart send your 
lumbermen home, by the time you try to reinvest, it is very 
difficult to get restarted. So, that has kind of a widespread 
effect, for example, on a timber-oriented culture.
    Mr. Hoyer. Mr. Chairman, excuse me.
    Mr. Porter. Mr. Hoyer?
    Mr. Hoyer. If you will yield.
    Mr. Porter. I yield.
    Mr. Hoyer. Joe Early, to whom I referred earlier--I do not 
know how many of you--most of you know Joe Early; he was and is 
an extraordinary fellow, and I learned a lot about NIH from Joe 
Early, and I sat--I was where Mrs. Northup sits now for about 6 
years. I think I filled the last rung on the ladder. And Mr. 
Porter----
    Mr. Porter. I was the last rung on the after end, which was 
the minority end.
    Mr. Hoyer. I was going to say: Mr. Porter, did you start in 
January of 1983?
    Mr. Porter. No, I started on the subcommittee in January of 
1981.
    Mr. Hoyer. Okay; Mr. Porter was on the committee 2 years 
before I was. But I can remember, John, as you can remember, as 
the eighties went on, the pay line went down,and Mr. Early used 
to raise the specter of the pay line, and I know it got down into the 
teens in a number of institutes, and I believe these were first time 
grants, not renewals. And he kept remembering, and then, we would have 
the markups. And he would come in with, we thought, an unbelievable 
amount of money. He would ask for a half a billion dollars more for 
NIH, and we all sort of rolled our eyes.
    And he was pretty successful. As you recall it, during 
those days, we had one vote on the committee. Mr. Natcher told 
us what we were going to do, and we all did it. But we tried to 
urge him to agree to our position. That was really what the 
deal was. But I can remember, Mr. Chairman, Joe got very 
concerned about how that pay line kept going down, even though 
we kept putting more money in NIH, and, to wit, your question 
of what has made the difference. Is my recollection right on 
that?
    Dr. Katz. For the NIAMS, it is certainly true in 1992 and 
1994, we were below 20 percent. We were in the high teens but 
below 20 percent.
    There is another factor, I think, going on here, and that 
is that in the eighties, particularly in the area of clinical 
specialties and support of clinical research, there was much 
more money within departments to provide for investigators who 
were not being funded. And now, as Dr. Varmus said, those 
people cannot stay in the system for as long and be rejected 
for as long, because that other support that used to come from 
patient care revenues and other sources of funding through 
pharmaceutical companies is much less today.
    So, we do not have that resilience that we once had.
    Mr. Hoyer. Mr. Chairman, that may be interesting. If you 
have those statistics, that analysis might be a good one, Mr. 
Chairman, for you as to why this is important, because the 
pharmaceuticals and the universities have less resources 
available to them. And so, even though we are spending more, 
the net resources are either even or declining.
    Mr. Porter. Yes; we have been talking about what can be 
done in this respect, because obviously, it is a very serious 
problem.
    Mr. Hoyer. Thank you, Mr. Chairman.
    Dr. Varmus. I did not give you entirely correct numbers. It 
was 25 percent in 1990, and some of the other numbers are 
higher. I would like to gather the numbers, if I could, and 
submit them for the record.
    Mr. Porter. Please.
    Dr. Varmus. And supply a more accurate rendition of what I 
just told you.
    Mr. Hoyer. Mr. Chairman, could you go back further, going 
into, say, 1985?
    Dr. Varmus. Oh, we can, yes; at that time, or earlier, it 
was really extremely high, in the forties.
    Mr. Hoyer. Well, it seemed to me it must have been high in 
the beginning eighties. And then, as we got into 1987 and 1988, 
it must have gone down, because I can remember: that is when 
Mr. Early really got concerned and a lot of questions to every 
institute director: what are your pay lines? And that is when I 
got into what pay lines were. I had no idea what he was talking 
about to begin with.
    But I learned, and obviously, the consequences of it were 
made known to us. So, Mr. Chairman, if, in your statistics, we 
can see that flow and then relate it to what resources are 
available from the--or the secondary or primary sources, 
however they looked at it----
    Mr. Porter. Dr. Varmus, since you will be here over the 
next few days, can we raise this question then rather than----
    Dr. Varmus. Sure.
    Mr. Porter [continuing]. Answering it for the record?
    Dr. Varmus. Sure.
    Mr. Porter. Can I ask one further question, since Mr. Hoyer 
raised it and you referred to it in your remarks earlier? And 
this is not a partisan question, although it may sound like it, 
but a year ago, when the President submitted the budget for the 
current fiscal year, he had NIH at a very low increase. I think 
it was like 2.6 percent.
    Dr. Varmus. Last year.
    Mr. Porter. Last year, which was the budget for this fiscal 
year. And, as a result of the balanced budget negotiations, NIH 
was not put at a high priority; in fact, we figured out that 
the outcome would be at 1.2 percent if we followed the 
President's budget at that point a year ago.
    This year, the President has come back and said gee, we 
have got to give NIH an 8.4 percent increase and double their 
funding over the next 5 years. What within the administration--
--
    Dr. Varmus. Forty-eight percent over the next 5 years.
    Mr. Porter. I am sorry; 50 percent, yes, 50 percent 
increase over the next 5 years; we are more ambitious than the 
White House. But what has caused this change of heart within 
the administration about this subject that seems to those of us 
who are on the subcommittee on both sides of the aisle to have 
been a high priority all along?
    Dr. Varmus. Well, I do not believe that there was lack of 
enthusiasm for the NIH in previous years. I think there was 
concern about how to meet the demands of balancing the budget. 
The President has always signed the bills and has been 
outspoken in praise of medical research and other forms of 
research. We actually were doing better in his budget proposal 
last year than some other agencies. Obviously, his proposal was 
not as beneficial to us as the ultimate appropriation bill was, 
but I would not see this as a change of heart so much as a 
change of circumstances and a response to it that is obviously 
welcome to both of us.
    Mr. Porter. Are you confident that the President will not 
come back next year and suggest another very low increase?
    Dr. Varmus. I believe that he will stay by his word, and 
the 5-year projection will be a good starting point in our 
negotiations.
    Mr. Porter. The President's budget included substantial 
revenues that are unlikely to be voted this year, and those are 
revenues that support discretionary spending which, of 
necessity, comes after entitlement spending. If the revenues 
are not there, what would your budget look like under the 
President's figures? In other words, if you took the amount out 
for this next fiscal year, which I think is something like $16 
billion, with $100 billion over 5 years, and you allocated it 
to NIH, what would his number be? Have you calculated that, by 
any chance?
    Dr. Varmus. I am not sure I follow the question. Are you 
asking me----
    Mr. Porter. Well, if you assume that you will not have the 
$100 billion worth of revenues in the President's budget that 
is partially the support for all discretionary increases, what 
would your increase drop to?
    Dr. Varmus. Well, what the President is proposing for NIH 
is an increase that is based on revenues that are brought in by 
tobacco legislation.
    Mr. Porter. All of it?
    Dr. Varmus. The increase.
    Mr. Porter. So, you would be level-funded if there are not 
any new revenues?
    Dr. Varmus. Well, let me finish. He is making that proposal 
as a way to request more money than would be available to us 
under the current caps that were imposed by the Balanced Budget 
Act of last year. He has said that he believes that tobacco 
legislation will be passed. If that does not happen, he will 
work with the Congress to find other ways to fund the research 
proposal that he has built. Obviously, at that point, he and 
the Secretary and the Vice President would have to negotiate 
with Congress to find another source of funds for those things 
that he considers high priority.
    Mr. Porter. My worst nightmare in this respect is 
thatCongress does very well by biomedical research, not so well by some 
of the other priorities that the President has in mind, and we end up 
in a negotiation with the White House where the President decides it 
was not such a high priority after all. And without the revenues being 
present, I think we are going to face possibly the kind of problem that 
I am worried about.
    I am hopeful that that is not the case and that this is a 
real look at all of the priorities, and we have many of them 
within our portfolio, and that the President feels that 
biomedical research is at or near the very top of the list.
    Dr. Varmus. So I have been assured.
    Mr. Hoyer. Mr. Chairman?
    Mr. Porter. Mr. Hoyer?
    Mr. Hoyer. We have another problem, of course, in that the 
Senate bill and, I presume, the House bill, when it comes to 
the floor, will have another $26,000,000,000 in ISTEA, which 
will be $5,000,000,000 a year against the caps, which is going 
to impact on all of the rest of discretionary spending if we do 
not change the caps. So, we have some very significant funding 
challenges that confront us, notwithstanding whether the 
tobacco settlement is adopted.
    Mr. Porter. I think it is very clear we are not going to 
change the caps, and that is why I have been saying as often as 
I can I think we have to realistically look at the start of 
this 5-year increase, whether it is 50 percent over 5 years or 
100 percent over 5 years next year, not this year, because 
things are going to be pretty rough to get the budget finally 
into balance, and that all assumes that we have an economy that 
is expanding at the rate that it has been recently.
    It is a very tough question for us here.
    Dr. Katz, we thank you for the fine job you are doing.
    Dr. Katz. Thank you very much.
    Mr. Porter. We thank you for your excellent testimony and 
appearance here today, and the subcommittee will stand in 
recess for 3 minutes.
    [The following questions were submitted to be answered for 
the record:]


[Pages 1839 - 1912--The official Committee record contains additional material here.]



                                           Tuesday, March 17, 1998.

                 NATIONAL CENTER FOR RESEARCH RESOURCES

                               WITNESSES

DR. JUDITH L. VAITUKAITIS, DIRECTOR
DR. LOUISE E. RAMM, DEPUTY DIRECTOR
DR. DOV JARON, ASSOCIATE DIRECTOR FOR BIOMEDICAL TECHNOLOGY
ANNE E. SUMMERS, BUDGET OFFICER
DR. HAROLD VARMUS, 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 of the National Institutes of Health with 
the National Center for Research Resources, and we are pleased 
to welcome its director, Dr. Judith L. Vaitukaitis. Dr. 
Vaitukaitis, if you would introduce the people you have brought 
with you and then proceed with your statement, we would 
appreciate that.
    Dr. Vaitukaitis. Thank you, Mr. Porter.
    To my left is Dr. Dov Jaron, who is the associate director 
for Biomedical technology. To his right is Dr. Louise Ramm, who 
is the deputy director for NCRR. To my immediate left is Ms. 
Anne Summers, who is our budget officer. And you know the 
gentleman, Dr. Varmus to my right and Mr. Williams to my far 
right.

                              ncrr request

    Mr. Chairman and members of the committee, I am pleased to 
present the President's budget for the National Center for 
Research Resources for fiscal year 1999, a sum of $423 million 
which is an increase of $51 million or 13.9 percent above the 
comparable fiscal year 1998 non-AIDS appropriation. Including 
the estimated allocation for AIDS in both years, Federal 
support proposed for NCRR is $514.8 million or an increase of 
$60.9 million over the 1998 appropriation.
    It is a pleasure once again to have the opportunity to 
discuss the accomplishments and future directions of the NCRR, 
which fills a unique and indispensable niche in the family of 
NIH institutes and centers. Unlike the other components of NIH, 
which focus on particular biomedical disciplines, diseases or 
organ systems, NCRR provides the essential tools and 
infrastructure that facilitate all lines of NIH-supported 
research, ranging from basic to clinical investigations.
    NCRR can best be described as a catalyst for discovery, for 
without advanced instrumentation, up-to-date research 
facilities with access to specialized expertise, and animal 
models for human diseases, the scientific enterprise would be 
slowed and more costly. Each year, more than 15,000 
investigators, supported by more than $1.8 billion from the NIH 
categorical institutes, utilize NCRR-supported research 
resource facilities as integral parts of their research.
    Shared instrumentation grants and repositories for both 
biomaterials and animal models are also invaluable resources to 
thousands of additional investigators. Our fundamental 
objectives are to direct NCRR's support to maximize sharing of 
research resources and technologies, enhancing 
multidisciplinary research by fostering collaborations among 
investigators and leveraging Federal funds.

                 advanced instrumentation and computers

    Advanced instrumentation and computers have a fundamental 
role in most biomedical studies, yet, they also account for 
some of the largest expenses. To help reduce costs while 
providing access to the most sophisticated research tools, NCRR 
supports shared instruments and resources, including a network 
of more than 60 biomedical technology resource centers that 
develop and provide access to critical technologies for health 
research, ranging from those for degenerative brain disorders, 
cancer, and cardiovascular diseases to AIDS.
    Shared resources are essential tools in efforts to unravel 
the complexities of the human genome as well as to define the 
genetic defects that lead to diseases such as sickle cell 
anemia, cystic fibrosis and a variety of cancers. This enormous 
undertaking requires an array of sophisticated and costly 
instruments such as sequencers, mass spectrometers, analytical 
ultracentrifuges and nuclear magnetic resonance imagers. By 
awarding grants for these instruments as shared resources, 
their utilization is greatly increased. On average, more than 
15 investigators share each instrument provided through NCRR's 
Shared Instrumentation Grant program. In fiscal year 1999, NCRR 
will significantly expand this unique program to assure that 
investigators have state-of-the-art research tools.
    In recent years, it has become increasingly clear that a 
complete picture of the genome can only be obtained if gene 
identification efforts are supplemented with studies to 
characterize the proteins produced by the genes. At anNCRR-
supported microscopy and imaging resource at the University of 
California, San Diego, scientists are developing microscopic methods 
that permit mapping of both genes and their products in situ for 
Alzheimer's Disease, for example.
    Resource facilities like this and others will accommodate 
investigator access and permit remote control of sophisticated 
instruments over the Internet and facilitate electronic 
communication with colleagues at other sites. Such arrangements 
will permit interactive tasks as if the collaborators are in 
the same laboratory. Continuing developments in computer 
technology and establishment of the ultrafast Internet-2 will 
allow extensive scientific collaboration and sharing of 
research resources and technologies. In fiscal year 1999, NCRR 
plans to expand these initial efforts, so in a few years, 
cooperating university Internet sites will provide gateways to 
access sophisticated technologies, investigators and databases 
across the research community.
    X-ray crystallography provides the ultimate details of 
molecular structures. The ultrabright synchrotron-generated x-
rays have made it possible to increase resolution to levels 
that were not believed possible just a few years ago. For 
example, NCRR-supported scientists at Stanford University 
recently determined the detailed structure of the protein 
fibrinogen, which is essential to stop bleeding but also 
contributes to heart disease and stroke. As the human genome 
project identifies more genes, more proteins of unknown 
structure and function will require characterization in order 
to define the causes of disease and to develop novel therapies 
for them. In fiscal year 1999, NCRR plans to increase its 
support for investigator access to synchrotron beamlines.

                         advanced technologies

    As research problems become more complex, their solutions 
require more sophisticated technologies that demand an 
integrated approach. For example, the attached figure 
summarizes the interaction of several costly, advanced 
technologies that contribute significantly to the development 
of novel drug therapies. This approach is commonly referred to 
as structure-based drug design. Either high-energy x-rays, high 
field nuclear magnetic resonance or both technologies provide 
essential data about the structure of a purified protein. In 
the figure before you, high-energy x-rays, generated at the 
Advanced Photon Source at the Argonne National Laboratory, 
provide a key tool to analyze a crystallized protein. However, 
that crystallographic data may not be enough. That same protein 
may also need to be studied by high field nuclear magnetic 
resonance at an NCRR-supported research resource facility such 
as the Massachusetts Institute of Technology's Center for 
Magnetic Resonance to gain additional information to discern 
the protein's molecular structure.
    Data from synchrotrons or NMRs can be analyzed by special 
software designed to run on a supercomputer, which may be 
located at the University of Pittsburgh. That processed 
information may then be moved over the Internet and analyzed by 
3D visualization tools, using the investigator's own 
workstation. The image in the center of the figure was created 
with a molecular graphics system at the NCRR-supported 
University of California at San Francisco's Computer Graphics 
Laboratory. Visualization tools help identify the site on the 
molecule at which a drug may interact.
    Candidate drugs and proteins which may bind at the active 
site can be selected from databases over the Internet at sites 
somewhere in the U.S. or Europe. The molecule displayed is HIV-
1 protease (shown in green and yellow) along with a drug 
candidate (depicted in magenta) bound within the enzyme's 
active site. The drug inhibits or blocks the biologic action of 
the protease and is a potential new treatment for HIV infection 
in man. The structure of HIV-1 protease was solved by members 
of the Crystallography Laboratory of the National Cancer 
Institute. Structure-based drug design is a faster and more 
cost-effective approach to drug development than the empirical 
approaches used in the past.
    Other recent developments in areas related to genomic 
research will generate major new multidisciplinary initiatives. 
Areas such as laser light source technology and design of 
extremely small-scale tools using nanofabrication and 
nanobioengineering techniques are now so advanced that 
engineers and scientists are constructing devices for detection 
of single molecules and miniaturizing instruments that will 
save expensive reagents and man hours. For example, the 
development of microchips for ultrasensitive DNA analysis is a 
revolutionary approach to miniaturization. Manufacture of these 
chips requires multidisciplinary expertise in production of 
computer chips, molecular biology, optics, and gene sequencing 
that will bring together physicists, engineers and biologists.
    NCRR plans to extend its support to provide these powerful 
tools to identify genetic risk factors which may be modulated 
by diet, changes in lifestyles or other approaches to prevent, 
delay or treat disease.

                       biology of brain disorders

    Thanks to powerful new technologies such as functional 
magnetic resonance imaging, or fMRI, and multiphoton laser 
scanning microscopy, scientists have gained increasingly 
detailed insight into the biology of the human brain. NCRR-
supported researchers at Carnegie Mellon University, University 
of Pittsburgh Medical Center, and Pittsburgh Supercomputing 
Center have combined the powers of fMRI, high-speed networks 
and a supercomputer to produce high-quality 3-D images of the 
working brain within seconds of recording. To capitalize on 
these technological enhancements, NCRR will support development 
and acquisition of instruments that provide images of the 
brain, including images of tissue damaged by neurodegenerative 
diseases such as Parkinson's or Alzheimer's, in even more 
detail than currently possible.
    In addition, NCRR will support development of user-friendly 
database structures to facilitate investigator analysis and 
synthesis of vast data sets.

                            genetic medicine

    Nonhuman biological and disease models are indispensable to 
biomedical research. To understand gene function in cancer, 
diabetes and cardiovascular diseases, for example, scientists 
have developed thousands of genetically altered animal models 
in mice and rats. To assure preservation of these models, which 
are expensive to maintain, NCRR will create additional national 
and regional repositories to assure that novel genetically 
altered mice and rats can be distributed to investigators 
nationwide.
    Certain studies with great implications for human health 
can best be carried out in nonhuman primates. Examples include 
development of a vaccine against AIDS and in-depth 
understanding of the immune system. Scientists at NCRR-
supported Regional Primate Research Centers have developed 
procedures for producing genetically identical monkeys. 
Availability of these animals will facilitate development of an 
AIDS vaccine and provide a unique model to more effectively 
study tissue rejection associated with organ transplantation. 
NCRR plans to further develop this model.
    Gene therapy is still at an early age but holds great 
promise. NCRR, in collaboration with the National Cancer 
Institute, the National Heart, Lung and Blood Institute and the 
National Institute of Diabetes, Digestive and Kidney Diseases, 
supported the establishment and maintenance of three National 
Gene Vector Laboratories that produce clinical-grade gene 
vectors or carriers. These gene carriers are used in human gene 
therapy to transport therapeutic genes into cells where they 
are needed to alleviate or cure diseases such as cystic 
fibrosis, atherosclerosis and an array of cancers. But the 
technique still needs refinement, and additional vectors need 
to be developed and studied. Because the safety of new vectors 
must be extensively examined, NCRR plans to support the 
development of additional vectors as well as their preclinical 
evaluations at NCRR-supported research resource facilities.

                           research capacity

    NCRR administers an NIH-wide extramural construction grant 
program that requires matching institutional funding. The 
awards support renovation or new construction of 
researchfacilities at medical schools, hospitals, universities and 
research institutions. According to a 1996 survey conducted by the 
National Science Foundation, academic institutions had deferred $3.6 
billion worth of needed biomedical construction and repair or 
renovation projects. To help alleviate this need, NCRR plans to 
continue funding of construction projects to upgrade biomedical 
research facilities.
    General Clinical Research Centers play a key role in 
patient-oriented research, and that research reflects that 
supported by the NIH categoric institutes. The GCRCs host 
nearly 9,000 investigators who conduct nearly 6,000 research 
projects annually. The GCRCs provide infrastructure to academic 
institutions through the support of inpatient and outpatient 
research facilities and other resources vital for state-of-the-
art, patient-oriented research. The GCRCs also provide an 
effective forum for training and junior career development for 
mentored, patient-oriented clinical research.
    The GCRCs need to expand research activities into less 
traditional GCRC research areas, such as intensive care, 
emergency rooms, trauma units and other specialized units. 
Seriously ill patients are increasingly studied at GCRCs, and 
the need for specialized testing and research nurse staffing to 
support those research studies has increased markedly. To 
address this need, NCRR in fiscal year 1999 will enhance 
support for the network of GCRCs which provide a critical 
interface to assure that scientific advances for rare diseases, 
cancers, diabetes mellitus, AIDS, cardiovascular and many other 
diseases are transferred from the laboratory to the patient.
    To enhance research on diseases such as renal disease, 
diabetes mellitus and cancer that disproportionately affect 
minority populations, NCRR will support establishment of 
Centers of Clinical Research Excellence at NCRR-supported 
Research Centers in Minority Institutions that are affiliated 
with medical schools. The centers will recruit new faculty, 
established investigators in clinical research, who will serve 
as mentors to junior investigators in an effort to build 
effective clinical research teams.
    Congressman Louis Stokes played an essential role in 
getting the Research Centers in Minority Institutions program 
started in 1985 and fostering it along to the great success it 
has become. We all owe him a debt of gratitude for his 
foresight and tenacity, not only for his support of that 
program but also for his support of NIH programs in general. 
His retirement from this Congress is a loss to the biomedical 
research community.
    The activities of the NCRR are covered within the NIH-wide 
annual performance plan required under the Government 
Performance and Results Act. The fiscal year 1999 performance 
goals and measures for NIH are detailed in this performance 
plan and are linked to both the budget and the HHS GPRA 
strategic plan which was transmitted to Congress on September 
30, 1997. NIH's performance targets in the plan are partially a 
function of resource levels requested in the President's budget 
and could change based upon final Congressional appropriations 
action.
    NIH looks forward to Congress' feedback on the usefulness 
of its performance plan as well as to working with Congress on 
achieving the NIH goals laid out in this plan.
    My colleagues and I will be happy to respond to any 
questions you may have.
    [The prepared statement follows:]


[Pages 1919 - 1925--The official Committee record contains additional material here.]



                             ncrr resources

    Mr. Porter. Thank you, Dr. Vaitukaitis. Lou's staff will 
make sure he hears your very kind comments about his work, with 
which we all agree on the subcommittee. We also appreciate that 
your examples came from Illinois with Argonne; MIT which I have 
had some contact with, and the University of California at San 
Francisco. Ms. Pelosi will be pleased.
    I need a little more basic education, so let me ask you 
some very basic questions. Do the resources that you provide 
get distributed both intramurally and extramurally; in other 
words, do you provide them on the NIH campus and to NIH 
grantees?
    Dr. Vaitukaitis. Our resources are primarily for extramural 
investigators funded with their own research project grants. We 
do host some intramural investigators who use those resources; 
for instance, they may go to some of the high field NMR sites 
or to a synchrotron site that we support.
    Mr. Porter. So, if it is on-campus research, that is 
someone else's responsibility, not yours.
    Dr. Vaitukaitis. Yes.
    Mr. Porter. And yours are all, except for those instances 
you just named, for NIH grantees.
    Dr. Vaitukaitis. That is correct.
    Mr. Porter. In other words, when a grant is made by NIH, 
the grantee may then apply to you for resources that they need 
to carry it out.
    Dr. Vaitukaitis. The investigator who applies for an NIH 
grant, for instance, to the National Institute of General 
Medical Sciences, may need to do crystallographic studies at a 
synchrotron site. He or she has an award received from NIGMS, 
and then, he or she applies to the synchrotron site to access 
the synchrotron beam line for a certain length of time.
    Mr. Porter. Okay; but some of these are mobile resources 
such as animals for example, aren't they?
    Dr. Vaitukaitis. The animals can be mobile enough. They can 
be shipped to the research laboratories to investigators who 
make appropriate requests.
    Mr. Porter. And some of the things that you provide are not 
used up but merely lent, in effect. So, when the research is 
finished, they return them to you; is that true or not?
    Dr. Vaitukaitis. It depends on the nature of the resource.
    Mr. Porter. You said many of them are reused many times, 
right?
    Dr. Vaitukaitis. They are shared.
    Mr. Porter. Ah, shared, not reused.
    Dr. Vaitukaitis. For instance, a DNA sequencer may be used 
by 30 investigators, depending on where and when they need it. 
It is a cost-effective approach for a university and for us.
    Mr. Porter. So, is there any way of determining what 
percentage of the resources used in extramural research are 
actually provided through NIH or through NCRR?
    Dr. Vaitukaitis. We carefully monitor the number of users 
who are funded by NIH as principal investigators who access the 
resources. For instance, at the network of 75 General Clinical 
Research Centers that we currently support, those investigators 
receive competitive support from other NIH institutes to the 
level of a little over $1 billion. For the network of 
biomedical technology resource centers, those investigators 
receive something on the order about $800 million of research 
support from the other components of NIH. We track all of this 
information to make sure that the resources are being used by 
many investigators from multiple sources. The investigators may 
also be supported by the National Science Foundation or from 
private sector funds as well as by private societies.

                            shared resources

    Mr. Porter. And the academic institutions, do they have an 
investment in their own equipment and resources?
    Dr. Vaitukaitis. There are institutional funds for 
instrumentation through the Shared Instrumentation Grant 
program, which is the best example of that. We request that 
they provide those instruments on a wide basis to their 
facultythrough a shared facility if at all possible or at least to 
multiple groups of investigators.
    Mr. Porter. Who pays for those resources?
    Dr. Vaitukaitis. We pay for the instrument itself. The 
institution pays for the maintenance of that equipment at their 
institution.
    Mr. Porter. So, the capital investments in almost all 
research resources are NIH's?
    Dr. Vaitukaitis. If they are at our resource centers, we 
pay for a major portion of them but not all of them, because 
they are quite expensive.
    Dr. Varmus. Well, I think you are asking a question we 
probably cannot answer, which is how much of the equipment 
infrastructure available to our investigators is actually paid 
for with NIH money as opposed to institutional money.
    Mr. Porter. What percentage, yes.
    Dr. Varmus. It is hard for us to answer that question, 
because we do not really know what the Institutes are spending.
    Mr. Porter. What they have.
    Dr. Vaitukaitis. What the denominator is.
    Dr. Varmus. Certainly, traditionally, there was a fairly 
substantial investment, especially at academic health centers, 
in the equipping of new investigators for that money.
    Mr. Porter. Their own investment.
    Dr. Varmus. Right; they would provide setup funds for new 
investigators as part of a recruitment package. That actually 
is one of the instruments of supporting new investigators that 
has been undermined by the change in patient care revenues to 
academic health centers. But in any case, we do not really have 
the numbers that would allow us to determine what our 
percentage would be in providing the equipment that any 
investigator would be using.
    Mr. Porter. Am I correct, then, that the reason your center 
has the largest rate of increase in NIH is simply because we 
have to address this problem that is not being addressed 
otherwise?
    Dr. Varmus. We have cut back on, for example, shared 
instrumentation grants, which as Dr. Vaitukaitis has just 
pointed out, is an incredibly efficient way for us to supply 
equipment, high-quality equipment that reflects technological 
development to our investigators. So, I feel strongly that is a 
program that we should be supporting as our budget prospects 
brighten. They were cut back at a time when we were simply 
trying to find the money to fund new grants.

                          human genome project

    Mr. Porter. With respect to the human genome project, what 
sort of drawdown do their grants have on your resources? Has 
that caused a large utilization of your resources?
    Dr. Vaitukaitis. The genome project has created 
opportunities. In the NMR and synchrotron facilities, the 
increased demand for access is a reflection of what is going on 
with the genome project, as well as at our mass spectrometry 
facilities, which help characterize the proteins that are 
expressed by those genes. There is a ripple effect, and the 
investigators need shared instrumentation equipment for doing 
sequencing work or doing crystallographic work where it is 
appropriate at their own university.
    Mr. Porter. Was these a need to create new research 
resources that did not exist before the project, or were the 
types of things that they use already in existence and they 
simply utilized them more?
    Dr. Vaitukaitis. There were resources already in place, but 
they had to be modified for enhanced throughput. For example, 
mass spectrometry has been markedly changed because of the 
requirement to look at what happens to the proteins after they 
are translated--referred to as post-translational 
modifications--as well as the need for high-throughput for 
looking at the components of DNA as well, not just looking at 
the proteins.

                                internet

    Mr. Porter. What effect has use of the Internet had on what 
you do?
    Dr. Vaitukaitis. It is an enabling tool. The current 
problem that we have with the Internet is its slowness, and 
with the advent of Internet-2, which will have greater speed 
and a wider bandwidth, it will allow near-real time 
transmission of data. In the example that we showed here, we 
cannot adequately do what we would like to do with the 
instrumentation over the current Internet, because it is too 
slow.
    Several universities now, about 120 of them, have gotten 
together and created what is known as Internet-2, and that will 
allow us, in real time, to send information from those 
resources to the supercomputer then back to the investigator in 
San Francisco, to look at drug interactions at a binding site, 
or any other structural biological question. It is really an 
enabling technology. It is going to allow real time access to a 
wider range of technologies across the country that 
investigators in the past had to physically go to, but it 
creates an extra demand on our resources to provide more staff 
to service more investigators.
    Mr. Porter. And this is really going to revolutionize 
further the whole research enterprise, is it not?
    Dr. Vaitukaitis. Absolutely.
    Mr. Porter. Mr. Stokes?
    Mr. Stokes. Thank you very much, Mr. Chairman, and Dr. 
Vaitukaitis, nice to see you again, and thank you for your nice 
statement.
    Mr. Porter. She said some very nice things about you when 
you were not here.
    Mr. Stokes. I see her statement here, which I have read. It 
is very kind of her, and I appreciative of it very much.
    Dr. Vaitukaitis. We have really appreciated your help over 
the years.

               research centers in minority institutions

    Mr. Stokes. Thank you. It has been a pleasure working with 
you, and I am going to miss working with some very fine people 
when I leave here. It has been a great experience for me, too.
    Dr. Vaitukaitis, in last year's committee report, the 
subcommittee recommended that NIH programs which focus on 
improving minority health receive an increase in funding at a 
level that is at least proportionate to the overall NIH 
increase in funding. Has this occurred with respect to Research 
Centers in Minority Institutions, the RCMI program and others 
under the center's auspices?
    Dr. Vaitukaitis. The RCMI program received a 10 percent 
increase in its budget for fiscal year 1998, which is 
significantly greater than the NIH budget increase, as well as 
NCRR's budget increase. We were pleased to be able to provide 
that additional support for the RCMI program.
    Mr. Stokes. That is great, I appreciate knowing that. Thank 
you, Dr. Varmus, also.
    How will the increases be invested?
    Dr. Vaitukaitis. The increases are to be invested in 
helping to recruit junior faculty to the RCMI institutions to 
conduct both basic and clinical research. There is a concerted 
effort to try to increase the clinical research capacity at 
these institutions by bringing in established mentors to help 
develop junior faculty to work on those diseases which 
disproportionately affect minority populations. In addition, 
they will support some initial efforts that we have with the 
neurology institute to develop neuroscience centers of 
excellence at selected NCRR-supported RCMI sites.
    There is also a new application from an institution that 
formerly was not supported by the RCMI program which will 
probably be funded this fiscal year.

                        extramural construction

    Mr. Stokes. Good.
    Dr. Vaitukaitis, the fiscal year 1998 funding level for 
facility construction is $20,000,000. Has the center been able 
to comply with the statutory requirements that focus 25 percent 
of these funds on institutions of emerging excellence?
    Dr. Vaitukaitis. Yes; in fiscal years 1996 and 1997, we 
were able to use 29 percent of the $20,000,000 appropriated for 
each of those respective years. Among the four awards that we 
made to Centers of Emergency Excellence in the last fiscal 
year, 1997, two of them were to HBCUs which are badly in need 
of this source of funds. The applications for this year have 
been received but have not yet been reviewed. So, yes, we have 
been able tomeet the setaside.
    Mr. Stokes. What is the fiscal year 1999 budget request for 
NCRR extramural facility construction?
    Dr. Vaitukaitis. It is $20,000,000, the same as in 1997, 
and 1998.

                   rcmi clinical research initiative

    Mr. Stokes. Your budget justifications, Doctor, mention 
that RCMI recipient medical schools will be the focus of a 
clinical research initiative. Can you elaborate on what the 
initiative is intended to do, and the size of that investment?
    Dr. Vaitukaitis. The size of the investment may be 
something of the order of between $2,000,000 and $3,000,000. It 
is to be modelled on a program we currently have underway in 
collaboration with the neurology institute at the Morehouse 
School of Medicine that focuses on neuroscience, where we bring 
in an established investigator who can serve as a mentor to 
more junior faculty to help them develop research expertise in 
a specific area, neuroscience in this case. We are hoping that 
comparable activities can be initiated at other institutions 
within neuroscience or in other disciplines that the applicant 
institution decides are best for them.

                          hbcv competitiveness

    Mr. Stokes. Okay. During previous hearings, the center 
indicated that it would work to strengthen infrastructure at 
the HBCUs in an effort to help them better compete for NIH 
research grants. What specifically is the center doing in to 
facilitate this?
    Dr. Vaitukaitis. Each year for the past couple of years, we 
have held technical assistance workshops for HBCUs and other 
institutions who wish to submit grant applications to the 
construction program that we talked about earlier. In addition, 
through the RCMI program, there are workshops held 
approximately twice a year in areas of possible investment, 
where staff talk to them about different opportunities for 
research, and about submitting research project grants or other 
types of applications for enhancing their research support.

                clinical training and career development

    Mr. Stokes. What is the center doing to enhance training 
and career development for clinical researchers, and what is 
the condition of the pipeline?
    Dr. Vaitukaitis. The clinical research pipeline needs to be 
fixed. Between 1994 and 1997, there is almost a one-third drop 
off in the number of M.D.s applying for new grants from NIH. It 
is very disturbing, because the pool size is very small, 
probably for several reasons. The impact of managed care has 
placed greater pressure on physicians' time to see patients to 
generate parts of their salaries or their entire salaries. The 
relatively low success rates for junior investigators in the 
past and inadequate salaries provided through training grant 
mechanisms or through junior career development programs are 
other reasons.
    About 2 weeks ago, I presented the new K-23, K-24 and K-30 
programs for clinical research support to the leadership of the 
GCRC program across the country, and they were ecstatic, 
because the K-23 provides, for the first time, adequate, robust 
support for clinical research career development in terms of 
competitive salaries, adequate research support and the length 
of time of support that gives them a fair chance to learn the 
tools of clinical research and complementary laboratory 
research.
    A separate program, the K-24, will provide 5 years of 
additional support after the K-23, for protecting physicians 
time to do clinical research and complementary laboratory 
research within their institutions.
    Academic health centers are under a lot of stress because 
of the impact of managed care. There is a lot of pressure for 
investigators to see more patients, to generate more income, 
which takes away from their productive research time. They are 
so exhausted, they cannot even really come up for air to think 
creatively about their next research project. We are very 
pleased with the new mechanisms that are about to be initiated 
in the early part of fiscal year 1999.

                            shared resources

    Mr. Stokes. Dr. Vaitukaitis, how critical is the center's 
shared resources program to the conduct of biomedical research?
    Dr. Vaitukaitis. NCRR provides critical infrastructure for 
shared resources on a regional and national basis as well as 
providing institutional support for shared instrumentation; it 
provides biological models and disease models to investigators 
across the country. It provides high-end technology access at 
no cost to investigators along with appropriate expertise to 
help them interpret their data.
    Because of the consequences of the genome project, which 
are considerable, investigators will not be able to learn to 
use every single technology that is out there; there just are 
not enough hours in the day or days in the week. It is 
necessary to provide additional expertise for interpreting data 
and helping them with handling their samples at our 
sophisticated resources, in order to get the most information 
we can out of the research that NIH collectively supports.

                        research infrastructure

    Mr. Stokes. Let me ask you this: research infrastructure is 
a major determinant of a university's ability to successfully 
compete, to compete for and conduct quality research. What is 
the state of the research infrastructure at the NIH's leading 
grantee institutions?
    Dr. Vaitukaitis. I cannot specifically address the NIH's 
leading institutions. I am aware of no data that specifically 
addresses that.

                         new rcmi institutions

    Mr. Stokes. Okay; all right.
    I am told there may be new schools added to the RCMI 
program. Is the increase in the budget proposal adequate enough 
to provide funding to the new schools while ensuring that 
existing programs do not suffer?
    Dr. Vaitukaitis. In fiscal year 1998, we will probably be 
making a new award to one institution, and we can do that 
within the budget that we have for 1998. In last year's report 
language from the Senate, we were asked to consider the 
University of Alaska as an institution to be included in the 
RCMI portfolio. We currently have negotiations going on with 
Alaska, and they will be submitting an application. There is 
also one other institution that will be submitting an 
application. So, it is possible that one or two additional 
institutions could be funded in fiscal year 1999, and we would 
have to work within our budget to support those institutions. 
We have no idea of the scope of their needs at this point, 
because we have no applications in hand.
    Mr. Stokes. Dr. Vaitukaitis, I want to thank you for the 
work that you are doing in these areas in which I have specific 
concern. I do not know of any other institute that has given us 
a better report, than you, on these areas. I also want to 
congratulate you and express my appreciation to you.
    Dr. Vaitukaitis. Thank you, Mr. Stokes.
    Mr. Stokes. Thank you.
    Thank you, Mr. Chairman.

                             rare diseases

    Mr. Porter. Thank you, Mr. Stokes.
    Dr. Vaitukaitis, it is often difficult to develop and test 
new therapeutic agents for rare diseases because the limited 
number of affected patients makes it difficult and expensive to 
get statistically significant data. To accelerate development 
of new therapies in a more cost-effective manner, you plan to 
initiate a pilot project with the Cystic Fibrosis Foundation to 
establish a data monitoring center. Would you describe this 
initiative in more detail? And do you think this venture will 
lead to more collaborative public-private partnerships?
    Dr. Vaitukaitis. Rare diseases are not so rare across the 
network of GCRCs. Collectively, rare diseases account for about 
15 to 20 percent of all of our research protocols. Of the over 
6,000 protocols supported across the GCRCs, cystic fibrosis is 
a key disease that is studied to a limited extent by a number 
of them.
    This partnership that you have described that we intend to 
set up will help foster cystic fibrosis research in 
collaboration with the Cystic Fibrosis Foundation, and we are 
hoping that it will be successful, because there are many other 
rare disease organizations which have similar interests. The 
Cystic Fibrosis Foundation has come forward towork with us in 
supporting the clinical trials for cystic fibrosis on the GCRCs, which 
is totally permissible and facilitates clinical research not only for 
cystic fibrosis but for other rare diseases.
    We see this as likely leading to partnerships with other 
rare disease organizations and probably with some of our sister 
institutes, to help support some of the primary research within 
some of those rare disease areas.

                         collaboration with nci

    Mr. Porter. How do you handle the circumstance where one of 
your general clinical research centers is located at the same 
facility as an NCI cancer center? Do they share patient 
populations and researchers or are they totally separate 
entities?
    Dr. Vaitukaitis. A little bit of both; currently, we have 
an initiative where we are working with the National Cancer 
Institute to bring together the resources of the NCI 
comprehensive cancer centers with those from the GCRCs. Many of 
the clinical research studies are carried out either in some 
part of the hospital that is not part of the GCRC or on the 
GCRC. With the impact of managed care, more and more of the 
clinical research that has been sponsored by the comprehensive 
cancer centers are moving to the GCRCs. We can accommodate it, 
and we are working it out so that if there is a 
disproportionate pressure from cancer-based research on the 
GCRC above one-third of all its resources, that NCI will help 
fund, the amount that is above the one-third, in order to 
protect other areas of research.
    This arrangement between the GCRCs and the comprehensive 
cancer centers will decrease the administrative burden for 
review of protocols as well, so that the investigator does not 
have to have his or her protocol reviewed at both the cancer 
center and the GCRC; there will be one review; the process will 
be streamlined. The cancer centers will share some of their 
research resources, and we will share ours with them, which is 
a natural partnership. There is no reason why this partnership 
should not work out extremely well.

                           clinical research

    Mr. Porter. How will you implement the recommendations made 
in the NIH Director's Advisory Committee report on clinical 
research? Do you have a plan of action?
    Dr. Vaitukaitis. One thing we are going to be doing is 
changing the Clinical Associate Physician award program to, 
instead of using a competitive supplement to a GCRC, use a K-23 
type of mechanism that we are currently developing in order to 
provide more robust support to young investigators at GCRC 
sites for junior career development.
    In addition, we are enhancing the role of the GCRCs as an 
institutional resource for clinical research where it is 
appropriate; in some cases, the institutions have the GCRCs as 
the lead for helping direct clinical research at that 
institution. In addition, the President's budget request for 
the GCRC program is the largest President's budget increase 
that I have known over the last 25 years.

                         research collaboration

    Mr. Porter. You have partially answered this question, but 
let me allow you to expand on your answer. Your center has been 
a leader in fostering an environment where collaborative 
research opportunities are conceived and evolve. However, we 
have heard that private industry withholds data out of 
proprietary interest. In your opinion, do you believe the 
environment for collaborating has gotten better or worse over 
the last few years?
    Dr. Vaitukaitis. I think the environment has gotten much 
better for collaborative, multidisciplinary research, because 
research has become much more complex. The kinds of resources 
that we support require the multiple disciplines to interact 
with investigators from other institutions. We see research 
becoming much more multidisciplinary and much more 
collaboration going on.
    Mr. Porter. Dr. Vaitukaitis, thank you for your good 
statement and answers to all of our questions. Obviously, the 
request that you have made is a very important one and a high 
priority for all research, and we are going to do the best we 
can to get you the resources you need so that you can get them 
to the investigators so they can carry on their research at the 
highest possible level.
    So, thank you for appearing today. We appreciate it very 
much, and thank you for the fine job you are doing.
    Dr. Vaitukaitis. Thank you.
    Mr. Porter. Thank you, Dr. Varmus.
    Dr. Vaitukaitis. Thank you very much.
    Mr. Porter. The subcommittee stands in recess until 10:00 
a.m. tomorrow.
    [The following questions were submitted to be answered for 
the record:]


[Pages 1935 - 1973--The official Committee record contains additional material here.]



                                           Tuesday, March 17, 1998.

        NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

                               WITNESSES

DR. DUANE ALEXANDER, DIRECTOR
DR. YVONNE T. MADDOX, DEPUTY DIRECTOR
DR. FLORENCE P. HASELTINE, DIRECTOR, CENTER FOR POPULATION RESEARCH
 BENJAMIN E. FULTON, ASSOCIATE DIRECTOR FOR ADMINISTRATION
ARTHUR D. FRIED, BUDGET OFFICER
DR. HAROLD VARMUS, 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 National Institutes of Health with 
the National Institute of Child Health and Human Development. 
We are very pleased to welcome Dr. Duane Alexander, the 
Director of the Institute. Dr. Alexander, good morning.
    Dr. Alexander. Good morning, Mr. Porter.
    Mr. Porter. Happy St. Patrick's Day.
    Dr. Alexander. The same to you.
    Mr. Porter. I forgot to wear my green.
    Dr. Alexander. That is a nice green tie you have. 
[Laughter.]

                       Introduction of Witnesses

    Mr. Porter. Yes. Why don't you introduce the people at the 
table with you and then proceed with your statement, please.
    Dr. Alexander. Thank you, Mr. Porter. On my left is Dr. 
Florence Haseltine, the Director of our Center for Population 
Research; next, Mr. Ben Fulton, our Executive Officer; our 
Budget Officer, Mr. Art Fried; Dr. Varmus; my Deputy Director, 
Dr. Yvonne Maddox; and you know Mr. Williams.

                           Opening Statement

    Mr. Chairman, it is my pleasure to appear before the 
committee and talk about the request for the NICHD. Congress 
established our Institute 35 years ago to help the people of 
this nation have healthy children at the time that they want 
them and to help those children survive, learn, and develop in 
ways that allow them to reach adulthood free of disease and 
disability and able to contribute fully to society.

                        research accomplishments

    As we have been celebrating our 35th anniversary this year, 
we have looked back at some of the accomplishments of our 
research that have made major progress toward achieving these 
goals. For example, NICHD-supported scientists developed and 
demonstrated the effectiveness of newborn screening tests for 
PKU and hypothyroidism. Every newborn infant in the United 
States now receives these tests, and thanks to their use, we 
prevent over 1,200 cases of mental retardation each year.
    Another example was NICHD's diabetes and early pregnancy 
study. It showed clearly that rigid control of a diabetic 
mother's blood sugar before and during pregnancy markedly 
reduced her elevated risk of having a stillborn or malformed 
infant. That regimen has now also become standard care.
    NICHD scientists conceptualized and developed a vaccine to 
prevent Hemophilus influenza Type B meningitis, and with that 
vaccine now standard care for all infants, this disease has 
gone from being the leading cause of acquired mental 
retardation in the United States to near elimination.
    Through a combination of improvements from NICHD research 
on our ability to care for premature infants, such as better 
ventilation, surfactant to prevent respiratory distress 
syndrome, improved nutrition and better control of infection, 
this nation's infant mortality rate has fallen by 70 percent in 
those 35 years.
    Leading the way in this decline in the last four years has 
been a marked reduction in sudden infant death syndrome. As 
shown in the poster over to my left, for many years, SIDS 
deaths were really remarkably stable, at about 5,400 per year, 
or 1.4 deaths per 1,000 infant births. Following the 
recommendation of the American Academy of Pediatrics in 1992 to 
place infants to sleep on their backs and the NICHD-led ``back 
to sleep'' campaign launched in 1994, back or side sleeping has 
increased from 28 percent to 78 percent and the rate of SIDS 
deaths has declined dramatically, from 1.4 to 0.5 deaths per 
1,000 births. This represents a reduction of nearly two-thirds 
from the old steady state condition.
    [The information follows:]


[Page 1977--The official Committee record contains additional material here.]



                             birth defects

    Dr. Alexander. While strides have been made in reducing 
several causes of infant mortality, less is known about its 
leading cause, birth defects. Our studies here range from basic 
investigations in genetics and developmental biology to 
epidemiologic studies of cause and therapeutic and prevention 
research. We are working to translate leads from basic studies 
in animal models to understand human disorders such as neural 
tube defects, skeletal anomalies, primary immune deficiencies, 
and disorders in the formative stages of the nervous system 
that lead to mental retardation or learning and behavior 
problems.

                            vaccine research

    Progress in science is incremental. One example is the E. 
coli 0157 vaccine. This organism is a bacterial food 
contaminant that causes mild to fatal disease in about 20,000 
people a year in the United States. The new vaccine was 
produced by our same intramural scientists who developed the 
Hib vaccine. We recently reported success in inducing high 
levels of antibody production against E. coli in adults and we 
are now testing whether this vaccine can prevent the disease in 
humans by eliminating the organism at its source by vaccinating 
cattle.

                                genetics

    Applications of advances in genetics, especially from the 
Human Genome Project, continue to benefit NICHD. One case in 
point is microarray technology, which Dr. Varmus displayed in a 
poster in his opening presentation. This technique permits 
study of thousands of genes at once to determine which ones are 
functioning or turned on at a given time.

                            premature labor

    Our scientists are applying this technology to study gene 
expression in women in premature labor with the goal of 
determining at a genetic level its causes and mechanisms. These 
studies also offer the potential to develop a much-needed 
diagnostic test to determine whether a woman is truly in 
premature labor, as well as identifying targets for therapeutic 
intervention. Research to reduce prematurity is a critical part 
of our effort to eliminate racial differences in infant 
mortality as part of the President's initiative on race.

                   reading development and disability

    Other new scientific technologies are allowing us to 
combine studies in biology and behavior to achieve a 
fundamental understanding of the origins of problems such as 
reading disability. One technique being used is called 
functional magnetic resonance imaging. The pictures you see 
displayed on the poster on the left are composites of images 
reflecting brain activity during reading tasks by adults with 
good reading ability on the right and adults with significant 
reading disability on the left.
    [The information follows:]



[Page 1979--The official Committee record contains additional material here.]




    Dr. Alexander. The disabled readers show none of the 
activity in the three regions at the back of the brain used by 
the good readers in the reading tasks, and increased activity 
in the front area of the brain, reflecting intense effort to 
try to overcome the apparent block in function at early stages 
of the task. This study provides the first clear evidence of 
organic brain dysfunction in reading disability.

                             child day care

    Results of research on the association between 
characteristics of child day care and children's development 
are continuing to come from NICHD's study of early child care. 
This year, scientists continued to find that family income, 
quality of home environment, maternal education or language 
ability, and mothers' behavior toward the child are stronger 
predictors than child care itself of children's cognitive, 
language, and social development. Our scientists also found 
that children in exclusive maternal care do not have a 
cognitive or language advantage over children in child care.
    Most recently, investigators reported that the 
characteristics of quality child care provision that can be 
regulated, such as adult-to-child ratio, group size, provider 
education and training, are related to cognitive and social 
outcomes of children at three years of age.

                        women's health research

    With the funds provided by the Congress in fiscal year 1998 
and requested in fiscal year 1999, NICHD will be launching two 
major initiatives to improve women's health. First, to increase 
the number of obstetrician/gynecologists engaged in research, 
NICHD, with support from the Office of Research on Women's 
Health, is establishing a group of women's reproductive health 
career development centers. At these sites, newly-trained OB/
GYN clinicians will be given training to assist them in 
pursuing research careers, focusing on problems of women's 
reproductive health.
    Second, we are working with the OB/GYN community and other 
institutes to expand research directed toward the long-term 
consequences women suffer as a consequence of childbearing--
incontinence, uterine and rectal prolapse, chronic pain, and 
other harmful and disabling conditions.

                         pediatric pharmacology

    There is great hope that the proposed new FDA rules 
requiring drugs to be tested in children, in combination with 
the pediatric pharmacology network established by NICHD, will 
finally end the decades-long era of children being therapeutic 
orphans. To further facilitate the testing of drugs in 
children, the funds requested for fiscal year 1999 will allow 
NICHD to expand this network from seven to ten sites and to 
initiate a broad range of studies to help guide drug testing in 
children.
    Mr. Chairman, the President's budget request for NICHD for 
fiscal year 1999 is $727,000,000, including $72,000,000 for 
AIDS, an increase of 7.7 percent. I will be glad to answer any 
questions.
    [The prepared statement follows:]


[Pages 1981 - 1985--The official Committee record contains additional material here.]



                            family planning

    Mr. Porter. Thank you, Dr. Alexander.
    Let me first focus on one of your opening remarks where you 
refer to the Institute being created, to help the people of 
this nation have healthy children at the time they want them. 
Why did you mention ``at the time they want them'' and what 
relationship does that have to the health of children?
    Dr. Alexander. This Institute focuses on families and 
children and improving the health of children overall. One 
factor that improves the health of children is the wantedness 
of that child. A major component of our Institute is our Center 
for Population Research that focuses on family planning 
research, among other activities, including both infertility 
research and research focused on contraceptive development. So 
we go at both ends of the issue of helping families have 
children at the time they want them, approaching research on 
infertility as well as research on contraception.
    Very clearly, children who are born wanted and at a time 
that parents want them fare better than children who are born 
when they are not wanted, at a time that is bad for parents to 
be having a child. Unfortunately in this country, we are in a 
state of affairs where more than half of pregnancies are 
unwanted or unintended at the time that they occur. This has 
been running at about 54 percent. The most recent figures show 
that this has dropped just a little below 50 percent.
    So there has been some improvement in recent years in the 
wantedness and timings of pregnancies that occur. But still, 
close to half the pregnancies in the United States occur at a 
time that they are not wanted or when they are not wanted at 
all. Clearly, our research in contraception needs to be pursued 
further to try and address this problem.
    Mr. Porter. You may not have done any quantifying of this 
issue, but let us say that every child in the United States 
could be born at the time they were wanted. What effect would 
that have on the health of the population in the long term? 
Would that have a significant effect or a minor effect?
    Dr. Alexander. We think it would have a significant effect. 
First of all, there are data to support the fact that infant 
mortality rates would decline significantly if pregnancies were 
wanted rather than unwanted. Clearly, our abortion rate would 
virtually disappear if we had conceptions occurring that were 
wanted rather than unwanted.
    Overall, children are healthier when they are born wanted. 
Their developmental course is more favorable and their long-
term health aspects as well as their achievement, 
accomplishments, and social and educational performance all 
improve when they are wanted children and when they are born at 
a time that the parents want them, can afford them, and really 
want to have them.
    Mr. Porter. Dr. Alexander, we have had a debate going on 
here in Congress for some time now on the whole concept of 
abortion, which to me is understandable as a moral issue. At 
the same time, we have a direct assault on family planning, 
although it is couched in terms of opposition to abortion, and 
we have barely won enough votes in the House on Title X 
programs that provide family planning services to poor women in 
our country.
    How do you, if you can, reconcile these matters and don't 
you agree that it is very short-sighted for people who morally 
oppose abortion to also oppose family planning?
    Dr. Alexander. The surest way, as you point out, Mr. 
Porter, to reduce the need for abortion is to provide adequate 
family planning services with agents that are effective and 
that can be used by people and are accepted by people of 
varying beliefs. Part of our problem is ineffective use of 
contraceptive agents that are available. Part of it is failure 
of the agent itself. This is why it is important for us to 
continue our research to develop better and more effective 
agents, as well as methods to increase their acceptability and 
effective use.
    But if we are, in fact, serious about reducing the abortion 
rate in this country, a key component of that effort must be 
provision of adequate family planning services.Women and men 
must have access to contraceptives that are safe, effective, and 
acceptable to them in terms of their particular values. If we do not 
provide contraceptive programs, family planning programs, we have no 
hope of ending the unwanted abortions.
    Mr. Porter. I could not agree with you more. In fact, I 
believe that it is a basic human right of every person on this 
planet, every family on this planet, to plan their children 
including the number and spacing of them and that our programs, 
both domestically and internationally, for people who cannot 
otherwise afford the services are probably one of the most 
important things that we can do. I cannot understand a view 
that says this is not a basic human right that ought to be 
supported.

                                dyslexia

    Let us talk a minute about dyslexia, which effect many 
young children. We find that a lot of people who are diagnosed 
as dyslexic somehow overcome this difficulty during their 
lifetime. Is there any evidence from research that later 
pathways are developed that changes this look at the brain?
    Dr. Alexander. That is a very interesting question, Mr. 
Porter, and one that we are eager to pursue and actually are 
pursuing. This particular study reported from Yale University 
by the Shaywitzes and their colleagues was done in adults, so 
the images that were obtained and reported were done on adults. 
The group is currently studying children, as well, and looking 
at whether we see similar patterns of brain abnormalities and 
function in children that we have demonstrated here in adults.
    What we want to do, if we find these abnormalities in 
function in children before they have had reading experience, 
is follow them as remediation is applied to see what happens to 
these patterns of brain functioning on functional magnetic 
resonance imaging. We will look to see whether the pattern sort 
of corrects with training, such that these other areas do start 
to function, or whether alternative pathways develop as the 
child overcomes the problem and learns to read. If the child is 
not able to overcome the problem and never learns to read, we 
will examine what kind of brain pattern and functioning we see.
    These studies are underway. I hope maybe next year I will 
be able to give you an answer to your question.

                               child care

    Mr. Porter. The administration has a major initiative on 
child care and I wonder if you could tell me what input you had 
in formulating that initiative as it was developed as a policy 
matter.
    Dr. Alexander. There has been intense interest in the 
Department of Health and Human Services in this study. The 
Child Care Bureau, people in the Administration for Children 
and Families have been in close contact with us, have kept up 
to date with all the reports of the research that have come 
from this study to be aware of what the findings were in terms 
of impact on child development of the child care experience, 
the impact on the children's development, on family 
relationships, and so forth.
    I think that, in part, it was with some reassurance from 
the findings of the child care study that people felt 
comfortable in moving ahead with a larger investment and 
program of support for child care programs. In addition, I 
think the information that our study has provided on quality of 
care has been extremely important for the people in the Child 
Care Bureau.
    There are two things that are most consistent in these 
studies. First of all, the family situation and the mother are 
far more important an influence on virtually all aspects of the 
child's development than the child care situation. Number two, 
the quality of the child care that is provided is extremely 
important. Whether we are looking at language development, 
cognitive development, behavior, social interaction, health, 
whatever, quality of care makes a significant difference to 
kids.
    And also, they have demonstrated very clearly that there 
are regulable aspects of child care, as I mentioned in the 
testimony, such as group size, education and training of 
providers, adult-child ratio, and so forth that also correlate 
very clearly with the quality of care overall and with better 
outcomes for kids.
    So with this information in mind, the Administration for 
Children and Families and the Department worked with other 
parts of the Administration in developing this initiative to 
help support child care with Federal assistance.
    Mr. Porter. Can I conclude from what you said that it is 
not enough just to put some money out there, we have to make 
sure that the child care that is being given is regulated so 
that the quality is maintained?
    Dr. Alexander. I think that is a very clear message, Mr. 
Porter. The quality does make a difference as do regulations, 
probably formulated at the State level as they are now, that 
are developed in accordance with standards suggested by 
organizations such as the American Academy of Pediatrics, the 
American Public Health Association, and the Society for 
Education of Young Children.
    Mr. Porter. Thank you, Dr. Alexander.
    Mrs. Northup?

                  reading disabilities-early screening

    Mrs. Northup. Yes. Thank you, Doctor. I have a couple of 
questions. I would like to start with the question of dyslexia. 
I have read a number of reviews of studies you all have done 
and know that there are a significant number of children that 
fall behind in reading and actually never catch up that may not 
actually be diagnosable as dyslexic, but come to the system 
perceptually immature and never catch up. Can you tell me, I 
was interested also interested in this subject last year, when 
you think there will be on the market an early diagnostic test 
and how early we can apply that to a child?
    Dr. Alexander. There are several tests that purport to 
serve as screening instruments for picking up children early. 
One has come from our research that looks very, very promising 
in identifying kindergarten children as having potential 
problems with learning to read. It probably identifies maybe 25 
to 30 percent of children who are in this category. Now, these 
are not dyslexics.
    Mrs. Northup. Right.
    Dr. Alexander. These are kids who are going to have more 
difficulty than usual in learning to read and probably need 
some kind of special help tailored to their particular 
problems.
    The dyslexics are probably a hard-core group of three, 
maybe five, perhaps as much as seven percent of kids, but 
probably in the three to five percent range, who, in spite of 
some added instruction, the phonemic awareness approach that we 
have championed in particular, still need additional 
assistance. These are probably the children who have the brain 
functioning abnormalities that are demonstrated in the adult 
study by the Yale group that I showed in the poster.
    But what we can do with the particular screening instrument 
that we have available now is check these kids in kindergarten, 
determine in advance which ones are the ones most at risk of 
having problems in learning to read, and focus efforts on them 
in a classroom tailored toward their particular problems.
    Mrs. Northup. And you say that can be done in kindergarten, 
but I am not sure whether you said when that test will be on 
the market.
    Dr. Alexander. It is available now. I am not sure that it 
is actually sold on the market. It has been published. People 
know about it.

                 reading--when to diagnose disabilities

    Mrs. Northup. Doctor, I continue to be concerned about the 
schools and the old fashioned, and I consider it old fashioned, 
perception that no child should be diagnosed as struggling with 
reading. Actually, I sort of consider dyslexia and being behind 
in perception sort of a long continuum and sort of where you 
fall in it. But there was the idea that we should not diagnose 
children as challenged in reading until maybe even third grade. 
Would your more recent studies dispute that?
    Dr. Alexander. Absolutely. Third grade is too late. If they 
have not been diagnosed and had some sort of remedial 
interventions attempted before then, they are going to 
haveextreme difficulty learning to read.
    There is probably with reading what we refer to in other 
areas as sort of a critical period where you are primed to 
learn. If you do not get it at that time, you have extreme 
difficulty in getting it later on. Third grade is certainly, by 
all the research that we have done, too late to have this 
picked up.
    It is important that these kids be identified early, not 
stigmatized, not singled out, but identified at least to a 
teacher as someone who is going to need some extra help with 
the reading process. In most instances, this could probably be 
accommodated in the regular classroom so that there is no need 
for pulling kids out for a special effort outside the 
classroom. Our research again is trying to address these kinds 
of issues.

               reading development--getting the word out

    Mrs. Northup. What are you all doing to get the message out 
to those many school districts that still insist that children 
should not be tested or diagnosed or screened even until later?
    Dr. Alexander. Well, the message is getting out. We are 
publicizing the results of our research ourselves. We are also 
working with some of the reading organizations, such as the 
National Center for Learning Disabilities, the Learning 
Disabilities Association, to publicize results of this 
research. In addition, some of our staff members have made 
presentations out in the field to school districts, to State 
school systems, to other groups about the results of the 
research and the importance of early identification of children 
likely to have problems with reading and the importance of 
teaching reading in a scientifically demonstrated, effective 
manner.
    I think you are also aware of the fact that the Congress in 
last year's appropriations bill directed me to work with the 
Secretary of Education in establishing a national reading 
panel. The purpose of that panel is to review the current 
research literature and make judgments about what in that 
literature is ready for application in the classroom and ready 
for application in the preparation of teachers to teach 
reading. That panel has been appointed. We will have our first 
meeting in April and our intent is to finish our report and get 
it to the Congress and the Secretary of Education and HHS by 
November.
    We are also collaborating with the Department of Education 
in publicizing the results of our reading research and working 
extensively with them to get this information out.

                    child care and long term effects

    Mrs. Northup. I also noticed that you talked about 
emotionally connected teenagers to their families and that 
often their health and other factors were affected by those 
that are emotionally connected to their families. I wondered if 
you are doing any long-term research to help give us some 
answers. I know you talked about the child care research that 
you are doing. Can you give us some quantitative and 
qualitative insight into the long-term effects of what are good 
day care options.
    I know you talked about specifically children that are in 
an organized day care system, but I think we are also 
struggling in this country with whether or not to enhance our 
day care systems. As more and more moms are in the workforce, 
we must ask is grandmother taking care of the child, is an aunt 
taking care of the child. Does that build the relationship, the 
nurturing side?
    You spoke so well about how important the relationship is 
with the mother and the child. So when the child is away from 
the mother for long periods of every day, every week, is an 
organized, structured day care program better for the child in 
terms of learning and lifelong habits or would being in a 
home--and I realize it depends on the home, but you seem to be 
wandering into the area or getting into the area of trying to 
make some determination in that area, and I just wondered what 
sort of long-range studies you are doing.

                      the adolescent health study

    Dr. Alexander. Okay. There are two major NICHD studies that 
feed into the answer to your question. The first relates to 
where you started, which was the feeling of connectedness in 
relationship with the family. These findings come from the 
National Longitudinal Study of Adolescent Health, the 
adolescent health study that NICHD has supported. The first 
results from this study were reported last September.
    There were two very striking findings here. One was that 
there was an association between children who were doing well, 
staying away from risky behavior, performing well in school, 
and that was a feeling of connectedness with the family, a 
feeling of wantedness, of interaction with parents, of comfort 
in a home setting and of sharing as a family member.
    And closely associated with that was a connectedness to 
school feeling, a sense that teachers were interested in them, 
that teachers were fair and that the school setting was one in 
which they were encouraged to do well and perform.
    The investigators doing that study are doing further 
analyses of the data to try to see what is it that creates this 
sense of connectedness, this feeling of belonging and a 
positive sense of value in association with both family and 
with school.
    In addition, we are, as part of the adolescent health 
study, doing a one-year follow-up, and we expect to get a 
proposal for an extended five-year follow-up, of all the sample 
that was included in the original adolescent health study so 
that we can see how these factors play out over time in terms 
of all the data that we have collected on these children as 
they become young adults.

                        the nichd day care study

    Then the other part is day care and how these kids get 
started in life and get these kinds of habits established and 
the feeling of connectedness with family, if you will, and a 
connectedness with some other kind of a care setting.
    The NICHD day care study has looked at different kinds of 
settings and different kinds of care provision to try to tease 
out whether these differences in the setting are associated 
with the child's performance and interaction with the family as 
well as the child's cognitive language and social development. 
So we will have that.
    The original child care study was to end at age three. It 
has been extended once to carry these children through age 
seven and we anticipate there will probably be an effort to 
extend that for another five years to follow these children 
longer, at least into adolescence, to try and get at some of 
the very issues that you raised. So we will be following these 
as questions and I think they are very important ones for us to 
be addressing.
    Mr. Porter. Thank you, Mrs. Northup.
    The subcommittee is currently proceeding under the ten-
minute rule, and if any more members of the subcommittee come 
in, we are going to be in trouble time wise. Ms. DeLauro?

                           child care effects

    Ms. DeLauro. Thank you, Mr. Chairman.
    Dr. Alexander, it is good to have you back and it is good 
to see everyone here today, Dr. Varmus, and also I have to 
mention my friend and colleague and constituent, Dr. Haseltine.
    I would like to pursue the child care issue for a moment if 
I can, because we have talked about the study, we have talked 
about the connection, the relationship between quality care and 
development, bonds between children and parents. There have 
been several articles that have used quotes from NICHD-
supported articles to come to a conclusion that I personally 
find troubling, but in any case I want to get your views to 
this, that putting children in day care while a parent is 
working is bad for children and is particularly bad for low-
income, disadvantaged, or at-risk children.
    Again, the conclusions are being drawn out of studies that 
you all have done, and what I would like to hear from you is 
are these conclusions in the studies consistent with the 
findings of NICHD.
    Dr. Alexander. Ms. DeLauro, I have seen at least several of 
the articles that you make reference to and they have been a 
little bit disturbing to me because I believe that some of the 
findings have been cited out of context to make points that are 
not supported by the overall study.
    Let me say at the outset that this study was not set up to 
say whether child care is good or bad for kids. It was an 
attempt to look at various factors within the child care 
setting and in the family setting and make judgments aboutwhich 
of those contributed positively or negatively to child development in 
the language, cognitive, and social arenas, as well as to parent-family 
interactions, and that is what we have tried to stick to.
    First of all, it is not possible to conclude that child 
care overall is good or bad for kids. Some child care settings 
do very well by children. The quality varies enormously and 
some child care settings are not real good and they do not 
benefit children.
    Our effort, though, should not be to brand all child care 
as bad. It should be to make all child care as good quality as 
it can be, and the findings from our study, I think, help us to 
identify further the qualities of child care provision that are 
associated with good outcomes.

                          child care concerns

    Now, all child care features that we examined did not turn 
out to be positive. There are some concerns, some red flags 
raised. The articles that you make reference to picked out 
these concerns and waved several red flags. Now, these are 
legitimate concerns and they relate to primarily mother-child 
interaction and relationships.
    There was a segment of the child care population that had a 
finding of diminished quality of mother-child interaction when 
they were studied at 15 months and again at 24 months of age. 
These were confined primarily to children of mothers who were 
low in self esteem and low in interaction with the child to 
start with and this was the population that this finding was 
largely confined to. Here again, though, the child care setting 
tends to ameliorate the severity of this kind of a finding and 
the children who were in better quality care tended to have 
less of this finding show up.

                      child care study fact sheet

    We are in the process at NICHD of putting together a fact 
sheet on the child care study with all the findings that have 
been reported to date assembled in one place. It will probably 
be about a 15-page fact sheet. It puts the whole study in its 
context and lays out all the findings that have been reported 
so far in terms of language development, cognitive development, 
social development, parent-child interaction, health, behaviors 
of children up to age three.
    Now, we are still following these kids. We have done the 
four-and-a-half-year evaluations. We are in the process of 
analyzing the data, and we are just now starting the seven-year 
evaluations in these kids. So there is a lot more data to come, 
but we are going to pull all the available data together in one 
place so we can give a composite picture of what we have 
learned from this study. This should be available probably 
within two weeks. I will be glad to make a copy of that 
available to you.
    Ms. DeLauro. I would appreciate that. I expect that other 
members of the committee would appreciate that, as well.
    The work is, in my view, critically important because I 
believe that we are at a threshold with regard to child care in 
this country, particularly ages zero to three. What we do not 
want to do is to make similar mistakes, if you will, that we 
did with the Head Start program. We are trying to correct and 
evaluate the Head Start example so that we know what we can try 
to do with Early Start.
    What we do not want to do is to go down a road where 
conclusions are pulled out of context and used to the 
disadvantage of looking at quality child care, environments in 
which we are creating an environment for development for 
children. That is the kind of, in my view, what we ought to be 
searching out and seeking because economic realities today do 
not make it possible for all parents to stay home, one or the 
other, or to have aunts or uncles around. I went to my 
grandmother's after school, my grandmother's pastry store, and 
had lots of aunts and my grandmother.
    Those days, for the most part, are gone, so that aunts, 
uncles, grandmothers, everybody, are in the workforce. So how 
do we then ensure that our babies, that our kids are in 
environments in which they can grow and develop in a way that 
we would want them to. So your work is critically important to 
what decisions can be made here, I believe in the next few 
months, if we do the job that we are supposed to do with a 
piece of child care legislation that is on the table. That kind 
of contact with you and this kind of reporting, I think is 
enormously helpful to how we proceed further and to use your 
help, if you will, to dispel any of the misinterpretation, on 
either side of the debate, of the data that you are producing, 
which can only help us really to conform and to move forward in 
this arena, and we thank you for the work.

                 testing prescription drugs on children

    Last year, we also talked about the importance of testing 
prescription drugs on children because we know that kids do not 
always react to drugs as adults. You said that the Institute 
was encouraging the pharmacological industry to take advantage 
of metabolic studies that you have done, as well as your 
network of pediatric pharmacology researchers. Has the industry 
shown a willingness to work with you on this? Has the FDA's new 
rule affected your level of research into this area?
    Dr. Alexander. Yes. The pediatric pharmacology research 
unit network has been a very positive force in encouraging 
testing of drugs in children. I believe that it was a factor in 
the FDA's decision to be comfortable about requiring drug 
testing in children of new drugs put out by the pharmaceutical 
industry, the fact that there was a quality place for these 
tests to be done. We had shown that it could be done in an 
effective way and that it could be done safely and ethically in 
children.
    Industry has shown an increasing interest in the pediatric 
pharmacology research network. We get more inquiries and more 
studies funded by industry in the network all the time. As a 
consequence, we are increasing the number of sites in the 
network from seven to ten so that we can do more studies and do 
them faster. Also, since the FDA's proposal, we have had even 
more interest on the part of the pharmaceutical industry in the 
network as a test site.
    So yes, I think the network has been extremely important in 
this whole movement to get drugs that are used in children 
tested in children.
    Ms. DeLauro. What is your sense of timing on information 
that will be useful in terms of getting it moved to doctors' 
offices and so forth and so on? I mean, I know we are at the 
beginning of the process, but what is your assessment of the 
time frame?
    Dr. Alexander. It depends on the phase of study for a drug. 
Some drugs are already marketed for adults and they need 
additional studies in children just to get labeling for safety 
and dosage for children and FDA approval. Those can get done 
relatively quickly. They do not require large numbers of 
children.
    But if we are talking about an earlier phase study, a drug 
that is still under development for adults and we are starting 
at a phase two process and including children at that time, it 
is a much longer process, in terms of several years rather than 
several months. So it depends on the stage of drug development 
that we are talking about. But having that number of sites 
available with expertise, with recruiters, with data 
collectors, and a central data management point in this network 
enables us to do these studies very efficiently.
    Ms. DeLauro. Thank you very much.
    Mr. Porter. Thank you, Ms. DeLauro.
    Ms. Pelosi?
    Ms. Pelosi. Thank you, Mr. Chairman.
    Dr. Alexander, Dr. Varmus, all of you, welcome. Thank you 
for your testimony. Dr. Alexander, I think you must have the 
best job in the country.
    Dr. Alexander. I think so. I often think as I am driving to 
work in the morning how lucky I am to be in the position that I 
am. I would rather be doing what I am doing than anything else 
in the world, and not everybody gets to say that.
    Ms. Pelosi. Well, how lucky we are that you are there, 
because you are working with our most important resource, our 
children, and child health and human development, I think that 
has to be the most important subject that we address. So we are 
all well served by your enthusiasm as well as the experience 
and judgment that you bring to your job.
    Dr. Alexander. Thank you.

                      child care as public policy

    Ms. Pelosi. My colleague, happily for me, used a gooddeal 
of her time on the child care issue, so I will associate myself with 
the concerns that she expressed in terms of the balance that we need to 
hear so that some negative aspects of the child care experience could 
not be extracted without us understanding the context within which they 
were presented. I think this is an important issue and it is a crucial 
time because we as a country, I think, have not addressed the child 
care issue soon enough and we all stipulate to the importance of it.
    I see it all differently now as a grandmother, of course, 
telling my daughters to stay home and take care of their 
children. [Laughter.]
    Ms. Pelosi. But what does that mean from the standpoint of 
public policy? I do not want to bring that bias to the table. 
Some people do not have that option.
    What is interesting to me is that when you say that in a 
situation where there is a less optimal mother-child 
interaction over the first three years, child care can 
ameliorate the situation for the child.
    Dr. Alexander. That is correct.

                     pediatric environmental health

    Ms. Pelosi. It would be interesting to see that in the 
scheme of things. Certainly, it would be better, of course, to 
have a better mother-child interaction, and is this 
amelioration just improving that situation or is it bringing it 
up to a level that would be acceptable? Is that good enough is, 
I guess, what my question is. In any event, when we get this 
fuller report, I am sure those kinds of questions will be 
answered. If you want to address that, that is fine.
    I wanted to go on about environmental health. We have 
talked about this other environment that children are in, the 
child care environment, but then more specifically the 
environment as we know it. How the Institute see its role in 
the field of pediatric environmental health? In what areas are 
your specialties? Where do you feel the Institute has a special 
leadership role? How does the Institute do, working with other 
agencies such as the National Institute of Environmental Health 
Sciences, the CDC, or the Agency for Toxic Substances and 
Disease Registry, to leverage resources to further 
understanding in this field?
    Dr. Alexander. It varies with the particular issue at hand, 
Ms. Pelosi. For the most part, the National Institute of 
Environmental Health Sciences has taken the lead at NIH in 
relation to children's environmental health. They keep us 
closely posted on their activities. We have a number of 
opportunities where we work together with them. The President, 
by executive order, has just created an interagency committee 
on children's environmental health and safety. NIEHS represents 
NIH on that committee and keeps the other institutes, including 
NICHD, apprised of those activities and opportunities for 
program development and collaboration.
    Our interest focuses primarily on birth defects and 
environmental causes or triggers of birth defects, as well as 
what we might call the social environment of children as much 
as the physical, and research related to keeping that social 
environment in which children develop as healthy and as 
positive an influence as possible.

                      welfare reform and children

    Ms. Pelosi. I appreciate that. Speaking of the social 
environment, clearly, welfare reform legislation has led to 
important changes in the lives of many families and their 
social environment. Does NICHD do any research which can help 
us understand how changes in our welfare system are affecting 
poor children in our country? Is there research relevant to 
understanding children's needs and services during experiences 
like this?
    Dr. Alexander. We supported research over a period of many 
years that relates to many of the issues associated with 
children's development as it may be affected by the welfare 
reform activities.
    In response to the specific things that are happening in 
the country with welfare reform, we have in existence a child 
and family research network, a group of seven different 
university sites with data sets and interest in a number of 
these developmental issues. This network has been poised to 
serve as a vehicle for conducting research related to welfare 
reform and changes in children and families as they occur as 
part of this process.
    We have been working very closely with the office of the 
Assistant Secretary for Planning and Evaluation in the 
Department in terms of design of studies that others might do 
as well as studies that could be done in this network and have 
just initiated several studies to look at issues related to 
impact on child, family, mother as a consequence of the welfare 
reform activities that are going to be taking place.
    So we are right in the middle of it. Some of the resources 
of the Institute are going into this. Some resources are coming 
from the office of the Assistant Secretary for Planning and 
Evaluation and from others. It is a major issue and one that we 
want to stay involved with.
    Ms. Pelosi. And will we see some data that will come from 
that?
    Dr. Alexander. Yes, you will. They are just getting 
started.

            pelvic floor disorders and urinary incontinence

    Ms. Pelosi. Thank you, Doctor.
    As you know, a significant percentage of NICHD funds are 
allocated for reproductive-related research. You mentioned 
before birth defects. It is my understanding that two of the 
aspects of women's health that have not received adequate 
research attention were pelvic floor dysfunction and urinary 
incontinence. Can you tell me what your Institute is doing in 
conjunction with the National Institute of Diabetes, Digestive, 
and Kidney Diseases to enhance fundamental basic and clinical 
research in these areas?
    Dr. Alexander. Yes. We have been very interested in this 
area, which we agree with you is one that has been not 
researched as intensively as probably it should be in the past, 
the whole area of pelvic floor disorders, urogynecology, 
urinary incontinence. I met with the leaders of the American 
UroGynecological Society about these issues and, in fact, Dr. 
Haseltine worked with me to organize a meeting that was held 
yesterday with representatives of the American UroGynecological 
Society, other institutes at NIH, and our own staff within 
NICHD, to plan a conference on pelvic floor disorders, 
urogynecology, and incontinence that will probably be held in 
September. This will be a research planning workshop format to 
identify particular needs for research in these areas, which 
will be followed by solicitations for research applications in 
these areas.
    As part of Dr. Varmus's areas of emphasis that are included 
in the fiscal year 1999 budget, we have a urogynecology 
initiative to focus on these disorders and have received 
additional funds to begin this effort in fiscal year 1999.

                    smoking prevention for children

    Ms. Pelosi. Thank you, Doctor.
    I have a general and specific question. I will be fast 
because I do not have much time left. We have had a number of 
questions over the last week about changing behavior and 
learning more about promoting healthy behavior in children, and 
then specifically to the tobacco issue. Could you tell us, do 
you have any research findings to share with us that would be 
relevant to the current tobacco control issues before Congress, 
particularly the use of educational messages and policy 
approaches to prevent the initiation of smoking by young 
people?
    Dr. Alexander. We have supported some research in that area 
over the years. The key issue is keeping children from starting 
smoking, and we know that just telling them not to does not 
work. There have to be other ways to deliver that message, and 
the earlier that message is delivered, the more effective it 
is. It cannot wait until middle school. It has to start in 
elementary school.
    We have been part of a solicitation spearheaded by the 
National Cancer Institute for research applications related to 
prevention of initiation of smoking among children. We funded 
one grant from that last year. It has been issued again and we 
are part of it again this year. So that is an active area of 
research activity and I do not have any specific findings above 
and beyond that to report toyou, but these are studies that are 
getting underway.
    Ms. Pelosi. It is interesting, just anecdotally, one of the 
elevator operators here told me that she stopped smoking 
because she saw a picture of her lung, and we have said before 
we should show kids pictures of their brain, what happens if 
they use drugs. I used to say to my children when they were 
growing up, you can smoke if you want, if you want to have 
wrinkled skin, tobacco breath, and yellow teeth.
    Mr. Porter. I hope it worked.
    Ms. Pelosi. That worked for the girls, anyway. But I 
thought when Bonnie said, ``I saw a picture of what it was 
doing to my lung,'' and I know kids all think that they are 
invincible. I come back to my basic point all the time. If we 
tell them that they should not smoke because it is injurious to 
their health, then we should make their health a very important 
priority by giving all of them access to quality health care, 
and I think nothing would deliver the message more clearly 
about the importance of maintaining good health.
    Dr. Varmus. I happen to have with me a picture that Dr. 
Leshner from the NIDA provided me that shows the brain on 
tobacco.
    Ms. Pelosi. That is so compelling.
    Dr. Varmus. It shows a measurement of an enzyme that is 
important, because it metabolizes dopamine. It compares a 34-
year-old normal man and a 31-year-old smoker. So the brain on 
cigarettes is also quite illuminating.
    Ms. Pelosi. Very eloquent. Hopefully, you will have that 
blown up for us one of these days.
    Dr. Varmus. It has been.
    Ms. Pelosi. Oh, it has been? I think that that will send a 
very important message.
    Unfortunately, my time has expired--unfortunately for me. 
Thank you all very much for what you do and for your testimony.
    Dr. Alexander. Thank you, Ms. Pelosi.
    Ms. Pelosi. Thank you, Dr. Alexander.
    Mr. Porter. Thank you, Ms. Pelosi.
    Mr. Hoyer?
    Mr. Hoyer. For those of you in the audience who could not 
see it, the picture depicts a yellow, wrinkled brain. 
[Laughter.]
    Dr. Varmus. The yellow is good in this case.
    Ms. Pelosi. The green part. [Laughter.]
    Mr. Hoyer. I was shocked that Ms. Pelosi did not observe in 
saying something about Dr. Alexander, who is indeed one of the 
bright lights in America, in my opinion----
    Ms. Pelosi. That he is from Baltimore.
    Mr. Hoyer [continuing]. That he graduated from Johns 
Hopkins University. It was not the University of San Francisco, 
but it was Johns Hopkins from Baltimore when her brother was 
the mayor of Baltimore.
    Ms. Pelosi. I did not want to sound too chauvinistic. I am 
very proud that Dr. Alexander was born in Baltimore.
    Mr. Hoyer. And we happen to believe that Nancy has been 
assigned by Maryland to represent California temporarily. 
[Laughter.]
    Ms. Pelosi. Do not tell my constituents that.
    Mr. Hoyer. No, I will not.

                    sids and the minority community

    The Back to Sleep campaign has been very successful, but it 
has not been as successful in the minority community. Can you 
explain the disparity and what we are doing to determine why 
that disparity exists?
    Dr. Alexander. I would like to address that, but I would 
also like, if you could put the Back to Sleep and SIDS poster 
back up again, you missed this, Mr. Hoyer.
    Mr. Hoyer. I apologize for being late. Did you mention 
this?
    Dr. Alexander. Not the minority issue. I am going to get to 
this. But I just want to make sure you see this poster, which 
demonstrates the dramatic drop with the Back to Sleep campaign 
in SIDS deaths. It was a very stable public health measure for 
many years until the Academy of Pediatrics recommendation for 
back or slide sleeping and then the Back to Sleep campaign, 
which has really dropped it by almost two-thirds from where it 
started. So it has been a very dramatic public health activity.
    You are right on two accounts. Just like infant mortality 
overall being double the rate in blacks as in whites, the SIDS 
rate is also double in blacks as in whites. Actually, in Native 
Americans, it is about three times as high as in whites.
    With the back-to-sleep campaign, the rate of SIDS deaths 
has come down in both the black and the white population, but 
it has come down about parallel. We have achieved about only 20 
percent tummy sleeping in the white population. We still have 
about 40 percent tummy sleeping in the black population. We are 
intensifying our efforts to get across the message within the 
black population as well as the Native American population 
about the importance of back or side sleeping, ideally back, 
but avoiding the tummy sleeping position at all costs.

                     back-to-sleep outreach efforts

    We will be increasing our outreach efforts in this area. 
All along we have included messages in Spanish for the Hispanic 
population. Our videotapes, our brochures, our other materials 
are in Spanish, so we have tried to reach that minority 
population. We have so far not been as effective as we would 
like to be in reaching the African American population and we 
are intensifying our efforts to do that in the course of this 
year.
    Mr. Hoyer. I know my colleague and I and everybody on the 
committee is at least pleased to hear that there apparently has 
been a commensurate reduction, notwithstanding the fact that 
the disparity remains.
    Dr. Alexander. That is right. It has come down. It has come 
down parallel, but it has not----
    Mr. Hoyer. That is the two-thirds that we have seen in the 
white community?
    Dr. Alexander. Yes.
    Mr. Hoyer. That is real progress and I am pleased to hear 
that.
    Dr. Alexander. Yes.

                             rett syndrome

    Mr. Hoyer. I want to associate, as Ms. Pelosi did, myself 
with the remarks of Rosa DeLauro. I am very interested in your 
findings with respect to maternal child care as compared to 
non-maternal child care and the quality of both. I think those 
are very important findings and will be very important in the 
debate. I will not ask further questions about child care, but 
I am very pleased with that.
    Doctor, as you know, you are doing a lot of work and we 
have now seen pictures in the neurological development area. As 
you know, I am very interested in Rett syndrome. Can you give 
me just a couple of seconds on where we are on Rett syndrome?
    Dr. Alexander. Yes. We still have not found the cause, Mr. 
Hoyer, but I think we are getting closer. Research in the two 
program project grants at Hopkins and at Baylor is continuing 
to do well. One of the exciting things is that they recently 
identified a family from South America where there are three 
affected girls with Rett syndrome. They have been brought to 
Hopkins, studied there, evaluated, tissues have been obtained 
for genetic studies, imaging studies were done, and these 
tissues are being shared with investigators elsewhere in the 
research community so that we hope that this will help us with 
this cluster in one family to try and identify the gene that 
must be on the X chromosome, since it affects only girls, that 
is causing this particular disorder.
    We are continuing with our natural history study, with the 
imaging studies that are going on at Hopkins, and along with 
this, some efforts related to improved feeding and dietary 
treatment of these girls. We still, however, do not have an 
effective treatment or an effective diagnostic test--it is 
still a clinical impression--or a specific diagnosis of where 
that gene is or what it is doing.
    Mr. Hoyer. I hope and pray that there is going to be a 
dramatic breakthrough in light of the fact that there appearsto 
be normal development for the first 14 to 20 months of development of 
the female children that are affected. Maybe there can be an 
intervention prior to whatever goes wrong.
    Dr. Alexander. Yes. There is some hope along that line 
because it seems that there is an arrest of development rather 
than a death of cells.
    Mr. Hoyer. Yes.
    Dr. Alexander. It may be that we are, in fact, able, once 
we know what is exactly going on here, to intervene to correct 
that process. There is probably a window of opportunity to 
intervene because these girls do start out apparently normal.
    Mr. Hoyer. Thank you.
    Doctor, last question. The President is doing a Medicare 
press conference at ten o'clock here on the Hill----
    Ms. Pelosi. At eleven.

                                 autism

    Mr. Hoyer. I am sorry, eleven o'clock. What did I say, ten? 
It is eleven o'clock. We had some compelling testimony by 
Congressman Steven Rothman and his brother. His brother has an 
autistic child and his brother is a medical doctor. We had a 
discussion, about what kind of resources we devote to autism or 
other neurologically similar disorders. Can you tell me where 
we are? Dr. Penn, as you may have heard me say, and I know Dr. 
Varmus did, was kind enough to come by my office and give me a 
copy of the conference that was held on autism.
    Dr. Alexander. The state of the science conference? Yes.
    Mr. Hoyer. Can you tell me where we are on autism and what 
your thoughts are?
    Dr. Alexander. Yes. The investment in NIH research in 
autism has more than doubled in the last couple of years. Dr. 
Varmus has directed some of his discretionary funds to autism 
to assist the four institutes that are involved with autism 
research. Following up on the state of the science conference, 
we formed an autism coordinating committee among the four 
institutes that Dr. Hyman from NIMH and I co-chair.
    We have issued a request for applications from NICHD and 
the National Institute on Deafness and Other Communication 
Disorders for research focusing on the neurobiology and 
genetics of autism. From that, we have funded ten different 
sites, called Collaborative Programs of Excellence in Autism, 
that represents an investment of $27,000,000 over the next five 
years for a coordinated approach with interaction and 
collaboration between these different sites and studying a 
large number of children in families with autism and trying to 
get at the genetic or neurobiologic underpinnings of this 
particular disorder.
    This is not a single gene defect. There are probably 
several different genes involved. It is going to be 
complicated, but we have some good leads that we are pursuing 
and I think people are very optimistic that we are going to 
come up with something with regard to autism.
    Our other studies in autism have also increased, from not 
only NICHD but the other institutes, as well. The investment is 
well over $20,000,000 now, with about $11,000,000 from NICHD 
and a similar amount from NIMH and some from neurology and from 
deafness.
    We are also meeting with the parent advocacy organizations 
at least once a year, and in the summer we are going to be 
sponsoring with them and with several of the professional 
societies a conference growing out of our diagnostic procedures 
within the autism network on the diagnostic workup and 
evaluation of a child thought possibly to have autism. This 
will serve as guidance to the medical community, from the 
medical professional organizations to practicing physicians, on 
when to suspect autism and what you do as part of an initial 
diagnostic workup and referral and management of children 
thought to possibly have this disorder.
    Mr. Hoyer. Thank you very much, Dr. Alexander.
    Thank you, Mr. Chairman.
    Mr. Porter. Thank you, Mr. Hoyer.
    Mr. Stokes?

                   minority children health disparity

    Mr. Stokes. Thank you very much, Mr. Chairman.
    Dr. Alexander, it is nice to see you. Let me start with a 
reference to your formal testimony here today. As I look at it, 
I see you have it broken down into several subcategories. For 
instance, you tell us about research accomplishments, birth 
defects, vaccine research, premature labor, reading development 
and disabilities, child day care, women's health research, 
pediatric pharmacology. I am just wondering, in light of the 
testimony that you just gave to Mr. Hoyer relative to the 
health disparity that exists between majority children and 
minority children, was that not important enough for you to 
perhaps give us at least a subcategory here of this disparity 
in health care between minorities and majority people in this 
country?
    Dr. Alexander. Mr. Stokes, I would probably have had to put 
it in many of the categories. It is specifically referenced in 
the category related to infant mortality and premature labor, 
where we talk about trying to reduce the disparity between 
white and minority populations in infant mortality and 
premature labor.
    Premature labor is really the basic problem in the black-
white discrepancy in infant mortality. As just one indicator, 
in white infants, the leading cause of infant mortality is 
birth defects. In black infants, it is premature labor and 
premature delivery. If we want to get at the difference in the 
racial discrepancy in infant mortality, the key to approaching 
it is premature labor.
    In many of the other areas that I emphasized, as well, an 
undertone, if you will, in many of these is majority/minority 
differences, whether it is in reading disability, in the need 
for day care and the importance of day care as a developmental 
experience, or in many of the other categories. Unfortunately, 
there is a racial disparity in many of those. Rather than 
separate it out as a different category, it is subsumed in each 
of those.
    I very much appreciate what you have done over the years in 
your emphasis in these areas and you have always been a very 
staunch supporter of the Institute and its efforts to try and 
attack the racial differences in infant mortality, premature 
labor and delivery, and other areas. I guess the only one where 
I specifically singled it out was in premature labor, but there 
are differences in many of these other areas, as well.

                       lung hemorrhage in infants

    Mr. Stokes. And I guess that is what disturbs me so, 
because not only do you not have a category on it but even in 
the subcategories where you treat it, you do not highlight that 
particular fact, and that is disturbing to me.
    Let us talk about lung hemorrhage in infants. As you know, 
that is a recent illness that has brought a tremendous toll on 
infants, particularly in the Cleveland area.
    Dr. Alexander. Right.
    Mr. Stokes. Is there not a large disparity there between 
white and African American children in lung hemorrhage?
    Dr. Alexander. There does seem to be a difference. This is 
a condition that was initially misdiagnosed, I guess, as sudden 
infant death syndrome came to light with some epidemiologic 
investigation and was associated with a fungus as a cause of 
the condition.
    I do not think we have enough epidemiologic data yet beyond 
the Cleveland area to say with respect to this condition, 
whether it is a black-white discrepancy, whether it is an 
income discrepancy in terms of its epidemiology, whether it is 
just associated with certain kinds of housing, or even a 
geographical finding.
    So I cannot really give you a good answer on that. I do not 
know the data well enough and I think it is probably too soon 
in our investigations of this particular condition to say 
whether this is a racial discrepancy-disparity kind of an 
issue.
    Mr. Stokes. Are we doing any research in this area?
    Dr. Alexander. No, we are not. This is a condition that has 
been focused largely as an infectious condition within other 
institutes. NIAID has been the primary institute thathas been 
investigating that, along with the Centers for Disease Control. We have 
not been doing research on pulmonary hemorrhage other than its 
association with sudden infant death syndrome as a misdiagnosis.

                     mental retardation and gender

    Mr. Stokes. Dr. Alexander, according to the budget 
justifications, fragile X is considered to be the leading cause 
of mental retardation in children, appearing in one out of 
4,000 males and one out of 8,000 females. Have researchers been 
able to determine why the incidence is half as high in females?
    Dr. Alexander. This is a condition that represents an 
abnormality on the X chromosome. It is passed on from a female 
carrier to a male offspring. It is a very unusual disorder in 
that a woman who may have a very small abnormality of her 
chromosome can have that abnormality expand and grow in the egg 
that she produces that becomes her son.
    What happens in this condition is what is called a triplet 
repeat disorder, where there is an amplification of a specific 
part of the gene that becomes abnormal, produces an abnormal 
protein, then, that results in the mental retardation and some 
of the other findings of this particular disorder.
    The males are affected more than females with this 
condition, much more severely, because the female has a normal 
X chromosome that functions to counterbalance, if you will, the 
abnormality on one X chromosome. So males are far more 
frequently affected, and, in fact, we used to think that this 
was only a condition that affected males until we actually 
discovered the genetic basis of the disorder and studied 
females, as well.
    Males are much more severely affected in terms of their 
mental retardation. Females tend less frequently to be retarded 
and often just to have some mild learning disability, although 
they may be retarded, as well. It depends on a variety of 
things, how large this amplification is of the triplet repeat 
as well as which particular cells get X inactivation, a very 
complicated process which determines which expression of the X 
chromosome there is in particular cells in the female's body.

                         violence and children

    Mr. Stokes. Dr. Alexander, violence, of course, is one of 
the major public health problems in our country today. Is your 
Institute doing very much in terms of violence as it relates to 
children?
    Dr. Alexander. We are. We have been supporting a number of 
cooperative agreement studies in cities around the country, 
looking at community-based interventions for risky behavior, 
including violent behavior. These projects have worked with a 
number of different interventions, usually with targeting 
middle school youth as a means of reducing violence-prone 
behavior.
    We also have a study going in Charles County, Maryland, of 
risky behavior, again in middle schools, where violence is one 
of the behaviors which is targeted for reduction by the 
particular interventions that are being undertaken.

                      health profiles in children

    Mr. Stokes. Last year, the Institute reported that in order 
to get an accurate profile of the health of children, 
researchers must go beyond looking at just mortality and 
morbidity data. Are you doing that yet? What has the Institute 
done in that regard?
    Dr. Alexander. We are going beyond mortality and morbidity. 
We are looking at health behaviors, to start with, that are the 
generators of morbidity in the long term. When we look at, for 
example, the prevalence of smoking, the prevalence of risky 
sexual behavior, the prevalence of eating disorders, whether it 
is eating too much or too little, or other things like calcium 
intake in the diet, all these are risky behaviors that may not 
have any morbidity associated with them at the time, but do 
have morbidity associated with them in the long term.
    In a number of instances, we have interventions developed 
or underway trying to make a difference in influencing these 
health behaviors. As part of the fiscal year 1999 budget 
request, there is included in that a health behavior research 
initiative where we particularly seek to expand research in 
these areas of pre-morbidity, if you will, that portend 
problems later on.
    Mr. Stokes. Thank you, Dr. Alexander.
    Thank you, Mr. Chairman.

                       information dissemination

    Mr. Porter. Thank you, Mr. Stokes.
    Dr. Alexander, with the indulgence of the subcommittee, I 
want to ask you one or two more questions. We talked about 
getting the message across earlier. You have detailed for us 
this morning a great deal of progress being made in research, 
and I understand it is not your direct responsibility to get 
the message across, but is there any way you can tell us what 
percentage of your resources is spent on getting the message 
across as opposed to the research itself?
    Dr. Alexander. It is a relatively small percent, Mr. 
Porter. Most of the ``getting the message across'' funding 
comes from the Research Management and Support line in the 
budget, which has been extremely constrained, so probably no 
more than two percent of our overall budget is directed toward 
getting the message across specifically in terms of public 
information.
    Now, much of what we do in terms of publishing the results 
of our research is part of getting the message across. But I 
gather from your comments that you mean to the general public, 
to the practicing physician, to get the research results 
actually implemented.
    Here, we have things like the Back to Sleep campaign, a 
very successful example of getting the message across. Another 
campaign from the Institute that----
    Mr. Porter. How did you do that?

                         back to sleep campaign

    Dr. Alexander. We worked collaboratively with a number of 
organizations, with the American Academy of Pediatrics, with 
the SIDS professional organizations and SIDS program people, 
with a number of public health organizations in the States and 
elsewhere throughout the Public Health Service, first to make 
sure that the message was understood, to encourage its 
distribution and its dissemination.
    With Back to Sleep, we had a very specific target audience, 
newborns. Every newborn in the country was our target, to get 
the message to the mother at the time she took the baby home 
from the hospital that her baby should be put on its back 
rather than on its tummy to sleep. So we targeted a mailing to 
all newborn nurseries in the country, for starters, in addition 
to our work with the American Academy of Pediatrics, and asked 
that they make sure that the message was given to every mother 
taking the baby home from the hospital to put her baby to sleep 
on its back.
    We also provided brochures and stickers to put on the crib. 
These brochures were in Spanish as well as in English. In this 
way, we very specifically focused that information. We also 
produced public service announcements.Later on, we enlisted 
Mrs. Tipper Gore as the national spokesperson for the Back to Sleep 
campaign, who has been effective in carrying the message to the media 
as well as to senior citizens, the American Association of Retired 
Persons, because grandmothers and grandfathers were among the last to 
get this message and were traditionally still putting babies when they 
cared for them to sleep on their tummies.
    We are also getting the message out to day care centers, 
which is a place where many infants sleep these days, and had 
not effectively gotten the word about the importance of back 
sleeping.
    We have industry partnerships, as well. Gerber Products 
Company put the Back to Sleep message on the back of 5,000,000 
boxes of Gerber rice cereal. We are working with other 
industries at the present time, trying to get messages, for 
example, on diapers. This is an example of a campaign, part of 
it done with NICHD resources, part done with resources 
elsewhere in the Public Health Service, including provision of 
a hotline, an 800 number for parents to call, and partnerships 
with industry.

                         milk matters campaign

    We are doing a similar thing with the ``Milk Matters'' 
campaign, getting the message out on the importance of calcium 
in the diet of children, the fact that the window closes by 21 
to 24 years of age for adding more calcium to your bones. If 
you do not get it in before then, you do not get it. It is 
important to maximize calcium in the skeleton before you start 
the inexorable process of calcium loss that can eventuate in 
osteoporosis. The more calcium you take in to start with, the 
longer it is going to take for you to lose enough to develop 
osteoporosis.
    The Milk Matters campaign is a public education, public 
information activity. Here again, we have managed a partnership 
with industry, the Milk Producers Association as part of the 
milk moustache campaign. This has been extremely successful in 
promoting the idea of milk as a source of dietary calcium for 
kids.
    We work in other areas, as well. For example, I met 
yesterday with Fred and Vicki Modell from the Jeffrey Modell 
Foundation, where again we are partnering with them in getting 
information out about primary immune deficiency disorders to 
the practitioner, to the public. We are producing a booklet 
about the disorder, producing a treatment algorithm for 
physicians, and also working in other ways to get that 
information out. Those are three examples of the approaches we 
use.

                    information based interventions

    Mr. Porter. Dr. Alexander, we talked earlier with Dr. 
Varmus and other directors about how a great deal of our health 
care costs result from lifestyle. Last year, you and I 
participated in an event put on by Dr. Ernst Wynder of the 
American Health Foundation focusing on children's health and 
what we can do to get the message out to children, and 
presumably also to those who most affect their lives, to 
develop healthy habits early in life.
    What can we do to further that kind of effort? And the 
macro question I want to leave you with is, if we were to 
double your resources over the next five years, how would you 
use them? Would you use a portion of those to get the message 
out?
    Dr. Alexander. We certainly would. Part of it is learning 
how to get the message out most effectively and what 
interventions work versus what interventions do not work. There 
is still a research agenda here, as well as a get-the-message-
out agenda.
    As part of the fiscal year 1999 request, again, as part of 
Dr. Varmus's areas of emphasis, NICHD includes a health 
behavior research initiative, that focuses on research related 
to some of these behaviors, to calcium in the diet, to obesity, 
to smoking, to other health habits in kids.
    I have said here before and I will just say it again, the 
most effective time in life to get this information when it can 
have its maximum benefit is in childhood. That is when these 
lifetime habits are formed. Once they are formed, it is very, 
very difficult to break them or change them, and so it is 
important to reach kids early with the message in the most 
effective way that we can when they are very receptive and open 
and we can have the maximum influence. We need to learn how to 
deliver those messages most effectively.
    One objective of our health behavior research initiative is 
to learn how to do that most effectively. Another part will 
clearly be public information campaigns like Milk Matters, like 
Back to Sleep, like the Jeffrey Modell Foundation campaign on 
primary immune deficiencies and other disorders that we would 
like to get into.
    So this is a very useful area for investment, both in the 
research to learn how to deliver the message most effectively 
and in the actual funding of delivering the message.
    Mr. Porter. You may have the best job in the world. You 
probably also have one of the most important jobs in the world 
and we are delighted that you are there and doing it so well. 
We appreciate your excellent testimony this morning and your 
very direct answers to all of our questions. We have additional 
questions for the record that we will ask you to answer. Thank 
you, Dr. Alexander, for your testimony this morning, very much.
    Dr. Alexander. Thank you, Mr. Porter.
    Mr. Porter. The subcommittee will stand in recess for three 
minutes.
    [The following questions were submitted to be answered for 
the record.]


[Pages 2008 - 2149--The official Committee record contains additional material here.]



                                           Tuesday, March 17, 1998.

                 NATIONAL INSTITUTE OF DENTAL RESEARCH

                               WITNESSES

DR. HAROLD SLAVKIN, DIRECTOR
DR. DUSHANKA KLEINMAN, DEPUTY DIRECTOR
YVONNE DU BUY, EXECUTIVE OFFICER
EARLENE TAYLOR, BUDGET OFFICER
DR. HAROLD VARMUS, DIRECTOR, NATIONAL INSTITUTES OF HEALTH
DENNIS P. WILLIAMS, ASSISTANT SECRETARY, BUDGET, DEPARTMENT OF HEALTH 
    AND HUMAN SERVICES
    Mr. Porter. The subcommittee will come to order. We 
continue with our hearings on the National Institutes of Health 
and are pleased to welcome Dr. Harold Slavkin, the Director of 
the National Institute of Dental Research.
    Dr. Slavkin, let me apologize to you. I grossly 
underestimated the number of Members who would arrive and 
therefore we lost a lot of time that I thought was going to be 
available to you, but we will do our best. Why don't you 
proceed with your statement after you introduce the people who 
have come with you this morning.

                       Introduction of Witnesses

    Dr. Slavkin. Thank you, Mr. Porter.
    Immediately to my left is Yvonne du Buy. Yvonne is our 
Executive Officer; Earlene Taylor, who is our Budget Officer; 
our Deputy, Dushanka Kleinman; Dr. Varmus; and Mr. Williams.

                           Opening Statement

    This year is a very, very special year to come before you 
because this is the 50th anniversary of the National Institute 
of Dental Research, created on June 24, 1948, when tooth decay 
was rampant in this country, when being edentulous was a normal 
expectation of men and women turning 45 years of age, when 
there were essentially no strategies to address that.
    Since that genesis and the very wise decision of Congress 
to create the National Institute of Dental Research, we have 
come a long way. Through your investment over 50 years of 
$3,200,000,000, we are now saving the country $4,000,000,000 
per year as a consequence of the investment in the National 
Institute of Dental Research.
    When you look at this country today, with 50 percent of our 
nation's children having no tooth decay in their permanent 
teeth whatsoever, where edentulism in the adult population is 
now below seven percent, where people today expect to be with 
their teeth into the eighth and ninth decades of life, free of 
pain and discomfort, that has been derived by public health 
measures and an investment in science.
    When you go to your dental office and look around at the 
high-speed drills, the panorex x-rays, the digitized 
radiography, the infection control, the marvelous dental 
materials that have been developed, the dental sealants, the 
pre- and post-operative management of pain and inflammation, 
all of that comes to bear on America having the finest oral 
health in the world.
    It can be better. When we look at the opportunities today 
and anticipate the future, we, like many of the other 
institutes on the NIH campus, have taken an audit of where we 
are, we have formulated a vision of where we would like to be, 
and we have made a plan of how to get there. In so doing, we 
have come up with a strategic plan referred to as ``Shaping the 
Future.''
    We have reorganized our intramural program, our extramural 
program, and our Office of the Director, to focus on six major 
areas of research. First, the genetic diseases that are either 
inherited or acquired. Second, infection, meaning viral, 
bacterial, and yeast infections, as well as host immunity. 
Third, mouth cancer, oral and pharyngeal cancer. Fourth, 
chronic disabling diseases, such as temporomandibular joint, 
chronic facial pain, osteoarthritis, the consequences of 
diabetics in this country on the premature loss of teeth, et 
cetera. The fifth area is biomaterials or biomimetics, a whole 
new set of opportunities that are truly remarkable and are 
being pursued by many other institutes at the NIH. And then 
finally focusing on human behavior and the opportunities to do 
a better job in health promotion, both to the professions as 
well as to the many publics that we serve.
    To highlight three of the areas that are, we think, 
extremely exciting and promising, we have made a couple of 
visuals. The first one is an area of emphasis on the role of 
genetics in medicine and dentistry, and here in this diagram, 
what has happened through work that began at the early part of 
this century, researchers have basically mapped the genes 
responsible in establishing the geometry of the body form of a 
fruit fly, Drosophila melanogaster, and somewhat counter-
intuitively, genes that are involved in the head of forming 
Drosophila are highly conserved and reappear in the formation 
of zebra fish, in the formation of frogs and mice and human 
beings.
    In this particular example, a gene that is exclusively 
expressed in the head of the fruit fly is also expressed in the 
head of mammals, including human beings. Last year this gene 
turned out to be responsible for a human craniofacial syndrome 
called Rieger syndrome, located on chromosome number four that 
not only affects tissues of the head, face and teeth, but also 
is involved in eye defects, a predisposition for glaucoma, and 
also heart and limb deformities.
    Another area of emerging opportunity is the development of 
novel and innovative therapeutics. Once a knowledge base is 
established, either from doing the genomic studies and the 
post-genomic or functional studies to understand proteins and 
how they function, the next opportunity is to focus that 
knowledge on improving diagnosis and therapy, and this is work 
going on at the NIH campus, focusing on a very interesting non-
inherited but genetic disease called McCune-Albright syndrome.
    This is work that is done in collaboration with NIDDK, 
NICHD and the Clinical Center, and, in these studies, the idea 
is to isolate cells that normally reside in our bone marrow. 
These are so-called stem cells or stromal fibroblast cells. 
These cells normally help in the repair of bone. By modifying 
them, by adding bone morphogenetic protein to them, a class of 
genes was discovered by scientists supported by the NIDR over 
many, many decades of research and involving several other 
institutes. Those stem cells can be enriched and used to 
provide an incredible delivery system to enhance skeletal bone 
healing, whether it is in the head or the jaws or the rest of 
the body.
    This work is being published in April in the Journal of 
Clinical Investigations and is a ``proof of principle'' using 
biomimetics, the background of genetic understanding, and now 
applying it to humans to be able to heal bone.
    Our third example is a whole series of opportunities that 
are opening up around us. In the oral cavity, there are roughly 
as many bacteria as there are people on the planet earth, well 
over 6,000,000,000, but they live in an ecosystem, in an 
ecological unit called a biofilm, and they grow and live on the 
surfaces of our teeth. In a healthy, robust individual, they 
can be controlled through oral hygiene.
    But in many individuals, from children through senescence, 
they can become pathogenic and associated with cerebral 
vascular stroke, with cardiovascular disease, or with the 
induction of premature babies; about 250,000 babies are born 
every year in a premature, low-birthweight situation. Some very 
interesting new data indicate the importance of the oral 
healthstatus of the mother--these are young women between the ages of 
20 and 25 in a study we are doing in collaboration with NICHD in 
northern Alabama, that is opening up a very interesting association in 
which the status of the oral health of these reproductively active 
women is responsible for a seven-fold increase in the incidence of 
premature, low-birthweight babies. This is an opportunity that we will 
pursue.
    In addition, infections in the oral cavity, in particular 
yeast infections, often are transmitted into lung tissue and 
can be a cause of death for immunocompromised and elderly 
individuals.
    So the role of biofilm in systemic disease is becoming a 
significant set of new opportunities for the institute and its 
role, working with other institutes at the NIH and with other 
agencies. With that in mind, the effort of the NIDR strategic 
planning effort was essential to identify three major strategic 
initiatives.
    First, to pursue the scientific opportunities that we have 
attempted to highlight.
    Second, to address the research capacity, the training of 
clinical scholars, men and women who can cross-over between 
different disciplines and take advantage of this knowledge base 
in the delivery and management of disease.
    And the third area is to significantly improve health 
promotion--how we transfer knowledge from discovery into the 
practice of clinical medicine, dentistry, pharmacy, nursing, 
and all the other related areas.
    A variety of changes in the institute has positioned us, I 
think very effectively, to meet these challenges. Looking at 
ourselves in the context of changing patterns of disease, 
changing demographics in this country, changing patterns in the 
management of health care, changing opportunities of how we do 
science, and the kind of consortium efforts that are now 
practiced, the new public/private partnerships that are 
available--this all makes the future look very bright.
    These developments I believe are fostering a climate of 
increased cooperation, collaboration and communication, not 
only within our NIH community, but also between the NIH and the 
many other communities that we serve.
    Communicating the facts of biomedical science is the best 
means we have to empower Americans to make decisions and life 
style choices to improve their health and prevent disease. That 
goal was intrinsic to the NIDR 50 years ago and it continues to 
be a driving force as we look forward to the next century.
    My colleagues and I will be very happy to answer your 
questions.
    Thank you, Mr. Chairman.
    [The prepared statement follows:]


[Pages 2155 - 2165--The official Committee record contains additional material here.]



                              fluoridation

    Mr. Porter. Dr. Varmus, I think I said this last year, but 
it is wonderful to see the enthusiasm that Dr. Slavkin brings 
to his testimony and to his work. It is just infectious, I 
think. [Laughter.]
    Am I correct, Dr. Slavkin, that when I was in, I guess the 
7th or 8th grade in 1948, that was about the time that 
fluoridation of water began to be undertaken across our 
country. In my town of Evanston, I think it was either 1947 or 
1948, that water fluoridation began. There was initially some 
negative political reaction to it, but it was pushed ahead. 
That was at the same time that the NIDR was created, as you 
mentioned in your testimony. Is about the right time frame?
    Dr. Slavkin. Yes, from 1948 into 1954 is when the studies 
were undertaken across the country, but really starting in the 
Midwest. Studies in Grand Rapids, Michigan, and in Illinois, 
were really the beginning of this public health measure.

                           future directions

    Mr. Porter. Now let us look 50 years down the line. We have 
had 50 years; let's look 50 years into the future. It seems to 
me, from what you have told us this morning and what you told 
us previously, that we could very likely have no more dentists 
in America. That every child will be formed with a perfect set 
of teeth, that look like movie stars, and that we will live 
until 100 years old with no oral problems at all.
    Is that entirely possible? In other words, could you be the 
first Institute to go out of existence because you have nothing 
left to do?
    Dr. Slavkin. Being very serious, I think it should be 
intrinsic to the goal of our entire enterprise. I mean, if we 
can--and regardless of whether it is 50 years or whether it is 
100s of years, I think all of us are really trying to maintain 
health, and contribute so that diseases--like smallpox and 
polio and dental caries and so forth--are eliminated, and I 
think that has been demonstrated by many institutes.
    What we are looking at today--and 50 years I believe is not 
a realistic projection into the future--is that the problems of 
chronic diseases and disorders are incredibly complex.
    Many of us thought that many diseases would be explained by 
mutations in one gene. Now we have coined the phrase, complex 
human diseases, and acknowledge that there may be a dozen 
different genes, with a different burden or load, that 
predisposes some of us for certain conditions and others of us 
to be resistant.
    The other formidable issue that this morning you have 
repeatedly addressed, and throughout your career, is human 
behavior. The issues of really improving prenatal care, the 
early childhood development, K-12 development, those issues are 
linked to health literacy and to people making choices,wise 
choices to reduce the preventable diseases. I think that this is really 
an area that is not our strength, and that we need to do better on the 
basic understanding of how people make choices.
    I think there is an enormous challenge before us. But there 
will be dentists in 50 years. [Laughter.]
    Mr. Porter. They may be doing a lot different things than 
they do now.
    Dr. Slavkin. Yes; exactly.

                        change in institute name

    Mr. Porter. I have heard that there is a legislative 
proposal to change the name of your institute. What is the 
proposed name change, and what is the reason behind that 
thinking?
    Dr. Slavkin. Right. We started the process of strategic 
planning when I had the privilege of joining the institute two 
and a half years ago. We have had focus groups from organized 
dentistry, from various patient advocacy groups, from 
scientists, and most people feel that our name does not 
describe our portfolio, either three decades ago or two decades 
ago, or currently.
    The NIDR is very much involved in temporomandibular 
disorders. It is very much involved with cleft lip and cleft 
palate and all the craniofacial malformations.
    So, in working closely with the American Dental Association 
and their leadership as well as the leadership of the American 
Association of Dental Schools, the American Association of 
Dental Research, Dr. Varmus, and a large number of people, the 
thought was to add a C to our acronym, and convert it to NIDCR, 
the C being craniofacial. So the name change would clarify the 
scope of what we are trying to attain, which is really the 
health of the human face, inclusive of the mouth and the oral 
issues.

                       oral and pharyngeal cancer

    Mr. Porter. Can you describe for us the national strategic 
planning conference for the prevention and control of oral and 
pharyngeal cancer you are sponsoring along with CDC and the 
American Dental Association. What other collaborative efforts 
are you planning with nongovernmental organizations?
    Dr. Slavkin. The problem of--depending on the language--
mouth cancer, or oral, tongue, pharynx, tonsillar area--is 
linked to fairly well-established risk factors. All tobacco 
products, alcohol, and direct sunlight are very well-
established causative factors in inducing this particular 
condition.
    It is also clear, like all other cancers, that these are 
multi-gene mutations that go from normal to a pre-malignant to 
a malignant stage. Therefore, to address that problem, which is 
sixth most prevalent in this country, fourth most prevalent in 
African American populations, it is necessary, essentially, to 
bring a lot of different people together.
    So we have partnered with the National Cancer Institute, 
the National Institute of Deafness and Communicative Disorders, 
which has a large number of otolaryngologists associated, with 
the National Institute of Environmental Health Sciences, with 
the American Dental Association, with CDC, and with a number of 
not-for-profit outreach groups that deal with Little League 
baseball, teachers who coach and model behavior in various 
parts of the country, and we are trying to leverage our 
resources with the other groups to address this challenge.
    In Bethesda, in the Intramural Program, we have a new 
branch that focuses exclusively on oral and pharyngeal cancer, 
with input from many institutes.
    Our extramural activities involve the American Cancer 
Society, and there is an oral cancer advocacy group in Atlanta, 
one in New York, one in Chicago and one on the West Coast that 
we are working with.
    We are trying to raise the consciousness of all the 
American dentists and dental hygienists. That is 140,000 
dentists and another 100,000-plus dental hygienists who see 200 
million Americans every year, and can perform a wonderful 
function in early detection.
    One of the problems with this malignancy--it is detected 
too late, and the prognosis, therefore, after 5 years, is that 
half of the patient population is dead. So at this rate, we 
think that this private/public consortium, using professional 
organizations as well as NIH and other governmental agencies, 
is the way to really reduce the burden of oral and pharyngeal 
cancer.

                       gender differences in pain

    Mr. Porter. Thank you.
    It is thought that men and women have different pain 
pathways contributing to the fact that women report greater 
sensitivity to pain. It is also thought that men and women 
react differently to pain medication. How does this information 
affect the way you design clinical research studies? For 
example, do you require that the studies be comprised equally 
of men and women?
    Dr. Slavkin. Well, as you know, and before I arrived, and I 
think through the efforts of Congress, an Office of Women's 
Research was developed at the NIH, so there has been an 
increasing sensitization to all of us who are in the different 
institutes. In the area of pain, in particular, Harold Varmus 
created a trans-NIH pain consortium which includes 21 of the 
institutes who share an interest in pain. We are having a 
conference next month on gender and pain. A paper came out in 
November of 1996 from a group in San Francisco, showing for the 
first time that the kappa receptors on women's cells were very 
different than on men.
    The response to analgesia was very different. Since the end 
of 1996, that information has defused to the scientific 
community. We had a trans-NIH major meeting on ``New Directions 
in Pain Research'' where gender biology was discussed, and I 
think there are a lot of bright people who had not previously 
thought that there would be a gender difference of this 
magnitude, who have become interested, scientifically, and I 
think are going to ``push the envelope'' of this problem area.

            periodontal disease and low-birth-weight babies

    Mr. Porter. Dr. Slavkin, periodontal disease itself is not 
a life-threatening disease, but it may lead to other life-
threatening conditions. For example, women with periodontal 
diseases are seven times more likely to deliver low-weight 
babies prematurely.
    Dr. Slavkin. Right.
    Mr. Porter. A Seattle-based company that produces a Sonic 
toothbrush has donated 2,000 of them to low-income expectant 
mothers. Is your Institute or someone else following these 
women to see if they make a difference in the incidence of 
premature births?
    Dr. Slavkin. Yes. That issue has two interesting parts. In 
the Small Business Inovation Research program, the NIDR 
provided the start-up money for a project conducted by a 
company in the State of Washington to develop the Sonicare oral 
hygiene device. It was one of the fastest-rising companies in 
the country, earning, from 1992 to 1996, well over $100,000,000 
a year.
    This company has in fact donated these tooth devices, the 
Sonicare. The study is going on, which is a consortium effort 
between the University of North Carolina, the University of 
Alabama, and Meharry University, and it is focusing on women at 
risk for low birthweight, premature babies.
    By a modest investment of improving oral health, we hope 
that this will dramatically reduce the number of children 
requiring neonatal intensive care, the costs of which are 
remarkably high, sometimes $225,000 per child. The investment 
in oral hygiene is a very cost-effective way of reducing that 
burden.
    Mr. Porter. Dr. Slavkin, we are pleased to welcome to the 
subcommittee Mr. Jay Dickey of Arkansas.
    Mr. Dickey.
    Mr. Dickey. I have no questions but I appreciate the 
deference from the Chair.

                        public health education

    Mr. Porter. Thank you, Mr. Dickey. I understand that about 
40 percent of the population doesnot see a dentist.
    Dr. Slavkin, do we know why this is? It seems to me that if 
more people started seeing a dentist on a regular basis, even 
once a year, we could save a lot of personal pain and suffering 
and a lot of money on health care costs.
    We now know that dental caries and periodontal diseases are 
infections associated with bacteria. We think that there is a 
link between periodontal disease and the incidence of low-
weight premature deliveries and cardiovascular disease. With 
some 400 species of bacteria living in the mouth, who knows 
what other problems poor dental hygiene is causing. What is 
being done to address this problem? Do we need to spend more on 
education? Do we need to get outside groups involved? What 
suggestions do you have?
    Dr. Slavkin. Both of the suggestions you just raised would 
be very important to the approach to this problem. This is 
going to sound like an extension of Duane Alexander's beautiful 
testimony earlier this morning--and that is the emphasis on 
very early childhood development when habits of mind and 
certain kinds of behavior are established, including oral 
hygiene, would be the best investment to focus on, to really 
reduce these problems.
    People who form these habits, and then they are modeled by 
their caretakers, typically go on and are not problematic with 
oral hygiene conditions. So a major effort is health promotion 
using preschool and K-12 education, and giving people the 
empowerment to properly take care of their oral health, as well 
as all of their health.
    We have, coupled with Duane, tried to sensitize all the 
dentists in the country to be cheerleaders for the use of 
drinking low-fat milk, among children, to not only build the 
bone density of the whole skeleton but also of their dentition.
    Many of these strategies carry over between institutes, 
very effectively, with the same target--early childhood 
development, and beyond. It really becomes a collaborative 
effort between a number of school districts around the country, 
it involves athletic coaches who have incredible influence on 
children, the modeling of some of the bigger-than-life athletes 
who children often emulate--all of these kinds of influences 
could reduce this problem and promote health.

                              diagnostics

    Mr. Porter. Is it true that everything in the blood is also 
found in saliva and that early signs of disease such as 
diabetes or AIDS can be detected in the oral cavity?
    Dr. Slavkin. Yes.
    Mr. Porter. Then why aren't doctors using saliva tests more 
often instead of blood tests? Wouldn't these tests be less 
costly and painful for the patient and provide the doctor with 
quicker results?
    Dr. Slavkin. Right. Using saliva is clearly noninvasive, 
and some of us believe could be very cost-effective, and I 
think one of the things that our institute wants to do, and I 
believe other parts of the NIH and Government, is really to 
move dentistry much closer, or integrate it into medicine.
    This is an experiment, as you probably are aware, the 
segregation of these fields in the mid-19th century, and 
clearly, primary care physicians need to have a better 
education of oral health, and various dental health 
professionals need to have a much better understanding of 
principles of internal medicine, and how to work together 
effectively to address these problems.
    So we are trying to broker the American Association of 
Medical Colleges and the American Association of Dental Schools 
to come together and share curriculum and have more crossover.
    We are also trying to achieve that through a new initiative 
called Centers of Discovery, where we are trying to stimulate 
in major research centers in the country, in an academic health 
setting, much more integration between pharmacy, dentistry, 
medicine and nursing, to the enhancement, I think, of all the 
fields.

                              biomimetics

    Mr. Porter. You are making great strides in a new area of 
science called biomimetics, which aims to create replacement 
parts for bones and body tissues. Do you see a future where we 
will be able to grow body parts such as knees and hips on 
demand for surgery, and no longer use artificial replacements?
    Dr. Slavkin. Yes. This--as Dr. Varmus knows, because we 
have had a chance to talk about this on a number of occasions--
is a tremendous opportunity.
    The FDA, as you may know, has already approved a cartilage 
tissue approach for knee injuries, so that in that case 
biomimetics has gone from the bench to application, and now to 
clinical trials.
    The NIH sponsored, the end of February, a tremendously 
successful conference on bioengineering, involving about 800 
people from around the country, with a very, very significant 
interest.
    We have teamed up with the Heart Institute and the 
Arthritis Institute to put out an RFA to support and stimulate 
research in this area. We received 124 applications. They were 
truly remarkable, from all over the country. A significant 
number will be funded in the summer councils of the 
participating institutes. They will be funded, probably, in 
July of this year.
    There is a real excitement between physicists, 
mathematicians, engineers, clinicians, molecular biologists, 
putting their minds together and really developing a 
newgeneration of materials.
    In dentistry, thinking of silver or gold fillings will 
become obsolete. That will not be the way to restore teeth. We 
hope to regenerate enamel and dentine, to replace bone, hips or 
jaws, instead of using metal or plastic, to be able to augment 
normal bone repair and regeneration.
    That is the goal, and whether it is nerve tissue or muscle 
tissue or salivary gland--whatever part of the body--many, many 
very bright people are trying to find out how to understand the 
biology, and then mimic it in the design and fabrication of new 
materials or new strategies to address these issues.

                         professional training

    Mr. Porter. There are numerous diseases and illnesses such 
as bulimia, diabetes, and vulnerability to strokes that can be 
detected in the oral cavity if dentists and hygienists know 
what to look for. Do you think enough training is provided to 
them to look for these signs?
    Dr. Slavkin. No. This is an area of terrific opportunity. 
We need to catalyze our efforts with the health professions, to 
raise the awareness of men and women who practice dentistry, to 
be able to identify eating disorders appropriately, and to 
really be part of the network of being able to provide the 
patient with the venue to get the kinds of various therapies 
that would be effective.
    This also applies to child abuse, to heighten the awareness 
of health care professionals, to be able to identify and 
provide better venues for people to be addressed in those 
areas.
    We need a much better education, and I am hoping that the 
American Dental Association, the American Association of Dental 
Schools, our colleagues in medicine, nursing, pharmacy, will do 
more crossover, so we will be more effective.

                            budget increases

    Mr. Porter. Dr. Slavkin, some might say that NIDR is making 
so much progress, that your area would be the one where you 
would least need the doubling of your budget. What would your 
answer be to that?
    Dr. Slavkin. I think we could use some modest 
encouragement. If you look at our portfolio and everything that 
I have described, I think the plan that we have outlined is 
very appropriate.
    We have identified the key areas, and what we really need 
to do is establish the bench strength to make these things 
happen. We need to train more people and much better in the new 
tradition.
    We need to increase our efforts to bring these things to 
fruition in a more focused and in a more effective fashion, and 
I think with combining training with the scientific 
opportunities, looking 5, 10 years down the road, the training 
is the most important. We need to train people in the kind of 
modern genomics, modern physical chemistry, modern statistics 
and epidemiology, and behavior, to be able to address these 
issues, and I think that is going to be a major issue.
    The loan that students have when they graduate from medical 
and dental schools today, somewhere between $60,000 to $70,000 
on the low side, to a couple of $100,000 on the high side, is a 
significant deterrent to recruitment of all the bright young 
people in the pipeline, to bring them into these areas, and for 
them to be able to contribute.
    From a policy point of view, that will be very helpful for 
us.
    Mr. Porter. Dr. Slavkin, I wish that Mr. Hoyer were here, 
so I could claim to him that you are Chicago born.
    Dr. Slavkin. Yes.
    Mr. Porter. But then Ms. Pelosi would say you deserted 
Chicago and went to California. So maybe I am glad they are 
both not here. [Laughter.]
    Mr. Porter. Let me thank you for your excellent testimony 
today, and not only for your enthusiasm, but obviously the 
tremendous intelligence and imagination you bring to your work 
at NIDR, and thank you for the tremendous job you are doing 
there.
    Dr. Slavkin. Thank you.
    Mr. Porter. Thank you so much. Thank you, Dr. Varmus.
    The subcommittee will stand in recess until 2:00 p.m.
    [The following questions were submitted to be answered for 
the record:]


[Pages 2173 - 2234--The official Committee record contains additional material here.]



                                          Thursday, March 19, 1998.

                  NATIONAL INSTITUTE OF MENTAL HEALTH

                               WITNESSES

STEVEN E. HYMAN, M.D., DIRECTOR
RICHARD K. NAKAMURA, ACTING DEPUTY DIRECTOR
WILLIAM T. FITZSIMMONS, EXECUTIVE OFFICER
J. RICHARD PINE, BUDGET OFFICER
GEMMA M. WEIBLINGER, SPECIAL ASSISTANT TO THE DIRECTOR
    Mr. Porter. The subcommittee will come to order. We 
continue our hearings this afternoon on the budget of the 
National Institutes of Health with the National Institute of 
Mental Health, and we are pleased to welcome its Director, Dr. 
Steven Hyman.
    Dr. Hyman, it is good to see you. If you would introduce 
the people to your left and then proceed with your statement?
    Dr. Hyman. Thank you, Mr. Chairman. To my far left is Gemma 
Weiblinger, who is my special assistant and congressional 
liaison; my budget officer, Mr. Richard Pine; the Acting 
Deputy, Dr. Richard Nakamura; and my executive officer, Mr. 
Bill Fitzsimmons.
    Mr. Chairman, it is indeed a pleasure to be here. The 
President in his fiscal year 1999 budget has proposed that the 
NIMH receive $701.8 million, an increase of $52.4 million over 
the comparable fiscal year 1998 appropriation. Including the 
support for AIDS, the total budget for the NIMH would be $809.7 
million, an increase of $59.5 million over fiscal year 1998.

             excessive disability stems from mental illness

    Mr. Chairman, mental illness is a serious burden for the 
American people and for the entire world. The Global Burden of 
Disease study, which no doubt you have heard about more than 
once, sponsored by the World Health Organization, the World 
Bank, and the Harvard School of Public Health, has clearly 
established the enormous contribution of brain disorders to 
disability.
    As you can see, this poster on the left shows all causes of 
disability in what are called established market economies, 
that is, the United States, Canada, Western Europe Japan, and 
Australia. And as you can see, in the United States the leading 
cause of disability is unipolar major depression, a disorder 
that in its most serious forms affects 17 million Americans.
    [The information follows:]


[Page 2236--The official Committee record contains additional material here.]



    Dr. Hyman. Also high on the list are three other mental 
disorders: schizophrenia, manic depressive illness, and 
obsessive compulsive disorder. Also on this list are alcohol 
use, dementia, stroke, and drug use. Thus, eight of the ten 
leading causes of disability in the United States are seen to 
be related to brain and behavior.
    Mental illnesses are in this top ten list not only because 
they are disabling, but also because they begin early in life. 
It is common for mood disorders and schizophrenia to begin 
during young adulthood, just when families and society as a 
whole are waiting to see a person flower as a result of their 
investment in upbringing and education. Not only do mental 
illnesses begin early, but they are also often chronic or 
recurrent.
    Fortunately, we are making substantial progress in the 
treatment of these real and diagnosable disorders. But progress 
in treatment and prevention begins with basic research. For the 
NIMH and, indeed, for all of the brain-related institutes to 
fulfill their missions, this research must be both bottom-up, 
based on genes and molecular biology, and top-down, based on 
the study of behavior, how it emerges from the workings of the 
brain, and, conversely, how the environment changes the way the 
brain works.

                     mechanisms of cellular memory

    Today, I would like to describe for you one example of 
``bottom-up'' research, which concerns how the brain records 
experience. There are many forms of memory besides our 
conscious memories of persons, places, and events. Some of 
these forms of memory, such as emotional memory, initiate 
powerful physiologic cascades in our bodies even before we are 
aware of them. Each of the 100 billion or so nerve cells in our 
brain makes thousands of connections with other nerve cells. 
These connections, which are called synapses, are the 
fundamental sites of information transfer.
    Whenever we remember something, whenever we learn 
something, the physical structure of our brains is actually 
altered. Memory is the result of physical changes in these 
synapses or connections.
    Using a variety of animal models, including recently mice 
with experimentally altered genes, neuroscience has provided 
many details about the precise molecular changes that are 
required to produce memory. What has remained elusive, however, 
has been the ability to correlate actual learning due to 
experience with direct physiologic evidence of a functional 
change in the strength of these synaptic connections.
    Several months ago, two separate research groups provided 
evidence for this long suspected correlation between learning 
and a physical change in the brain. The discovery was made in 
response to learned fear in a part of the brain called the 
amygdala, deep in the temporal lobes of humans or, in this 
case, rodents.
    Preceding this research, several labs using rodent models 
had traced the pathways responsible for fear and found them to 
involve the amygdala, which in turn activates the sympathetic 
nervous system, racing heart and so on, and a variety of 
physiologic mechanisms that would save us from becoming, for 
example, a carnivore's lunch.
    With this model and with this knowledge from animal models, 
several investigators have now used functional magnetic 
resonance imaging, or fMRI, to demonstrate that if you show an 
individual a fearful visual stimulus, such as a fearful face, 
we can literally see the representation of fear in the human 
brain. In this poster (figure 2), you will see vividly the 
activation of the amygdala in response to an individual seeing 
a projection of visual scenes designed to elicit negative 
emotion.
    [The information follows:]


[Page 2239--The official Committee record contains additional material here.]



    Dr. Hyman. To survive, an organism, including a human 
being, must be able to predict danger. Thus, a major function 
of the amygdala is to record in memory the circumstances under 
which we have experienced and can expect danger.

               brain mechanisms underlying panic disorder

    What does this mean for human health? Well, for example, we 
believe that panic attacks, which affect a substantial number 
of Americans, with disaproportionate numbers of women affected, 
result from internal false alarms that activate the amygdala. 
What is the role of memory in all of this? If an individual 
experiences a spontaneous panic attack while, say, on a bus or 
in a shopping mall, they will develop powerful emotional 
memories telling them falsely that this bus or this shopping 
mall is a place of extraordinary danger. The life of afflicted 
individuals often constricts progressively, leading to a 
profoundly disabling condition called agoraphobia. In addition, 
emotional memories have important negative consequences 
following trauma.
    As befits a system that evolved to predict and respond to 
danger, the amygdala matures very early in life. However, the 
hippocampus, another part of the brain, which is required for 
conscious memories, matures much later. And as a result, none 
of us have continuous memories before the age of 4 or 5.
    If a child is abused or neglected early in life, he or she 
will not, of course, remember consciously because the 
hippocampus is not mature. And the conscious memories of these 
episodes, despite recent controversies, cannot be recovered in 
any way because there was no substrate on which to record them.
    However, the emotional memories, which don't rise to 
consciousness, are undoubtedly recorded by the amygdala, with 
consequences that we are now only beginning to understand, but 
which at a minimum reset the brain's control of the stress 
response in the direction of over-responsiveness with 
potentially harmful subsequent physical effects.
    How will this kind of research be translated to the benefit 
of patients with anxiety disorders, mood disorders, and so on?

                    brain molecular anatomy project

    Among NIMH priorities listed in my written testimony, we 
want to clone essentially all of the genes expressed in the 
brain under both resting and stimulated conditions. This is the 
so-called B-MAP project, which is a collaboration with NINDS, 
the National Institute on Aging, and several other institutes. 
This project will involve cloning the genes for 
neurotransmitter receptors and signaling molecules that are 
actually found in the amygdala. These receptors and molecules 
can become targets for drug development.
    We also plan top-down research, that is, research to map 
behavior onto the brain. What you saw in the MRI I showed you 
(Figure 2) is the result of a great deal of preparatory animal 
work that has helped us understand brain circuits.
    We also want to emphasize various imaging technologies 
because we obviously want to bring these applications to the 
human as quickly as possible.
    Finally, NIMH is working to establish clinical trials 
networks, something that we have not previously supported but 
has been supported by other institutes. Clinical trials 
networks will permit us to test new psychotherapies and 
pharmacotherapies in a more rapid and efficient manner and, by 
incorporating health services research, will produce results 
which will be applicable to the real world.
    I thank you, and I will be pleased to respond to any 
questions.
    [The prepared statement follows:]


[Pages 2242 - 2248--The official Committee record contains additional material here.]



                    neurobiology of fear and anxiety

    Mr. Porter. I was just thinking I could listen to you all 
afternoon. It is a fascinating subject.
    Can I ask an unrelated question? It's something that 
interests me. We are talking about a fear reaction. If a person 
goes to a horror movie and they know very well that what they 
are seeing is not real, do they have the same kind of imaging 
that your chart would show?
    Dr. Hyman. Actually, probably yes, but not the same kind of 
emotional memory. And the proof of it is that during a horror 
movie, even if you know cognitively that it is not real, you 
notice your heart is racing. If we measured your blood 
pressure, it would be up. If we measured adrenalin levels, they 
would be increased. If we measured cortisol levels, they would 
be up. So, indeed, you get this physiologic response.
    Now, I have asked my children why they actually like going 
to horror movies and being frightened, and they swear to me 
that they enjoy it, but they cannot actually tell me what it is 
about it they find so enjoyable.
    Mr. Porter. The rush from all those--
    Dr. Hyman. I guess all those hormones, that is exactly 
right. [Laughter.]
    Mrs. Lowey. Same thing on a roller coaster.
    Dr. Hyman. That is right, yes.
    Mr. Porter. Yes, but with a roller coaster, you might have 
a reasonable fear that there is a chance of being injured. 
[Laughter.]
    Dr. Hyman. It is actually true, in all seriousness, these 
stress hormones are meant actually to sharpen cognition. They 
do create arousal and alertness because in evolution these 
would be here in order to help you escape real danger. And I 
think part of the enjoyment is this intense arousal.
    Mr. Porter. But we don't need them anymore, usually. 
Sometimes we do.
    Dr. Hyman. Well, we don't need them all the time, but 
actually we do more than we think. Some of these same systems 
help teach us to avoid things that could hurt us by virtue of 
their causing pain, for example. But it is true these systems 
evolved a long time ago, and now when they work to excess or 
get activated without good reason, they lead to problems for 
physical health that we need to learn how to manage.
    Mr. Porter. Part of what we call mental illness you 
described, I think, is an over-response to certain stimuli.
    Dr. Hyman. In the case of anxiety disorders, that is right. 
We believe--and, actually, there is increasing evidence--that 
there might be a false alarm setting off this cascade and 
setting it off at full tilt. And, of course, the person will 
have what is known as a panic attack, this overwhelming feeling 
of anxiety and dread.
    Mr. Porter. What is the relationship between that and 
autoimmune diseases where your system also has an over-reaction 
to whatever the stimulus is, but it is more automatic?
    Dr. Hyman. Well, I think the metaphoric connection is that 
systems evolve which are required to protect us from real 
dangers. But we pay a price. These systems have a certain 
threshold set, so they are not supposed to go off with a mild 
or inappropriate stimulus. But sometimes, as in the case of 
anxiety disorders, the thermostat, by virtue of genes and 
environment, is set wrong. In the case of autoimmune disorders, 
a mistake occurs in which a molecule which is part of our 
normal body is mistaken for an invader.
    Now, there is also a non-metaphorical connection between 
the two in that the activation of these stress hormones does 
have an impact on our immune system. Indeed, cortisol, one of 
the major stress hormones, actually suppresses immune function, 
this may occur during a period of danger, famine, or escape. In 
these situations, You don't want to use your metabolic energy, 
presumably, to be activating your immune system. There is a big 
metabolic cost. In addition, an escape is not the time to get a 
swollen knee if you have been injured. You want to suppress 
that and wait until later, and then you can get a swollen knee 
when you are safe and you want to splint it so you don't hurt 
it again.
    I am obviously speculating.

                     explanation of functional mri

    Mr. Porter. Is the chart the brain of a human or an animal?
    Dr. Hyman. This is a human. This is a normal volunteer. 
This is from Richie Davidson at the University of Wisconsin.
    Mr. Porter. Could you just for my edification give me an 
indication of how you go about doing brain imaging?
    Dr. Hyman. Yes.
    Mr. Porter. This procedure is used in many of the 
Institutes. Dr. Leshner was here talking about NIDA, and, of 
course, they use it.
    Dr. Hyman. Yes, absolutely. I have dabbled in it, actually, 
myself before I came to NIH.
    Basically what happens is that a subject will go into a 
magnetic resonance imaging machine. Now, this is rather 
forbidding at first. Some people feel claustrophobic inside. 
And the other thing is, when the machine is on, it makes rather 
loud noises.
    Mr. Porter. I have done this, several times.
    Dr. Hyman. You have done it for your back, so you know----
    Mr. Porter. Exactly.
    Dr. Hyman. It is not the optimal environment for cognitive 
and emotional tests. You have to allow people to habituate. 
Often you will train people in a mock magnet for a while so 
that they get used to it.
    In addition, you can give them earphones, depending on the 
experiment, to keep those awful bangs from disturbing them.
    And then what you can do is you can project from the rear 
onto a screen various images. So in the case of experiments 
having to do with fear, you can put up various scenes, such as 
an auto accident, or a happy face versus a fearful face. And 
the person sees it, and then--literally, while you are 
scanning--the scanner provides an indirect measure of the 
activity of nerve cells in the brain.
    When nerve cells fire, they produce carbon dioxide, they 
need oxygen and glucose. And so the micro-circulation in the 
brain responds after about a one-second delay to these 
metabolic needs. And there is a fairly tight correlation 
between this change in blood volume and blood oxygenation which 
alters in some way the actual magnetic properties of 
hemoglobin, the oxygen-carrying part of blood, which can be 
detected and then reconstructed in a computer.
    Mr. Porter. So it is completely non-invasive.
    Dr. Hyman. Completely.
    Mr. Porter. And you can actually do it quite easily.
    Dr. Hyman. That is correct. It is completely non-invasive.
    Now, there are a lot of frontiers that we would love to get 
to. One, because we are dependent on the change in blood flow, 
we have to work with one-second delay, but one second is an eon 
in the nervous system. The actual nerve cell firing events are 
on the order of milliseconds. We would love to be able to 
combine this technology with things like magneto-
encephalography so that we could get both the temporal and the 
spatial dimensions and actually see processing.
    I know you saw recently pictures of dyslexia when Dr. Duane 
Alexander of NICHD testified. Again, he showed images not just 
of the anatomic locations of dyslexia but of the actual order 
in which the brain does things. Timing and sequence are very 
important to understand when thinking about problems with 
reading, for example, or problems processing information.

         nimh plans for effective use of significant new funds

    Mr. Porter. Now for the macro question. If we were able to 
double the funding of NIMH over the next--maybe not the next 5 
years, but soon--could you reasonably use that money in an 
effective way? How would you use it?
    Dr. Hyman. I believe we really could. I think that 
neuroscience in general is a field that is just coming into 
maturity. Based on the complexity of the brain, it has taken a 
long time to have the tools to truly investigate the brain.
    Now, frankly, some of the tools are provided by the genome 
project. Some of the tools are provided by molecularbiology 
coming, say, from the Cancer Institute. At this point we have both 
genetic and molecular tools; that is, we can clone important genes in 
the brain and understand the products of those. But we can't just end 
up with a pocketful of DNA. We have to put it back together into a 
whole brain. So we have to understand what these genes are doing in 
development, how they are regulated by environmental experience.
    We need to get more behavioral scientists and 
neuroscientists working together to map things like emotion as 
Figure 2 depicts, and cognition onto the brain. So we would 
utilize more funds literally to understand the building blocks 
of the brain at a molecular level, how the brain is built both 
as a result of genes and of the environment, how the brain 
works as a whole, including how the environment impacts on the 
genes.
    Then the next issue for us is how does this kind of 
knowledge get translated into clinical research that is going 
to help people with mental illness? Here, on the one hand, you 
see an image that is very helpful in understanding the 
circuits, and, again, if we had additional funds, this is the 
sort of thing I think we ought to be doing more of. We know 
there is something wrong with the amygdala in this disorder. We 
suspect there is something wrong with parts of the frontal 
lobes in schizophrenia. This will pinpoint postmortem studies 
in human brains. Instead of searching for a needle in a 
haystack, we will have directed research looking for the 
molecular pathology, the better to produce novel treatments.
    Once one has novel treatments, which in our case also would 
include psychotherapies, we have to prove their effectiveness. 
We have been, I think, lacking in the past at NIMH because we 
have not had the kinds of clinical trials networks which would 
allow us to test rapidly the kinds of complex treatments that 
are needed for patients with mental illness.
    The pharmaceutical industry does a lot, but we can't expect 
them to test combinations of psychotherapy with 
pharmacotherapy. That is something we really have to do.

             accomplishments during the decade of the brain

    Mr. Porter. We are nearing the end of the decade of the 
brain. Can you tell us generally what we have accomplished in 
that endeavor?
    Dr. Hyman. It is staggering what has happened in the last 
ten years, or eight and a half. It is also staggering how much 
we still have to learn.
    When I started as a post-doctoral fellow or, better yet, 
got my own laboratory, which was just about 10 years ago, it 
was still amazing us that, for example, environmental 
experience turned genes on and off in the brain. This is now 
commonplace, and we know the detailed mechanisms.
    At that time, MRI was a new tool just to look at brain 
structures. No one could imagine that we would actually be able 
to use this wonderful tool to look at brain function.
    Clinically, we were treating people with depression with 
drugs that were effective, like Elavil and Tofranil, but which 
had awful side effects. And as a result, some people didn't 
know whether their illness or the treatment was more of a 
discomfort. Now we have a whole variety of wonderful 
medications.
    But what remains for us to learn is the specific pathology 
of this whole variety of extremely disabling mental disorders 
that I have described to you. And it is with both humility but 
also excitement that we begin to apply the tools we now possess 
what I think really has to be the century of the brain. I think 
it was a bit of hubris to think that a decade of the brain 
could really solve the problems that we need to solve in order 
to do well by our patients.
    Mr. Porter. We have difficulty getting Congress to think in 
more than 2-year terms. [Laughter.]
    Thank you, Dr. Hyman.
    Mrs. Lowey.
    Mrs. Lowey. Thank you, Mr. Chairman.
    I just want to welcome you again, Dr. Hyman, and tell you 
what a real privilege it is for me to be here listening to you, 
reading your testimony, and although we did loan you to New 
Haven and Cambridge, I am particularly proud that New York 
reared you.
    Dr. Hyman. Fair enough, yes. The Upper West Side.
    Mrs. Lowey. Exactly. And I just want to bring greetings to 
you from an admirer and someone who has really been a partner 
in this effort, the Liebers. Connie Lieber is a good friend and 
a constituent of mine, and she has the greatest respect for you 
and all you are doing. And you can see in talking to her the 
excitement she feels that we are on the verge of some 
tremendous breakthroughs. So I just want to thank you.
    Dr. Hyman. Thank you.

      medication and psychotherapy in treating depressive illness

    Mrs. Lowey. I have several questions, but, first, I wanted 
to ask you about a question related to your budget 
justification. You refer to a recent study on patients with 
manic depression, showing that those who are treated with 
medication and psychotherapy do better than those treated with 
drugs alone. I am very concerned that managed care plans are 
relying too heavily on drugs and too little on psychotherapy 
for those with serious mental illness.
    First, can you comment on why psychotherapy is an important 
component in the treatment of patients and the care of the 
mentally ill? And, second, can you comment on trends in the 
care of the mentally ill who are in managed care plans? Are 
they receiving adequate psychotherapy?
    And I just want to comment from an experience with a 
constituent, where I became aware of this serious problem with 
this young woman, and checked with the person who was managing 
her case at the HMO. I think they call it an assist--I don't 
even remember the name or the title, the assistant who was 
giving her medication, one week, two weeks, three weeks, four 
weeks, five weeks, until I called again, and they said this 
does not kick until, whatever, six weeks, and I said, ``Well, 
who is the doctor seeing her?''
    At any rate, I pursued it; she got an additional opinion; 
she went into psychotherapy. If it were not that I called, she 
still would have been seeing this assistant or practitioner, 
whatever you call it, and I expect this is a major problem.
    Dr. Hyman. It is, Mrs. Lowey. Actually, it points to the 
fact that there have been profound misunderstandings of mental 
illness, but also of psychotherapy.
    Now, I have to confess that part of the misunderstandings 
are due to the history of psychiatry. We are emerging from an 
era where there were dominant psychoanalytic theories, but we 
have emerged, and I do not think everybody has realized that.
    Now, let me just use the example, before I get to 
psychotherapy, of treatment for coronary artery disease. Let us 
imagine somebody had coronary artery disease. You wouldnot just 
write a script for several medications. You would prescribe changes in 
diet, changes in exercise, perhaps rehabilitation.
    If the patient had side effects, say, from a beta blocker--
very common--you would engage in the proper handholding and 
dosage adjustment. Well, in many ways, psychotherapy is 
analogous to treating a heart patient. It is analogous to the 
rehabilitation, to the changes in diet, to the changes in 
lifestyle that are critical.
    There are reasons for this, one of which you pointed out. 
Many of our medications take many weeks to work. They work 
wonderfully, once you have given them four or five weeks. But 
in the meantime, a despondent and depressed patient, for 
example, who may be experiencing even mild side-effects, and no 
therapeutic effect, may give up on the medication, may give up 
on the treatment.
    In addition, during this period, individuals may be 
suicidal, and psychotherapy is not simply a matter of 
handholding. It is actually helping; in the case of depression, 
giving people appropriate coping skills, dealing with their 
inappropriately negative thoughts. I do not want to take too 
much time, but I think you can get the gist.
    I think what you point out, which is that the lack of 
available comprehensive treatments, which involves 
psychotherapy in managed care, is a grave concern.
    One of the things that we at NIMH really must do is to 
provide the data on the value of these treatments because it is 
clear that without this kind of data we are not going to get 
them accepted.
    Mrs. Lowey. I appreciate that. I will get on, too, because 
I know we are limited in time. But I think this is such a 
serious problem, and I am very concerned that the cost benefit 
analyses are accurate and are thoughtful.
    The chart is not up there now.
    Dr. Hyman. We can put the other chart back up.

    opportunities for expanded genetics research and clinical trials

    Mrs. Lowey. No, that is okay. I have it here someplace. But 
it is clear that serious mental illness, such as schizophrenia, 
a manic depression, are enormously costly to society.
    In your testimony, you do include this chart, which shows 
that very clearly. The illnesses can be extremely disabling, 
resulting in increased costs for programs such as Social 
Security and, of course, the productivity lost when individuals 
simply cannot function in society.
    Are we devoting adequate attention and resources to these 
severe mental illnesses and does NIMH have plans to increase 
funding for them? I am hoping we will double them, at least, as 
our Chairman has said, and can you please comment now or for 
the record how many new awards in manic depressive illness and 
schizophrenia do you intend to fund this fiscal year?
    Dr. Hyman. We can give you the number of awards for the 
record, but I think the issue, to my mind, is the quality and 
the focus of research.
    I just want to illustrate important areas where I have made 
significant changes in the last two years. These are genetics 
and clinical trials.
    The area of genetics is critical for mental illness, but 
nature has handed us a pretty stacked deck; that is, we have no 
mental disorders, that are called mental illnesses, which 
result from a single gene, or so-called Mendelian disorders. 
All mental disorders involve many genes in interaction with the 
environment.
    Last year, I supported the National Advisory Mental Health 
Council in convening what I considered to be the best group of 
geneticists imaginable in the United States. They have given 
the NIMH advice on how to proceed with the study of manic 
depressive illness, schizophrenia, and depression. We already 
have issued a request for applications seeking new approaches 
to the genetics of these disorders. This a very substantial 
beginning.
    In addition--and this is a good example of the really 
important inputs we get from advocacy groups--it was pointed 
out to us by a number of groups that we really had lagged in 
our support of clinical trials in manic depressive illness. We 
were not spontaneously getting these applications from the 
field, and I think there are a lot of reasons for that, which 
boil down to the fact that such trials are very difficult.
    But we have just issued a request for proposals, again, for 
a very substantial trial, to test promising new anticonvulsant 
drugs alone or in combination with lithium in manic depressive 
illness.
    Finally, one of the things that I have learned about 
priority setting, which is really quite striking, is that NIMH 
had a National Plan a number of years ago for schizophrenia, 
and what that plan did was to rob Peter to pay Paul; that is, 
people who had been investigating manic depressive illness 
moved over and started studying schizophrenia.
    I recognize that we have to plan our priorities in a more 
holistic way to avoid making these errors again.

                       childhood mental disorders

    Mrs. Lowey. Dr. Hyman, I am very interested in the treating 
of mental illness in children because I feel that if we can 
identify it early the costs to society are clear, 
notwithstanding, the decreased pain and suffering. If you could 
highlight for us this afternoon the major advances you are 
making in diagnosing mental illness in children.
    For example, I understand in conversations that there is a 
link, not necessarily one following the other, but there is a 
link between Attention Deficit Disorder and later development 
of manic depression.
    Can you comment on the diagnosing of mental illness as 
early as possible in an individual's life as a way to impact 
the disease later on?
    Dr. Hyman. First, let me say that you raise a point that I 
feel is absolutely critical. We often worry a great deal about 
the cognitive development of children, and we think that if 
their IQ is at a certain level everything is all right. But, in 
fact, children who have emotional disturbances may have fine 
cognitive equipment, but cannot learn and may get into a great 
deal of trouble.
    You may have seen an article on the front page of the New 
York Times just a few weeks ago talking about the mentally ill 
in prisons, and it pointed out that at least 20 percent of 
incarcerated children have a diagnosable mental illness. 
Clearly, if that diagnosis had been made earlier, the child 
likely would have been on a very, very different life course.
    Now, indeed, we have inadequate knowledge about diagnosis 
of mental disorders early in life. And, it is very difficult 
for parents, for pediatricians to tell the difference between a 
passing stage and a serious warning.
    We, therefore, plan to initiate a series of longitudinal 
developmental studies aimed at precisely this: learning which 
child who is inattentive, impulsive, and hyperactive has 
Attention Deficit Hyperactivity Disorder versus which one is 
likely to go on and exhibit manic depressive illness.
    I think only by doing longitudinal studies and, again,these 
are major undertakings, will we see, if a child looks this way now, 
what he or she is going to look like later. I think we now have the 
tools to ask wise questions in these kinds of studies.
    Mrs. Lowey. If I may, you are saying you have the tools to 
identify this?
    Dr. Hyman. No, no. The tools to do these studies; meaning 
we now have an appropriate group of epidemiologists and people 
who understand what the issues are in pediatric diagnosis, so 
that we can actually launch longitudinal studies and expect to 
gain valuable information that will provide answers to the very 
good question that you asked.
    Right now, pediatric mania is an extremely poorly 
understood diagnosis. NIMH recently convened about 20 experts 
to talk about just this. I have to tell you there was a great 
lack of unanimity on this difficult problem.
    Mrs. Lowey. Are we going around again or should I just beg 
your indulgence for one more question?
    Mr. Porter. We have time, so we are going to have a second 
round.
    Mrs. Lowey. Go right ahead, Mr. Chairman. You are the 
Chairman.

                progress in research on eating disorders

    Mr. Porter. NIMH has been supporting a longitudinal study 
of anorexia and bulimia for the last nine years. What have you 
learned from this study and can you give us at least some of 
the highlights?
    Dr. Hyman. We have learned--and I think it is an important 
finding--that anorexia and bulimia, once thought to be entirely 
distinct, are actually not so distinct; that is, many women--
and it is largely women--who start out with anorexia nervosa 
may actually develop bulimia later in life. Now, as dire as 
that sounds, indeed, it turns out that bulimia is more 
treatable, and this may actually be a step toward recovery.
    We know from this longitudinal study, actually, that 
anorexia nervosa is often a chronic disease with a lifetime 10 
percent mortality. We really do not have ideal treatments for 
anorexia nervosa.
    In research on bulimia, on the other hand, we have found 
that the SSRIs, the Prozac-like antidepressants, plus 
psychotherapy really have a marked effect on improving the 
outcome, on both binging and purging and also a person's self-
concept.
    I would say that eating disorders, in general, is an area 
where we should encourage additional research. I would point 
out that a great deal just has been learned about the biology 
of satiety with the discovery of molecules that act in the 
brain, such as leptin and, are produced by fat cells. These 
molecules, their brain receptors, and many other novel leads 
are key to understanding satiety.
    I think it is time, with modern tools, to revisit these 
very problematic and morbid clinical disorders.
    Mr. Porter. You mentioned Prozac. What is the status of the 
study on the effectiveness of St. John's Wort as an alternative 
treatment for depression? What would be the advantage of St. 
John's Wort over other commonly prescribed antidepressants such 
as Prozac?
    Dr. Hyman. Well, all medications come with side effects, 
and different people have different side-effects. One person 
can tolerate one medication and not another.
    St. John's Wort, which we do not yet know to be efficacious 
has had very few side-effects in European trials. So, if indeed 
it turned out to be efficacious, it would be a wonderful 
addition to the armamentarium. Indeed, some people who are 
currently on one kind of antidepressant who have difficult side 
effects might want to switch.
    Now, the issue is we do not know whether it is efficacious. 
As you know, we have embarked on a three-year clinical trial 
comparing St. John's Wort to placebo, but also to a standard 
Prozac-like antidepressant, specifically Zoloft. We feel we 
need to do this because the European studies, which point to 
the possibility that St. John's Wort may be very helpful, were 
rather short-term and, also, enrolled people who were very 
mildly depressed. We really want to study people who are more 
seriously depressed.
    The coordinating center for this trial is an excellent 
group at Duke University. The trial is underway and will take 
about three years, as I mentioned, for patient enrollment.
    Mr. Porter. We will have the staff make a note for three 
years from now.
    Dr. Hyman. Absolutely. [Laughter.]
    I think the newspapers will remind us. They are very 
interested.

                       behavioral clinical trials

    Mr. Porter. The management of certain diseases such as 
diabetes and congenital heart disease can cause significant 
psychological problems for children and young adults. Is NIMH 
conducting research in this area?
    Dr. Hyman. Yes, we are. We have a very substantial 
developmental psychology portfolio, and we have a great deal of 
research aimed at developing ways to help young people, but 
also caregivers, cope with stress. What I think we are lacking, 
however, is research that is the equivalent of a clinical 
trial; that is, asking whether the behavioral approaches that 
we might use to help people cope with stress are truly 
efficacious in broad populations.
    Now, these kinds of behavioral clinical trials are 
certainly more than possible as illustrated by our AIDS 
behavioral prevention portfolio, and I think that would be an 
important area to pursue.
    Mr. Porter. The National Advisory Mental Health Council 
Work Group on Mental Disorders Prevention Research was 
scheduled to release its report on the status of NIMH 
prevention research, along with the recommendations for future 
research directions. What were the findings and recommendations 
of this group and do you agree with what they reported?
    Dr. Hyman. There was an extraordinary array of 
recommendations. I want to give you what I think is the 
intellectual highlight, which I find very gratifying.
    Prevention of an infectious disease is very different from 
prevention of a mental disorder. For an infectious disease, for 
example, you can give a vaccination. We cannot vaccinate people 
against schizophrenia or depression or manic depressive 
illness. Rather we have to understand these illnesses as 
affecting the whole life course.
    So, for us, prevention is not simply a matter of primary 
prevention, but, in a broad public health sense, decreasing 
prevalence, incidence and, above all, disability. What this 
panel did is expanded the definition of prevention for our 
portfolio to include prevention of relapses, which are common 
in all of these diseases and prevention of disability, and it 
has given, I think, a new and healthy public health focus to 
our prevention portfolio.
    Indeed, it has made it relevant to serious mental illness. 
Previously, given the lack of knowledge and inability to do 
primary prevention for mental illnesses, the portfolio studied 
important problems, but not actually diseases like 
schizophrenia or depression.

        Dissemination of Research Results and Science Education

    Mr. Porter. Dr. Hyman, this was, I think, just before your 
watch began, but often research projects sound strange to the 
public ear. There have been groups that have criticized some of 
the research that NIMH particularly was doing, saying that it 
was a waste of public funds.
    Now, Prime Time Live did a report on this and said that was 
not true; that they were very important research findings. What 
are you doing to educate the public that the work you do is of 
very great significance and importance to them?
    Dr. Hyman. We do have very substantial public education 
campaigns on mental disorders; in particular, on depression and 
on anxiety disorders that have been useful to broad groups of 
people, both consumers, providers, but also, interestingly, 
employers.
    This is something of a problem for us. Much of our public 
education campaign is in this so-called RMS budget, and we feel 
that, in prioritizing this money, the most important thing we 
can do is to destigmatize mental illness and get mental illness 
understood to be treatable brain disorders.
    What we have not done adequately is to talk about the basic 
science, which is exactly what was attacked. As I remember, one 
of the things that was attacked was research on bird song. Now, 
what could bird song possibly have to do with mental illness or 
the human brain?
    Well, it turns out that song birds are the only higher 
species that actually reproduce new neurons, new nerve cells on 
a regular basis in their brains. Thus, it is the premier model 
for studying the production of, in this case, a whole new 
organ.
    Now, interestingly, there is recent evidence in primates 
and rodents of new nerve cells being born, but nothing like the 
concomitant development of organization there is in these song 
birds. So, in fact, it is rather simple to explain, but we are 
in a difficult position in terms of explaining things like that 
proactively.

           How NIH Educates the Public About Medical Science

    Mr. Porter. Dr. Varmus, beginning three years ago we talked 
about the need for NIH, in general, not to thwart negative 
things or things that people think are negative, but to put out 
a positive message of what is being achieved in respect to the 
investment of public dollars in biomedical research. Can you 
describe for the subcommittee what you are doing in that area, 
generally.
    Dr. Varmus. As you know, Mr. Porter, the amount of money we 
can devote to these issues is not as large as I would like.
    We do have a public education program that spends something 
on the order of $150,000,000 a year. Of course, that addresses 
a large number of problems, not simply advertising the 
usefulness of what we do, but actually describing the results, 
so they are available to health care providers and to patients.
    I think one of our most effective means of talking about 
research is through our appearances on television and through 
newspapers. Many of our Institutes have been featured in 
stories in papers. For example, the Aging Institute [NIA] was 
featured this week in a discussion of perimenopause syndrome in 
the Washington Post. The Mental Health Institute [NIMH] has 
been featured in a number of major publications.
    You heard yesterday about the way in which the National 
Library of Medicine's work has appeared on E.R. Dr. Leshner was 
very modest this morning and neglected to point out his own 
involvement in guiding E.R. in their display of drug addiction 
in a current series of episodes.
    That does not directly address the NIH efforts, and I think 
the problem we face there is we try to take advantage of the 
news media, which has a large audience, to display our wares. 
They, of course, are looking for news, not so much seeking to 
be vehicles for advertising what the NIH, as a Government 
Agency, does.
    Mr. Porter. That is true. But on the other hand, there is a 
response mode and an initiative mode and, to the extent that 
you can initiate something that they would find is of great 
interest to the public at large, I think you have a ready 
resource available to you.
    Dr. Varmus. Well, we do, and we have taken advantage of 
that to a much more appreciable extent in the last couple of 
years. The director of our Communications Office, for example, 
is putting out weekly or monthly announcements of NIH research 
that appears in journals. The journals, themselves, are 
advertising that research.
    I think the average reader of a newspaper is seeing an 
increasing number of articles about our science. Now, I think 
there are potential pitfalls there. One has to be careful that 
we do not over-advertise and we do not make claims that would 
be excessive in the interest of getting news for our Agency.
    One of the most effective ways for us to be portrayed is 
through a kind of article that does not all that frequently 
appear in the newspaper, but we try to encourage reporters to 
cover it, and that is a story about a scientist at work. The 
New York Times sometimes does this. But the human interest of a 
young scientist or a middle-aged scientist, actually, engaged 
in bench activities for the good of humankind is a story that 
can be interesting.
    Mr. Porter. I agree with that. There are news articles and 
then there are feature articles. There are articles that are 
written by reporters, and there are articles that are written 
by publicists and picked up by publications that do features in 
some depth on what NIMH does or how they go about doing it.
    I think, to the extent that you can initiate features that 
give people some insights as to what NIH is all about, I think 
that is all to the good.
    Now, a year or two ago we had a public television series 
that was being considered. Can you tell us what happened there 
or what is happening there?
    Dr. Varmus. Yes. That show does exist. It is called Health 
Week, and I believe it is still being run out of the Baltimore 
station of public television as a weekly show. It does not have 
a primarily NIH purpose. It talks about health advances, and 
some of us are advisers to the show. Some weeks the show does 
report NIH-supported research, but most weeks it simply reports 
advances in health.
    Mr. Porter. And that is Maryland Public Television, right? 
It is not picked up in----
    Dr. Varmus. Oh, it is many stations. I could find out for 
you.
    Mr. Porter. It is run outside----
    Dr. Varmus. We can find out for you how many of the 
affiliates have picked it up, but I believe it is quite a few.
    Mr. Porter. I should know this, but I do not have time to 
watch television.
    Dr. Varmus. We are in a similar position, Mr. Porter.
    Mr. Porter. Mrs. Lowey.
    Mrs. Lowey. Thank you, Mr. Chairman.
    I do not watch too much television either, but I have a 
feeling that showing the scientists at work would not be quite 
as compelling to viewers as talking about St. John's Wort or 
ginkgo.
    I had a wonderful meeting with Dr. Kirschstein and some 
other people previously because right now, as we are saying, 
the health food stores and E.R. are really providing consumers 
with their information and health care.
    So, to the extent to which you could get the public 
involved by providing information that would directly affect 
their lives----
    Dr. Varmus. The St. John's Wort story actually has appeared 
in many newspapers, including----
    Mrs. Lowey. Right, that absolutely.
    Dr. Varmus. Including extensive descriptions of the study 
that Dr. Hyman's Institute is conducting.
    Mrs. Lowey. Great.
    Dr. Varmus. So that has gotten a lot of publicity, and I 
assume it will help accrual of patients and move the study 
along.

          Multiple Audiences for Science and Health Education

    Mrs. Lowey. In fact, I had a meeting in my district 
recently on eating disorders. The Chairman mentioned anorexia 
nervosa, and the sad stories that we heard were really 
extraordinary. What I have found from following up with these 
cases, whether it was the young girl who was a gymnast and she 
thought the most important thing in the world was to stay thin, 
and the tragedies of the parents who had no idea what was 
happening or the coach who had no idea what was happening.
    So I think the question that we were talking about before, 
and I feel very strongly about, is what are the connections 
that are made between the research that is being done, and the 
public health service--the dissemination of this information. I 
just think it is vital, whether it is on television, that we 
just have to get that information out.
    Anorexia nervosa was a perfect case, where they felt if 
only they had known.
    Dr. Hyman. I think you have actually hit on a very 
interesting and troublesome area. In some sense, we need to 
educate ballet instructors, gymnastics instructors, athletic 
coaches about the risks to young women, especially, but also to 
young men, about losing that extra three pounds to do this, 
that, and the other thing.
    I have to tell you, though, that this is an area where 
prevention programs, well-meaning, have sometimes backfired; 
that is, there was a prevention program at a major leading 
university for bulimia which, actually, when studied--it was 
sort of an educational program--increased the incidence of 
bulimia.
    So we, basically, have to be not only getting the news out, 
but we also have to study who the targets are and how to do it.

       Research to ensure the Safety Of Medications for Children

    Mrs. Lowey. I asked a question before about the research on 
children and the critical necessity, in my judgment, of being 
able to identify those children who are at risk earlier.
    In a related question concerning psychiatric medication on 
children, it is my understanding that the medication used for 
children is, essentially, the same as that used for adults. Is 
there research that is supporting medication specifically for 
children?
    Dr. Hyman. Yes, but it is really very inadequate research 
at this point. One of the things that I have been struggling 
with--and this is, in some sense, different from the answer I 
gave you before about epidemiology--is the need to recruit 
people into the field of childhood treatment. A director ought 
to be competing to lure the very best investigators to these 
problems.
    I believe that actually, there, are not enough child 
psychiatrists. We need to build that area. But, at the same 
time, I would like to lure some adult psychiatrists, some 
pediatricians, some pediatric neurologists into this area.
    It was only in the last calendar year, and you may have 
seen it in my written testimony, that we had a really well-
designed trial showing that Prozac actually works to treat 
depression in young people.
    One troubling finding, however, is that it did not work 
quite as well as it works in adults. We already know that the 
older tricyclic compounds do not work particularly well at all 
in children. So we really need to enhance both the development 
of treatments and clinical trials.
    Now, I should tell you that just to stimulate this, we have 
issued a request for applications in the area of pediatric 
clinical trials. But, across NIH, we need to make a stable 
long-term investment in building this field, making it an 
important and attractive career in order to serve children 
well.

    Protecting Clinical Research in the Evolving Health Care System

    Mrs. Lowey. I think that is a very important answer to a 
question that I was about to ask. So I really thank you because 
this has been my concern, as you know. I have a strong interest 
in developing more clinical research, and you have pretty much 
answered it.
    But if there is anything you want to add in addition to the 
importance of clinical research to the field of mental health 
and, essentially, what you are doing to increase clinical 
research at the NIMH, and is there any way that Congress can 
assist you in attracting new individuals to this field?
    Because Dr. Leshner, in fact, this morning commented on 
that, and I would be interested to know what you are doing to 
recruit new, talented researchers.
    Dr. Hyman. Yes. Well, certainly, NIH, as a whole, under Dr. 
Varmus' leadership has just been working on new training 
vehicles, and I recall that you asked about them when he gave 
his testimony and, indeed, this represents a real increment in 
our training awards----
    Mrs. Lowey. You had a feeling I would be asking that.
    Dr. Hyman. Yes. But I think I have already, in some sense, 
said the most important thing. It is a place where you do play 
a role. Clinical researchers now, to some degree, are 
demoralized. Managed care has squeezed all of the discretionary 
funds out of clinical departments. NIH cannot possibly fill 
that gap.
    I think one of the critical things that young people need 
to understand is that there will be a stable investment in 
their future; that is, that if they choose now to go into 
acareer in clinical research, NIH will not simply be supporting them 
maybe for one year or two years, but that, together, we intend to 
maintain a long-term vision about the health and vigor of clinical 
research. I think there is no more important message, and I think it is 
one that you all have given in a way that is often more credible and 
stronger than we can do.

        contribution of neurobiology to panic/anxiety treatment

    Mrs. Lowey. Lastly, if I have time, because I know my 
colleague has just arrived, I was particularly interested in 
your testimony concerning agoraphobia because it is so 
widespread, and it is so debilitating, and so many people 
really cannot function as a result of it.
    You are saying there information processing events occur 
and the mechanism by which they are--may permit us to develop 
highly targeted treatments--and you are connecting it to 
depression, and anxiety----
    Dr. Hyman. Yes.
    Mrs. Lowey. And I am sure you can give us some additional 
information. But if you can just give us some comments.
    Dr. Hyman. Yes. Very briefly, we actually have fairly 
reasonable treatments for panic disorder with agoraphobia. 
These are Prozac-like antidepressants, plus behavioral 
psychotherapies, which literally slowly expose people to their 
phobic stimuli. If you have abolished the panic attacks, now 
they can go to a place where they used to experience panic 
attacks. The panic attack does not occur and slowly they can 
increase the breadth of their lives.
    But there are many people who are treatment refractory. 
Understanding the pathways in the brain that underlie these 
disorders will allow us to not rely on luck or variations on 
old themes, but really to develop novel and really focused 
treatments.
    And the really wonderful thing about this research is these 
are not only pharmacologic treatments, but they are potentially 
also behavioral treatments.
    Mrs. Lowey. I thank you. Thank you, Mr. Chairman.
    Mr. Porter. Thank you, Mrs. Lowey.
    Mr. Stokes.
    Mr. Stokes. Thank you, Mr. Chairman. Dr. Hyman, nice to see 
you.
    Dr. Hyman. Nice to see you.

         co-occurrence of mental and general medical illnesses

    Mr. Stokes. Thank you.
    Doctor, it is often said that if we would address patients' 
mental health problems on the front end that this would 
dramatically reduce compromising physical health conditions. 
What is your position on this relationship?
    Dr. Hyman. I think, Mr. Stokes, that this is a really 
critical relationship.
    There was last year a spate of reports, for example, that 
showed that after cigarette smoking and treatment of 
hypertension the leading modifiable risk factor for coronary 
artery disease and, indeed, for heart attacks--myocardial 
infarctions--was depression and that the major risk of 
reinfarction, again, after somebody had had a first heart 
attack, was depression.
    This is just a symbol of the way in which our stress 
systems, our minds, our mental health are intimately and 
inseparably connected with the body. I could go on, but I think 
it is----

              health status of under-privileged minorities

    Mr. Stokes. Sure. I think you have answered, with respect 
to my question, what I was trying to get on the record.
    Let me ask you, in terms of children's mental health, and I 
noticed in your formal testimony that you talked about it a 
little bit, but I would like to ask you what the extent is of 
mental conditions in children and across racial ethnic 
populations?
    Dr. Hyman. We are currently engaged in studies to refine 
our understanding--there are a whole variety of statistics--but 
we believe that, perhaps, 10 percent to 20 percent of children 
have, at some time, mental conditions that actually interfere 
with their ability to form normal peer relationships or to do 
well at school.
    The actual rates of mental disorders are not different 
between minority populations, including underprivileged 
minorities, and the remainder of society, but often the access 
to early diagnosis and treatment is quite different.
    One of our major concerns is--and I know this has come up 
previously in testimony--is the gap in health status between 
underprivileged minorities and the rest of our society.
    We are hoping to undertake a series of longitudinal studies 
in both minority and in nonminority populations in order to 
understand those differences in health status in a way that 
will make them addressable.
    In the meantime, I am happy to say we are funding a number 
of minority research centers. This year we have just begun 
funding James Jackson at the University of Michigan and 
Margaret Spencer at the University of Pennsylvania, both 
studying African Americans and looking at the specific factors 
having to do with illness and, interestingly, with resilience 
in minority populations.
    I just have to say people often are only looking at risk 
and never looking at the social and cultural sources of 
strength, and both of these centers are addressing not only 
risk, but also the strengths conferred by their communities.
    Mr. Stokes. I am glad to know that you are looking at that 
because those who are sociologically disadvantaged are the ones 
who often times get their hospital care in emergency rooms, as 
opposed to doctors' offices.
    Dr. Hyman. That is right.
    Mr. Stokes. I think we are talking about that category.
    Dr. Hyman. Absolutely. We know, tragically, that in primary 
care settings--we do not know about emergency rooms--but in 
primary care settings the likelihood of a child having an 
appropriate diagnosis, for example, of depression is only one 
in five, and this is where issues of public education really 
come to the fore, as well as additional research.

        nimh efforts to reduce stigmatization of mental Illness

    Mr. Stokes. In that very same vein, I would just like to 
ask you this: Because of the negative stigma that is still 
associated with the label ``mentally ill,'' children's mental 
health problems, it seems, are often ignored. What is the 
National Institute of Mental Health doing to address this very 
serious problem?
    Dr. Hyman. Yes, sir. I think there are many factors leading 
to it being ignored. I think none is greater than the factors 
of ignorance and stigma. I think that our society really has it 
wrong.
    If a child has appendicitis, the parents will bring the 
child to the doctor. If a child is depressed or if a child is 
starting to fail in school or get in trouble, the parents 
either treat it as simply a lack of will on the part of the 
child or, alternatively and frequently, are too ashamed.They 
feel it reflects something about their parenting and that inhibits 
their willingness to bring the child for medical attention.
    It is very important that we make it understood that a 
child having depression or Attention Deficit Disorder or being 
over-anxious is not a parent's fault. This, just like any other 
illness of any other organ, represents a complex gene 
environment interaction. There is no cause for shame.
    But this is going to take an extraordinary effort to 
educate parents, but also teachers and pediatricians. At the 
same time--and Mrs. Lowey had asked, but at the risk of 
repetition--the research we are now engaging in and really have 
to do is research which will provide easier and better 
diagnostic tools to caregivers and also improve treatments.
    I think doctors tend to recognize things more readily if 
they know they can do something. If they feel helpless, they 
tend sometimes not to make these diagnoses. So I think this is 
a matter of public education, but also a very important matter 
of research, both in diagnosis and in treatment.
    Mr. Stokes. While acknowledging precisely what you are 
saying in terms of your Institute, what are you doing in terms 
of this kind of outreach in order to educate physicians on the 
diagnosis and treatment of mental health problems in children 
as well as the public, parents and others?
    Dr. Hyman. Well, right now we are only in a position to do 
some of that, and we have chosen depression, through our DART/
campaign, and anxiety disorders as our initial targets because 
we think these are very common and very much misunderstood and 
underdiagnosed.
    I would really like to be in a position to be able to 
participate in broader efforts to educate the public in these 
matters.
    One other area where it is really critical and where there 
is a lot of ignorance is within the criminal justice system. I 
mentioned it previously, but a recent New York Times article 
pointed out what we know, which is that 20 percent of children 
and abolescents who are incarcerated have a mental disorder. 
There is really no appropriate or available treatment in those 
circumstances, which condemns these children, I think to having 
no future.
    Mr. Stokes. To what extent, Doctor, is the research that is 
conducted by your Institute designed to also study the social, 
cultural, and environmental factors that are associated with 
these types of disorders?
    Dr. Hyman. These factors are critical, and we do study 
them. To be specific, just, actually, these two minority 
centers I just mentioned--the James Jackson Center and Margaret 
Spencer Center--are perfect examples of treatment research 
centers where cultural and community factors are very much 
taken into account in the pathogenesis and treatment of these 
illnesses.

          linking clinical trials to health services research

    Mr. Stokes. Doctor, to what degree do you utilize clinical 
trials in terms of the work of your Institute?
    Dr. Hyman. I have to say that one of the things that I have 
undertaken in my now merely two years at NIMH is to expand our 
capacity to do clinical trials, but also to change how we do 
them.
    I do not want to launch into a long discussion of clinical 
trial design, but in just a minute, there are trials that have 
a design that are really aimed at the FDA, sort of a regulatory 
design, where everything is very rigorous. But you exclude, for 
example, in a depression trial, any potentially confounding 
subjects who might have heart disease or drink too much 
alcohol.
    The result is that the trial, although it may produce very 
important results, is not really applicable to general 
populations, where there are people with other medical 
disorders or people from minority populations or elderly people 
or young people.
    So we are, in important cases, trying to wed our clinical 
trials program with our health services research program and 
perform trials that not only have this wonderful, crystalline, 
internal validity, but also sort of external validity with 
respect to the real world. This is challenging, it is 
expensive, but I feel that we really must engage in those kinds 
of trials.
    Mr. Stokes. I am glad you took the time to explain it 
because I think it is important for us to understand that sort 
of unique approach you are taking in your clinical trials.
    I hear the bells, so that means my time has expired. Thank 
you very much.
    Dr. Hyman. Thank you very much, Mr. Stokes.
    Mr. Porter. Thank you, Mr. Stokes.
    Dr. Hyman, thank you for the very enlightening testimony 
and answers to our questions that you have given this 
afternoon, and thank you for the wonderful job you are doing at 
NIMH and the wonderful job NIMH is doing within NIH.
    Dr. Hyman. Thank you very much, Mr. Porter, and the 
committee for your support, which makes it a pleasure to do 
these things.
    Mr. Porter. Wonderful. Thank you.
    The committee will stand briefly in recess.
    [The following questions were submitted to be answered for 
the record:]


[Pages 2267 - 2353--The official Committee record contains additional material here.]



                                          Thursday, March 19, 1998.

                      NATIONAL INSTITUTE ON AGING

                               WITNESSES

RICHARD J. HODES, DIRECTOR
TERRIE WETLE, DEPUTY DIRECTOR
COLLEEN F. BARROS, EXECUTIVE OFFICER
KARYN S. ROSS, FINANCIAL MANAGER
HAROLD VARMUS, DIRECTOR, NIH
DENNIS P. WILLIAMS, DEPUTY ASSISTANT SECRETARY, BUDGET, DHHS

    Mr. Porter. The subcommittee will come to order. Next we 
welcome Dr. Richard Hodes, the Director of the National 
Institute on Aging. Dr. Hodes, thank you for appearing. We 
would ask that you introduce the individuals that you brought 
with you and proceed to making your statement.

                           Opening Statement

    Dr. Hodes. Thank you, Mr. Porter.
    At the far end of the table is Ms. Colleen Barros, the 
Executive Officer of the Institute; Dr. Terrie Wetle, the 
Institute's Deputy Director; and Ms. Karyn Ross, the Financial 
Manager.
    Mr. Porter, thank you for this opportunity to highlight 
some of the efforts of the National Institute on Aging to 
extend, through research, the quality of life and active years 
of all Americans. Over the past years, a steady and dramatic 
increase in research findings has led to what is now an 
unprecedented opportunity for further investment in discovery 
and research. In the case of aging research, this comes at a 
particularly opportune time, as some 75 million members of the 
baby boom generation approach age 65 over the next 10 to 15 
years.

                            biology of aging

    Basic biology research over the past decade has fueled a 
real revolution in aging research. This progress is illustrated 
in the award over the past year of a Nobel prize in medicine to 
Dr. Stanley Prusiner, a long-time grantee of the National 
Institute on Aging, the National Institute of Neurological 
Disorders and Stroke and other NIH components, for his 
discovery of prions, a new genre of disease-causing agents.
    Over this past year, Dr. Prusiner has elucidated the 
relationship between the structure of prions and the 
transmission of diseases such as kuru and bovine spongiform 
encephalopathy or ``mad cow'' disease, an elucidation which 
will have implications in basic research and also for efforts 
to prevent spread of such diseases.
    Another area of basic scientific discovery has been in 
understanding the processes that regulate the ability of cells 
to divide. One mechanism illustrated on this first poster has 
been that which is mediated by structures called telomeres. 
These are protein DNA complexes that cap the end of all 
chromosomes and that appear to be necessary for maintaining the 
stability of these chromosomes.
    [The information follows:]


[Page 2357--The official Committee record contains additional material here.]



    Dr. Hodes. The nature of DNA replication is such that in 
the absence of any compensatory mechanisms, every time a cell 
divides, every time a chromosome divides, a bit of the end of 
each telomere is lost from the cell. And so, again in the 
absence of any compensatory mechanisms, as cells continue 
through division they reach a point at which telomeres are 
short, cell division is no longer possible, and cells have 
reached a state of what is called senescence.
    Over the past years, discovery has been made of an enzyme 
called telomerase which has the ability to synthesize new 
telomeres and so to compensate for the loss that occurs with 
cell division and DNA replication. In the past year, the 
important achievement was made of cloning the gene, encoding a 
critical component of telomerase, and showing that it could be 
introduced into cells that are nearing the point of senescence. 
As a result of that introduction, cells acquired the ability to 
synthesize telomeres and to continue dividing.
    This very basic and impressive intervention in the 
regulation of cell replicative capacity is the kind of 
discovery that will have implications both for basic research 
and for its applications. These unprecedented scientific 
opportunities extend, as well, to disease-targeted research.

                          alzheimer's disease

    Alzheimer's disease remains the most common cause of 
dementia in older Americans, afflicting some 4 million 
Americans, their families, caregivers and society with 
disastrous and profound consequences. Over the past years, 
fortunately, there has been translation of genetic 
identification of risk factors, and of the mechanism of action 
of gene products in the generation of disease. Most recently 
the creation of animal models has occurred by introducing 
Alzheimer's related genes into mice, reproducing some of the 
pathologic and behavioral defects in these animals, and 
creating for the first time a chance to useanimal modeling to 
understand the disease and the design interventions.
    Perhaps of most immediate importance to those suffering 
from or at risk for Alzheimer's disease are the opportunities 
in the area of clinical intervention in disease, involving a 
number of strong candidates for clinical trials. The results 
shown in this poster are the outcomes of one clinical trial 
completed and reported in the New England Journal of Medicine 
this past year, which looked at the effect of one class of 
compounds, antioxidants--vitamin E and selegiline--treating 
patients who had mild or moderate Alzheimer's. The line in 
blue, representing those individuals who received placebo, a 
noneffective treatment, showed that in 440 days on average 
individuals with this disease progressed to the point of losing 
their ability to sustain independence or of requiring 
institutionalization, and that the use of drugs, in this case 
selegiline or vitamin E, was capable of inducing a modest but 
nonetheless significant prolongation of quality of life before 
those end points were reached at 655 or 670 days.
    [The information follows:]


[Page 2359--The official Committee record contains additional material here.]



    Dr. Hodes. This important progress in delaying the 
progression of symptoms in individuals with Alzheimer's will 
now lead to design of studies which for the first time will 
attempt to treat individuals before they have a diagnosis of 
Alzheimer's disease; that is, to treat individuals at high risk 
and attempt to prevent or delay onsets of disease.
    Two additional lines of epidemiologic evidence have pointed 
to additional candidates for intervention trials. On the left 
is the outcome of a study carried out in the intramural program 
of the National Institute on Aging. A 15-year-old longitudinal 
study, part of the Baltimore Longitudinal Study of Aging, found 
that those individuals who had a history of taking NSAIDs, or 
non-steroidal anti-inflammatory drugs, such as ibuprofen had a 
dramatic 50 percent decrease in the prevalence of Alzheimer's 
disease.
    [The information follows:]


[Page 2361--The official Committee record contains additional material here.]



    Dr. Hodes. Similarly, on the right, the results of another 
study also carried out as a part of the Baltimore Longitudinal 
Study on Aging, and matched by additional studies supported by 
NIA in extramural institutions, demonstrated that women who had 
a history of postmenopausal use of estrogen had an even more 
striking, that is, somewhat more than 50 percent decrease in 
the prevalence of Alzheimer's disease.
    Now it should be stressed that these are epidemiologic, or 
associative, studies as opposed to direct medical trials. 
However, they will lead most surely to clinical studies that 
directly test the hypotheses that these drugs are capable of 
slowing the onset or progression of disease.

                    reducing disease and disability

    As we succeed in extending the life span, we must continue 
to look for interventions to prevent morbidity and disability, 
from a variety of the common causes of disease and mortality in 
older Americans, including cardiovascular disease, cancer, 
diabetes, and osteoporosis.
    An example of clinical studies already ongoing in this area 
is shown here, a study carried out collaboratively between the 
National Institute on Aging and the National Heart, Lung and 
Blood Institute, attempting to reduce disease by treating 
individuals with hypertension, in this case isolated systolic 
hypertension. Treatment in this case was with a low-cost and 
relatively well tolerated drug, a low dose diuretic.
    [The information follows:]



[Page 2363--The official Committee record contains additional material here.]




    Dr. Hodes. In 1991 early observations from this study 
indicated there was a significant decrease in stroke as a 
result of treatment. Now in this past year still more 
encouraging results were reported, an analysis demonstrating a 
decrease of 50 percent overall in heart failure, which has come 
to be a leading cause of hospitalization and death among older 
men and women.
    Even more striking, for those individuals with a prior 
history of heart failure, therefore at still greater risk for 
congestive heart failure, there is an 80 percent decrease in 
congestive heart failure in this population. This study, too, 
now will lead to further studies to understand the mechanisms 
of these effects and the design of even more effective 
interventions and treatments.

                     behavioral and social research

    The use of behavioral and social research tools is also an 
important part of the Institute's portfolio and provides an 
important means for enabling individuals to maintain the 
quality of both physical and cognitive life. NIA, for example, 
supports the development of strategies for promoting long-term 
health behaviors that will decrease risks of disability and 
disease.
    There has recently been established a program of centers, 
established jointly by the National Institute on Aging and the 
Office of Research on Minority Health, to better understand the 
specific problems of minority elder populations and to address 
them. Cognitive research is being carried out to both 
understand and modify cognitive function in older individuals, 
and this year will see the initiation of a novel intervention 
study, a clinical trial designed to examine the ability of 
interventions to promote cognitive function in older Americans.
    Mr. Chairman, members of the committee, NIA looks forward 
to continuing its efforts and commitment to maintaining the 
quality of life in older Americans. The proposed President's 
Budget for fiscal 1999 is $556,070,000. I would be happy to 
address any questions that you might have.
    [The prepared statement follows:]


[Pages 2365 - 2370--The official Committee record contains additional material here.]



                          alzheimer's disease

    Mr. Porter. Thank you, Dr. Hodes.
    Can we go back to the chart that depicts vitamin E and 
selegiline?
    Dr. Hodes. Yes.
    Mr. Porter. Now does selegiline have any relationship to 
selenium?
    Dr. Hodes. No. Selegiline is a drug with anti-oxidant 
properties that has also been used in treatment, for example, 
of Parkinson's disease. It is a prescription drug, in important 
contrast to vitamin E, which, as we all know, is among those 
agents which are freely available.
    Mr. Porter. There was some thought in the popular press 
that selenium had something to do with preventing the onset of 
Alzheimer's disease. Has that ever been tested?
    Dr. Hodes. There have been no positive data confirmed, 
certainly to my knowledge, of the role of selenium. Similarly, 
there was a proposal that aluminum played a role, and there 
were people very much concerned about that.
    Mr. Porter. That was a negative role, though.
    Dr. Hodes. Yes. But these trace elements, although they 
have been proposed to have a role, have not been rigorously 
established in epidemiologic or intervention studies.
    Mr. Porter. Now looking at the chart, I suppose it is not 
possible or maybe it is, but can you conclude from the chart 
that taking vitamin E might help to prevent the onset of 
Alzheimer's disease? This is a treatment rather than a 
prevention, correct?
    Dr. Hodes. Yes, correct. Your question is an extremely 
important one. Alzheimer's disease, by the time that symptoms 
have occurred, is associated with anatomic lesions on the brain 
and death of nerve cells, which make it particularly difficult 
to envision treatment that will reverse or prevent serious 
symptoms. The initial trials of most agents are of necessity 
carried out in patients with mild forms of the disease to see 
whether progression can be arrested.
    Because the effects at a later stage in disease are so 
difficult to achieve, there is hope and hypothesis that the 
same treatments which have even modest effects in progression 
of already established disease, may be effective, if instituted 
at a stage before symptoms have appeared, in preventing disease 
in process.
    That is the kind of study which will be novel in the 
history of Alzheimer's disease therapy, and that is now being 
planned. Individuals who have demonstrated high risk of 
developing Alzheimer's disease but, who do not have the disease 
diagnosed, will be the subjects in a clinical trial which will 
compare, for example, vitamin E against a control.
    Mr. Porter. Since vitamin E is something you can get from 
food, how do you find a proper placebo, since people may be 
ingesting it outside the capsule form?
    Dr. Hodes. That is a very important point in design of the 
studies. The doses which appear to be effective are at a level 
which are far in excess of what practically can be achieved by 
normal dietary intake.
    Mr. Porter. What sort of doses?
    Dr. Hodes. In the range of 800, 1,000 and 2,000 units per 
day. However, although these are nearly impossible to achieve 
through diet, they are not so uncommon in the vitamin 
supplementation of a large portion of the population. 
Increasingly, in studies of this sort, it does become a 
challenge to attempt to carry out responsible studies in the 
face of what at times is public consumption of agents of not 
yet rigorously demonstrated efficacy. That, indeed, will be a 
challenge in construction of this study, but one which pilot 
studies indicate can be met, meaning a population can be 
identified as a control which will not be using vitamin E in 
anything near the hypothesized therapeutic levels.

                               depression

    Mr. Porter. Depression is said to be a very serious problem 
of aging. Do you work with Dr. Hyman, or do you have studies of 
your own underway dealing with depression as relates to aging?
    Dr. Hodes. The studies of depression in aging are 
predominantly carried out by the National Institute of Mental 
Health, with whom we work very closely. Your question provides 
an opportunity to emphasize the importance of that kind of 
cooperation across institutes.
    In the Alzheimer's area, for the past three years, research 
at NIH has been carried out with very effective cooperation 
across institutes. This past week was the most recent meeting 
of Steve Hyman and myself and the directors of the National 
Institute of Neurological Disorders and Stroke and the National 
Institute of Nursing Research, who regularly meet to coordinate 
our efforts in areas of common interest, e.g., Alzheimer's 
disease, neuro- degenerative diseases, and depression in the 
elderly.

                           nasa collaboration

    Mr. Porter. Senator Glenn is going to go back into space 
this fall. Have you or your Institute been involved in 
preparing for that? Is there anything we can discover about the 
aging process resulting from his next mission?
    Dr. Hodes. The National Institute on Aging and many 
institutes at NIH have had a longstanding and ongoing 
collaboration with NASA. On the mission in which Senator Glenn 
is now scheduled to fly, there are several scientificstudies 
that have been planned long prior to identification of crew members, as 
a result of common interests of NASA and the National Institute on 
Aging.
    These include, for example, a study of the use of melatonin 
and effects on circadian rhythm and sleep. Sleep disorders are 
a common problem in the elderly, also clearly a problem in 
astronauts whose circadian cycles are very much perturbed by 
the in-orbit day-night cycles. This is the kind of research 
which we are carrying out jointly. It is one study in which 
Senator Glenn, together with other crewmen, will be 
participating.
    Senator Glenn has been particularly interested in exploring 
potential common scientific interests of NASA and of NIA as 
they reflect on problems of aging and those of space flight, as 
the example I just mentioned of circadian rhythm disturbances 
and sleep. Others include vestibular problems and balance 
disorders, also in astronauts and in the elderly; bone 
resorption as a result of weightlessness and prolonged flight, 
again with a relationship to bone loss and osteoporosis in the 
elderly.
    These are some examples of the scientific areas of 
interaction between these two fields of science, and they have 
been the grounds for joint funding and reviewing of scientific 
projects.

                          parkinson's disease

    Mr. Porter. Dr. Varmus, you may want to comment on this, as 
well.
    Morton Kondracke has been a very, very strong proponent for 
additional spending on Parkinson's disease, and Dr. Varmus, you 
were present as the Master of Ceremonies when he was recently 
honored for his advocacy in that regard. He pointed out on the 
Today Show this morning that NIH spends only about $30 per year 
per Parkinson patient, versus $2,000 per year per AIDS patient. 
How do you respond to this criticism that is made? Dr. Hodes 
first, and then Dr. Varmus.
    Dr. Hodes. The majority of research support for Parkinson's 
research is, of course, carried out through the National 
Institute of Neurological Disorders and Stroke. It is one of 
the neuro- degenerative diseases in which our multiple 
institutes are working cooperatively.
    Certainly I am happy to defer to Dr. Varmus----
    [Laughter.]
    Dr. Hodes [continuing]. But there is a large body of the 
research carried out, for example, in support of Alzheimer's 
disease, as another neurodegenerative disease, which crosses 
the boundaries of disease specificity and which serves the 
common research base for these multiple diseases. I think we 
attempt to use a strong structure of basic research to support 
related disease-targeted research, and that indeed we are 
driven primarily in our scientific planning, within NIA and 
NIH-wide, by the search for scientific opportunity and the 
allocation of resources accordingly.
    Dr. Varmus. We recognize Mort Kondracke's special interest 
in Parkinson's but we also appreciate his advocacy for the work 
done by NIH in general and his interest in ensuring that we 
have the resources we need throughout the NIH.
    With respect to the funding of Parkinson's research, as you 
know, I prefer to look at this as a major challenge for medical 
research, not to carry out a comparison disease-by-disease, but 
instead to say, what is there we can do in addition to what we 
are already doing to help patients with Parkinson's disease?
    Indeed, the advocacy that Morton and his colleagues 
represent has been a stimulus to some of the work you have 
heard presented by Dr. Collins and you will hear further 
presented when Dr. Penn testifies next week: that is, the 
identification of a gene that is mutated in certain Italian and 
Greek families that have familial Parkinson's disease, a gene 
that encodes a protein that appears to be a major component of 
one of the classical histopathological features of the disease, 
namely Lewy bodies. We think this is one of the great clues 
that has emerged in Parkinson's research.
    In addition, there are many other ways in which Parkinson's 
research is being furthered by discoveries that have been made 
in allied fields. Of course, as is always the case, the numbers 
that represent the amount we spend on this disease are subject 
to discussion, depending on whether one narrowly focuses on 
that money which is explicitly devoted to studies of treatment 
of Parkinson's disease as opposed to studies of dopamine and 
dopamine-producing cells and the metabolism of dopamine. Then 
the amount becomes larger.
    Furthermore, we are learning that this is a disease like 
many others with respect to the way in which nerve cells die. 
Research in many allied fields is having a very salutary effect 
upon our approach to this disease.
    Mr. Porter. Am I right or wrong that Parkinson's is 
considered a disease of aging? It generally strikes older 
people, although it can strike younger people. Is that correct?
    Dr. Hodes. Yes, exactly. It is a disease that has a very 
strong age-related increase in risk.
    Dr. Varmus. But it is fair to say that not all patients who 
have the disorder are aged. In fact, many of us have friends in 
their forties and fifties who have the disease and----
    Mr. Porter. Such as Morton's wife.
    Dr. Varmus. Yes, and when the disease occurs in families it 
is particularly likely to occur at an early age.

                          alzheimer's disease

    Mr. Porter. Mr. Stokes.
    Mr. Stokes. Thank you, Mr. Chairman. Dr. Hodes, nice to see 
you.
    First, what form does selegiline come in? How is that 
administered to patients?
    Dr. Hodes. A pill.
    Mr. Stokes. That is also a pill? I see. And that is only 
utilized for those who have had some diagnosis with reference 
to Alzheimer's?
    Dr. Hodes. This study was reported just this past year and 
is the first study showing effectiveness. As is typical under 
some circumstances, there is caution as yet in generalizing as 
to whether this now should achieve status as a general therapy. 
Rather than award that status as yet, from a research 
perspective we think this is now strong impetus to confirm and 
extend the finding. It has not yet----
    Mr. Stokes. Had a clinical trial.
    Dr. Hodes. Precisely.
    Mr. Stokes. Right. Okay. According to your opening 
statement, we are facing a century with 75 million baby boomers 
who will turn 65 years of age. It is specifically this 
magnitude that causes a number of health providers to suggest 
that the study of Alzheimer's disease should be the Nation's 
highest priority.
    In your professional judgment, are we doing enough inthis 
area of research, and if not, what specific research should we be doing 
in this area?
    Dr. Hodes. I think the area of Alzheimer's research, as I 
illustrated in my remarks and testimony, has seen enormous 
progress, but that very progress has now created opportunities 
of a magnitude that far exceed what has existed before. Yes, I 
think we could wisely invest increased amounts of resources to 
fund research in Alzheimer's disease.
    The spectrum of areas that need further investment now 
include clinical trials of the sort that I mentioned, which are 
critical and clearly expensive. It also involves, however, a 
need to continue the basic science studies that have led us to 
the verge of these clinical opportunities.
    And it is perhaps worth pointing out that some of the most 
dramatic successes, the research findings in Alzheimer's, have 
come from a broad base of research, the outcome of which was 
unanticipated. For example, the identification of 
apolipoprotein E as a genetic polymorphism and a strong risk 
factor was facilitated very much by research on cardiovascular 
disease, where this protein that is important in lipid 
transport is most active. Some of the other genes that were 
uncovered as risk factors had previously been studied only in 
worms.
    So we need to continue studying the basic mechanism of what 
determines the life and death of cells in neurodegenerative 
disease, and to understand those basic mechanisms and translate 
them in tandem with our attempts to provide clinical tests to 
new therapies.
    There is also an enormous amount to be gained in the 
epidemiologic area. I commented that two of the drugs being 
tested have received their initial support from epidemiologic 
studies.
    I should point out that perhaps an important exemplar of 
future epidemiologic studies is one reported this past month 
which looked in greater detail than had been done before at 
genetic risk factors and overall risk for Alzheimer's disease 
in populations that were ethnically diverse. In this case 
comparisons involved Caucasian, African American, and Hispanic 
populations. The striking finding from the study was that 
although in Caucasians the well-described increased risk of 
expressing ApoE4 was again observed, ApoE4 was not a risk 
factor of the same magnitude in African Americans or in 
Hispanics. Although the risk of Alzheimer's disease was similar 
in individuals with ApoE4 regardless of their ethnic origin, 
African Americans, for example, who lacked ApoE4, had four 
times a higher risk of Alzheimer's disease than Caucasians who 
did not have the disease.
    So among the opportunities arising are those which come 
from a greater appreciation of the complexity in genetic, 
ethnic, as well as in potentially environmental factors which 
establish risk for Alzheimer's. It is in all these areas that 
NIA and Alzheimer's research would hope to share in increased 
research support NIH-wide.
    Mr. Stokes. And so if I understand your testimony 
correctly, we are not yet at the point where we know how to 
slow the onset of Alzheimer's?
    Dr. Hodes. I think that is a fair statement, in the sense 
that there has been no demonstrated effective intervention 
which will prevent or slow the onset of disease. However, it 
should be pointed out that only now are we for the first time 
prepared to do studies to test that; that only now will we 
begin to do studies in high-risk populations who do not yet 
have the disease to see, by direct clinical testing, whether we 
can prevent onset, indeed an important juncture in Alzheimer's 
research.
    Mr. Stokes. Nor, doctor, do we understand at this point in 
time the causes relative to the disparity that exists between 
African Americans, Hispanics, and the white population in terms 
of the higher existence of the disease in minorities.
    Dr. Hodes. We do not. One kind of epidemiologic data 
pertaining to this question is from an interesting study 
carried out comparing Japanese living in Japan, Japanese 
Americans living in Hawaii, and Caucasians. The evidence from 
this study is that not only are genetics important in the risk 
of Alzheimer's disease, but apparently some environmental 
components are also. That is, there is an apparently lower 
incidence of Alzheimer's disease in Japanese living in Japan 
than there is in Japanese Americans living in Hawaii.
    This simply points out that there are environmental factors 
to be identified. Their identification has not yet occurred.

                 baltimore longitudinal study on aging

    Mr. Stokes. Doctor, in terms of the Baltimore Longitudinal 
Study on Aging which is now in its 40th year, can you tell us 
anything that may have been learned from that study about the 
impact of Alzheimer's disease on African Americans?
    Dr. Hodes. The data which I showed looking at overall risk 
factor analysis in Alzheimer's was generated from the Baltimore 
Longitudinal Study on Aging. There are as yet, however, no data 
from that study which have looked at the effect of race or 
ethnicity on Alzheimer's disease, and the major reason for that 
is simply that the size of the overall study is limited.
    Currently there is a participation of about 16 percent of 
African Americans in that study, but the total number of 
individuals in the study is around 1,000. Not all of them have 
reached the age at which risk is high for Alzheimer's disease, 
and so that particular study has not yet contributed 
information in that arena.
    But, again, these two demonstrations of reduced prevalence 
of Alzheimer's disease associated with use of anti-inflammatory 
drugs or estrogen do derive from that Baltimore Longitudinal 
Study on Aging. They are not in sufficient numbers to ask 
whether subgroups, such as those of different race or 
ethnicity, have differential risks.

                            clinical trials

    Mr. Stokes. Doctor, you mentioned clinical trials. What is 
the size of your investment in clinical trials?
    Dr. Hodes. The overall clinical trials budget anticipated 
in the next year is approximately $21 million. I should point 
out that over the last two years this will represent increases 
of approximately 13 percent in both years above previous 
investments. Given the kinds of opportunities that I have 
mentioned in the clinical trials arena, we are expanding 
clinical trials at a rate even greater than the overall growth 
of the Institute's budget.
    Mr. Stokes. Do you have any clinical trials that are 
currently unfunded?
    Dr. Hodes. We certainly have trials that are unfunded 
because of judgments of scientific merit. There are, however, a 
number of clinical trials which are under review and being 
considered during this year, which will certainly stress 
theability of funds accessible. We certainly would anticipate, with 
increased budgetary allocations next year and in subsequent years, 
using such resources to take advantage of meritorious clinical trials 
in increased numbers which are currently in hand and which we 
anticipate in future years.
    Mr. Stokes. Do I still have more time?
    Chairman Porter. About a minute.

                           genetics of aging

    Mr. Stokes. Okay. Doctor, according to your opening 
statement, the Institute plans a new initiative to identify 
genes that modulate the rate of aging in humans. This appears 
to be a critical component of the Institute's research 
portfolio. What major activities were already under way in this 
area and how much is included in your Fiscal Year 1999 request 
for the new initiative.
    Dr. Hodes. I should point out briefly the context for these 
studies. Over the past years, there have been some striking 
observations in animal models to indicate the enormous impact 
that genetic differences can have on longevity. Some of the 
most noteworthy have used species such as c. elegans, a 
roundworm, or drosophila, a fruitfly, and have indicated that 
changes in individual genes can even double the life span of 
some of these organisms.
    It is much less clear at present to what degree genetic 
polymorphisms, differences in genetic makeup, contribute to 
overall longevity. We are therefore at an early stage of 
discovery in this area, in which we will be convening some 
major planning meetings this year to provide us with evidence 
of best future direction. These future directions will tie to 
the NIH-wide efforts, including those led by the Genome 
Institute, which is identifying polymorphisms through the whole 
genome, the markers against which we can compare the phenotype, 
the observed characteristics of longevity.
    We are anticipating investments in the overall genetics 
area of approximately $27 million next year. The balance of 
that will be directed to phenotyping, genotyping of human 
populations. How much will need to be done still in subhuman 
species will be determined by the outcomes of some of our 
planning meetings.
    Mr. Stokes. Thank you, Dr. Hodes. Thank you, Mr. Chairman.
    Mr. Porter. Thank you, Mr. Stokes. Ms. Pelosi.

                          alzheimer's disease

    Ms. Pelosi. Thank you, Mr. Chairman.
    Dr. Hodes, Dr. Varmus, all of you, welcome. Thank you for 
your testimony.
    Can we go back to the previous chart? Because I want to 
make sure I am drawing the right conclusion from it. Thank you.
    It looks to me that each of these is more effective than 
taking them in combination. Is that correct?
    Dr. Hodes. That is correct. The numbers for selegiline and 
vitamin E alone are higher than the number for selegiline plus 
vitamin E. When one looks to ask whether any of those 
differences are statistically significant, the answer is no, so 
that it is not clear whether there is any real difference 
between them.
    The conclusion which can be drawn, perhaps most 
importantly, is that there is no evidence that the two together 
are any better than either alone, which was one of the 
hypotheses being tested. This has indicated that in designing 
further studies, there does not appear to be compelling reason 
to use this combination of drugs as opposed to testing one 
alone.
    Ms. Pelosi. And then for the placebo, that is statistically 
significant?
    Dr. Hodes. Yes.
    Ms. Pelosi. How did the placebo work, just----
    Dr. Hodes. The placebo essentially reflects the natural 
history or the course of progression of Alzheimer's disease. 
Presumably people not taking the placebo would have done as 
well as those taking the placebo.
    This is consistent with the natural history of untreated 
Alzheimer's disease as has been observed for some time. A 
progression from the state of diagnosis to the state of 
dependent living has typically followed a time course such as 
shown in the placebo group here.
    Ms. Pelosi. Our Chairman has enabled us to hear the stories 
of many families from across the country, very sad stories to 
tell of how they are affected by illness, but I don't think I 
ever was as struck or surprised as the day we had the gentleman 
with Alzheimer's who was about 45 years old. He was here with 
his wife, and their children were college age. He was the 
breadwinner, and now he was--his wife was doing everything for 
him, really. But he did attend.
    How prevalent is Alzheimer's in younger people?
    Dr. Hodes. Approximately 10 or 15 percent of Alzheimer's 
disease falls in a category that can be related to specific 
genetic mutations, and the vast majority, nearly all of 
individuals who will have onset of disease in the age range 
that you were discussing fall into that category.
    The larger category of disease, the remaining 85 or 90 
percent of disease which is not yet associated with single gene 
mutations, has a very much more age-dependent onset. For 
example, in individuals in the age range 65 to 74 there is 
approximately 3 percent prevalence rate of those affected. This 
goes up exponentially with age. Those 85 years and older are 
associated with estimates as high as 47 percent. If one 
extrapolates the aging of the American population without 
change in that kind of prevalence, the magnitude of suffering, 
emotional and social cost is indeed staggering.
    Ms. Pelosi. So that would be very bad news for this 
gentleman's children, as well?
    Dr. Hodes. Each individual case must be diagnosed 
separately, but if his early onset disease is associated with a 
known mutation in one of those genes associated with early 
onset Alzheimer's, sadly, there is a substantial chance of 
inheritance of that gene.
    Ms. Pelosi. And what other reason would there be for 
someone to have Alzheimer's so young?
    Dr. Hodes. It is possible, at the far end of a probability 
scale, that such early onset could occur in the absence of one 
of these familial mutations, though extremely rare.

                         estrogen and vitamin e

    Ms. Pelosi. Interesting, interesting. Well, your report is 
pretty exciting, actually, in terms of slowing--why aren'twe 
all on estrogen and taking vitamin E? Is there a down side? Perhaps not 
for you, but some of us. Is there a down side to it?
    Dr. Hodes. It is a very important and timely question that 
is clearly driving the behavior of many people. Let me answer 
at two levels.
    The first is to emphasize again that the study of those 
agents, estrogen, for example, is based to date on 
epidemiologic data that show an association, but, as yet, no 
direct demonstration by clinical trial of effectiveness. 
Estrogen clearly has potential implications for many important 
aspects of health: cardiovascular disease, cancer risk, and 
others. The possibility that estrogen may play a role in risk 
of Alzheimer's, if confirmed in a clinical study, will become a 
part of this very complex equation and decision for each woman 
of the relative risks and benefits of estrogen.
    In the case of vitamin E, this is a first study, and 
although it was indeed a clinical trial and shows significance, 
it shows a modest effect which clearly needs to be retested 
before acceptance as a generality. We don't know, for example, 
how applicable this advantage will be to a more generalized 
population than that used in this particular study.
    The second level associated with your question of why not 
take it if it might be good, relates to the fact that there are 
reported risks associated with each of these agents, estrogen 
and vitamin E. We work very hard in our public information 
function to inform the public of both what is known but also 
what is not known and may constitute risks about using as yet 
unproven or incompletely characterized agents.

                       information dissemination

    Ms. Pelosi. Well, since you ended on the note of 
information dissemination, I wanted to ask you about your 
research findings on both osteoporosis and osteoarthritis. Can 
you talk a little bit on how valuable research like this is 
disseminated? Are we doing enough to reach seniors with health 
information that could help them lead longer and more enjoyable 
lives?
    Dr. Hodes. Yes. We have an important component of our 
mission at NIH related to the dissemination of information. The 
findings which are newly reported are communicated initially as 
scientific findings in the scientific community. The way in 
which these are translated to the public is critical. We 
communicate these findings to the public through multiple 
modes, including television, ``Age Pages'' which are 
informative sheets distributed widely and in bulk at 
institutions such as supermarkets, as well as through direct 
responses to the public. More and more widely used is our 
electronic web access. But, of course, we understand that none 
of these reaches the full breadth of the population who needs 
to be aware of and profit from our findings. So we continue to 
work, as Dr. Hyman was pointing out, with at times restrictions 
in our budgets allowed for public information function, to, 
through all media available, communicate to the public, 
findings at an appropriate time.
    I should point out that in addition to communicating to the 
public, the communication is often best coordinated through 
informing health care providers. One recent example of this 
kind of communication strategy involved the importance of 
immunization against flu or pneumococcal pneumonia. The 
approach taken was first through a series of meetings and then 
through bulk distribution of information to target general 
practitioners. This was a result of studies which showed the 
primary reason elders were not being immunized was because 
their doctors never brought up the subject.
    So we carried out an extensive nationwide campaign with the 
cooperation of health care providers and medical organizations, 
followed immediately thereafter by communication to the public, 
so that when individuals go to their doctor to say, ``I heard 
that it might be appropriate for me to receive immunization,'' 
they were not confronted by caregivers who were unaware and 
unable to confirm or act upon that information. This is typical 
of the kind of exercise we try to carry out to inform the 
public.

                          special populations

    Ms. Pelosi. I appreciate that. You know, my colleague, Mr. 
Stokes, has been a leader in making sure that all of the 
information that we have for the opportunity for clinical 
trials or the training of health care scientists and health 
care providers, et cetera, reaches into the minority 
communities. And many of us share his concern in that area.
    I had a little more specific question in that regard. I 
have the privilege of representing a very diverse district, San 
Francisco. And for a long time now, I have been approached by 
people who deliver health care services to seniors in the gay 
community about the specific needs of lesbians in regard to 
aging. Is there anything going on at your institute in that 
regard? I do not know what the specific health needs might be, 
but I am told that there are such concerns.
    Dr. Hodes. We serve, as we should and must, all components 
of the population. An example of some of the special concerns 
that we have tried to address has been in studies of HIV in 
older Americans and in older men and women, including gay and 
homosexuals. One of the major emphasis areas in the Institute's 
AIDS arena is, in fact, in the behavioral area. We attempt to 
understand both risk factors, risk factor modification, but 
also the social and support structures that are there for older 
people, be they married, single, in homosexual or heterosexual 
relationships. To that extent, we have involvement with this, 
among other, special populations.
    Ms. Pelosi. I appreciate that. Thank you, Dr. Hodes. Thank 
you, Dr. Varmus.
    Thank you, Mr. Chairman.

                           funding stability

    Mr. Porter. Thank you, Ms. Pelosi.
    Can I ask one final question, and that is--and if Dr. Hodes 
could answer first again, then Dr. Varmus, to what extent does 
the availability of funding influence scientific opportunity? 
In other words, I think you were here when Dr. Hyman talked 
about moving funds from one area to another and how scientists 
and the science then moved where the money went. Can you give 
us some insight, both of you, as to what influence the dollars 
have on scientific opportunity in a general way?
    Dr. Hodes. I think for the vast majority of scientists, the 
original components of motivation have to do with scientific 
interest and service of public good. I think during a time when 
resources are stably assured--and I would strongly agree with 
Steve Hyman that an enormous good can be served by this 
Committee'sefforts to assure stability of growth--that under 
conditions where stability of growth is reasonably secure in the 
perception of investigators, that they will follow these joint 
motivations of scientific interest and public service.
    That judgment may be altered by a perception of 
differential funding and stability itself is threatened, and 
that becomes a tertiary aspect of motivation, secondary to 
those two which I first mentioned.
    Dr. Varmus. Well, I think the answer is not a simple one 
because it depends on the context in which the shift in funding 
is made. As Richard points out, if times are hard and people 
are underfunded or unfunded for their research, then they turn 
their interests to an area where there seems to be a greater 
availability of money. Of course, under those circumstances, it 
is likely that many of those who shift fields are those who 
have not been so successful and may not be the highest caliber 
of investigators.
    Under circumstances where the money is being moved into one 
area because of specific need--for example, when we had a clear 
indication a few years ago that there was an increased 
incidence of drug-resistant tuberculosis and we were 
underfunding tuberculosis research and had, in fact, failed to 
nurture a cadre of people who were skilled at working with 
tuberculosis--extra money then moved highly competent people to 
that area, recognizing there was a new, important intellectual 
problem that had big public health import. There was a real 
need. There was also an incredibly interesting scientific 
opportunity and new tools with which to approach the question 
of how we develop better therapies for drug-resistant 
tuberculosis. Then that shift was very appropriate.
    The question has been asked of me many times: can't you, in 
fact, develop a field by investing more heavily into it? I 
think the answer is yes, you can. But when money is limited, as 
it always is in some sense, you have to ask yourself: How much 
ground do I gain for each dollar? I would argue that if you are 
simply moving the money because this is what you care about and 
you are not paying attention to the other issues that are 
involved in priority setting, like scientific opportunity and 
public health need and the actual balance that currently 
exists, I would contend that you are likely to make a shift 
that would result in less progress than might have occurred in 
areas where things are moving faster. Yes, some progress, but 
not an optimal level of progress would occur in an area that 
has been expanded by that shift.
    Mr. Porter. Let me thank you. We always thank you, Dr. 
Varmus, because you have been here for the last two weeks. Dr. 
Hodes, let me thank you for your very good testimony and your 
good answers to our questions and for the fine job you are 
doing at the National Institute on Aging. Thank you for 
appearing.
    The subcommittee will stand in recess until 10:00 a.m. 
Tuesday.
    [The following questions were submitted to be answered for 
the record:]


[Pages 2382 - 2444--The official Committee record contains additional material here.]



                                            Friday, March 27, 1998.

        NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKES

                               WITNESSES

AUDREY S. PENN, M.D., ACTING DIRECTOR, NATIONAL INSTITUTE OF 
    NEUROLOGICAL DISORDERS AND STROKE
CONSTANCE W. ATWELL, Ph.D., ACTING DEPUTY DIRECTOR
ANDREW C. BALDUS, BUDGET OFFICER
HAROLD VARMUS, M.D., DIRECTOR, NATIONAL INSTITUTES OF HEALTH
BILL BELDON, DIVISION DIRECTOR, BUDGET, DEPARTMENT OF HEALTH AND HUMAN 
    SERVICES
MARY MIERS, PLANNING AND LEGISLATION
JOHN H. JONES, ACTING EXECUTIVE OFFICER

    Mr. Porter. The subcommittee will come to order. Today we 
have Dr. Audrey Penn from the National Institute of 
Neurological Disorders and Stroke. Dr. Penn, welcome. Will you 
please introduce the people at the table with you and proceed 
to your statement?
    Dr. Penn. Yes, sir. Mr. Chairman and members of the 
committee, today I appear before you as the Deputy Director and 
Acting Director of the National Institute of Neurological 
Disorders and Stroke.
    I should like to introduce the others at the table of NINDS 
with me today: Mr. Bill Beldon, Office of the Assistant 
Secretary for Management and Budget; Dr. Harold Varmus, 
Director, National Institutes of Health; Dr. Constance Atwell, 
Acting Deputy Director; Mr. John Jones, Acting Executive 
Officer; Mr. Andrew Baldus, Budget Officer, and Ms. Mary Miers, 
Planning and Legislation.
    As a neurologist, a former grantee of NINDS and a former 
member of its Advisory Committee, I welcome the opportunity to 
be able to personally discuss with you the promise of new 
insights into some of our most difficult disorders. We have 
been a part of some amazing success stories over the past 
several years. I'd like to tell you more about two of them 
today.
    Parkinson's disease is a neurodegenerative disorder in 
which neural cells in specific regions of the brain die off. 
Affected individuals show tremor, rigidity of movements, 
stooped posture, and they slowly deteriorate in their ability 
to move and function. We would like to tell you about the 
exciting implications and possibilities coming from the 
investigations of some of the inherited forms of Parkinson's 
disease.
    As you know, a gene has been identified. Now we know that 
this gene is the blueprint for a protein that has been known 
for some time, but not in this context. The protein was named 
for its localization in synapses, the connections between nerve 
cells or nerve and muscle. So it was called synuclein.
    At first, relationships seemed obscure, but investigators 
at the University of Pennsylvania, following the findings by 
our Genome Institute, have found that synuclein is present in a 
structure which is a hallmark of Parkinson's disease called a 
Lewy Body. This is particularly intriguing because this Lewy 
Body occurs in Parkinson's which is not inherited. So we have 
good reason to believe that our new knowledge of the gene 
product involved in the uncommon inherited form of the disease 
has much to teach us about the more common sporadic form.
    The Lewy Body is an abnormal clump of protein which we call 
an inclusion body and it is found within brain cells.
    Here you see a Lewy Body as it appears in an affected 
Parkinson's cell after a regular tissue stain used in 
pathological examinations.
    Here is a Lewy Body stained with a specific probe in the 
form of an antibody to synuclein. This inclusion body may 
result from abnormal breakdown of this protein, so that it 
piles up and results in cell damage or it may be a product of 
the tendency of the abnormal synuclein to stick to itself and 
to other proteins. In either case, current evidence suggests 
that interference with the tendency of the abnormal synuclein 
to form clumps may provide treatment.
    Not only that, but synuclein is a precursor for one of the 
components of the proteinaceous material called plaques, found 
as a hallmark of Alzheimer's disease. This has also galvanized 
the field because it provides a link between two major 
neurodegenerative disorders--Parkinson's and Alzheimer's--and 
reinforces the idea that abnormal interactions between proteins 
resulting in actual deposits of protein aggregates in cells 
leads directly to cell death. This idea is generating much new 
investigation using cells in tissue culture and experimental 
mice made to express the defective gene--with almost monthly 
new information reinforcing this evidence. This, then, is an 
excellent example of the catalytic effects of scientific 
opportunity upon well-known observations from the clinic.
    The idea of interaction between proteins resulting in 
abnormal deposits in cells has been also raised by the so-
called ``triplet repeat'' diseases. As you know, the genetic 
code which resides within DNA produces proteins. The coding 
units of DNA designate the building blocks of a protein 
molecule called amino acids: each DNA coding unit consists of 
three bases, hence triplet. Each triplet codes for a specific 
amino acid. Over the past several years, a whole group of 
unexplained serious neurodegenerative disorders have been shown 
to result somehow from abnormal genes in which a single triplet 
code is repeated many times, so that the resulting protein 
contains long stretches of the same amino acid.
    Here you see a segment of a gene with typically varied 
coding units which produces a protein with varied amino acids, 
including occasionally a short repeat sequence; here you see a 
``triplet repeat,'' with its product, long sequences of an 
amino acid called glutamine.
    The long glutamine repeat folds upon itself and binds one 
portion to the other in a ``hairpin'' and the involved protein 
molecules bind to each other in aggregates.
    The disorders in which these overly-long stretches of the 
amino acid, glutamine, are found are some of the most disabling 
neurological disorders with which we deal. The strength, 
balance, or mentation of affected individualsdeteriorate, and 
we have been unable to treat. These disorders vary from Huntington's 
disease in which there is dementia and abnormal dancing movements of 
the limbs called chorea to a series of disorders of balance called the 
hereditary ataxias and even to one of the muscular dystrophies.
    Some of these disorders affect young children. They are 
often inherited in a dominant fashion, so that one-half of the 
children in such a family will be affected.
    The explosion of new information linking these 
neurodegenerative disorders to abnormal chemical interactions 
between proteins raises exciting possibilities. The abnormal 
clumps of protein are found within dying brain cells in the 
regions of brain which are affected by the disorders. The new 
information represents an excellent example of bench research 
finally providing new insights into baffling diseases and of 
how finding a gene may open really new lines of investigation.
    It energizes the clinicians who provide materials from 
patients, so that investigators can add to their findings. The 
clinician-investigators may confirm or extend the findings on 
their own patients within their own laboratories. Patients and 
families are important partners in these efforts, and we are 
gratified by their help.
    It also provides encouragement for all to begin to think 
about the disorders as potentially treatable and to plan toward 
drug therapies. The new hypotheses--that protein-protein 
interactions which result in abnormal aggregates in vulnerable 
brain cells may be critical to specific neurodegenerative 
disorders--form the basis for one of the major initiatives in 
our budget request.
    As you can tell, Mr. Chairman, we are very excited about 
the pace and promise of neuroscience research and its impact 
upon neurological disorders.
    I would be pleased to answer any questions.
    [The prepared statement follows:]


[Pages 2448 - 2452D--The official Committee record contains additional material here.]



    Mr. Porter. Just so I can try to understand this a little 
better, if Parkinson's is a genetic-based disease, then 
presumably you have this abnormal gene from the time you're 
born. Why does it only show up later in life then?
    Dr. Penn. Presumably, this gene will continue to slowly 
produce an abnormal protein, and it does take time, and we know 
this from many of the disorders that I've already referred to, 
for some of these to fully express themselves. These do come on 
slowly and stay a long time.
    It also would suggest that there are other influences; 
other proteins must be present. Perhaps the normal systems in 
which these proteins are broken down are in place and for a 
while they are managing the situation, and then later those 
systems are overwhelmed.
    There are, obviously, other pathways and other proteins 
that are binding in to make these clumps, but this is just such 
a wonderful clue to what's going on. We haven't known what's 
going on.
    Dr. Varmus. It might be worth mentioning, Mr. Porter, that 
in the families in which the mutation has been identified, the 
onset of the disease tends to be earlier than in the sporadic 
cases that occur in the general population.
    Dr. Penn. Yes.
    Mr. Porter. I think I know the answer to this question, and 
the answer would be no, but let me ask it anyway and see if I 
can understand this further. You talked about drug therapies 
that might be developed to address this kind of condition for 
Parkinson's disease. Is there any possibility that a drug 
therapy used to control the disease would, perhaps after a 
period of time, not control it? In other words, is there any 
possibility that the nature of the disease could change in a 
way that would defeat the kind of drug therapy that would be 
given? For example, with respect to bacteria, there are strains 
that have developed to avoid our antibiotics and seem to do so 
more and more successfully, which is a real problem. Is it also 
a problem in this kind of therapy?
    Dr. Penn. Potentially, it's a problem. I think we may have 
seen something like that, because what we have tried to do for 
the past 30 years is to replace the normal chemical, which is 
missing in these disturbed cells. When we did that, other cells 
continued to die off, and we were faced with the situation 
where some of the things that we were giving caused side 
effects that were somewhat unacceptable. So that this disease 
is a gradual die-off of cells that have this chemical. So, yes, 
indeed, you could do that.
    Mr. Porter. So I didn't know the answer because the answer 
is yes.
    Dr. Penn. You have to try to get around that. We'd like to 
put the cells back someday.
    Mr. Porter. Well, then, I think we go back to the larger 
question, and that is, of all the work that we now do to unlock 
these secrets and develop therapies for them, because there is 
an ability to metamorphosis into a different form, can this 
work be defeated? In other words, can the disease change and 
require constant development of new therapies?
    Dr. Penn. I see where you're coming from. I do not want to 
imply that it will change that radically or that often, but I 
will say with you that there are times when we start a new 
therapy with the best intentions and, as we learn more about 
the disease, we have to deal with its effects on either normal 
cells or the fact that the abnormal cells just do not respond 
when they're totally gone, like the frozen addict story. We're 
working on that, too, to try to find out what we can to do when 
the cells are just gone.
    Dr. Varmus. We wouldn't expect in this case for cells to 
undergo genetic changes that would allow them to escape 
treatment, as is true in the case of bacterial resistance, when 
bacteria undergo mutations that make them resistant to 
antibiotics and give them a growth advantage. The brain cells 
are destined for death, so the cells that would survive would 
be the ones responding to therapy.
    Mr. Porter. In respect to bacteria, we know that changes 
can occur. With respect to viruses, don't we also know that 
changes can occur as well?
    Dr. Varmus. Absolutely.
    Mr. Porter. So you can have in those two instances at 
least, two different forms of infection or invasion of the 
body. You can have changes, but not in this type----
    Dr. Varmus. Well, there are two important differences. One 
is that viruses and bacteria are turning over extremely 
rapidly, so they're generating a lot of genetic change just by 
growing.
    Secondly, in therapies addressed against viruses and 
bacteria you're trying to kill the bacteria and viruses. Here 
the therapy will be intended to allow the cells that are 
programmed for death to instead live. We'd be encouraging the 
cells that respond to the therapy to survive.
    Mr. Porter. Is there any importance in the fact that 
bacteria and viruses both come from outside the body, and these 
diseases are within your cell structure? They are not an 
invasion of the body by some foreign----
    Dr. Varmus. That makes it much more difficult. 
Understanding the complexity of a human cell is obviously a 
greater challenge than trying to understand the complexity of a 
simple bacterium or virus.
    Mr. Porter. It helps my understanding. It's a curiosity 
more than anything.
    Dr. Penn, the budget request includes funding to pursue new 
approaches in neuroradiology for diagnosis and treatment of 
brain disease. Would you describe the process of neuroradiology 
in further detail, as well as your plans in this area for next 
year?
    Dr. Penn. Neuroradiology is a specialty that is allied to 
ours, and it's extremely important to the diagnosis, and really 
at times, treatment of neurological and neurosurgical 
disorders. Over time we have evolved the computerized 
tomography, the CT scans. We've evolved magnetic resonance 
imaging. We now are into a phase where we can actually detect 
function of the brain as the brain does certain tasks, with 
functional MRI. So that it adds a diagnostic component as well 
as a research component.
    We perceive that over about the next certainly five years 
that neuro-imaging, as we are also calling this, has a 
tremendous future. It can give us enormous amounts of 
information.
    The positron emission tomography, the PET scanning, and its 
similar SPECT scanning, a lot of it has been used on the NIH 
campus for a long time. It's given us enormous amounts of good 
information. Those entities are extremely expensive, and not 
every place in the country can have one, partly because it 
requires isotopes of very short half-life. We feel that over 
time this would be an enormous thing to have, not only to look 
at people, but in the research arm there are actually magnets 
in the magnetic resonance imaging studies that can be used for 
some of these mice and rats that are expressing these genes. 
And therefore, we've put a considerable emphasis on the future 
of neuro-imaging as it not only applies to basic science, but 
to disorders.
    Mr. Porter. Dr. Varmus, let me ask you a question at this 
point. The idea of creating a new Institute of Radiology is 
being heard again. Can you tell us what position NIH has on 
that idea?
    Dr. Varmus. Well, we haven't fully formed an official 
position as yet. As you know, we begin from the assumption that 
imaging of various kinds is important to the activities of 
virtually all our institutes, and that creates, in my view, a 
reason for not segregating radiology and imaging into one 
place. I believe it should be integrated, just as any 
fundamental technique, like molecular biology or DNA sequencing 
would be integrated into the fabric of many research 
institutes' activities.
    Furthermore, I'm always reluctant to set up yet another 
administrative structure in an organization that's already 
extremely complex. I have yet to hear the compelling argument 
that we should do so.
    As you know, a year or two ago, we created the Bio-
engineering Consortium, which includes among itsprincipal 
components imaging technologies and radiology. We believe that within 
the confines of that consortium the concerns of the radiology and 
imaging community can be satisfactorily met. I am perfectly willing to 
meet with individuals from that community, as I have in the past, to 
see whether that claim is true.
    Mr. Porter. Often these are matters of pride and 
recognition that the institute or the existence of an institute 
gives a specialty within the profession. Perhaps there's some 
way that the recognition of the importance of radiology can be 
made without creating a separate institute.
    Dr. Varmus. We'll also look at that possibility.
    Mr. Porter. In public witness testimony before the 
subcommittee, it was brought to our attention that NINDS was 
spending 13 percent less on Batten's disease in fiscal year 
1997 than it did in fiscal year 1994. Is this an accurate 
assessment of the situation? And if so, can you tell us why 
funding has been reduced in this area?
    Dr. Penn. The reason that the numbers seem to have gone 
down is that we have had enormous success because we now have 
the genes for all four forms of Batten disease. During that 
period of time, our grantees have actually found the gene for 
the late infantile form of this problem, and that means that 
the emphasis and the research should be toward, again, finding 
out what the gene product is in terms of the protein, and 
working toward developing all the models that are necessary to 
figure out what they do. That way we can really impact the 
disease.
    Also, several very successful projects over time which are 
not directly into the genetic areas have somewhat lapsed. So we 
have not given up on Batten's disease, but we are working 
toward really the cutting-edge new frontier for it.
    Mr. Porter. After finding the gene, is it a harder job 
often to find a therapy or is finding the gene initially the 
harder task?
    Dr. Penn. I would say in 1998 perhaps finding the gene. It 
cannot always be easy; we have several diseases in which it 
took well over five years--Huntington's is an example of that 
and the Facio-scapulo humeral dystrophy is an example where 
they're still looking. They find a locus on the chromosome, but 
they don't have the gene yet.
    But I would say finding the therapies is not going to be 
easy, either, and I would equate them in difficulty.
    Mr. Porter. Thank you very much, Dr. Penn.
    Mr. Stokes.
    Mr. Stokes. Thank you, Mr. Chairman.
    Good morning, Dr. Penn.
    Dr. Penn. Good morning, sir.
    Mr. Stokes. Dr. Penn, generally speaking, do the victims of 
stroke receive some type of warning signals?
    Dr. Penn. They may. It is particularly important that 
everybody be aware that there are warning signals for stroke, 
and those warning signals are derived from where in the brain 
the blood vessel is being blocked. So that you could have 
sudden weakness or difficulty using a hand. You could have one 
eye in which you suddenly couldn't see, and you could have 
difficulty feeling. If you begin to think that that is really 
happening to you, and that it isn't going away within seconds, 
then you have to be aware that it could be the onset of a 
stroke.
    We have something called transient ischemic attacks. Those 
are a signal to get in, get your arteries looked at, and 
perhaps have therapy. Unfortunately, in some of our stroke 
victims this happens really early in the morning, so we don't 
always have that much time. However, there is enough warning, 
when you feel, as people will tell you, their face just sort of 
feels like it's hanging; they can't move their tongue very 
well. In some situations they suddenly can't talk. I mean, 
everything should happen--911, the emergency services should be 
called promptly; people should be gotten to an emergency room 
promptly and handled promptly. These are all available to us 
now. They were available before, but we have to make sure that 
people know about it.
    Mr. Stokes. I ask that question because I suppose what you 
have just said to me is news, perhaps, to a lot of people in 
this room here this morning. To what degree is the Institute 
trying to utilize outreach and education, to increase the 
general public's awareness and understanding of the warning 
signals relative to stroke?
    Dr. Penn. We're relatively horrified that so many people do 
not know the warning features of stroke the way they do of 
heart attack. And so we've tried to rename this ``brain 
attack,'' and we've begun a public information campaign to try 
to tell people about these symptoms and to get them into the 
hospitals, into the emergency areas of the hospitals, promptly. 
Because one of our major therapies can only be really 
successful if it's used within the first three hours from the 
symptoms. So when your face begins to droop and your speech 
goes, you've got to move.
    Therefore, we have used the media. Media have been 
wonderful to help us put this message out. As you know, we've 
actually had a segment of ``ER,'' and we've actually had a 
workshop where we brought people from the EMS services, the 
emergency rooms, every conceivable step in the process, the 
neuroimagers, all together to say, look, we've got to get this 
going. We have a lot of help from the Stroke Association on 
this, and so on.
    Mr. Stokes. Do you find that people go into a state of 
denial with reference to this, in the same manner that many do 
with reference to heart attacks? I understand that one of the 
problems relative to heart attacks is that people say, ``ah, 
this couldn't be happening to me,'' and they sort of ignore the 
signals or ignore the signs. Do you find that to be true with 
stroke?
    Dr. Penn. I'm afraid it is true, but it is different. In 
heart attack, every once in a while people think they've just 
got indigestion. Stroke symptoms really don't really represent 
anything else perhaps except the beginnings of a migraine. A 
lot of people do not have migraines. So they have to be aware 
those are serious and they should be checked out right away.
    Mr. Stokes. Let me ask you this, Dr. Penn; It is thought 
that African Americans have a two-to-threefold greater risk of 
stroke and are 2.5 times more likely to die of stroke? Do we 
know what causes this increased risk amongst African Americans?
    Dr. Penn. There are several, components of that risk. Part 
of it is environment. Part of it is not perhaps paying proper 
attention to things that we all know about that we have heard 
repeatedly: If you're diabetic, if you have hypertension, if 
you're overweight and don't exercise, there's all of that.
    There's also just an intrinsic risk, which I would have to 
say is another genetic influence. It's also the issue offolks 
not particularly wanting to go to doctors right away, which comes back 
to your other question.
    Mr. Stokes. To what degree do you work with national 
African American organizations and groups in order to try to 
facilitate outreach toward African Americans in general?
    Dr. Penn. We have several investigators working in order to 
do the trials of the clot-busting drug. The African American 
community, all of the minority communities were involved in 
that. We also work with the National Medical Association. We 
work with the Student National Medical Association, and our 
folks go to their meetings and will be presenting some 
information to them further on the TPA story. In the brain 
attack coalition, they are involved.
    Mr. Stokes. As you're keenly aware, spinal cord injuries 
take a devastating toll on families across the Nation. What 
success are we having in this critical area of research in 
general, and with respect to spinal cord regeneration in 
particular?
    Dr. Penn. We have more success than we used to because we 
understand it better. I mean, the research has told us that. 
We've had a tremendous breakthrough in confirming that a 
corticosteroid--namely, methyl prednisolone--will really 
benefit, if given within the first eight hours after injury. We 
know now, that this whole study's been extended, that patients 
receiving it within three hours can benefit from a 24-hour 
dosage, and those treated within three to eight hours, should 
be treated for 48 hours.
    Exactly which pathways of destruction that it is hitting 
are still to be worked out. We have many investigators working 
on how to get cells and pathways to regenerate. We had a very 
large workshop sort of in honor of both Mr. Reeve and Dr. Bunge 
of the Miami Project, to discuss all of these issues and to try 
to galvanize the field to get going. So we've had this 
wonderful model of the rat in which the peripheral nerves were 
stretched over the hole in the spinal cord, and the rat begins 
to move, but we need a lot more information than that. It has 
to be reproduced and worked on. If we could find out about that 
kind of thing, we're going to find a lot about stroke and head 
trauma as well.
    Mr. Stokes. Dr. Penn, I'm very concerned about the impact 
of cerebral palsy, autism, and other neurological disorders on 
children. Do we know the extent of the problem with regard to 
neurological disorders in children in the United States?
    Dr. Penn. To give you an exact number, I am not quite able 
to do that, though we could certainly supply that number for 
you.
    [The information follows:]

                   Neurological Disorders in Children

    The extend of neurological disorders in children is 
enormous. The developing brain and nervous system are 
particularly vulnerable to damage, whether genetic or 
environmental, and as many as 4 of every 1,000 babies born in 
the United States die because of disorders in which the nervous 
system fails to develop properly. Of the more than 4,000 known 
single gene disorders, it is estimated that as many as one-
third are primarily neurologic or have significant neurologic 
involvement. More than 1 of every 15 babies is born 
prematurely; these babies are uniquely vulnerable to damage 
from brain hemorrhage (stroke) which can lead to lifelong 
mental deficits, epilepsy, cerebral palsy, and behavioral 
problems. At least 5,000 children with moderate or severe 
congenital cerebral palsy alone are born each year. Defects in 
the formation or maintenance or brain cell connections may 
result in mental retardation, learning disabilities, and 
neurobehavioral disorders such as autism. During a child's 
first five years of life constant remodeling of neural networks 
allows noxious insults to produce lasting effects in brain 
function.

    Dr. Penn. It is a major problem. Cerebral palsy is one of 
the leading problems in neonatology and for infants to make 
sure--because prematurity and low birth weight are the highest 
causes of cerebral palsy. So it is something we are very 
concerned about. We have currently a major clinical trial going 
to try to prevent cerebral palsy in low-birth-weight infants, 
using something very simple, which is used on hypertensive 
mothers, called magnesium sulfate that we will be able, 
hopefully, to report further on.
    We also have done things to reduce hemorrhages which happen 
in low-birth-weight and premature infants, using a drug for 
inflammatory arthritis called indomethacin, and this has been 
carefully studied in appropriate clinical trials.
    Mr. Stokes. Last year the Institute discussed its 
collaborative and co-funded activities with the Office of 
Research on Minority Health and the Morehouse School of 
Medicine. What progress do you have to report on these 
initiatives?
    Dr. Penn. We continue to work with this office very 
productively. We are very proud of what's going on at 
Morehouse. They really have a major neuroscience program and 
center under the leadership of Dr. Peter McLeish and Dr. 
Sullivan, who is the president of Morehouse. We've just had 
regular site visits of their program, meaning by that that they 
have been asked to compete as everybody else is competing. They 
have been successful. So we moved to the next phase, adding 
more investigators and building that program, and so far we're 
using it as an example to other minority institutions and we're 
moving toward adding a program, on a competitive basis, of 
course, at some of the other institutions, to see if we can get 
neuroscience added to the minority institutions' research.
    Mr. Stokes. Thank you, Dr. Penn. Thank you, Mr. Chairman.
    Mr. Porter. Thank you, Mr. Stokes. Mr. Hoyer?
    Mr. Hoyer. Thank you very much.
    Dr. Penn, welcome.
    Dr. Penn. Thank you.
    Mr. Hoyer. It's nice to see you again. I want to thank you 
for taking the time to visit with me in my office. I gave, the 
folder or the paper that you gave me on autism to Congressman 
Rothman, and he was very appreciative.
    Dr. Penn. Thank you.
    Mr. Hoyer. So I thank you.
    Doctor, as you probably know, I'm very interested in Rett 
syndrome because of a personal experience I've had with a Rett 
syndrome child, but, obviously, as well, thegeneral application 
of why the neurological development is arrested after about 18 months 
in female children. Can you tell me the status of Rett syndrome, your 
involvement, your Institute's involvement. And if you don't know, 
that's understandable, and you can put that in the record.
    Dr. Penn. We will, again, give you more information, but it 
is among several disorders in which there are really sort of 
growth arrest for the brain or great difficulty with attention 
and cognition. We have more than one. As I understand it, we 
don't have a specific grantee at this moment, but we do work, 
along with Child Health, and we are, as you know, very much 
into autism. In fact, the autism group is a consortium of four 
institutes, of which we are one.
    [The information follows:]

                             Rett Syndrome

    Children with Rett syndrome apparently develop normally 
until 6 to 18 months of age. These children then show signs of 
impaired language, loss of purposeful hand skills, and 
repetitive hand movements. The cause is not known. Rett 
syndrome is one of the many brain disorders of childhood, such 
as autism, learning disabilities, mental retardation, and 
cerebral palsy in which NINDS and the National Institute of 
Child Health and Human Development (NICHD) share interest. 
NICHD is the lead institute for research on Rett syndrome. 
However, NINDS has been involved to the extent that we support 
basic research on the development of the brain, and research on 
related brain disorders, such as autism, that can contribute to 
research efforts in Rett syndrome. NINDS also provided support 
for an international conference on Rett Syndrome, held in 1994, 
and NINDS staff participated at a recent conference sponsored 
by NICHD on genetics of Rett syndrome. I am committed to 
furthering NINDS efforts in brain disorders affecting children. 
We plan to continue to work closely with our colleagues in 
other institutes which share our interests in neurological 
disorders of childhood.

    Mr. Hoyer. I am pleased with that, and we will work with 
your office on some language on autism becoming a bill. I 
talked to Steve Rothman about it.
    I asked a general question of the previous directors. What 
pay-line level will your institute be at, do you think, in 
terms of extrinsic grants--extramural grants?
    Dr. Penn. Extramural? Our success rate is up 28 to 29 
percent, and----
    Mr. Hoyer. Twenty-eight to 29 percent?
    Dr. Penn [continuing]. Yes, we hope to go higher----
    Mr. Hoyer. Fine.
    Dr. Penn [continuing]. All things being equal.
    Mr. Hoyer. At that level, do you think we have sufficient 
investment in basic research to encourage both the retention of 
those researchers that we now have and the encouragement of 
young researchers to come in?
    Dr. Penn. We hope that--I mean, we do work very closely, 
and there are some really staunch supporters, the Society for 
Neuroscience, and all the basic researchers, because, without 
them, we can't go on with these breakthroughs that we 
desperately need.
    In terms of training and development, we have been very 
much into this, both in terms of the basic scientists and the 
clinician investigators, and we have several developmental 
awards to keep the clinicians in this. It's fine for clinicians 
to be practicing in their wonderful specialities--my colleagues 
know what they're doing--but we also need people who can ask 
the questions on their own patients. This is to say patient-
oriented research. So we have made an investment in that, and 
we are going to continue to do that, to develop people who can 
sort of work at both the bedside and the bench, and go on to 
full faculty status successfully.
    We will use the new award that Dr. Varmus has announced to 
you, this new award for patient-oriented research and 
development, as well, but we will continue also to train people 
to do both.
    Mr. Hoyer. Thank you. Doctor, Parkinson's disease, you 
started your testimony with reference to Parkinson's disease. 
Obviously, our friend Morton Kondracke, as you may know, his 
wife is suffering from Parkinson's disease, and Moe Udall. Can 
you tell me--you reference in your statement, obviously, some 
breakthroughs or some progress. Do we foresee the ability to 
reverse, do you think, the effects of Parkinson's disease, as 
well as to intervene in its onset?
    Dr. Penn. I would say we would be working at the moment--we 
are trying. There are several things which happened sort of 
simultaneously, and it's not just what I started with in the 
testimony.
    Various of our industrial pharmaceutical companies are 
trying to make sort of drugs that last longer and do somewhat 
of a better job. But, again, this requires that you have some 
residual cells that are able to function.
    We would like to intervene very early. Therefore, the 
diagnostic criteria or markers for this are critical. We think 
we have them, but it would be a very good idea to have even 
better ones, because there are other disorders in which there 
are features of Parkinson's disease.
    So that there will be a multi-pronged, we hope, 
pharmaceutical attack on this, and we hope actually at some 
point to be able to put back cells and/or factors that will 
preserve what's there and add to it.
    Mr. Hoyer. I note that also, when you talk about 
regeneration on spinal cord injuries, obviously, that has been 
a great challenge for the scientific community, to see whether 
or not we can regenerate cell activity, nerve activity, so that 
it is possible to regain, after a traumatic spinal cord injury, 
regain some use or maybe total use of limbs and the body. Where 
are we on that? You reference it in your statement, but where 
do you think we are on that? How close are we?
    Dr. Penn. I think we have major investigators working 
extremely hard on this. I think the good news is that thereare 
stem or progenitor cells in the central nervous system, as well as in 
the periphery--you know, because nerves in your arms and legs will grow 
back. It takes forever, but they do it. We would like very much to 
permit them to grow, so we need to know all the things that are acting 
against them and all the factors that are positive. It's almost like 
cooking. You're going to add a little of this--we have to figure out 
what it is that makes the whole thing proceed.
    Remember that the experiment that I described had to do 
with peripheral nerves used to carry signals, and so we need to 
get the nerves and central nervous system to regenerate. I'm 
more hopeful than I used to be.
    Mr. Hoyer. And you used to be of the opinion that this 
would not be possible?
    Dr. Penn. We were taught that it didn't happen, that nerve 
cells did not regenerate in the central nervous system. Now 
there's considerable evidence that they actually do. There are 
cells left and they can be turned on in the proper places, but 
we have to be able to control that, if we're going to do it.
    Mr. Hoyer. I suppose that one of the secrets to being a 
successful basic researcher is that you get over very quickly 
that which you were taught could not begun. [Laughter.]
    That's a constraint on all of us----
    Dr. Penn. Yes.
    Mr. Hoyer [continuing]. In whatever endeavor we are.
    Dr. Penn. Right.
    Mr. Hoyer. Thank you very much, Mr. Chairman. Dr. Penn, 
again, thank you.
    Mr. Porter. Thank you, Mr. Hoyer. We will have a second 
round.
    Dr. Penn, in the area of Parkinson's disease, you have a 
clinical trial in progress to evaluate the replacement of 
dopamine cells by transplantation of fetal tissue. Can you 
update the subcommittee in this area?
    Dr. Penn. We have one trial that has finished accruing its 
40 patients and is now about to assess the results in those 
patients. I am blinded to the results as are those who are 
actually conducting the study. We have a performance and safety 
monitoring committee that's right on top of this. Things so far 
are reasonably positive in terms of gathering the needed 
information.
    The other trial is just getting going, and they're in the 
middle of their patient accrual. So that we should have some 
hard evidence for you, I would say, in about a year, because 
you have to watch and see what happens with people that got it. 
We don't know who got it.
    Mr. Porter. Since fetal cell therapies probably are not 
likely to be widely used, is there anything going on to develop 
a substitute for fetal cells?
    Dr. Penn. Several major investigators are working--it's 
almost back to the question of Mr. Hoyer--to try to develop 
cell culture systems, cells, that can be used. Again, I would 
have to check on exactly where each group has gotten, but it's 
a major area of endeavor.
    [The information follows:]

                          Parkinson's Disease

    Several approaches for creating alternatives to the 
implantation of primary fetal tissue are being developed. There 
has been progress in the effort to persuade primary fetal cells 
to grow and proliferate in culture. One of the most exciting 
research approaches to develop neural cell lines is the use of 
embryonic stem cells. These cells can be expanded in culture to 
provide a limitless supply of neurons. Many laboratories across 
the country are attempting to enrich this neuronal population 
and create dopamine producing cells. Other groups are using 
viral vectors to replace lost synthetic enzymatic machinery for 
the production of dopamine or to re-engineer cells to produce 
growth factors which would help cells survive. The use of 
synthetic polymer capsules containing growth factors is being 
used to provide the slow release of molecules necessary to 
maintain neurons.

    Mr. Porter. What research is planned to advance basic and 
clinical research and treatment for forms of seizure disorders 
that are uncontrolled, like epilepsy?
    Dr. Penn. This is a major problem. It's especially a major 
problem in children. There are certain seizure disorders that 
are controllable, and people have to be followed and take their 
medications and actually not do foolish things like drink 
alcohol. However, there are other seizure disorders in which 
we've never had really good control. There is a surgical 
approach to one of them called partial complex seizures, which 
emanate from lesions probably in our memory centers in our 
temporal lobes. That's been very, very successful, and a lot of 
major medical centers have that capability.
    However, some of the others are still very hard to treat. 
We have in our extramural program a drug development program 
for this, and it's been going on for 40 years, because we feel 
that there's such a need for good and better drugs. Again, 
we've got some better ones, and we're currently using them. It 
doesn't seem to be perfect, and often you have to use 
combination drugs, but we're well aware that it's not perfect.
    Mr. Porter. If the epilepsy community was to say to you 
that you're not doing enough research in this area, what would 
your reply be?
    Dr. Penn. I would say we would talk with them and work with 
them to do more. We work very closely with both the voluntaries 
and the professional societies in epilepsy. They are actually 
working on the genetics type of thing that went on with 
Parkinson's themselves. We talked about it, and they said, 
well, we're ascertaining the families and we're going to figure 
this one out. We have advisory committees for both our drug 
program and to deal with the community--so far, I think they 
think we're trying; we're really out there for them.
    Mr. Porter. There was a study released by the National 
Academy of Sciences last year that leads to the conclusion that 
dyslexia is a neurological disorder. What research is NINDS 
currently funding to study learning disabilities such as 
dyslexia?
    Dr. Penn. I would say that we are probably on the edge of 
this. This is partly the imaging story, because you find out, 
from the functional MRI and using certain groups of patients, 
what's going on, and you find out that very important areas of 
brain are involved when you try to speak or write or read.
    Learning disabilities as part of cerebral palsy, as part of 
mental retardation, as part of all of these diseases of 
children that we have, are clearly very important to us, until 
we can figure out how to put an enzyme back or treat. This is 
also under the purview of Child Health, and we work with them. 
So we're doing more of what I discussed before, trying to 
prevent cerebral palsy or actually make sure who's got cerebral 
palsy at birth and deal with it that way.
    Mr. Porter. Your Institute has supported scientific 
symposiums on dystonia research. Have these efforts led to more 
research being supported, and do you collaborate with the 
National Institute of Deafness and Other Communication 
Disorders in this area?
    Dr. Penn. Well, dystonia is another movement disorder, 
which is not as common as Parkinson's disease, but it's in that 
ball park with Parkinson's disease and Huntington's. Again, it 
turns out to be rather more often genetic, and we have 
something like eight forms of dystonia, and we just had a major 
lecture in that area this week describing those eight forms.
    We're sort of where we are with several of our other 
diseases, including Huntington's, trying to figure out what the 
gene makes, so we can get on to what that protein is actually 
doing in the nervous system, and then try to deal with it that 
way.
    Otherwise, we certainly deal with the Deafness Institute, 
and I will have to check on exactly what we're doing with them 
on this area, dystonia.
    Mr. Porter. Thank you, Dr. Penn.
    Mr. Stokes.
    Mr. Stokes. Thank you, Mr. Chairman. Dr. Penn, in 1985, the 
Secretary's Task Force Report on Minority Health was released. 
This critical report explained the disparate situation that 
exists between the health status of majority and minority 
Americans health. That was approximately 13 years ago. Stroke 
and low birth weight were two of the specific areas cited in 
that task force report. Have we made much progress over the 
last 13 years in terms of those two areas?
    Dr. Penn. I would say we've made a lot of progress on 
stroke in the minority population. We have a series of 
investigators who go on out to find out the scope of the 
problem, then to ascertain in mixed populations which 
influences are important toward stroke, some of the things that 
we mentioned. We found that there's a lot more stroke than we 
thought because, once they got into communities, for instance, 
in Cincinnati, we found that the numbers of strokes are much 
higher because a lot of folks in the African American community 
don't always report these.
    So we know that stroke has been impacted since that report. 
We're pretty sure that infant mortality is better, but how much 
better is a little difficult to get the hard numbers, and we're 
actually working on that answer for you.
    Mr. Stokes. I'm glad you mentioned the infant mortality 
situation because I've got a copy of this international 
comparison of infant mortality health statistics where they say 
that the United States ranked 25th among selected countries for 
infant mortality. The latest figures tell us that we're 25th in 
the world. Am I correct?
    Dr. Penn. Well, I think you're right. As I said, we can't 
compare it yet to 1985. We're still trying to answer those 
questions. My sense is that it should be much better.
    Mr. Stokes. Tell me, Doctor, in terms of infant mortality, 
for instance, the rate per 1,000 live births for Japan is 4.4; 
the United States is 8.4, and there are 23 other countries in 
between--Finland, Singapore, Hong Kong, countries of that sort.
    Do we know why this type of disparity exists in a country 
that is one of the most affluent countries in the world?
    Dr. Penn. Yes, I would like to know which areas are most 
impacted. I think we can suppose as to which areas are most 
impacted, and there's been a lot of work to improve this. In a 
hospital that I'm very familiar with they work very hard to get 
at the infant mortality in the community of Harlem, but it 
takes time and it takes multiple persons involved. It takes 
good perinatal care. It takes access to intensive care units at 
this age, and needs a lot of these descriptors that we're 
beginning to development. When you have low birth weight which 
can occur, there are all the influences that you're well aware 
of in the community, too, unfortunately--drugs and alcohol.
    Mr. Stokes. Doctor, obviously, clinical trials are a major 
component of biomedical research. What type of investment is 
your Institute putting into clinical trials?
    Dr. Penn. I'm delighted to say that, as a neurologist, that 
we're finally ready to do some clinical trials. We've done 
several major clinical trials in stroke over time. We're now 
into the magnesium sulfate study for cerebral palsy in low-
birth-weight infants. We're doing the clinical trials of the 
cell transplants in Parkinson's and also of pallidotomy, the 
surgery. We have full intent of doing more, and, as our 
communities or our investigators actually understand these 
diseases and we have more therapies to test, we want to be able 
to do it. Currently, we're up around $32 million in clinical 
trials.
    Mr. Stokes. Do you have any major clinical trials that are 
currently unfunded?
    Dr. Penn. Currently, absolutely unfunded, it's hard to say 
that. Some are in the pipeline. In the pipeline also includes 
some work to get the best possible clinical trials by helping 
the community--through feasibility studies, we call this a 
pilot grant, and also throughplanning, because if they don't 
plan, then they don't get funded the first time around, and everybody 
spends time and effort to try to bring these about.
    But we have I don't think any major unfunded ones. They're 
just waiting. They're not really totally unfunded.
    Mr. Stokes. Thank you, Dr. Penn. Thank you, Mr. Chairman.
    Mr. Porter. Thank you, Mr. Stokes. Mr. Hoyer.
    Mr. Hoyer. Thank you, Mr. Chairman.
    One area, Alzheimer's, you do not mention it as a specific 
topic in your statement, as a specific screening topic, but, 
obviously, you deal with that. Would you expand somewhat on 
where you see your institute as it relates to Alzheimer's and 
where you see our research generally on Alzheimer's? Then we 
will have you comment on the treatability of Alzheimer's. 
Obviously, one of the problems Medicare has had is that it has 
not been historically perceived as a treatable disease.
    Dr. Penn. We work very closely with the Aging Institute 
from whom you've heard in the area of Alzheimer's. We tend to 
be more involved in the basic science of this, and we're 
working on how Alzheimer's actually starts in the cells or 
brain and its connections. We have had a working group with the 
Aging Institute, the Nursing Institute, and Mental Health for 
about the past year and a half to look at issues like that: Who 
exactly is doing what, and can we identify areas that aren't 
covered?
    There are a lot of my clinical colleagues who are working 
on Alzheimer's disease for sure, and they have been working on 
the risk factors, the APOE-4 business, and some of the others. 
They happen to be getting more money at the moment from the 
Aging Institute, but we are all, again, working more closely 
together to try to solve this.
    Therapies--there is no perfect therapy. There are some 
things that probably, again, if you give it early, help people 
think a little better. All of the things that we've been 
mentioning pretty much for stroke even could pertain because 
there are forms--if you get hit on the head, get a serious head 
injury, it makes your Alzheimer's worse. Certainly, if you have 
small strokes throughout the brain, it can make an appearance 
of Alzheimer's and it probably makes Alzheimer's worse. So 
there are multiple things that we would like to do early for 
these people.
    This gets into an area that I really don't want to discuss 
in terms of, if you identify people, what it does to your 
insurance and all this stuff. But there will be markers for 
this coming; there are already. But to say that you can take a 
pill today and clear your mind, your mentation, it's not really 
ready--you had to have a good heart and go exercise, I guess. 
[Laughter].
    They don't have a perfect therapy.
    Mr. Hoyer. I'll tell you a story about that. I seem to be 
the member on this committee here with a lot of personal 
stories. I have a cholesterol problem, and the doctor said stop 
eating, you know----
    Dr. Penn. Everything.
    Mr. Hoyer [continuing]. Milkshakes, ice cream, eggs, all 
that sort of stuff. So for about five months I was very 
religious--I'm into McDonald's. I'm sort of a junk food freak, 
potato chips, all the wrong things. So I stopped eating most of 
that. Five months later, I went in for a cholesterol check. My 
cholesterol had been 260; it went down to 259. [Laughter.]
    The doctor shrugged his shoulders. So I'm into drugs. 
[Laughter.]
    Thank you, Mr. Chairman.
    Mr. Porter. Thank you, Mr. Hoyer.
    Dr. Penn, thank you very much for your excellent testimony 
this morning and for the fine job you're doing at NINDS and for 
your appearance.
    Dr. Penn. Thank you very much.
    [The following questions were submitted to be answered for 
the record:]


[Pages 2467 - 2547--The official Committee record contains additional material here.]



                                            Friday, March 27, 1998.

             NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

                               WITNESSES

DR. MARVIN CASSMAN, DIRECTOR, NATIONAL INSTITUTE OF GENERAL MEDICAL 
    SCIENCES
DR. W. SUE SHAFER, DEPUTY DIRECTOR, NATIONAL INSTITUTE OF GENERAL 
    MEDICAL SCIENCES
MARTHA PINE, EXECUTIVE OFFICER, NATIONAL INSTITUTE OF GENERAL MEDICAL 
    SCIENCES
G. EARL HODGKINS, FINANCIAL MANAGEMENT OFFICER, NATIONAL INSTITUTE OF 
    GENERAL MEDICAL SCIENCES
DR. HAROLD VARMUS, DIRECTOR, NATIONAL INSTITUTES OF HEALTH
BILL BELDON, DIVISION DIRECTOR, BUDGET, DEPARTMENT OF HEALTH AND HUMAN 
    SERVICES

    Mr. Porter. We're very pleased to welcome Dr. Marvin 
Cassman, the Director of the National Institute of General 
Medical Sciences. I want to note, and I wish Ms. Pelosi and Ms. 
Lowey were here, that Dr. Cassman is a Chicagoan, educated at 
the University of Chicago. Ever since Nancy started this with 
Dr. Varmus and California, we've gone back and forth.
    Dr. Cassman, it is wonderful to welcome you again. Why 
don't you introduce the people on your left and then proceed 
with your statement, please.

                       Introduction of Witnesses

    Dr. Cassman. Thank you, Mr. Chairman, and good morning.
    To my far left is our Executive Officer, Ms. Martha Pine. 
Next to her is the Deputy Director of the Institute, Dr. Sue 
Shafer. And to my immediate left is Mr. Earl Hodgkins, our 
budget officer.
    Mr. Porter. Just to be further provincial, I will note that 
Dr. Shafer is from Illinois as well.

                           Opening Statement

    Dr. Cassman. That's right. There are quite a few of us, 
even at NIH.
    The goal of the National Institute of General Medical 
Sciences is to ensure the continuing productivity of basic 
biomedical research. This has provided the foundation for many 
of the really outstanding advances in biomedical sciences.
    It is difficult to quantify our contributions, but one 
reflection of how well we've done is that in the roughly 35 
years since the Institute was established, we have supported 
over 60 percent of the American Nobel Laureates in chemistry 
and in medicine or physiology.
    But I don't have to go back 30 or 35 years to trace the 
contributions of the basic research of NIGMS. I want to provide 
just a few striking scientific advances from this past year. 
They are all characterized by the fact that they were done in 
model systems, that is, organisms such as yeast, bacteria and 
the fruit fly.
    Nevertheless, even though they were done on these 
comparatively simple organisms, they shed light on such diverse 
concerns as Lyme disease, neurodegenerative disorders and 
cocaine addiction.
    Now the first example is a study that may lead to a 
significant therapeutic approach to Lyme disease. It was done 
in a rather esoteric class of bacterium called the 
archaeobacteria. These are found in inhospitable environments: 
the deep ocean floors, hot acidic springs and high salt 
environments.
    One of our investigators was interested in the very 
fundamental question of how these organisms carried out protein 
synthesis. This is a basic phenomena that is a necessary 
process in all living organisms. He found, when he examined it 
carefully, that apparently one of the keycomponents needed for 
protein synthesis was missing in this bacterium, and he was curious to 
see how the organism survived without it.
    Well, when he looked more carefully, it turned out that the 
component was present, but in a form unrelated to that found in 
all other bacteria and higher organisms, or almost all. When he 
looked more carefully at the genomes of the organisms that 
cause Lyme disease and syphilis, he found that in those 
pathogens, there exist compounds with similar structures to the 
material found in the archaeoabacterium, but with quite 
different structures from those found in humans.
    This structural difference may be exploited to develop new 
antibiotics to treat Lyme disease, because you could develop a 
drug that would selectively address just those organisms 
without affecting its human host.
    And I would like to say that parenthetically this is just 
one illustration of the importance of having genomic sequences 
of organisms other than humans, something that I think many of 
us are becoming familiar with.
    Now, a second example is a discovery in yeast that sheds 
lights on certain kinds of neurodegenerative disorders in 
humans. And this sounds inherently unlikely, certainly it 
couldn't have been predicted. After all, even if a yeast cell 
did have a form of dementia, how would we know?
    But the relationship is not in behavior but in the 
existence of a particle called a prion. Prions are thought to 
be infectious protein particles that are implicated in the 
initiation of diseases such as the Mad Cow Disease that we've 
heard so much about recently.
    An NIGMS investigator has recently shown that there is a 
protein in yeast that has many of the same characteristics as 
the prions found in mammalian brains. For example, the yeast 
protein generates the same kind of fibers formed by mammalian 
prions, and those are comparable to those found in autopsies of 
humans and animals that have died of diseases where prions were 
implicated.
    And in the figure to my left, on the left hand side you see 
the fibrils that are generated by the yeast proteins, and on 
the right, the long extended fibrils that are formed by 
mammalian prions.
    [The information follows:]


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



    Dr. Cassman. These studies now provide a model system to 
investigate an immensely complex problem in a comparatively 
simple organism, yeast. And they even begin to suggest a new 
target for potential therapies.
    Finally, we arrive at the common fruit fly, which is a 
nuisance to most people, but an invaluable tool to biomedical 
researchers. One of our investigators has spent many years 
studying fruit fly genes that are involved in the nervous 
system and in behavior.
    In the course of his work, he used volatile or crack 
cocaine as a tool to stimulate neurological responses in flies. 
That led him to observe that flies and mammals respond to 
cocaine in strikingly similar ways. Now, it's very difficult to 
show you a behavioral response in a static picture, but the 
image you see over here is a time lapse photograph of the very 
familiar fruit fly going around in circles. This is a 
characteristic display of movement patterns that one finds in 
rodents and primates in response to crack cocaine.
    [The information follows:]


[Page 2554--The official Committee record contains additional material here.]



    Dr. Cassman. This, along with other behaviors, suggests 
that the fundamental neuralpathways involved in cocaine 
response and in the linkage to behavior are retained across 
species. This now seems to be a very promising model to look at 
cocaine sensitization, for example.
    I'd also like to point out that this investigator was one 
of the first whom we supported through our interim funding 
mechanism. He resubmitted within a year, he did extremely well 
in peer review, and he's once again fully supported without 
having a potentially damaging hiatus in his research, just 
exactly what we hoped would happen when we initiated the 
interim funding mechanism.
    Now it's striking that in all of these examples, health-
related applications emerged almost immediately from basic 
research studies. Of course, I don't want to implythat this is 
the norm for the research that we support. And yet, it's not so far 
from the reality of modern biology.
    The mosaic of scientific research has expanded to the point 
at which basic research and its applications follow very 
closely. I'd like to quote a comment made by Louis Pasteur in 
1871, who said, ``There does not exist a category of science to 
which one can give the name `applied science'. There are 
science and the applications of science bound together as the 
fruit and the tree which bears it.'' What I hope I have given 
you are examples of a few such trees and their early fruits.
    Now, it's clear that the past and the present have produced 
a bounty of information, important outcomes from basic research 
that can be applied to the problems of health and disease. I 
only want to give you a few examples of initiatives that we're 
planning for the future that I think will be even more 
exciting.
    One is an attempt to bring mathematicians, physicists, and 
engineers into the biological sciences, particularly to look at 
the question of the analysis of complex systems. This involves 
the integration and understanding of large numbers of 
interacting components.
    A second area that I want to discuss is a new training 
effort. A new initiative we are planning for the coming year is 
to enhance traditional post-doctoral training by promoting the 
development of teaching skills through innovative programs that 
involve assignments at minority-serving institutions.
    We feel that this initiative will provide several benefits. 
First, it will be of particular value to many scientists who, 
during their graduate careers, become interested in teaching, 
but have little or no opportunity to develop these skills. We 
have lots of evidence there are many such individuals out in 
the community who would like to have the opportunity to learn 
how to teach, as well as to learn how to do research.
    The other benefit is that it will provide minority-serving 
institutions with access to individuals who are on the cutting 
edge of their disciplines, while relieving scientists at those 
institutions from some of their teaching burden and allowing 
them time for research and collaborations.
    Finally, before I conclude, I want to point out that over 
the past 25 years NIGMS has been involved in many efforts, such 
as the one I just discussed, to increase the number of 
underrepresented minorities involved in biomedical research. I 
would like to take this opportunity to especially thank Mr. 
Stokes for his continuing effort and support of these 
activities. This is just one important part of his legacy on 
this subcommittee.
    The proposed Fiscal Year 1999 budget for NIGMS is $1.145 
billion--I always have a hard time saying billion, but that's 
what it is. This is an increase of $79.5 million over Fiscal 
Year 1998. I would be pleased to answer any questions that you 
or the committee may have.
    [The prepared statement follows:]


[Pages 2557 - 2564--The official Committee record contains additional material here.]



                         Basic Research at NIH

    Mr. Porter. Thank you very much, Dr. Cassman. You 
characterize 100 percent of your work, your grants, as basic 
research. Is there any way to characterize a breakdown of the 
other Institutes as basic or disease-specific research. In 
other words, other Institutes do basic research as well. Do we 
have a breakdown?
    Dr. Varmus. We do.
    Mr. Porter. Where would the next highest concentration 
come, do you recall?
    Dr. Varmus. That I would have to look up, but overall, I 
believe basic is 57 percent overall.
    Mr. Porter. Of all research done through NIH or its 
grantees?.
    Dr. Varmus. That's correct. And then we categorize the rest 
of it as applied or developmental.

                      Sharing Research Information

    Mr. Porter. You had the fruit fly chart up there and you 
talked about the effect of cocaine. Can you describe for us, 
Dr. Cassman, the mechanism by which you would bring this 
information, let's say, to Dr. Leshner at NIDA. What structures 
do you have for doing that?
    Dr. Cassman. There are really not a lot of formal 
structures, but there are a great many informal structures. We 
collaborate very closely with many of the other Institutes, and 
in fact, there are a number of examples I can give you where 
grants that began at NIGMS as basic research, as they moved 
into more directed areas--I won't even call them applied--but 
more directed areas of research, moved to the appropriate 
Institute.
    One very recent example is a research project that looked 
at the genetic basis of various forms of behavior, a very 
general project. It wound up having very specific relevance to 
the National Institute of Mental Health and it's now being 
supported by the National Institute of Mental Health.
    So there are a number of ways, including common discussion 
groups in which we all take part, that allow for exchange of 
information.
    Mr. Porter. You don't see a need for more formal 
structures, then.
    Dr. Cassman. I don't really think so. I think we actually 
do a pretty good job, given the diversity of NIH and its size. 
We interact on a variety of levels, including the individual 
program people who talk to their counterparts in many different 
venues.

                      Research using Synchrotrons.

    Mr. Porter. I read in the budget justification where you 
plan to provide funds to support and enhance the capabilities 
of your grantees to utilize shared synchrotrons. Why are you 
doing this instead of the Center for Research Resources? Isn't 
this really the job of Dr. Vaitukaitis?
    Dr. Cassman. We're doing it jointly, as a matter offact. 
The National Center for Research Resources has specific resources 
located at various synchrotrons for specific purposes. However, there 
are broad uses, basic service needs that are more generally required. 
We also have a few initiatives that we are considering that will 
require heavy use of synchrotron facilities.
    For those initiatives in particular, we plan to try to make 
synchrotron facilities more available. We are working very 
closely, not only with NCRR, but also with the Department of 
Energy and the National Science Foundation, to develop 
integrated schemes for supporting research at synchrotron 
facilities.

                    High Risk, High Impact Research

    Mr. Porter. Dr. Cassman, last year, you announced a program 
to provide support for innovative research proposals that have 
the potential for highly significant outcomes but involve 
substantial research risk. You received 100 applications by the 
first submission deadline. Can you tell us how many were you 
able to support and give us a few examples of some of these 
proposals.
    Dr. Cassman. We are still in the very early stages of that 
program. I expect that we will be able to support probably 40 
applications or thereabouts for perhaps $4 million. These 
proposals span a very wide range of research, including some 
very innovative concepts of how cells integrate their behavior 
through genetic and cellular mechanisms.
    It's a little early to be able to tell--in fact, it 
probably won't be for three to five years before we can really 
tell--how successful this program has been in stimulating truly 
innovative approaches. Because it's high risk research, I 
assume there may be a high failure rate. That's the necessary 
consequence. What I'm hoping is that a significant proportion 
will provide significant benefits.

                            Research Centers

    Mr. Porter. You're proposing to establish 12 new 
specialized research centers in fiscal year 1999. What will be 
the areas of research in these new centers?
    Dr. Cassman. We are beginning one specific initiative that 
I think will use centers. That is an attempt--and again, this 
is a collaborative effort with other agencies, with the 
Department of Energy and with the National Science Foundation, 
in particular--to develop a classification and structure 
resource of all of the ways that proteins fold, all the ways 
their separate motifs align themselves, and to try to relate 
that to function.
    This will probably be best done through central activities, 
integrated centers, and a number of these centers are designed 
for that purpose.
    Mr. Porter. Thank you, Dr. Cassman. Mr. Stokes.
    Mr. Stokes. Thank you, Mr. Chairman, and welcome, Dr. 
Cassman. It's good to see you again, and thank you for your 
very kind remarks.
    Dr. Cassman. Thank you, Mr. Stokes.

            UnderRepresented Minorities in Research Pipeline

    Mr. Stokes. I appreciate, in your formal statement and also 
your oral presentation this morning, your reference to 
underrepresented minorities. You state, in fact, in your formal 
testimony, that ``we continue our efforts to train tomorrow's 
scientists and to bring more underrepresented minorities into 
careers in biomedical research''. Then, you talk about the 
things that you are doing. I appreciate that very much.
    Also, in your budget justification, you mention that the 
Institute plays a vital role in bringing an appropriate number 
of new investigators, including those from underrepresented 
groups, into the biomedical research system through both 
training and research support.
    Dr. Cassman, what is the condition of the research 
investigator pipeline and the current workforce of career 
researchers in general, and particularly as it relates to 
African-American and other underrepresented minorities?
    Dr. Cassman. The best indicator of the nature of that 
pipeline for us, particularly, is Ph.D. production. That's 
still woefully low, because the level of underrepresented 
minorities receiving Ph.D.'s in the biomedical sciences is 
about six percent. And for African-Americans, I believe it's 
about 2.3 percent.
    This is nowhere near where we would like to have it. The 
efforts we are making are designed precisely to affect the 
pipeline at the levels at which we can influence it, that is, 
at the graduate school level and in the senior and junior years 
of undergraduate training.
    I must say, however, that I think a lot more work has to be 
done at earlier stages, at the K through 12 level, in order to 
really produce the kinds of results that we would like to see.

         Evaluation of National Research Service Award Program

    Mr. Stokes. I quite agree with you that if we are going to 
really attack this problem, it has to be attacked early on in 
the early stages of development.
    What's the status of the evaluation of the National 
Research Service Award Program, and what results do you have to 
report?
    Dr. Cassman. That's being done for NIH centrally. I think 
it's pretty well along. I don't know when the report is due, 
but it's----
    Dr. Varmus. It's being carried out in a quadrennial process 
by the National Research Council. Dr. Howard Hiatt is the 
chairman of the committee, and we expect a report, I believe, 
in the fall.
    Dr. Cassman. But there's also an analysis being done at NIH 
of outcomes in our NRSA program, and I believe sometime later 
this summer that report will be completed as well.

        Funding for Historically Black Colleges and Universities

    Mr. Stokes. Okay, thank you. Dr. Cassman, I understand that 
initially Historically Black Colleges and Universities received 
86 percent of the Minority Biomedical Research Support Funds. 
Last year, you reported that they received 40 percent in Fiscal 
Year 1996. What was the percent in Fiscal Year 1997, and what 
is the anticipated percent in Fiscal Year 1998?
    Dr. Cassman. The percentage in 1997 was essentially 
identical to that in 1996; it was just about 40 percent, in 
MBRS.
    Mr. Stokes. Is that right?
    Dr. Cassman. Yes, in MBRS, in 1998, we hope to have it 
higher. At the moment, the last data we have is for 1997, and 
that's still about 40 percent.
    Mr. Stokes. All right. I am going to ask you to include in 
the record, if you will for me, a chart that displays the 
amount and percent of MBRS and MARC funding that the NIGMS 
provided to Historically Black Colleges and Universities, 
Hispanic-Serving Institutions and non-HBCU's and non-HSI's, 
over the last 10 years, if you'll do that for me.
    Dr. Cassman. Yes, sir.
    [The information follows:]

                                        RECIPIENTS OF MARC AND MBRS FUNDS                                       
----------------------------------------------------------------------------------------------------------------
                                                      Historically Black   Hispanic Serving   Other institutions
                                                           Colleges          Institutions             \1\       
                     Fiscal year                     -----------------------------------------------------------
                                                       Funding   Percent   Funding   Percent   Funding   Percent
----------------------------------------------------------------------------------------------------------------
1989................................................   $17,191      46.2    $8,302      22.3   $11,707      31.5
1990................................................    18,516      45.8     7,981      19.7    13,967      34.5
1991................................................    20,185      45.0     8,741      19.5    15,908      35.5
1992................................................    20,219      43.3    10,337      22.1    16,148      34.6
1993................................................    20,076      43.7     8,722      19.0    17,100      37.3
1994................................................    21,731      43.8    10,905      22.0    16,945      34.2
1995................................................    23,035      42.8    12,571      23.4    18,152      33.8
1996................................................    16,961      30.2    12,379      22.0    26,878      47.8
1997................................................    18,491      32.5    13,498      23.7    24,944      43.8
1998 est............................................    18,583      31.1    13,566      22.7    27,639      46.2
1999 est............................................    21,185      30.0    15,465      21.9    33,858      48.0
----------------------------------------------------------------------------------------------------------------
\1\ The ``Other institutions'' column reflects institutions either that serve Native Americans or Pacific       
  Islanders or that have mixed student populations with significant numbers of underrepresented minorities.     

                       research related to lupus

    Mr. Stokes. As you are aware, lupus affects 500,000 
Americans, 90 percent of which are young women and African-
American women. As your budget justification indicates, 
African-American women have a high rate of the disease. It is 
estimated that one in 250 will get the disease.
    What major research studies are supported by your Institute 
that would help to further advances in the study and treatment 
of lupus?
    Dr. Cassman. We don't deal significantly with lupus, Mr. 
Stokes.
    Mr. Stokes. I understand that NIAMS is the lead institute. 
However, your budget justification did speak to your 
Institute's direct involvement.
    Dr. Varmus. It's mainly NIAMS, and to a lesser extent, 
NIAID and my Institute, NIGMS.
    Mr. Stokes. Okay, on another very important matter, last 
year, the Institute indicated about 40 percent of its past 
supported trainees have gone on to receive NIH research grants. 
This percentage is higher than that for others that are 
preparing for careers in biomedical research.
    Do we know what percentage of minorities that have been 
NIH-supported grant trainees have gone on to receive NIH 
research grants?
    Dr. Cassman. I don't have that exact number for you. We 
will try and get that.
    Mr. Stokes. For the record.
    Dr. Cassman. For the record.
    [The information follows:]

    Unfortunately, it is too early to provide good information 
on the percentage of minority trainees who go on to receive NIH 
research grants. NIH has only recently been given approval to 
begin collecting information on the race/ethnicity of its 
trainees, and even now, it is provided on a voluntary basis. 
So, although we do have information on the race/ethnicity of 
recent trainees, a substantial period of time would be required 
for these students to achieve positions in which they would be 
able to apply for and receive NIH research grants. In addition 
to the time required to complete their graduate training, many 
will need to complete post-doctoral training, and will then 
need to secure positions that would allow them to apply for NIH 
research grants.

                            research on hiv

    Mr. Stokes. Your Institute has played a role in terms of 
research relative to AIDS and HIV, am I correct?
    Dr. Cassman. Yes, sir.
    Mr. Stokes. And I think especially as it relates to the 
development of protease inhibitors.
    Dr. Cassman. We had, I think, a significant role there, 
yes.
    Mr. Stokes. Can you tell us what progress has been made by 
the grantees that are working to determine the structure of 
potential new targets of HIV drugs and to understand the 
structural basis of resistance to HIV drugs?
    Dr. Cassman. Yes, there has been a great deal of progress. 
Many of the proteins that are involved in the virus's 
infectivity or in the locations where the virus interacts with 
the cell have been elucidated or to some degree or another--not 
all of them, as yet, but very many.
    Probably the most exciting recent results are the 
structures of the surface proteins of the virus, which have 
given some very important clues as to the nature of the 
residues involved and how the virus links up to the cells and 
so on. I think those studies will have significant influence.
    In addition, we continue to support research to develop a 
detailed understanding of drug interactions with various 
structural components of the HIV virus.

                   support for marc and mbrs programs

    Mr. Stokes. Dr. Cassman, last year's House report included 
language indicating that the Committee expects theInstitute to 
continue to support the MARC and MBRS programs at levels reflective of 
their importance.
    What was the Fiscal Year 1997 and Fiscal Year 1998 funding 
level for each of these programs? And, tell us what percentage 
change is reflected in each of these figures.
    Dr. Cassman. For NIGMS funding the 1997 level was just a 
bit over $38 million for MBRS. The 1998 appropriation was 
almost $41 million. For MARC, the increase was smaller, as with 
most training programs. The only significant increases with all 
of our training programs was the stipends. It was a small 
increase in stipends, so the MARC program went up just 
slightly. I think the stipend increase was about 2.2 percent. 
But that's, as I say, consistent with all of our training 
programs.
    Mr. Stokes. What's the Fiscal Year 1999 estimated funding 
level?
    Dr. Cassman. Yes, the Fiscal Year 1999 increase is going to 
be considerably larger. For MARC, it should increase about nine 
percent. For MBRS, we expect the increase to be over 20 
percent.

                  fellowships funded by more division

    Mr. Stokes. I understand the NIGMS MORE program awarded 29 
new fellowships in 1997. How many of the applicants are there 
each year, and what percentage are accepted?
    Dr. Cassman. The total number--you are talking about 
national predoctoral fellowships or--yes, the MORE, right.
    Mr. Stokes. It's the More Opportunities in Research, what 
you call the MORE.
    Dr. Cassman. Right, it's the national fellowships. The 1997 
total numbers were 93. They've been moderately stable at about 
that level for a while. I'm not sure I know what the success 
rate is, but I believe it's pretty high, about 50 percent, I 
would guess, at least on that order. I couldn't give you an 
exact number for the success rate, but it's a very substantial 
success rate.
    Mr. Stokes. You can provide that for the record for us.
    Dr. Cassman. Sure, yes.
    [The information follows:]

    In FY 1997, the NIH success rate for National Predoctoral 
Fellowships was close to 50%. For NIGMS, the success rate was 
87%.

    Mr. Stokes. I appreciate that. Thank you, Dr. Cassman. 
Thank you, Mr. Chairman.

                            mstp evaluation

    Mr. Porter. Thank you, Mr. Stokes. We will have a brief 
second round if the gentleman from Ohio wishes to ask further 
questions.
    Dr. Cassman, at last year's hearing, I asked what 
information you had on the career outcomes of researchers 
who've completed the Medical Scientist Training Program. You 
were in the process of studying the program and hoped to be 
able to give us a report this year. What can you tell us now?
    Dr. Cassman. We are not quite finished with the report, but 
we are pretty far along. This has required accumulating a great 
deal of information, not only from the MSTP graduates, but if 
you want to make a reasonable comparison, you need control 
groups. So we have three separate control groups that we're 
looking at as comparison.
    We do have preliminary indications and not surprisingly, 
the MSTP graduates, by every indicator that we use, do better 
than any of the control groups, including--to me, somewhat 
surprisingly--M.D./Ph.D. graduates from the same institutions. 
So it's really quite impressive.
    The important piece of information that I can't give you as 
yet is the nature of their research activity, which is 
something that we're very interested in--where they're located, 
and in what kind of departments. I think we know, but not 
statistically. We have a good idea of what that data is, but we 
will know in much more detail when all of the data is analyzed.

              potential initiatives under budget increase

    Mr. Porter. You are asking for a budget of $1.1 billion. 
What if, five or six years from now, you had $2.2 billion to 
work with.
    Dr. Cassman. I'd be pretty pleased.
    Mr. Porter. Obviously. [Laughter.]
    But what would that allow you to do that you can't do now, 
and since you're not disease-specific, how would thatdiffer 
from what other Institutes do?
    Dr. Cassman. Well, I would like to break it down into 
categories. First, there are a number of initiatives that we 
have in the works, some we are currently planning, and some 
that we've already begun. I think that many of those would be 
able to develop to a much better degree than we could currently 
hope for at this point.
    Of course, when you're talking about five years down the 
road, what I would certainly hope is that there would be many 
things that we can't now imagine that would be important to 
support at that time. If that were not true, I would be very 
distressed.
    A second area is equipment and facilities. There is no 
doubt in my mind that over the last decade, for example, the 
ability of our investigators to carry out state-of-the-art 
research has diminished because their access to significant 
pieces of equipment and facilities has not kept up with the 
opportunities available. We would certainly want to do 
something about that.
    A third area is simply to increase the capabilities of 
existing investigators. We have put a number of constraints on 
our current supported investigators, limiting the increases in 
their grants to a point at which they are not fully able to 
take advantage of all of the opportunities that exist for them.
    And finally, I think, is the area of training. I think 
there are some opportunities for expansion, both in dollars and 
numbers. I'm not talking necessarily about huge expansion, but 
some. Again, there are constraints that we've put on over the 
years. One of them Dr. Varmus has already addressed in the 
Fiscal Year 1999 budget by increasing the stipend levels for 
students.
    There are also new areas of research training that we would 
like to address. One of them I have already alluded to, that 
is, we would like to bring more mathematicians, physicists, 
engineers into the system.
    It isn't only a matter of saying here are the ideas, here 
is some money, come and get it. You have to break down cultural 
barriers when you're bringing in people from diverse 
disciplines. You have to get them to be able to talk to each 
other, to understand each other. This requires a number of 
things. We're planning some week-long workshops where 
fundamental ideas can be explained and understood. But this 
also requires cross-training at the graduate and post-doctoral 
levels.
    So I think all of those areas would be very important and 
would be impacted significantly.
    Mr. Porter. Thank you, Dr. Cassman. Mr. Stokes.
    Mr. Stokes. Mr. Chairman, I may have one or two other 
questions to put into the record, but I don't have anything 
additional at this time.
    Mr. Porter. Dr. Cassman, thank you very much for your 
testimony this morning and for the excellent job you are doing. 
It is good to see a fellow Chicagoan over there.
    Dr. Cassman. Thank you, Mr. Porter.
    Mr. Porter. We will stand briefly in recess.
    [The following questions were submitted to be answered for 
the record:]


[Pages 2573 - 2--The official Committee record contains additional material here.]



                                            Friday, March 27, 1998.

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

                               WITNESSES

DR. HAROLD VARMUS, DIRECTOR, NATIONAL INSTITUTES OF HEALTH
DR. RUTH KIRSCHSTEIN, DEPUTY DIRECTOR, NATIONAL INSTITUTES OF HEALTH
ANTHONY ITTEILAG, DEPUTY DIRECTOR FOR MANAGEMENT, NATIONAL INSTITUTES 
    OF HEALTH
STEPHEN A. FICCA, ASSOCIATE DIRECTOR FOR RESEARCH SERVICES, NATIONAL 
    INSTITUTES OF HEALTH
FRANCINE LITTLE, DIRECTOR, OFFICE OF FINANCIAL MANAGEMENT, NATIONAL 
    INSTITUTES OF HEALTH
DENNIS P. WILLIAMS, DEPUTY ASSISTANT SECRETARY, BUDGET, DEPARTMENT OF 
    HEALTH AND HUMAN SERVICES
DR. JACK WHITESCARVER, ACTING DIRECTOR, OFFICE OF AIDS RESEARCH
BILL BELDON, DIVISION DIRECTOR, BUDGET, DEPARTMENT OF HEALTH AND HUMAN 
    SERVICES
DR. ANTHONY FAUCI, DIRECTOR, NATIONAL INSTITUTE OF ALLERGY AND 
    INFECTIOUS DISEASES

    Mr. Porter. The subcommittee will come to order. I've asked 
Dr. Varmus if we could do one of the portions that we had 
originally scheduled for this afternoon this morning so that we 
might be a little bit ahead, because we expect some votes early 
in the afternoon that will take substantial amounts of time.
    So we are going to proceed now with the hearing on the 
budget of the Office of the Director. Dr. Varmus, do you have a 
presentation?
    Dr. Varmus. I do.
    Mr. Porter. Please make your statement, and then we will 
proceed to questions.
    Dr. Varmus. Thank you, Mr. Porter.

                    Opening Statement--Director, NIH

    Let me very briefly review for you some of the major issues 
that face the Office of the Director. Let me begin by 
introducing Mr. Itteilag, who is the Deputy Director for 
Administration; Mr. Steve Ficca, who is the Director for 
Research Services, and will be here to answer questions about 
buildings and facilities; Dr. Whitescarver, who is the Acting 
Director of the Office of AIDS Research; and Dr. Kirschstein, 
my Deputy Director.
    The four major functions of the Office of the Director are 
as follows: management, that is, oversight of grants, 
intramural programs, and many fiscal information functions; 
second, policy, which involves a wide range of issues I will 
mention in a moment, next, oversight of buildings and 
facilities; and finally, oversight of many research activities, 
including those that involve transfer authorities, 
administration of my discretionary funds, as well as a number 
of coordinating offices, including the Office of AIDS Research, 
which you'll hear about from Drs. Kirschstein and Whitescarver.
    The President's budget request for the Office of the 
Director for FY 1999 is $254.7 million, a 5.4 percent increase.
    On the opening day of these hearings, we talked about the 
report of our administrative functions and I don't want to 
spend time reviewing that now. You'll recall that that report 
proposed a better relationship between the Office of the 
Director and the Institutes and Centers, made many 
recommendations that we're in the process of implementing, and 
gave us good marks for many things; but it also offered a 
number of important criticisms that we're trying to respond to.
    Let me give you a sampling of the policy activities, 
without going into detail, to give you some sense of the very 
high level of activity within my office on a variety of issues 
that affect the conduct of science and our relationship to 
society.
    Bioethics has been a major issue on a variety of topics, 
and recently, we formed a trans-NIH Bioethics Committee that is 
dealing with issues of privacy, with international standards 
for conduct of research, and many other issues that are created 
by innovation in biological science.
    We've been more involved in science education in areas such 
as the design of curricular supplements that are being used in 
a variety of schools, creation of web sites, and bringing 
interns to the NIH to learn about science issues that can be 
used in educational settings.
    We've been more involved in public education, as you 
yourself have asked us to do. We have more consumer health 
information on the World Wide Web. We have developed a number 
of web sites for communication of health to selected 
populations, and we are giving guidance to our Institutes and 
Centers with respect to their outreach activities.
    We have been very instrumental in thinking through issues 
regarding clinical research and clinical research training, and 
developing a data base for clinical trials as we're directed to 
do under the FDA Reform Act. And we've been developing a series 
of discussions with the managed care industry, and the 
pharmaceutical industry to try to make more effective our 
efforts in clinical research and clinical trials.
    We retain a good deal of supervisory activity in the area 
of gene therapy. In transitioning from our previous mode of 
oversight of gene therapy protocols, we have developed a series 
of gene therapy policy conferences that have beenextremely 
effective. We've been working with other members of the Department on 
xenotransplantation and through the National Foundation for Biomedical 
Research, we've been involved, as we discussed with Dr. Collins, in the 
development of better methods for educating medical personnel about 
genetic testing.
    Let me say a couple of things about buildings and 
facilities; you can ask further questions of Mr. Ficca. We are 
continuing construction of the Mark O. Hatfield Clinical 
Research Center, asking for an additional $90 million to 
support construction activities in this year. We are nearly on 
schedule but are a few months behind, partly as a consequence 
of having to make some design changes in response to the 
potential cost overrun that I was not prepared to permit. We 
are now back, certainly on cost schedule, and nearly on time 
schedule. Mr. Porter, you were present, I am happy to say, at 
our groundbreaking ceremony in the fall. Construction is going 
well.
    We are asking for another $9.1 million to complete 
construction of a vaccine research center, funds for which were 
appropriated last year, we are very grateful for these as we 
discussed earlier, the Center is also being formed 
intellectually, as well as being planned structurally.
    I would just mention that we are still on schedule in the 
construction of so-called building 50 (the Consolidated 
Laboratory Building), for which funds were appropriated in 
earlier years; it's important to note that the construction 
plans are proceeding on schedule and we expect to be occupying 
that building by the year 2000.
    A few words about research oversight. There are several 
research oversight activities that are uniquely mine. One is 
continued reviews of the intramural programs of the various 
Institutes and Centers and reviews of the activities of the 
individual directors, which we now carry out every five years.
    In addition, I maintain another kind of oversight of 
research activities that applies to my use of the one percent 
transfer authority and the expenditure of my discretionary 
fund. Details of how we have used those monies are available to 
you, but I do want to make the point that the use of one 
percent transfer authority has been an extremely useful tool 
for me in each of the years in which I have had it.
    We have been transferring $20 million or $30 million each 
year as a result of a very careful effort to identify 
initiatives at the beginning of each fiscal year. We bring 
outside advisors in to make recommendations to me about which 
of those proposals should actually be supported.
    Dr. Kirschstein is going to talk in a moment about the 
various offices in the Office of the OD. I do want to mention 
specifically two that have attracted special attention. One is 
the Office of Alternative Medicine, which as a result of 
activities on my part and the part of Dr. William Harlan, has 
gotten into a much more productive mode during this past year, 
with cooperative ventures with the Institutes and Centers to 
carry out high quality clinical trials of alternative 
medicines. In addition, we've created a transagency 
coordinating committee for alternative medicine that involves 
the FDA, the CDC, and AHCPR, and that has engaged the attention 
of many of my Institutes and we feel we are working much more 
collegially and much more productively with the Office of 
Alternative Medicine.
    Secondly, we talked several days ago about the Office of 
AIDS Research and the leadership that has been afforded by Dr. 
Whitescarver, subsequent to Dr. Paul's departure, and the fact 
that we will soon enter the final stages of our search process 
for a new director. Also, we talked previously about the steps 
we've taken to implement the recommendations of the Levine 
Report. I will leave it to Dr. Whitescarver to comment briefly 
about those efforts.
    At this point, I think it's useful to turn the microphone 
over to Dr. Kirschstein to hear about the coordinating offices, 
other than the Office of AIDS Research.
    [The prepared statement follows:]


[Pages 2623 - 2632--The official Committee record contains additional material here.]



                 Office of Research on Minority Health

    Dr. Kirschstein. The directors of those offices are sitting 
behind us and if necessary, can provide details. But I would 
like to use several examples to talk to you about how the 
program offices coordinate other activities in their particular 
areas.
    The first is the Office of Research on Minority Health. 
It's been deeply involved, not only in NIH studies and 
programs, but also in the Department's initiative to close the 
disparity in health between the minority and majority 
populations.
    As you know, the initiative has selected six areas: infant 
mortality, breast and cervical cancer, heart disease and 
stroke, diabetes, AIDS, and immunization. In the area of infant 
mortality, NIH, in cooperation with the Health Resources and 
Services Administration and CDC, will invest in perinatal 
research to increase the identification of problems that Mr. 
Stokes was mentioning earlier this morning: risk factors and 
biological markers for adverse pregnancy outcomes, low birth 
weight, and preterm births, and for Sudden Infant Death 
Syndrome among minorities.
    The NIH will launch a $1.25 million new outreach effort 
targeted to racial and ethnic communities. It will include new 
media efforts to reach non-English speaking parents and to 
reach health professionals who serve primarily minority 
communities and will better use ethnic radio stations to raise 
parental awareness of what we know about SIDS.

                  Office of Research on Women's Health

    In the area of breast and cervical cancer, the National 
Cancer Institute, along with the Office of Women's Health in 
the Department, in June of 1998, will host a major meeting on 
the racial and ethnic issues involved in breast cancer. There 
will be a breast and cervical cancer education initiative 
designed to provide clear, user-friendly information and advice 
to women, particularly minority women.
    The program has been developed in consultation with black, 
Hispanic, American Indian, Alaskan Native, Asian and Pacific 
Islander women to find out what they would like to know. We 
will put together a hotline for the National Cancer Institute's 
Cancer Information Service and form numerous other partnerships 
with community-based entities.

                        heart Disease and Stroke

    In the heart disease and stroke area, NIH is going to 
launch a new web site for health care professionals who provide 
care primarily to black patients. And this will report on new 
ideas that can be used to decrease blood pressure in 
hypertensives, decrease cholesterol levels as needed, and 
increase preventive health behaviors. And there will be a real 
attempt to put together materials such as cookbooks with 
recipes that will be attractive to and be available to both 
African-Americans and Hispanics.
    Similarly, we have launched, in conjunction with CDC, a 
National Diabetes Education Program with a public awareness 
campaign that will be funded at about $1.5 to $2.5 million in 
the next year.
    In that regard, Mr. Stokes, I would like, as everybody else 
has, but on a very personal basis, because you and I have been 
interacting for 25 years or more, to tell you how much I am 
going to miss you and to thank you for all you have done to 
help us with our minority programs and all the other programs. 
This is a very personal thank-you.
    Mr. Stokes. Thank you very much.

                  Office of Research on Women's Health

    Dr. Kirschstein. The Office of Research on Women's Health 
has just completed its review of what has happened over the 
five years since the original Hunt Valley Report. And Dr. Pinn 
and her colleagues put together a series of regional meetings 
culminating in a Washington meeting. There will be new 
initiatives as a result of this, in the area of women's health, 
in the inclusion of women in clinical trials, and also in 
advancing career development for women scientists, something 
that both she and I have a great interest in.

           Office of Behavioral and Social Sciences Research

    One more example is the Office of Behavioral and Social 
Sciences Research, which works cooperatively with the 
Institutes to refine methodologies used in such research, and 
which has been particularly concerned with issues related to 
preventing risk-taking behaviors, smoking, lack of exercise, 
improper diet, and alcohol abuse.
    These are but three of a number of examples that I could 
have given you. Thank you very much.
    [The prepared statement follows:]


[Pages 2635 - 2643--The official Committee record contains additional material here.]



    Mr. Porter. Thank you, Dr. Kirschstein.
    Dr. Varmus, my staff has just reminded me that we cannot 
proceed with the entire panel and finish before the hour of 1 
o'clock without notice to the minority because people may have 
questions, particularly for Dr. Whitescarver and yourself. So 
I'm going to ask if Dr. Whitescarver would hold his statement.
    And Mr. Ficca, could you withhold your statement until 1 
o'clock as well? I'm sorry, I thought perhaps we could go 
straight through and finish by 1:00 or 1:30. Apparently, we 
cannot do that. Can you stay after 12:00 briefly?
    Mr. Ficca. Of course.
    Mr. Porter. Well, let's see if we can go a little ways into 
this with you and come back, say, at 1:00, and finish up 
hopefully before 1:30 because we're expecting a number of votes 
right about that time.
    So at this point I think we'll have questions. I'm going to 
ask Mr. Stokes if he has questions right now to proceed.

                      Women and Minority Programs

    Mr. Stokes. Thank you very much, Mr. Chairman.
    Dr. Kirschstein, let me take a moment and personally 
express my appreciation for your very kind remarks. And, I 
dowant to say on the public record, that probably over the last 25 
years I've worked closer with you than any other director of the 
National Institutes of Health. And, our interaction goes all the way 
back to the MARC and MBRS programs many years ago. I think one of the 
areas in which I have the greatest pride, if we've had any impact at 
all, has been that particular area that I've seen as a result of some 
of the things that you've done working with that program. Young 
minority scientists have done such outstanding work in the field of 
science. That's just one of the areas in which you have been very, very 
responsive to my concerns and I want to express to you my appreciation 
for it.
    In your statement, you indicate that minorities in all 
stages of life suffer poorer health and higher rates of 
premature death than does the majority population. I appreciate 
the fact that you have taken time to highlight these areas of 
concern. As the Deputy Director of NIH, do you specifically go 
about helping to further the work of the Office of Research and 
Minority Health and the Office of Research on Women's Health in 
an effort to address these critical health concerns?
    Dr. Kirschstein. As Deputy Director of NIH, I have worked 
very closely with Dr. Ruffin and Dr. Pinn in order to enhance 
the activities of their offices in regard to coordinating 
activities with the Institutes. And I think we can't stress 
that too much; that their offices are in place in the Office of 
the Director to help plan and work with the various individual 
institutes regarding the diseases and the training programs, 
about which you heard from Dr. Kasman this morning, that 
sometimes require a jump start, sometimes further coordination, 
sometimes the knowledge that one institute is doing something 
that another institute ought to be involved. The offices can 
coordinate across institute lines, and also provide some funds 
that can make things possible that might not have been possible 
otherwise. I work very closely with both of those programs.
    Mr. Stokes. Dr. Kirschstein, were you present the morning 
that we received testimony from the CDC?
    Dr. Kirschstein. No, sir; I was not.

                   Closing the GAP in Minority Health

    Mr. Stokes. All right. Well, let me tell you, when they 
testified here, the agency indicated that the gap in minority 
health could be closed if an approach is used that is similar 
to the Nation's concentrated and targeted immunization efforts. 
My question to you is do you think that this statement could 
apply to the NIH's efforts with respect to closing the gap in 
minority health? Dr. Varmus, you may have been here when that 
statement was made.
    Dr. Varmus. I was not here, sir.
    Mr. Stokes. No? Okay.
    Dr. Kirschstein. Mr. Stokes, I believe the immunization 
issues is somewhat simpler than closing the gap in the 
disparities in the health of minority populations and the 
majority populations. We know what the target is in 
immunization. We have to get to the school children who should 
receive the vaccines that are needed and there is a way of 
directly approaching this through public health methods. I 
think, first of all, we do not totally understand, yet, all 
about the diseases that afflict all of the people of the United 
States, but those that, in particular are of a greater 
consequence in minorities--hypertension, cardiovascular 
disease, prostate cancer, et cetera. And, therefore, we have 
much knowledge, much more basic information, that we must gain. 
In addition, the ability to have a way of really preventing the 
risk-taking behaviors that the Office of Behavior and Social 
Sciences Research is undertaking is very difficult and we need 
to know more about how to approach that. We need to know how to 
reach the communities in a very broad way. We need to have 
minority women who become pregnant go for prenatal care much 
sooner than they are very often able to do often now. So I 
think it's a much more complex problem.
    Mr. Stokes. Let me pose this particular question to either 
you or Dr. Varmus, or both of you may want to comment. The 
President has recently taken very specific interest in the 
disparity in minority health and he has addressed it in his 
statement to the Nation, and so forth and so on. With the 
tobacco settlement that's on the horizon, some of the national 
minority health groups--the National Medical Association and 
others--have been thinking that perhaps some of the settlement 
funds should be placed over in such offices as the Office of 
Research on Minority Health. I wonder if there's been any 
thought at all given to whether this might be something that 
NIH would consider?
    Dr. Varmus. Well, as you know, Mr. Stokes, there has been a 
tremendous amount of thought given to the question of how that 
money would be spent and there, of course, is considerable 
uncertainty about whether the money will actually appear. There 
have been many formulas for how such money would be provided to 
the NIH. My own inclination is to side with what the President 
has done in his current budget. That is to say that, if there 
are revenues from the tobacco legislation, it would go to the 
NIH to be distributed to the NIH in accord with its overall 
direction. I think we run some danger if we start parceling up 
these anticipated revenues in a narrow way without using our 
priority-setting to address the concerns that we believe are 
most important. The President has already identified minority 
health as a major priority. I would prefer not to try to link 
that to a repackaging of any money that comes from the tobacco 
settlement.
    Dr. Kirschstein. We should add that the NIH has a deep 
commitment to working with the Department on what is called the 
race health initiative and Dr. Ruffin's office's and my 
attention to this is very great.
    Dr. Varmus. But that is a separate question. We have 
identified a number of initiatives, some of which you've heard 
about during the hearings, as extensions of what the President 
has spoken to.

                   Newly Appointed Advisory Committee

    Mr. Stokes. I appreciate that response. You tell us also, 
Dr. Kirschstein, in your opening statement about the advisory 
committee that will convene its first meeting in April.
    Dr. Kirschstein. On April 3rd there will be the first 
meeting of the newly-appointed advisory committee. Dr. Varmus 
will be present for opening remarks, and I will be there, and 
Dr. Ruffin will, of course, be there as well.
    Mr. Stokes. I think that's an important step.
    Dr. Kirschstein. We agree.
    Mr. Stokes. Can you give us some idea of the intended 
objective or goals of this group?
    Dr. Kirschstein. I think it is to have an outside group 
which can look at the activities that the office has undertaken 
not only on its own part, but in conjunction with the various 
institutes, to learn everything there is about these programs; 
to assure themselves and us that the quality of these programs 
is what we all would desire them to be; and to, perhaps, make 
suggestions about how we can go about doing what we all want, 
namely, to close the gaps, if you will, and increase the number 
of minority research scientists in more innovative and better 
ways.
    Dr. Varmus. I don't see this as special treatment for the 
office, Mr. Stokes. It's part of my general philosophy that 
everything that we do at NIH is very much helped by ongoing 
advice from extramural scientists and others in the community.

                                violence

    Mr. Stokes. I appreciate that.
    Dr. Varmus, as you know, violence is now one of the 
Nation's most challenging public health problems. It impacts 
every one of us in every community. We're seeing daily, through 
the news media, what's happening in our society.
    I see the bells have gone off and it is nearly time to 
vote. I would just like to finish my question, Mr. Chairman. 
Thank you.
    Tell us, Doctor, what major research and outreach 
activities are underway or planned by the NIH that are designed 
to address youth violence in general and minority youth 
violence in particular?
    Dr. Varmus. Well, I've been provided with a list of many of 
the things that are being done. Of course, much of the violence 
research is conducted by the National Institute of Mental 
Health, but there are at least four other Institutes that have 
major portfolios in that area and much of it is coordinated by 
the Office of Behavioral and Social Science Research and other 
agencies are involved as well. There is a new initiative 
conducted by several institutes that addresses, specifically, 
violence against women, violence within the family, and this 
too is being coordinated by the Office of Behavioral and Social 
Science Research. We can provide more detail of these projects 
for you for the record.
    Mr. Stokes. Yes, please feel free to expand upon them in 
the record.
    Dr. Varmus. We'd be happy to do that.


[Pages 2648 - 2649--The official Committee record contains additional material here.]



    Mr. Stokes. Thank you, Dr. Varmus and Dr. Kirschstein. 
Thank you, Mr. Chairman.

                           tobacco settlement

    Mr. Porter. Thank you, Mr. Stokes. Dr. Varmus, I have some 
titular questions left over from other Institutes and some 
policy questions, and then I'll save the remainder of my 
questions on your office and OAR and buildings and facilities 
for this afternoon.
    First off, on the issue of a tobacco settlement. There's a 
lot of action going on, particularly in the Senate, and my 
question really relates to what input you have to the 
Administration's policy in this area because it seems to me 
that the basic proposal is to provide a settlement whereby the 
tobacco industry can continue with some protection from 
liability and paying some costs for the past additions to 
health care costs as a result of tobacco use plus some 
protections regarding the use of tobacco by minors. There are 
many people in this country, and I count myself among them, 
that believe that this entire industry has forfeited any right 
to exist because it has engaged in a clear conspiracy to addict 
our children; to undermine our health when they knew very well 
what the effects of tobacco were on health; and that we should 
not, in fact, have a tobacco settlement. We should allow them 
to be picked apart by the lawyers and the Attorney's General 
and pay the price that they should pay for what they have done 
to the health of the American people--recognizing that there 
was a period when they didn't know, but also recognizing 
there's been a period where they knew all of these things.
    What impact do you have on the President and his policy in 
this area, if any, and what advice have you given him?
    Dr. Varmus. Well over two years ago, Dr. Klausner and I 
wrote a letter to the President describing the effects of 
tobacco use on health. I can't measure the impact of that 
letter, but I think it certainly was in accord with the views 
of many others of his advisors.
    Since then, most of our conversations with the 
administration about policy toward tobacco legislation has been 
conducted within the Department. The role of the NIH has been 
mainly to provide information about the effects of tobacco on 
health; about the kinds of research that are done in the 
tobacco arena; and perhaps most especially, in light of today's 
discussion, about what we view as beneficial to NIH in health 
research that would be part of any tobacco legislation. The 
position that I have taken and that has been outlined in the 
letter I wrote to Senator Jeffords, which we could make 
available to you, is that we strongly endorse the President's 
position that if money is made available to NIH through tobacco 
legislation, it should be basically a block grant to the NIH 
that we wouldthen divide among the institutes in accord with 
what we see as ongoing priorities for health research. We think it's a 
mistake to try to set boundaries between what is tobacco-related and 
not tobacco-related research, or even worse, to try to specify in 
advance how much money should go to certain programs or to certain 
Institutes because the money comes from tobacco.
    Mr. Porter. I have to say, I've told the Speaker very 
directly--and some think this Republican heresy--but I've told 
him very directly I would support tomorrow, with nothing 
attached to it whatsoever, a substantial increase in the 
tobacco tax so that we could afford some of the things that the 
President has mentioned in his budget, particularly additional 
support for NIH. I doubt that that is going to occur, but it 
seems to me that that makes a great deal of sense both in light 
of the burdens that tobacco and its use have placed upon our 
society, the health care costs attached to it, and the need to 
prevent young people from getting access to it easily. So I 
hope, in fact, that we don't go to a tobacco settlement, and we 
go straight to an increase in the tobacco tax. I think that 
makes a lot more sense then to take people off the hook for 
things that they knew were wrong when they did them.
    Let me ask you another question. Tell me about your concern 
for the affect on our academic medical centers of the changes 
occurring in our health care delivery system, particularly the 
managed care component and their desire to cut costs and not 
use the services that have been available to our teaching 
hospitals?
    Dr. Varmus. Mr. Porter, as you know, we've discussed this 
problem before. There have been various attempts to estimate 
the loss of patient care revenues to academic health centers 
from the NIH perspective because many of those revenues have 
been devoted, in the past, to research, to research training, 
and to general sustenance of an environment in which much of 
our research is done. We can't simply make up that 
differential, but we can do things to try strengthen the 
ability of academic health centers to conduct research, 
particularly clinical research. Some of the initiatives we've 
announced this year as part of the 1999 presidential budget 
request are intended to repair some of the damage that's been 
done by this change in patient care reimbursement. I think most 
obvious is the effort we're making to train clinical 
researchers through the new programs I've described earlier to 
provide early-and mid-career awards for investigators who would 
now otherwise be imperiled by the directive to spend more of 
their time doing clinical work to generate revenues for their 
institution.
    In addition, we are taking a more active role in the 
development of clinical trials and the general sustenance of 
clinical research in a variety of ways. So I think that's going 
to be the way in which we approach this--by being sure the 
clinical investigators are given a chance to be recruited and 
trained and sustained, and by being sure that our clinical 
research portfolio is diverse.

                        chronic fatigue syndrome

    Mr. Porter. Finally, for these catchall questions, there is 
some concern within the CFIDS community that research in this 
area is decreasing. Can you tell us what's happening and what 
progress you are making in CFIDS research?
    Dr. Varmus. I'll probably have to provide details for the 
record. I do have some numbers here indicating that we--we 
spend about $7 to $8 million a year. Those numbers have not 
shown any appreciable increase. We estimate $8 million in 
research activity in 1999, as well as in 1998. This has been a 
difficult problem for medical research because the syndrome has 
not been very precisely defined. We don't have a cause. There 
are, as the numbers suggest, perhaps a dozen or two dozen 
investigators working on the problem. There have been many 
claims for infectious and immunological causes for the 
disorder, and the NIAID has been devoting efforts to try to 
define this syndrome more precisely. My own view is that until 
a cause is found, it is going to be difficult to try to solve 
the problem. It remains a syndrome that's still somewhat vague 
in its characteristics.
    Mr. Porter. Wouldn't additional available funding help to 
find the cause?
    Dr. Varmus. I think that's hard to say. Many leads are 
being pursued. I think the opportunities become much more clear 
and the mode of address to the problem becomes a good deal more 
apparent once something has been identified. Whenever we 
receive a proposal to make a legitimate stab at finding a cause 
of a new disease, then that grant would be supported. I can try 
to supply through NIAID a more detailed response to the 
question of whether there are leads that are not being 
appropriately pursued.
    Mr. Porter. I'm sorry to spring this question on you. It is 
simply one that was left over that I wanted to ask and couldn't 
ask at the time.
    Thank you very much, Dr. Varmus.
    We stand in recess until 1:00 p.m.
    [Recess.]
    [The following questions were submitted to be answered for 
the record:]


[Pages 2653 - 2854--The official Committee record contains additional material here.]



                                            Friday, March 27, 1998.

                        OFFICE OF AIDS RESEARCH

                               WITNESSES

DR. HAROLD VARMUS, DIRECTOR, NATIONAL INSTITUTES OF HEALTH
DR. RUTH KIRSCHSTEIN, DEPUTY DIRECTOR, NATIONAL INSTITUTES OF HEALTH
ANTHONY ITTEILAG, DEPUTY DIRECTOR FOR MANAGEMENT, NATIONAL INSTITUTES 
    OF HEALTH
STEPHEN A. FICCA, ASSOCIATE DIRECTOR FOR RESEARCH SERVICES, NATIONAL 
    INSTITUTES OF HEALTH
DENNIS P. WILLIAMS, DEPUTY ASSISTANT SECRETARY, BUDGET, DEPARTMENT OF 
    HEALTH AND HUMAN SERVICES
DR. JACK WHITESCARVER, ACTING DIRECTOR, OFFICE OF AIDS RESEARCH
DR. ANTHONY FAUCI, DIRECTOR, NATIONAL INSTITUTE OF ALLERGY AND 
    INFECTIOUS DISEASES

    Mr. Porter. The subcommittee will come to order.
    Dr. Varmus, we understand that the votes will begin at 
precisely 17 minutes after the hour and will last----
    Dr. Varmus. I didn't know the Congress operated with such 
precision, Mr. Porter.
    Mr. Porter. Yes. They'll last perhaps, close to an hour, 
which is not good news at all. I suggest that when the bells 
ring, we go the extra 5 or 6 minutes and then we'll recess. 
It's probably reasonable to plan on 45 minutes. People can take 
a break and then we'll come back and finish. Is that 
acceptable?
    Dr. Varmus. Whatever you say.

                 Opening Statement--Acting Director OAR

    Mr. Porter. Why don't we go ahead with Dr. Whitescarver's 
statement first, and then go to questions.
    Dr. Whitescarver. Thank you, Mr. Chairman.
    My message this afternoon is a simple one. AIDS is not 
over. In the battle against the pandemic, it's the best of 
times and the worst of times. With new combination therapies, 
protease inhibitors and other antiretroviral drugs, death 
rates, infection rates, and hospitalizations are declining in 
many U.S. populations. We've dramatically reduced the number of 
infants born with HIV.
    Mr. Chairman, these drugs are not the silver bullet. We do 
not know how long their benefit will last, or if the immune 
function can be restored. And whereas the drugs have been 
effective for many people, there are others who simply can't 
tolerate the side-effects.
    We're now identifying adverse metabolic effects that may be 
the result of long-term use of these therapies. And drug 
resistant HIV is a very dangerous reality.
    AIDS cases continue to rise among women and minorities in 
our country. And AIDS is also increasing in another group--
people over 50 years of age.
    The news around the world is far worse. WHO now estimates 
that 2.3 million people died of AIDS last year, which is a 50 
percent increase over 1996. And more than 30 million people 
worldwide are living with HIV, with 16,000 new infections each 
day. And most of them in the world's poorest nations.
    Thus we face two great disparities: the disparity that 
exists among different populations within our own country, and 
the even greater disparity between the industrialized and the 
developing worlds.
    The NIH AIDS comprehensive research plan which is developed 
each year with the advice of non-Government and other experts, 
addresses these dualities. It balances the need for new and 
better therapies with the global imperative for a safe and 
effective vaccine. The plan is utilized each year by the 
institutes to develop their budget request. And it also 
continues to implement the recommendations and the priorities 
in the Levine report.
    Key among these recommendations was vaccine research, which 
is echoed by a specific challenge from the President. This 
budget request reflects an unprecedented commitment to this 
critical area of research. And the NIH has already taken a 
number of important steps to move the science forward: Dr. 
Baltimore's committee is established and working; the 
innovation grants; and the new Vaccine Research Center, which 
we'll hear a little bit about. We also have the OAR prevention 
science working group that has met on a regular basis and given 
recommendations for other priority areas of prevention 
research.
    NIH programs are pursuing their search for newer and more 
effective and less expensive drugs with increased potency, less 
complicated treatment regimens, and fewer toxic side-effects.
    And also the clinical trials for AIDS reflect a shift in 
demographics of the epidemic with increasing numbers of 
minorities and women being enrolled.
    I firmly believe that the steps taken by the OAR, along 
with the NIH institutes over the past few years, and the 
progress that's been made in this area of research, demonstrate 
that the Nation's investment is indeed well spent. That 
investment is also reaping rewards in our ability to understand 
and treat other infectious, malignant, neurologic, autoimmune, 
and metabolic diseases.
    But I say again, Mr. Chairman, the battle is far from over. 
But we do certainly appreciate the support that this committee 
has given for AIDS research.
    [The prepared statement follows:]


[Pages 2857 - 2862--The official Committee record contains additional material here.]



                       clinical research capacity

    Mr. Porter. Thank you, Dr. Whitescarver.
    Let me first ask two questions of Mr. Ficca. Can you update 
us on the cost estimates to renovate the existing clinical 
research center building so that it can be brought into 
conformance with modern design stipulations?
    Mr. Ficca. The Marks-Cassell report recommended, and the 
NIH has been following a plan, that upon occupancy of the new 
CRC, the vacated spaces in the existing clinical center--that 
is the core E and F wings would be used to carry out a phased 
renovation of that facility. A specific plan is not yet 
developed. There is a concept of a phased renovation that would 
entail renovating first the E and F center wings upon their 
vacancy, and then one distal wing which would be to the west 
and then to the east. That total plan would probably take about 
12 years after it's started. And the cost estimates would vary, 
but it is anticipated that the annual amounts would range from 
$30 million to $50 million per year.
    Mr. Porter. For 12 years?
    Mr. Ficca. There is no specific cost estimate. That's 
strictly based on the number of square feet and the unit cost 
that might be required to do that renovation.
    Mr. Porter. How does that compare with the cost of the 
entire new clinical center?
    Mr. Ficca. The CRC budget, as you know, including the 
design, is $333 million.
    Mr. Porter. So this actually could be more than that?
    Mr. Ficca. Well, it would be if it were to be completed 
over that time frame. But as I said, the specific plans have 
yet to be developed.
    Mr. Porter. What would be the first fiscal year where you 
would have outlays? In other words, when would you complete the 
building--and assuming you had a plan, then begin the 
renovation?
    Mr. Ficca. At this juncture, the concept entails beginning 
in the year 2002.

                        vaccine research center

    Mr. Porter. Of the $9.1 million requested for the 
completion of the vaccine facility, $3 million is being 
requested from the Buildings and Facilities account, and $6.1 
million is being requested from the Office of AIDS Research. 
Why aren't you proposing to fund the full amount from the 
buildings and facilities account?
    Dr. Varmus. Perhaps I should answer that Mr. Porter. The 
reason is that we consider the vaccine research lab to be 
directed, ultimately, to more than just AIDS vaccine. We expect 
to use the vaccine technologies we're developing there to 
address a number of other important vaccine problems, including 
tuberculosis and malaria.
    Mr. Porter. But aren't you answering it the other way 
around. Because if that's the case, why isn't all the money 
taken from buildings and facilities?
    Dr. Varmus. Oh, I'm sorry. [Laughter.]
    Because we feel that the first thrust here, the major 
thrust--usually the question is asked the other way--but the 
major thrust here will be AIDS.
    Mr. Porter. And that justifies taking the money out of the 
OAR account.
    Dr. Varmus. Correct.

                    consolidated aids appropriation

    Mr. Porter. Dr. Whitescarver, I know you are contemplating, 
or anticipating, this question and I don't want to disappoint 
you. Your budget again, proposes a consolidated appropriation 
for the Office of AIDS Research. I know you are obliged to 
support the President's request, but can you tell me if the 
approach we have used in the past few years for AIDS funding 
was workable, and if there are any differences between the 
approach we're using now and the one that we have used earlier?
    Dr. Whitescarver. Thank you, Mr. Chairman. Indeed I was 
anticipating that question. I might refer back to Dr. Fauci's 
answer, when as an institute director you directed that 
question to him, and his response that the way things are going 
now is working very well. The ideal situation would be a single 
appropriation. But to specifically answer your question: it is 
working well. I think it's important as this committee has 
provided us the opportunity to make any shifts across the 
institutes according to scientific priorities or changes in the 
scientific opportunities up through the time of conference, 
with both the Director of OAR and the Director of NIH making 
those decisions.

                     hiv/aids affected populations

    Mr. Porter. Dr. Whitescarver, a great deal of progress has 
brought about a longer and better quality of life for many HIV-
infected individuals. In fact, AIDS deaths have dropped 44 
percent from the first 6 months of 1997 compared to the first 
six months of 1996 and new AIDS diagnosis have declined by 12 
percent during the same period. However, are there demographic 
groups that are not sharing in this positive trend, or does it 
go across all demographic groups?
    Dr. Whitescarver. No, there are groups within the U.S. 
population among whom instead of decreases, in fact, there are 
increases and that's in the minority groups--Black, Hispanics--
and also among women. Both of those are increasing.
    Mr. Porter. How do we account for that? How do we account 
for that difference?
    Dr. Whitescarver. Probably due to the disparity of access 
to treatment amongst those, as well as the incidence of IV drug 
abuse.
    Mr. Porter. What can we do to improve those numbers?
    Dr. Whitescarver. We have to work harder in getting the 
behavioral models that are specifically directed to those 
populations, and continue our efforts, which we've been very 
successful with thus far, in recruiting these populations into 
clinical trials.

                       inexpensive drug therapies

    Mr. Porter. Dr. Whitescarver, researchers in Los Angeles 
and Washington have identified what may be the first 
inexpensive AIDS drug. The drug is inexpensive, no more than 
$30 per month, compared to the $1,300 monthly cost for protease 
inhibitors. Clinical trials are due to begin later this year. 
How long do you believe it will take before this drug may be 
made available to AIDS patients?
    Dr. Whitescarver. May I refer that question to Dr. Fauci, 
please, as he's the expert on treatment issues?
    Mr. Porter. Surely.
    Dr. Fauci. Are you referring to hydroxyurea?
    Mr. Porter. I think so, yes.
    Dr. Fauci. Mr. Chairman, the information that you are 
referring to is a preliminary study that was presented at two 
meetings--one in Chicago and one at the last International 
Congress--indicating that when hydroxyurea, which is already 
approved for chronic myelogenous leukemia, as well as sickle 
cell anemia and is a rather inexpensive drug, actually has an 
important effect on decreasing certain substances within the 
cell that actually is necessary for the replication of the 
virus. The reason it's important is because the virus cannot 
develop resistance to that because of the fact thatyour effect 
is on the cell.
    The clinical trials are necessary because some anecdotal 
reports originally from here in the United States and then some 
reports from Germany have shown that individuals that take 
hydroxyurea together with the drug DDI have a decrease in viral 
burden. In fact, if you look at the cells of these individuals, 
they seem to have much less of a reservoir of HIV. Given that 
result, these drugs are now being tested in NIH-supported 
clinical trials. If it proves to be effective, then certainly 
the company would ask for approval by the FDA to use and 
advertise for HIV.
    So we're optimistic about the concept, but as is always the 
case, the proof of the pudding is going to be in the clinical 
trial.

                      Origin of the HIV/AIDS Virus

    Mr. Porter. Thank you, Dr. Fauci. Last month it was 
reported, and Dr. Fauci you may want to answer this one as 
well, last month it was reported that researchers have 
identified the AIDS virus in a blood sample drawn in 1959 from 
a man, in what was then the Belgian Congo, making it the oldest 
definite case of the infection in a human being. Can this 
discovery help us establish a more precise time frame for when 
AIDS began? Can this information help us better understand how 
AIDS and other emerging infections behave over time?
    Dr. Fauci. The answer is yes, but what it has been, Mr. 
Chairman, is that these dates of about earlier than 1959, 
namely the late 40s and early 50s, were actually projected by 
what we call phylogenetic trees. When you look at the virus 
itself, and you determine what you can determine, the mutation 
rate--if you look at a virus that you isolate in 1980 and look 
at a virus that you isolate in 1998, you can actually map out 
these phylogenetic trees. The virus that was isolated in 1959 
gave investigators a very good anchor of knowing about when it 
made the jump from a non-human primate and adapted itself to 
humans. So the fact that we know that this probably occurred, 
if you back calculate, somewhere in the late-40s early-50s, 
which interestingly, was what was projected from the modelers a 
few years ago, even before we had that sample.
    In answer directly to your question, it does give us now a 
broader more comprehensive look of the rate of change of the 
virus so it will tell us more definitively, even though we were 
on the right track anyway, where we're going to be if the virus 
keeps changing in the year 2000, 2100, 2200 because the 
phylogenetic map, as we call it, is now more complete because 
you have more of an accurate assessment of the source point. So 
it is important information of historical interest.
    Mr. Porter. The map that you referred to, is it ever 
complete? You kind of indicated it keeps changing.
    Dr. Fauci. No, well, actually the map keeps changing as the 
different branches of the tree go out. But when you know what 
the source point is, you have a much more accurate historical 
perspective of where it started from. So right now, the 
information we have now, as we see mutations and greater 
diversity occur over the next 5, 10, 15 years, you will just 
see more branches on that tree.
    Mr. Porter. Is this true for all viruses or just this one 
type of virus?
    Dr. Fauci. It's more true of HIV because of its 
extraordinary ability to mutate. If you look at the less 
mutable viruses, the ones that generally stay conserved over 
generations, you'll see some divergence but nothing like the 
type of divergence you see with a retrovirus, which has a very 
poor ability to replicate itself in an exact replication of 
what it was before--we call it poor proofreading of the genetic 
code.
    Mr. Porter. Ms. Pelosi.
    Ms. Pelosi. Thank you, Mr. Chairman. As fate would have it, 
we're here.
    Mr. Porter. I was actually going to complete the hearing by 
about this time by going straight through the lunch hour and 
then we decided that wouldn't be fair because you might not be 
here.
    Ms. Pelosi. Oh, aren't you nice.
    Mr. Porter. So we put it over so you could be here.

                        Long-Term Nonprogressors

    Ms. Pelosi. As always, thank you, Mr. Chairman, for your 
graciousness and your leadership on this issue, and your 
recognition of how important this is to our community, and 
really, obviously, to our country as well.
    I know that the chairman has asked some very important 
questions on this issue, and in the interest of time--probably 
we'll have a vote--I may submit some of my questions for the 
record. But I wanted to join you in welcoming Dr. Whitescarver 
today, and Dr. Fauci, and Dr. Varmus, and Dr. Kirschstein, and 
everyone once again.
    Specifically, to OAR, and maybe you all would chime in on 
it, Dr. Levy at UCSF has announced that the study of people 
with HIV who are not progressing to disease may help us develop 
a vaccine for AIDS. I'm sure you're familiar with his 
announcement. There are these people who have had scores of 
exposures and have still not contracted HIV. Do you think that 
can tell us more that is useful in research? Can you tell us 
more about the evidence on nonprogresses and the implications 
for vaccine research?
    Dr. Fauci. What Dr. Levy was referring to was what as you 
said, long-term nonprogressors. For many years, Dr. Levy has 
been working on a factor that's secreted by a certain type of 
lymphocyte called CD-8 positive T-cell. He clearly was the 
first to identify it. Subsequent to that, a number of other 
factors that are made by this particular cell have been shown 
to be potent blockers of the binding of HIV to its cell--they 
are called chemokines. What Jay is dealing with is something 
that's above and beyond that; it's not that; it's a substance 
that he has not yet isolated to the point of being able to 
molecularly characterize it. The interesting thing that he 
found is that the CD-8 cells of these long-term nonprogressors 
secrete a large amount, disproportionately, of this suppressor 
substance that he calls a CD-8 suppressor substance. The point 
that he made at the meeting in San Francisco last week and that 
was reported in the press, is that if you can immunize 
individuals and induce CD-8s, when they recognize the virus as 
it gets into an individual initially--namely when you vaccinate 
somebody--that the CD-8 cell will recognize the virus and start 
secreting this suppressor substance and so block the ability of 
the virus to take hold and hence be an effective vaccine.
    It's an interesting thing because it diverges a little bit 
from classical immunology, which is a highly specific 
phenomenon of blocking a microbe. What he's talking about is 
something that is specific in its ability to be induced, but 
nonspecific in its ability to suppress the virus. So it's an 
interesting concept that he's closing in on.
    Ms. Pelosi. Well, what I reread in preparation fortoday, 
when I reread the press on Dr. Levy's announcement, I was reading it in 
light of your presentation last week. It was very interesting. Of 
course, the issue of a vaccine is one that we're all very hopeful and 
optimistic about.

                        Vaccine Research Center

    Dr. Whitescarver, or any of our guests, last year, the 
President announced the creation of a new vaccine research 
center at NIH to focus on HIV and other vaccines, can you bring 
us up to date on where we're going on that? Have we appointed a 
new director yet?
    Dr. Varmus. If I can comment briefly, Ms. Pelosi? We are 
still in the search process for a new director. However, the 
center is working as a center-without-walls. There are biweekly 
meetings; outside speakers are brought in. Those who are 
involved in vaccine activities on the NIH campus are 
interacting with Dr. Baltimore's outside advisory group. The 
construction plans, for which we already have about two-thirds 
of the funds from last year's appropriation bill, are in 
progress. We have designed the building, and we expect to have 
the building completed in about 2000.
    Ms. Pelosi. So we could infer from your remarks that the 
work of the vaccine center is complementing the work of NIH and 
the development of an AIDS vaccine. You're working----
    Dr. Varmus. We think that we are as far along as we could 
be. I would like to have a director for the center. I don't 
have one ready to name. The search process is still ongoing.

                     International AIDS Activities

    Ms. Pelosi. I want to just throw out two words. One is: 
international, and the other is: women. And whatever you said, 
I'd like you to say in light of those two things. I have a big 
long question, but I'm just going to cut to the chase to Dr. 
Whitescarver. Is there a formalized process in your office to 
share information and engage in joint planning on global AIDS 
activities? How does the OAR coordinate its research agenda and 
prevention efforts with other agencies in the U.S. Government 
in recognition of the great international threat that AIDS 
poses?
    Dr. Whitescarver. The OAR serves as a coordinating body on 
behalf of the Institutes, but the actual coordination efforts 
are handled almost at a program--or right down to the program 
level--in the various institutes. We do work with the CDC and 
other sister agencies on our international efforts, notably 
amongst that is the NIAID effort of the HIVNET and linked with 
that are some behavioral studies supported by the drug abuse 
institute and the National Institute of Mental Health.

                              HIV in Women

    Ms. Pelosi. Women?
    Dr. Whitescarver. Virtually the same holds true of women. 
We have studies in, again, the NIAID, an interagency women's 
health study, that includes other agencies like the CDC, and 
multiple institutes at the NIH.
    Ms. Pelosi. Do you work with the Office of Research on 
Women's Health?
    Dr. Whitescarver. Yes, we work very closely with Dr. Pinn's 
office on our research programs in planning and coordinating, 
as well as outreach activity.
    Ms. Pelosi. And including women in research?
    Dr. Whitescarver. Correct.
    Ms. Pelosi. Now, in terms of women and microbicides: in the 
United States, women represent, as you know, an increasing 
share of people with AIDS, unfortunately, and the latest 
estimates from the World Health Organization are that 40 
percent of new adult infections in the world occur in women. 
What is the status of research being performed through the 
Office of AIDS Research on STD and HIV prevention? When can we 
hope to have a proven microbicide, a proven, effective 
microbicide to prevent HIV, and what have you done to assure 
the availability of such a product in the developing world, 
where it's desperately needed?
    Dr. Whitescarver. The planning effort for microbicides 
specifically and STD in general, both treatment and prevention, 
is coordinated by the OAR's Prevention Science Working Group, 
newly established and chaired by Dr. James Curran, formerly of 
the CDC.
    The specific answer to the question of the likelihood and 
when of the microbicide, there are several trials ongoing now, 
including international sites, that are managed by the NIAID, 
and maybe Dr. Fauci might have a specific----
    Dr. Fauci. There are about two or three trials that are 
ongoing now. The most likely candidate is Nonoxynol 9, as an 
anti-HIV, which is a spermatocide that is used. One of the 
difficulties, that I mentioned during our hearing, is still 
we're not satisfied with our ability to avoid inflammatory 
response when they're used. So there's the possibility that 
women who use the topical microbicide, that they will have a 
dual effect, one of blocking HIV and other STDs, but the other 
in increasing vaginal and cervical inflammation which might 
actually propagate transmissibility.
    So that's still an obstacle that needs to be overcome, and 
what they're doing right now on animal models. It has been an 
interesting animal model of transplanting vaginal tissue and 
looking at different compounds, and different bases that you 
put the compound in, to see if you can get a noninflammatory 
response while you maintain the antimicrobial activity. So, I'm 
optimistic that it's going to happen. But it's something that, 
unfortunately, we've been inhibited by this inflammatory 
response that continually occurs when you apply these 
spermatocidal gels.
    Ms. Pelosi. So the challenge is still the same in that 
regard?
    Dr. Fauci. Yes.
    Dr. Whitescarver. May I just add a word to that insofar as 
the responsibility of the OAR is concerned. As you know, we 
have these coordinating committees which are made up of 
Institute representatives, and microbicides happens to fall 
within the purview of several of these coordinating committees. 
When they all come together, as a planning group, to establish 
the plan, and then the plan goes back to the Institutes to 
develop their specific projects, we play a very major role in 
behavioral research. In addition to the prevention science 
working group I've already mentioned, natural history and 
epidemiology, and the therapeutics group, all have an interest 
in microbicides and other treatments for women.
    Ms. Pelosi. Thank you. How are we doing on time, Mr. 
Chairman?
    Mr. Porter. We're a--I didn't keep track. [Laughter.]

                             HIV Therapies

    Ms. Pelosi. Oh, okay. I like it, I like it. We have you all 
to ourselves.
    Dr. Whitescarver, you mentioned in your opening statement 
efforts to develop drug combinations which are easier for 
people to take and can improve adherence to a therapy. Can you 
give us an idea of how therapies for HIV are likely to change 
over the coming year, in terms of the new drugs, andthe 
complexities of drugs that you mentioned?
    Dr. Whitescarver. I can begin the answer on that, and then 
Dr. Varmus and Dr. Fauci may have some specifics to add to it.
    The OAR just sponsored, in conjunction with several of the 
Institutes, an adherence conference which addressed the 
problems with the advent of the combination therapies and the 
problem associated with the complexities of taking these drugs, 
and the regimens. The recommendations from that conference will 
soon be out, and we will be distributing those for future 
research planning efforts. Now, some of the pharmaceutical 
companies have already come along with their second generation 
and third generation of drugs, which offer less complexities to 
the patient. Instead of four or five times a day, there are one 
or two drugs now that can be taken twice a day, as I recall.
    Dr. Fauci. A couple of things have happened. The companies 
are now putting a major effort, in addition to developing new 
drugs, to developing drugs that can be taken in combination. 
For example, there's one Glaxo Wellcome now has an 
administration that's a combination of the Zidovudine and 
Lamivudine, called Combovir. So you take one tablet and it's 
just like taking AZT and 3TC together. The other even more 
important one is drugs that have a longer half-life and a 
better tissue distribution. So that instead of having to take 
the total of 28 to 35 tablets and capsules a day, you can maybe 
take one in the morning.
    There's one particular drug that is at the stage that it 
only has a number, it doesn't have a name yet, that you can 
actually take it once in the morning. It has a greater than 12 
hour half-life, which means you could probably just take one a 
day, which would be wonderful. It doesn't have to be taken in 
association with meals and drinking, so it doesn't disrupt the 
eating habits of an individual.
    If we can get four or five of those over the next couple of 
years, then I think we would have made a major advance towards 
getting people to be more compliant, and make it more user 
friendly.
    Ms. Pelosi. That's very exciting.
    Dr. Fauci. Yes.

                             youth and hiv

    Ms. Pelosi. Because obviously part of the problem is to 
reach people and to have them comply with a routine. I did want 
to ask one more question about youth and HIV, following up on 
the America Agenda Report, Youth and HIV, can you bring us up 
to date on your Institutes' involvement in addressing the 
concerns raised in the American Agenda Report? When I say your 
Institute, I mean, the question is really addressed to Dr. 
Whitescarver, but I throw it out there to the National 
Institutes of Health.
    In our community, the emerging advocacy groups, continues 
to be young people They are emerging an even stronger voice, 
and they want a seat a the table. And I just wondered, your 
report states that, ``While NIH has opened pediatric clinical 
trials to adolescents up to 18, and the adult trials to those 
who are as young as 13, adolescents continue to face barriers 
in their participation to clinical trials. Basic research on 
adolescent reproductive and immune system development is 
lacking. Additional studies are needed to understand the 
natural history of HIV in adolescents, as well as expanded 
study of youth and their behaviors.'' That you may respond for 
the record, if you would?
    Dr. Fauci. Well, actually the National Institute of Child 
Health and Human Development has a major effort in that in 
looking at, as you eluded to, our clinical trials efforts. 
Unfortunately, in the past the adolescent has been that sub-
population that has sort of slipped between the cracks. Not 
that we were not trying to outreach to them, but because they, 
no one knew, no one was responsible for them. They didn't 
classically get into the pediatrics because many of them were 
runaways, and people who didn't have access, and yet they were 
not part of the adult establishment. But right now, as of at 
least a couple of years, that's been very heavily addressed by 
all the Institutes, NIAID, as well as Child Health. The NICHD 
has played a major role in trying to delineate the behavioral 
determinants that will allow us to better access those 
individuals.
    Dr. Varmus. The NIH, Ms. Pelosi, has just put together a 
position paper on the inclusion of pediatric patients in 
clinical trials. That would apply, of course, more generally to 
the problems we deal with, not simply AIDS.
    Ms. Pelosi. Well, I appreciate that, and our, again in our, 
speaking from the experience in our community, I meet with 
these young people and to talk about, well, AIDS is a very big 
issue for them, and they will give me the benefit of their 
experience in terms of what's out there in the community, and 
then I'll find out that they're 15 years old. And, I think, I 
hope, you know, I'm thinking of them as 18, 19, 20, and then 
I'll say, ``Well, now how old are you?'' Fifteen, 16, 15, 16, 
so they are, they fall into the category of pediatrics, but 
some of the behavior is very adult, and the challenge is great. 
And they know more about it than we ever could because they're 
living it.
    Thank you, Mr. Chairman. I want to thank everyone for this 
presentation. I'm particularly interested in the Office of AIDS 
Research, and I'm so delighted to see that this has all worked 
out, and everyone is, every Institute is reaching its 
fulfillment, and the Office of AIDS Research is able to do its 
job effectively. And I commend Dr. Varmus for his leadership on 
that, and Dr. Fauci for his cooperation on that. I thank you 
all for your testimony today. Thank you, too, Dr. Kirschstein, 
Dr. Whitescarver. Thank you, Mr. Chairman.

                         arthur andersen study

    Mr. Porter. Thank you, Ms. Pelosi. Let me advise the panel 
that we will have a 15 minute vote, a 5 vote and a vote on 
final passage, so I would judge that we would not be back here 
before 2:00 at the earliest. The subcommittee will stand in 
recess pending the votes.
    [Recess.]
    The subcommittee will come to order. Dr. Varmus, you talked 
in your opening remarks about the Arthur Andersen study, and 
the question I want to ask is, are there going to be follow-up 
reviews by Arthur Andersen to monitor your implementation 
process? In other words, do you plan to use them to assess what 
you're doing, and make certain you're following the 
recommendations?
    Dr. Varmus. We haven't contracted for that activity yet, 
but we are considering doing that, or having Jack Mahoney, who 
has been helping with the study as an intermediary with Arthur 
Andersen, help with that. We have established a panel of 
Institute directors, and other high-level executives to carry 
out an implementation plan, and I think the directions that 
were given to us by Arthur Andersen are clear enough that we 
can follow themand make some judgments ourselves about how 
we're doing. But we have given thought to having a more specific review 
of the implementation at some future date.
    Mr. Porter. Quoting from their report, they said, 
``Identifying and tracking costs and benefits by core function 
would better enable NIH to assess the costs and benefits of its 
basic functions, and better portray to Congress the full range 
of NIH activities.'' How do you plan to implement that 
particular suggestion?
    Dr. Varmus. That's a part of the plan that we're not so 
enthusiastic about. Mr. Itteilag has given a lot of thought to 
this issue and might want to respond briefly to summarize some 
of the concerns we've had about that part of the plan.
    Mr. Itteilag. The concern, Mr. Chairman, is that if we were 
to carry out what we believe to be the intent of the Andersen 
recommendation, it would give us much less flexibility in 
managing our administrative costs within the categories of 
extramural research, intramural research, and general 
administration, and it would put us in the position, 
potentially, of having more re-programming actions, and not 
having what we think is as smooth of an operation with the 
needed flexibility to be able to change during the fiscal year.
    Dr. Varmus. I thought I would emphasize here that this is 
the only major recommendation that was provided by Arthur 
Andersen that we disagree with.

                 complementary and alternative medicine

    Mr. Porter. Well, I'm not proposing that you should 
necessarily agree with all their recommendations by any means. 
They come in from outside and don't necessarily understand all 
the implications of some of their suggestions, but I just 
wondered about that particular one.
    A recent survey of complementary and alternative medicine, 
called CAM, in the United States, appeared in the New England 
Journal of Medicine, and estimated that 65 million Americans 
used complementary and alternative medicine to treat a serious 
condition in 1990 at a cost of $13.7 billion. Regional surveys 
indicate that millions of children are treated with CAM 
therapies.
    Last year, the Appropriations Committee provided $20 
million to the Office of Alternative Medicine, and specified 
that not less than $7 million should be used for peer-reviewed 
complementary and alternative medicine research grants and 
contracts that respond to program announcements, and requests 
for proposals issued by the Office of Alternative Medicine. Can 
you tell us what kinds of grants and contracts were funded with 
this $7 million?
    Dr. Varmus. We have followed those directives and we have 
initiated as you've heard in some detail, a study of St. John's 
Wort. In addition, we will fund a chiropractic center in the 
State of Iowa, and there's a study of acupuncture and its role 
in osteo-arthritis that will be funded jointly with NIAMS. 
Also, a trial of glucosamine in osteo-arthritis is also in the 
planning stage. These have not yet been funded, but they will 
be funded soon.
    Mr. Porter. Do you believe that this is a good use of the 
money, and should we be spending more in this area, Dr. Varmus?
    Dr. Varmus. We have had an increased budget for the OAM, 
and I believe that now we do have things on a better track. As 
I mentioned earlier in my testimony, we developed a trans-
agency advisory group that will meet intermittently to look for 
frequently used, promising therapies that will be then subject 
to further evaluation by William Harlan, the director of the 
Office for Disease Prevention, and by the OAM to make 
determinations in conjunction with the Institutes of what 
should be subjected to a careful clinical trial.
    I pulled together the Institute directors that have special 
interests in the areas of alternative and complementary 
medicine. That, of course, is virtually all of our Institutes 
that do clinical research. I asked them to try to identify 
targets. That's been done by the Cancer Institute, Mental 
Health, Aging, Arthritis, and quite a few other Institutes. 
There are now, in addition to those things I mentioned that are 
already slated for clinical trials activity, a number of other 
candidates that are undergoing further review. When these prove 
to look promising, based on anecdotal data and on the extent of 
the public health importance--for example, St. John's Wort is 
very widely used--we will carry out clinical trial and try to 
settle these issues for the American public.
    Mr. Porter. Dr. Varmus, are you aware of any other 
enterprise or institution that does clinical trials for 
research regarding alternative medicine therapies?
    Dr. Varmus. Well, there are many such trials carried out in 
Europe. One of the functions of the Office of Alternative 
Medicine is to try to pull together the published studies from 
such activities. In addition, there is an organization called 
the Cochran Group that tries to pull together what are 
frequently fairly inconclusive studies, but the effort is to 
try to assemble all the data, do what is called a meta-
analysis, and then try to determine whether or not these 
therapies show some promise.
    Mr. Porter. If I can say so, my concern is equally the 
other direction, and I understand why it would be to look for 
those that work. But it seems to me there's a lot of 
information out there that is bought by the American people 
about therapies that don't work, and they pay inordinate 
amounts of money for, and lose the benefits of good therapy in 
the meantime. There's nothing to tell them that it's a bad buy, 
that it doesn't work, and there's no scientific basis for it 
whatsoever. So it seems to me, part of the mission of NIH ought 
to be, not only to look for good therapies that do work, but to 
also test those that claim to work and show that they, in fact, 
don't.
    Dr. Varmus. Well, as I mentioned, one of the criteria that 
we use is the degree to which any thing is being used. One of 
the difficulties we face, of course, is that there are 
hundreds, indeed probably thousands, of alternative therapies 
in the marketplace. Many of these are very difficult to 
approach with clinical trials because they are not made by 
standardized methods, and they're not pure preparations. It's 
very difficult to do a trial with material that's not been 
subjected to a high degree of chemical analysis, and we simply 
have to sift through what is out there, and respond to the 
public health need.
    I agree with you, if something is very widely used and 
shows no evidence of efficacy, that should be something that 
gets better established than it has been to date. But I think 
that usually when things are very widely used, there are 
reports, perhaps anecdotal, perhaps not rigorous, that suggest 
that there is efficacy. That certainly has been the case with 
St. John's Wort and some of the other things thatI've mentioned 
today.

                          third party payments

    Mr. Porter. Well, there's other things in the market that 
could be dangerous that someone ought to test, especially under 
the law that was passed in 1992 that allowed health claims to 
be made without any scientific basis. It seems to me that NIH 
and the Office of Alternative Medicine is, or should be, the 
kind of first line of defense against these kinds of therapies 
that could be even dangerous, not only benign, but could be 
worse than benign.
    Dr. Varmus, our subcommittee, has provided one year 
authorizations for NIH to collect third-party payments for the 
cost of clinical services that are incurred in NIH research 
facilities, and specified that those payments should be 
credited to the NIH management fund. Can you tell us how much 
was collected in Fiscal Year 1997 and credited to that fund, 
and do you anticipate that this amount will remain constant 
from year to year?
    Dr. Varmus. Nothing has been collected, and we have given 
this issue to the Board of Governors at the Clinical Center for 
further discussion. They have looked at this matter carefully. 
They've consulted with outside experts, and they feel that it 
would be detrimental to our overall operation to try to collect 
third-party payments, that it would not be cost-efficient, and 
they recommend that we do not do so. And, as you may note, in 
this year's budget request there is no offset for third-party 
payments.
    Mr. Porter. Why would it be detrimental?
    Dr. Varmus. Because one of the traditions of the Clinical 
Center that has encouraged recruitment is that we don't make 
any distinction among patients who are and are not insured. To 
do so would create a large amount of paperwork that we have not 
been burdened with before. And we know that a substantial 
portion of our patient population which frequently comes from 
families with hereditary diseases or involves those with 
longstanding diseases are not insured. We think this might act 
as a means to either impair our ability to recruit such 
patients, or in fact change the direction of our research in a 
way that would really not be favorable to the Institution.
    Mr. Porter. I'm at a loss to understand why it would impair 
their willingness to come there since they haven't any 
coverage, and there wouldn't be any third-party payment to 
collect in regard to those patients anyway.
    Dr. Varmus. Well, the issue might be that we would be 
creating additional burdens for the referral physicians who 
would feel that there might be some additional paperwork and 
that we would be looking for financial return from patients who 
come. I can provide you with the report that was provided by 
our Board of Governors, if you would like further information.
    Mr. Porter. Why don't you put it in the record.
    Dr. Varmus. I'd like to do that, thank you.
    [The information follows:]


[Pages 2875 - 2891--The official Committee record contains additional material here.]



                        information technologies

    Mr. Porter. During last year's hearing, we discussed your 
efforts to integrate all computer systems on the NIH campus 
into a unified information technology system, as well as your 
plans to hire a chief information officer. What is the status 
of NIH's chief information officer position? Could you update 
us on what this project entails in terms of staffing and 
expenditures?
    Dr. Varmus. Well, I'm pleased to say, Mr. Porter, that we 
have not only completed our search, but just a couple of days 
ago, we received a final approval from the Office of Personnel 
Management to allow us to announce the appointment of Mr. Al 
Graeff to be the chief information officer. This was a 
prolonged search. I went through quite a few candidates before 
finding the person we wanted. Mr. Graeff and I are planning a 
series of meetings to decide exactly what his personnel and 
budget needs will be.
    Mr. Porter. So could you give us an estimate for the record 
of the cost-savings that might be expected to be achieved?
    Dr. Varmus. Yes, we can.
    [The information follows:]

                  Information Technology--Cost Savings

    The new Chief Information Officer (CIO) of NIH will provide 
leadership for comprehensive and consistent Information 
Technology (IT) planning across the NIH and will coordinate 
trans-NIH infrastructure and systems. A first priority will be 
an analysis and evaluation of current NIH systems as the basis 
for recommendations for improvement. Efficiencies resulting 
from compatible systems for shared information and resources 
will eventually accrue cost savings; NIH will continue to keep 
the Committee informed of its progress.

                               year 2000

    Mr. Porter. I don't think this is relevant because you 
don't have any kind of benefits to distribute to the public at 
large--but are you going to have, have you looked into year 
2000 problems? Do you have any problem with the year 2000 
computer configuration?
    Dr. Varmus. We have looked at this, and we appear to be 
well ahead of the game. Mr. Itteilag may want to correct me on 
this, but as far as I can tell, we think we're going to be 
well-equipped to make that transition from 1999 to 2000.
    Mr. Porter. I'm so concerned about this with the rest of 
our portfolio before the subcommittee that we're going to hold 
a special management hearing with each of the departments and 
agencies to see where we are overall in this area.
    Dr. Varmus. We would be happy to help with that hearing, if 
you like.
    Mr. Porter. Would you?
    Dr. Varmus. We can provide our advice about our experience 
with that transition.
    Mr. Porter. Yes, because we're very worried, particularly 
in reference to the larger institutions that have a lot of 
benefit payments that there could be serious problems, and, 
obviously, we don't want that to happen.
    Dr. Varmus. Right. Our major concerns, of course, have been 
pay checks and grant funds.

          the foundation for the national institutes of health

    Mr. Porter. The Foundation for Biomedical Research began 
operations last year. Can you tell us which projects it intends 
to concentrate its efforts on first, and what size of annual 
budget do you expect it to have?
    Dr. Varmus. Well, we, of course, hope in the long run that 
enough funds will be raised to pay for personnel out of the 
funds that are solicited. But, at the early stages, we have 
been very grateful for the monies that have been received from 
this Committee--$500,000 in the current fiscal year.
    The Foundation has, thus far, undertaken most of its 
activities in two areas. One is to support the clinical 
research training program for medical students who are 
currently spending time on the NIH campus. This year there are 
nine such students, recruited from a variety of medical 
schools. We expect to see that program increase in size over 
the next few years. One further supplementary activity in that 
area would be to raise money to build housing for those 
students commensurate with the housing offered to the Howard 
Hughes medical students who come to the campus to do laboratory 
research, as opposed to clinical research.
    The second area has been related to the training of health 
care professionals who do genetic counseling. When Dr. Francis 
Collins was here, we discussed the coalition formed by about 
100 groups interested in various aspects of genetics and 
clinical medicine, and the way in which that coalition is 
working with the Foundation to develop a program for 
instruction of nurses and other health care professionals to do 
genetic counseling and to prepare for an era of more activity 
in the arena of genetic testing. The pharmaceutical industry 
has made some contributions already to support these 
activities, and the Foundation is acting as the coordinating 
center and the bank for these very important educational 
activities.
    The Foundation is also interested in providing support for 
our AIDS vaccine effort, but to date there's been no need for 
financial contributions on that subject.

                       women's health initiative

    Mr. Porter. Thank you. The women's health initiative is a 
$628 million, 15 year project, involving 164,500 women, age 50 
to 79. It is a trans-NIH activity which focuses on strategies 
for preventing heart disease, breast, and colorectal cancer, 
and osteoporosis in older women. Have you kept this initiative 
on budget and on schedule?
    Dr. Varmus. The budget actually has increased in our 
proposal for 1999 as a result of additional costs that were not 
expected but are not incommensurate with the kinds of 
additional costs that frequently occur in a large clinical 
study of this kind. As you know, the Women's Health Initiative 
has been transferred----
    Mr. Porter. That's my question.
    Dr. Varmus [continuing]. To the Heart, Lung and Blood 
Institute.
    Mr. Porter. My question is why did you transfer it?.
    Dr. Varmus. Because the Heart, Lung and Blood Institute has 
had tremendous experience in managing large clinical trials of 
this kind, and we feel it is best suited to oversee the 
initiative at this stage, as data are accumulated.
    Dr. Kirschstein. Mr. Porter.
    Mr. Porter. Yes.
    Dr. Kirschstein. To add to that, the Heart Institute has 
developed a consortium since, as you mentioned, there are 
several diseases, and so, the Cancer Institute, the Arthritis 
and Muscular-Skeletal Diseases Institute, and the Aging 
Institute, since the study is in elderly women, are part of a 
consortium that the Heart Institute has developed to help 
manage that study, and contribute personnel and, perhaps, some 
funds as well.
    Mr. Porter. You anticipated my next question.
    Dr. Kirschstein. I'm sorry. [Laughter.]

                           pediatric research

    Mr. Porter. Last year, the Appropriations Committee 
provided $38.5 million in funding for the pediatric research 
initiative. These funds were made available directly to the 
Institutes through the NIH, areas of special emphasis which 
target those areas of research opportunity most likely to yield 
greater results on the Federal investment in biomedical 
research. Is this an effective approach, or would it be more 
effective to provide funding to the Institutes directly?
    Dr. Varmus. I believe it's more effective to provide them 
directly. There has been interest on the part of some Members 
of Congress to encourage the NIH to focus more attention and 
monies on pediatric disorders and to include children in 
research, particularly clinical research. We feel we have 
responded to that. The initiatives to be undertaken under areas 
of emphasis are one indication of our response. As those 
Members interested in expanding our efforts in pediatric 
research acknowledged, the areas of emphasis initiatives that 
we have developed include more pediatric projects than even 
they had anticipated.
    Last year, in order to simplify the distribution of money, 
we simply identified components of ouralready laid out plan as 
a pediatric initiative. At this stage, I don't believe that any further 
labeling of subdivisions of our plan as pediatric initiatives, with 
money flowing through the Office of the Director, is a very useful way 
to proceed.
    Mr. Porter. Dr. Varmus, you and your team of directors, 
indeed all the people at NIH, give us great confidence that the 
entire enterprise is in extremely competent hands, and that the 
public money is spent, not only wisely, but with a degree of 
imagination that leads us to results, and so we want to thank 
you for spending the last three weeks with us. We know it is a 
burden on your time, and we appreciate very much the 
opportunity to spend time with you, and each of the directors, 
and learn more about the fascinating things that are happening 
within NIH and its grantees. Thank you all very much.
    Dr. Varmus. Mr. Porter, I appreciate personally the 
attention you have paid to these hearings, and the very high 
level of questioning that we've had. I think it has been useful 
for all of us to reflect on what we do in this annual process, 
and I appreciate you spending so much of your time with it.
    Mr. Porter. Thank you, Dr. Varmus. Thank you all very much. 
The subcommittee will stand in recess until 10:00 a.m. on 
Tuesday.
    [The following questions were submitted to be answered for 
the record.]


[Pages 2896 - 2941--The official Committee record contains additional material here.]



                                           Wednesday, May 20, 1998.

                         NOBEL PRIZE RECIPIENTS

                               WITNESSES

DAVID BALTIMORE, PRESIDENT OF CALIFORNIA INSTITUTE OF TECHNOLOGY
STEVEN CHU, THEODORE AND FRANCIS GEBALLE PROFESSOR OF PHYSICS AND 
    APPLIED PHYSICS, STANFORD UNIVERSITY
STANLEY B. PRUSINER, M.D., PROFESSOR OF NEUROLOGY AND BIOCHEMISTRY, 
    UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, CALIFORNIA
JOSHUA LEDERBERG, RESEARCH GENETICIST
ALFRED GILMAN, BIOCHEMIST, PROFESSOR OF PHARMACOLOGY, UNIVERSITY OF 
    TEXAS SOUTHWESTERN MEDICAL CENTER
PETER DOHERTY, IMMUNOLOGIST, CHAIRMAN OF THE DEPARTMENT OF IMMUNOLOGY, 
    ST. JUDE'S CHILDREN'S RESEARCH HOSPITAL, PROFESSOR, UNIVERSITY OF 
    TENNESSEE MEDICAL SCHOOL

    Mr. Porter. The subcommittee will come to order.
    This is a special hearing on medical research. The 
subcommittee would like to welcome six of our Nation's most 
prominent researchers, each of whom has won the Nobel Prize.
    What I plan to do is make a very brief introduction of 
each, and then we will hear their individual statements. And 
we'll get an opportunity then to hear all six statements before 
we begin questions.
    Gentlemen, let me thank each of you for taking time from 
your very, very busy and full schedules to be with us.
    I begin with Dr. David Baltimore, who's a biologist, born 
March 7, 1938 in New York City. Nita Lowey's not here to remind 
us, but she will be, I think. He's President of the California 
Institute of Technology and won the Nobel Prize in Physiology 
or Medicine in 1975 for his work on virology. He was 37 years 
old when he won the Prize. He was appointed Chairman of the NIH 
AIDS Vaccine Research Committee in 1996. And Dr. Baltimore, 
we're very delighted to have you with us this afternoon.
    Mr. Baltimore. Thank you very much.
    I've been President of CalTech now for about seven months. 
Before that I was a Professor at MIT for many years and was for 
some time the President of the Rockefeller University. I have 
worked on viruses and on the immune system for over 35 years. I 
received the Nobel Prize for discovering the enzyme that allows 
cancer-inducing viruses to grow and to associate themselves 
permanently with cells.
    Howard Temin and I were jointly honored for this work, a 
colleague of Mr. Obey's.
    The enzyme we discovered came to be called the reverse 
transcriptase. This work established the notion that there 
existed retroviruses in the world. Ten years later, AIDS 
appeared and was discovered to be caused by a retrovirus. The 
reason we knew that was because it has the reverse 
transcriptase. So the discovery we had made 10 years earlier 
provided the basis for discovering how AIDS was caused.
    The enzyme is also central to the development of 
biotechnology, because it allowed important genes to be 
captured and used to make therapeutic products. Although it was 
an interest in cancer that fueled the discovery, it turned out 
to be central to other fields, proving once again that science 
often has unforeseen consequences.
    Because my worked turned out to help with the discovery of 
the AIDS virus, HIV or immunodeficiency, I followed the 
development of the field, and in 1986, I was asked by the 
national Academy of Sciences and the Institute of Medicine to 
co-chair a committee to evaluate the research on this awful 
disease. My committee recommended a greatly increased research 
effort that we estimated needed to reach $1 billion a year. In 
a few years, the U.S. was spending that amount of money, and 
the work led to the exciting advances in therapy that we are 
now seeing.
    At the end of 1996, Harold Varmus asked whether I would 
head a panel to oversee the U.S. effort in AIDS vaccine 
development. I agreed to do that, and in spite of my duties now 
as President of Caltech, I continue to chair the AIDS Vaccine 
Research Committee of the National Institutes of Health. It is 
advisory to both the NIAID and NCI efforts in vaccine 
development.
    I am committed to this work, because I believe that nothing 
is more important to public health world-wide than a vaccine 
against AIDS. There are about 30 million people in the world 
infected with HIV, and they are transmitting the virus at a 
fierce pace of about 7 million new infections per year. In the 
U.S., HIV infections continue, and although the new drugs can 
hold the disease in check in many people, the drugs are 
imperfect and exceedingly expensive. Only a vaccine is going to 
rid the world of the scourge of HIV.
    Making an HIV vaccine is testing all of the world's 
knowledge of virology and immunology. The reason is easy to 
see. Other viruses for which we have vaccines are ones that the 
immune system usually controls. The vaccine just helps the 
immune system get one step ahead of the virus.
    HIV, however, is almost uniformly fatal when untreated. 
Therefore, the immune system is unable to cope with it 
effectively. For other viruses, we need only harness the 
activity the virus ordinarily elicits. For HIV we have to be 
smarter than nature.
    Can we accomplish this feat? I have faith that the U.S. 
research community can do miracles and therefore an AIDS 
vaccine should be possible. But it's going to tax our knowledge 
base and perhaps require much new knowledge before we reach the 
goal.
    HIV is the prototype of an emerging infectious disease. We 
have no record that it ever infected people except perhaps 
sporadically, until the late 1970s. In less than 20 years, it 
has spread to become the most deadly virus in the world.
    In retrospect, we were lucky that it emerged in the 1970s. 
If it has come 10 years earlier, we would have had no reverse 
transcriptase assay, and we could not have found HIV.
    Since the world have never heard of a retrovirus in the 
1960s, we would have been at a total loss for how to find the 
cause of AIDS. And you can be sure that the confusion and fear 
of an unknown killer on the loose would have been monumental. 
If you remember, the disease was recognized a few years before 
the virus was found, and even in that short time, the social 
consequences were disconcerting.
    To be prepared for emerging diseases, we need the great 
possible knowledge of the whole world of biology. We need to 
know what bacteria, fungi and viruses lurk in our environment, 
and we need to study them in detail, so that if they ever do 
cause disease, we are ready to identify and cope with them.
    Luckily, Howard Temin and I were interested in 
retroviruses, without knowing that they might cause an 
epidemic. But we need to be equally vigilant about other 
organisms, and that means having strong biomedical research 
across the board. Not only do we need to study the organisms, 
we need to know how animals and humans react to the organisms. 
We need to study the immune system in all of its excruciating 
detail, so that we can marshal responses when we need them.
    In this sense, the attempt to make an AIDS vaccine is 
likely to have many spinoffs, because it will be a paradigm for 
responding to other organisms, even ones we do not recognize 
today.
    Finally, let me speak as a new university president. 
Caltech is a remarkable part of the U.S. educational system, 
because it is a school focused on basic research and its 
engineering applications. Caltech is very small by some 
measures, 900 undergraduates, 300 faculty. It is huge, however, 
in the innovation it spawns and in the range of its activities.
    I have learned at Caltech how much can be accomplished in a 
community that is devoted to interdisciplinary approaches to 
the toughest scientific questions. As the U.S. Congress debates 
whether to double the NIH budget, let me give one piece of 
advice. Be sure that the funds are able to bring to biomedical 
research the strengths of the other sciences, because they have 
much to offer.
    As a corollary, it is crucial that we expand research 
opportunities across the board in science, because the 21st 
century is going to see a cohesion of the sciences and a 
disappearance of their borders. Biomedical research will lead 
the way, because it so readily absorbs the power inherent in 
the other disciplines.
    Thank you very much.
    [The prepared statement follows:]


[Pages 2946 - 2954--The official Committee record contains additional material here.]



    Mr. Porter. Thank you very much, Dr. Baltimore.
    Next is Steven Chu, a physicist, professor of physics and 
applied physics, at Stanford University. Dr. Chu won the Nobel 
Prize on physics in 1997 for the laser cooling and trapping of 
atoms. Dr. Chu.
    Mr. Chu. Thank you.
    I just want to say how glad I am to be invited here and be 
on the same panel with these biologists and medical 
researchers. Because I'm a physicist and don't do medical 
research, I'm going to depart a little bit from the script and 
talk first about how the interplay between physical sciences 
and biology is actually occurring.
    Two messages I want to bring to you, that science is an 
interdisciplinary enterprise, and that many of the successes in 
medical research are the result of scientific and technological 
infrastructure that have taken a century to build.
    The other message is that I want to echo Dr. Baltimore's 
statements that there are indications that the biological 
sciences, and particularly at the cellular and molecular level, 
and the physical sciences, are drawing together intellectually. 
As physicists examine atoms and nanostructures, let's say 10-
atom science structures, they see the study of bio-molecules as 
a natural extension to this interest. And because of the 
remarkable success of molecular biology, biologists and medical 
researchers are beginning to ask the same type of questions 
that physicists like to ask.
    So first, what are the contributions of the physical 
sciences to medicine. They are very powerful diagnostictools, 
x-rays, CAT scan, MRI. These were, I would say, accidental discoveries 
in the sense that the inventors were not seeking medical solutions. 
Roentgen discovered x-rays quite by accident, but within a few weeks, I 
understand, he discovered that x-rays could cast shadows on film, but 
the bones would block those and create shadows.
    The roots of magnetic resonance imaging, or MRI, go back to 
methods developed in the 1930s to measure magnetic properties 
of atomic nuclei. That initial development led initially to 
magnetic resonance imaging, or MRI, which is one of the most 
powerful non-invasive medical imaging tools we have today.
    More recently, the discovery of functional MRI, namely, 
that you can use it to measure brain activity, has allowed 
researchers to study humans for long periods of time and how 
their brain is working. So instead of exposing them to 
radiation now, you can actually see an individual when they're 
thinking, what parts of the brain are lighting up.
    In the early 1900s, physicists found that x-rays could be 
scattered from crystals. And they used this to determine the 
size of crystals. Later this technique was extended and 
developed by many researchers and it eventually has been used 
to determine the structure of molecules, such as DNA and 
proteins. Knowing what molecules look like formed one of the 
real foundations of modern biology.
    Computer-assisted tomography, or CAT scans, developed by Al 
McCormick, who was a physicist working for a hospital, and 
assigned the task of improving the quality of x-ray pictures. 
He devised a conceptually simple method of taking three 
dimensional pictures. But while he did this, he was sure he 
invented something old, it was too simple, too obvious.
    And maybe it was. But what was new about it was that he was 
in unusual circumstances. He was in an environment working in a 
hospital, and he was aware of a problem and he had the 
resources to develop a solution.
    There's no reason to suspect that the developments in 
physical sciences would not continue to provide new tools for 
medicine. And I'll cite my own research as an example. I 
realize it's really conceited to suspect that my work in 
physics will have the same impact as x-ray diffraction or 
nuclear magnetic resonance, but stranger things have happened, 
I could get lucky.
    I shared the Nobel Prize in physics for laser cooling and--
I'm already lucky----
    [Laughter.]
    Mr. Chu. For laser cooling and trapping of atoms. We're 
able to cool atoms to about a millionth of a degree above 
absolute zero. That's 10 billion times colder than room 
temperature, where if you use the same energy scale, the 
temperature of us to the surface of the sun is only a factor of 
10. So these are very, very cold atoms.
    Once the atoms are that cold, they're easy to hold on to. 
You can move them around at will at a distance to a vacuum 
chamber. And this type of work has led to more accurate atomic 
clocks, gyroscopes and so on. So it has had impact in physics.
    But while we were doing this work in 1986, we decided to do 
another experiment. The same principles should have worked on a 
more macroscopic object, a 1 micron glass sphere. And a 
colleague of mine, Art Ashland, showed indeed that would work, 
and later went out to discover, again, by accident, that you 
can hold on to individual cells, live cells, bacteria, this 
way. Move them around in an optical microscope, turn off the 
light, and they would swim away.
    Other researchers found you can actually hold onto 
chromosomes within the nucleus of the cell without puncturing 
the membrane. And when I got to Stanford, I said, well, let's 
take this one step further. Can we hold onto individual 
biomolecules by gluing little plastic handles to the molecule 
and moving them all around, and so started to develop 
techniques to move single molecules of DNA around.
    What actually is going to come of this work, we don't know. 
Already other researchers have jumped in and are essentially 
doing experiments, looking at how individual biomolecules 
interact with one another and actually doing experiments in a 
very, very different way. Instead of looking at both samples, 
look at individual molecules.
    What is going to come of that work is hard to say. But we 
do know every time we have looked at individual molecules or 
individual surfaces instead of averages, we have discovered 
something new. It's happened with looking at atoms on surfaces, 
and it's happened in polymers. So it may happen again in 
biology. Again, one banks on being lucky.
    These are exciting opportunities. There is a marriage of 
the techniques and a marriage of the type of thinking of the 
physical sciences and the biosciences. And so instead of 
diverting, historically, I see them coming together. But these 
opportunities have to be nurtured. It's going to be a 
challenge, but I think it can be done.
    Thank you.
    [The prepared statement follows:]


[Pages 2958 - 2960--The official Committee record contains additional material here.]



    Mr. Porter. Thank you, Dr. Chu.
    Dr. Stanley Prusiner, born May 28, 1942, in Des Moines, 
Iowa, professor of neurology and biochemistry at the University 
of California, San Francisco. Dr. Prusiner won the Nobel Prize 
in Physiology or Medicine in 1997 for his work in understanding 
degenerative diseases of the central nervous system.
    Dr. Prusiner.
    Dr. Prusiner. Thank you, Mr. Chairman, members of the 
subcommittee and guests.
    In order to place my own work in perspective, I'd like to 
say a few words about two common neurodegenerative diseases 
that devastate the lives of millions of Americans. Such 
disorders are both chronic and progressive. While 
neurodegenerative diseases are relentless in their attack on 
the nervous system, the speed with which they kill the patient 
often varies for months up to decades.
    The first of these two illnesses I'd like to remark about 
is Alzheimer's disease, from which former President Ronald 
Reagan suffers. As most of you know, Alzheimer's disease is the 
fourth leading cause of death in America, after heart disease, 
cancer and stroke.
    Approximately four million people are afflicted with 
Alzheimer's disease in the United States, and 200,000 die 
annually from this illness. The cost of caring for patients 
with Alzheimer's disease is estimated to be about $100 billion 
a year, making it as costly as any illness that we know about.
    To depart from the prepared statement a little bit, I'll 
skip a few of the paragraphs. But I want to remark a little bit 
more about Alzheimer's disease, and say that 15 years ago, we 
did not know the cause of Alzheimer's disease. Over the past 
decade, mutations in three different genes have been discovered 
that cause early onset familial Alzheimer's disease. This is a 
small number of people with the disease.
    And a fourth gene has been identified that seems to 
modulate the age of onset of all forms of Alzheimer's disease, 
yet we still don't know the cause in most cases.
    The second neurodegenerative disease I'd like to make brief 
remarks about is that called ALS, or Lou Gehrig's disease. 
Jacob Javits, whom many of you knew, died of ALS. Patients with 
ALS are really the antithesis of those with Alzheimer's 
disease. These people have their intellect preserved, but the 
motor neurons in their spinal cord degenerate. Eventually, the 
patients with ALS die of asphyxiation because their diaphragm 
and chest wall muscles can no longer receive signals from the 
spinal cord.
    The motor neurons that degenerate in ALS are the same cells 
that are attacked by the polio virus. We are all aware that 
vaccination against the virus has made poliomyelitis a disease 
of the past. The polio vaccine was developed by the pioneering 
work of John Enders and his colleagues for which they received 
the Nobel Prize many years ago.
    What Enders did was to grow the polio virus with very high 
titres in cultured pieces of tissue. This was the breakthrough 
that allowed Jonas Salk and Albert Sabin to produce vaccines. 
Without these vaccines, I think it is easy to imagine that the 
iron lung industry would be bigger than General Motors today.
    After spending three years at the NIH working on proteins 
and bacteria, I returned to San Francisco to do a residency in 
neurology at the University of California in 1972. Two months 
later, I admitted a 60 year old woman from Marin County who was 
suffering from progressive loss of memory and difficulty 
performing routine tasks. I think back to this patient often, 
because she had trouble putting her car keys in the car door 
and the ignition.
    I was surprised to learn that she did not have Alzheimer's 
disease, but instead was dying of a disease called Creutzfeldt-
Jakob disease, or CJD. Only four years earlier, scientists at 
the NIH had shown that CJD could be transmitted to apes and 
monkeys. These transmission studies led them to believe that 
CJD was caused by a slow-acting virus.
    As I learned more about CJD, I found that some scientists 
were unsure if a virus was really the cause of CJD, since the 
causative infectious agent displayed many unusual properties. 
The amazing properties of this presumed ``slow virus'' 
captivated my imagination. I began to think about the molecular 
structure of this elusive agent. Scrapie of sheep was thought 
to be caused by a similar mysterious agent, and we now know 
that ``mad cow'' disease in Great Britain is caused by the same 
infectious agent.
    After nearly eight years of work, it seemed likely that the 
infectious agents of scrapie, CJD and now ``mad cow'' disease 
were not viruses, but infectious proteins. And to distinguish 
these infectious proteins from viruses, I introduced the term 
``prion'' in 1982.
    Over the next ten years, there was remarkable skepticism. I 
should say considerable, it wasn't remarkable. It was to be 
expected, in many corners of the scientific community. 
[Laughter.]
    But a large body of experimental data was accumulated that 
eventually convinced most scientists of the existence of 
prions.
    Prions represent an entirely new and unprecedented kind of 
infectious pathogen. All other infectious agents, as Dr. 
Baltimore has been talking about the AIDS virus, bacteria, 
fungi, parasites, carry a nucleic acid, DNA or RNA, that 
instructs the replication of their progeny. But prions are very 
different. They contain no nucleic acid. They are composed of a 
misshaped protein that can stimulate the production of more of 
itself.
    As I look back over the past 25 years, I am sure that the 
discovery of prions would not have been made in any other 
country besides the United States. Let me explain. First, few 
countries have a system for support of biomedical research like 
ours. The NIH investigator-initiated grant system allowed me to 
apply for support as a newly-appointed assistant professor in 
1974. Only some young, brash iconoclast would have chosen such 
a difficult and unusual problem to pursue.
    Secondly, our country is sufficiently large that the 
reviewers did not know me personally, so they could be more 
objective. Third, this work was very expensive. The NIH spent 
more than $56 million over the past quarter of a century on 
these studies. And fourth, I needed an outstanding institution 
like the University of California at San Francisco, with a 
large group of superb biomedical scientists to provide the 
proper intellectual environment for such research to flourish.
    But I hasten to add that the institutions of all my 
colleagues sitting here are among the 25 or 30 wonderful 
academic institutions where pioneering biomedical research 
occurs in this country.
    I'd like to look ahead briefly for a moment, which is of 
course always hard to do. Discovering the causes of diseases is 
not sufficient. We must also devise effective therapies. There 
are many wonderful opportunities emerging in all fields of the 
biomedical sciences to develop meaningful interventions.
    Neurology and especially neurodegenerative 
diseasesrepresent only a few of these opportunities that confront us 
now. Advances in our understanding of diseases like Alzheimer's 
disease, Parkinson's disease, ALS, prion disease, CJD, need to be 
exploited in the development of rationally designed effective drugs.
    But to make these discoveries, I think it's necessary that 
we continue to bring the brightest and the very best young 
people into the biomedical sciences. They need to perceive an 
exciting career path. And the best way to do this is to make 
the NIH grant system less stressful and less grueling. The only 
way we can do this is to increase funding for NIH. I think it 
is very urgently needed.
    I'd like to say in closing that my colleagues and I greatly 
appreciate the opportunity to share with you our excitement 
about the future of biomedical research. We are poised to 
exploit many discoveries made over the past two decades and 
develop unique therapies that I think were unimaginable five 
years ago. We are capable of stopping the devastation that so 
many dreaded diseases cast upon not only the victims, but also 
the families of these unfortunate people.
    I think with proper funding, we can deliver to the American 
people some remarkable advances in the fight against disease.
    Thank you.
    [The prepared statement follows:]



[Pages 2964 - 2968--The official Committee record contains additional material here.]



    Mr. Porter. Dr. Prusiner, thank you very much.
    Next, Dr. Joshua Lederberg, research geneticist, who won 
the Nobel Prize in Physiology or Medicine in 1958, for his work 
on bacterial genetics. He was only 33 years old when he won the 
prize. Dr. Lederberg retired as President of Rockefeller 
University in 1990. But he continues his research activities 
there in the field of DNA secondary structure and mutagenesis 
on bacteria.
    Dr. Lederberg.
    Dr. Lederberg. Thank you very much, Mr. Porter. I'm very 
grateful to you and the committee for the opportunity to be 
with you and make this presentation.
    Very appropriately, most of my colleagues have stressed 
their analysis of the public benefits that ensue from the overt 
products of biomedical research. It has been the pride of NIH 
to have sponsored innumerable discoveries on the biology of the 
human organism and of our microbial predators, discoveries that 
have assisted the ongoing defense against disease.
    I have a background paper which I have made available to 
you that has some graphics to illustrate these points.
    Even despite terrible setbacks like the HIV epidemic, life 
expectancy in the United States has steadily improved 
throughout this century, from 47 years in 1900 to 76 at the 
present time. Pushing up that expectation is even harder as we 
face the more difficult challenges of cancer, heart disease, 
cardiovascular disorder, neurological deterioration. But our 
progress has been steady in many areas, very exciting, 
especially with the insights derived from genetic analysis.
    But I will assert that equally important to the exclusive 
discoveries is the human capital, the skills, ideals, 
imagination and motivation of the scientific investigators, 
whose work depends absolutely day by day on research support 
from the NIH. We have discovered a deep fount of creativity in 
the young people we are training. And they have spilled over 
from academia as well as into government and industry.
    In the process, they have generated enormous economic 
advantage for the Nation. Most explicitly in biotechnology and 
pharmaceuticals, where the United States has unquestioned world 
leadership, directly derived from the support for basic 
research for which the NIH has been famous through these years.
    But even as generous as it has been, NIH funding has not 
kept pace either with the scientific opportunities nor with the 
talents that could be cultivated and brought to bear. So the 
prospect of the new acceleration in this domain are very 
encouraging. There can be no doubt that the investment will be 
repaid many times over.
    I will just put two topics on the table: infectious disease 
and aging, in its most fundamental aspects. In terms of the 
first, my own research for 55 years has focused on genetics and 
evolution of microbes, and has left me with a profound respect 
for their versatility in finding ways to adapt themselves to 
take advantage of us, to be the micropredators, the only 
organisms that dispute our place at the top of the food chain.
    In fact, one could remark that whether we live or die isa 
consequence of microbial viral infection is an unintended side effect 
of the machinations of these organisms. No virus or bacterium really 
gets much advantage by killing us, or even by making us very ill. And 
many of the most successful viruses and bacteria have more benign 
relationships that they have evolved in their association with us.
    It's their mistake that they are sometimes more lethal than 
they might have wished, if they had the intelligence to 
understand that. But we're the ones who suffer even more so.
    So we need really a very deep understanding of the vagaries 
of microbial variation, the tightrope that they walk in their 
attack on us. They have to be vicious enough to get a foothold 
and not so vicious, at least most of the time, they allow us to 
continue to work for them, to continue to provide the fodder 
that they need for their continued existence.
    This is a rather different perspective about microbial 
infection than people working on the front lines and seeing the 
tip of the iceberg, the killing effect of the microbes, will 
often have, when derived from genetic inquiry.
    The global pandemic of AIDS has been a poignant reminder of 
the need to maintain and strengthen our vigilance about the 
evolution and emergence of microbial threats to our health. We 
had another reminder last year with the episodes of avian 
influenza in Hong Kong. These had a very high mortality ratio. 
Six out of the 18 cases diagnosed as H5N1 in Hong Kong died, a 
very high proportion, 1 out of 3.
    As events turned out, we were very lucky. This flu was not 
readily transmitted from human to human. And what might have 
evolved into another 1918-like catastrophe, where influenza 
ravaged the world and killed 25 million people in the course of 
a single year, was nipped in the bud.
    This positive outcome, positive for the time being, was no 
accidental circumstance, but the rest of well-tuned 
international collaboration and energetic response on the part 
of the Hong Kong health authorities. In turn, they depended on 
studies of virus biology and diagnosis that had deep roots in 
NIH funded investigations over the past 30 years.
    All authorities in the field caution that such episodes 
will recur, if not influenza, then any of scores of emerging 
and reemerging infections. Similar problems challenge us in the 
spread of antibiotic-resistant microbes and the need to 
understand how these evolve, and how better to approach the 
design of new generation drugs, so that we can continue what we 
once called the miracle drugs, our capacity to suppress 
bacterial infection of kinds that used to be uniformly fatal.
    I'm sorry I have to bring up another point, but coping with 
new infectious disease has also become a depressing element in 
our national security planning. With the end of the Cold War, 
we are no longer locked in strategy of lethal deterrents with 
another superpower. Instead, rogue states, guerilla groups and 
psychopathic individuals have become endued with the powers of 
mass destruction through the use of chemical and biological 
weapons.
    At a basic level, our long-term strategy for defense is 
hardly different from that of protecting against naturally 
emerging infections. That will be the level at which NIH will 
operate. The need for prompt and accurate diagnosis, 
surveillance, powerful vaccines and drugs to prevent and treat 
infections from many exotic agents. Curiously, even the 
eradication of a disease, as we've had with smallpox, evokes 
new vulnerabilities with a population no longer exposed to 
immunizing doses, focusing sharply on the need for agile and 
multi-pronged agents to help protection to guard against the 
possibility of this ever recurring.
    NIH does not operate in a vacuum. Its research strategy 
needs to be and is informed both by scientific opportunity and 
public health priorities. Its creative people and findings must 
be and are readily transferred to the health care sector and to 
industry. All this is working quite well.
    And I particularly wish to commend the initiatives to make 
medical information universally available through the 
electronic media of MedLine from the National Library of 
Medicine, a component of the NIH.
    To turn very briefly to another topic, one could pick many 
areas of challenge and promise. But the biology of aging is one 
that seems especially ripe for advancement through the 
applications of medical molecular biology. This has not been 
the field of my own research, but I have been educating myself 
as an advisor to a new medical research foundation funded by 
Larry Ellison, working closely with the National Institute of 
Aging, to try to find the most creative ways for a private 
foundation to complement the very good work of NIH.
    What we have learned about the risk factors and the 
biochemical basis of Alzheimer's disease, as Dr. Prusiner has 
touched on, has already transformed our concepts of senility. 
We don't even use that word any more in medical parlance, 
because there are specific syndromes that are responsible for, 
and if taken care of, I think would abolish that notion that 
age is ipso facto connected with severe neurological and 
psychological deterioration, so much of which, in fact, has 
turned out to be Alzheimer's disease. But there are other 
conditions, as well.
    And these insights provide the hope that homing in on 
specific disease syndromes can offer substantial enhancement of 
healthy life extension well into the ninth and tenth decades.
    Thank you very much.
    [The prepared statement follows:]


[Pages 2972 - 2973--The official Committee record contains additional material here.]



    Mr. Porter. Dr. Lederberg, thank you very much.
    I'm informed that we have a series of four votes. What we 
will attempt to do is have Dr. Gilman make his statement, and 
then we probably will have to break at that point for as much 
as half an hour or 40 minutes, depending on how fast the votes 
go, and then resume. There's no other way we can do it, so we 
apologize to all of you in advance.
    Dr. Alfred Gilman, a biochemist, born July 1, 1941, in New 
Haven, Connecticut. He's a professor of pharmacology at the 
University of Texas Southwestern Medical Center. And he won the 
Nobel Prize in Physiology or Medicine in 1994. Dr. Gilman, 
we're delighted you could be with us.
    Dr. Gilman. Thank you, Mr. Chairman. It really is a 
privilege to be here this afternoon.
    Because I have very passionate feelings about the value of 
the bioresearch research enterprise in the United States and 
the appropriateness of Government support for this effort, if I 
somehow fail to convey that passion this afternoon, I will have 
done a very poor job.
    I was raised in the northeast, mostly in New York, and 
obtained my undergraduate degree from Yale University in 1962. 
I was then attracted to a new experimental program at Case 
Western Reserve University in Cleveland, a so-called combined 
degree program, where you obtain both an M.D. and a Ph.D. 
degree, hopefully in seven or eight years. A wonderful learning 
experience, and this program was the progenitor of the medical 
scientist training programs now funded by the National 
Institute of General Medical Science.
    I found that biomedical research appealed to me more than 
did actually clinical practice. So I then did a post-doctoral 
fellowship in public health service at NIH prior to obtaining a 
faculty position at the University of Virginia.
    I spent 10 happy years in Charlottesville before moving to 
the University of Texas Southwestern Medical Center at Dallas, 
where I have been a professor of pharmacology and chairman of 
the department of pharmacology for the past equally happy 17 
years.
    When I was considerably younger and at Virginia, I began to 
try to learn more about how cell function was controlled by 
chemical signals. For example, if you're suddenly startled or 
frightened, the hormone adrenaline is released from a gland 
called the adrenal medulla.
    This hormone orchestrates a very complex series of 
responses to get you ready to fight or run. Your heart rate 
increases and your heart beats more forcefully. Your liver 
breaks down stored sugar as fuel for your brain and heart and 
muscle. Some blood vessels contract to elevate blood pressure, 
while others relax to increase blood flow to muscle. Many other 
things happen as well.
    How do all of these tissues respond in these different ways 
to just one hormone? We now know a great deal about how this 
and related signaling systems work. There is an extremely 
sophisticated molecular switchboard that is built into the 
membrane that separates the contents of the cell from the rest 
of the world. Within this switchboard, there are three kinds of 
proteins that function together, together transmitting the 
message from the outside of the cell to the inside and telling 
the cell how to respond.
    The first type of protein in this pathway is called a 
receptor. It looks at the world outside the cell, and it 
recognizes hormones that are there and binds them. This 
activated receptor then communicates with a special kind of 
protein, called a G protein, which integrates information from 
many different kinds of receptors, and then in turn regulates 
the third type of protein in the pathway, the signal generator, 
to send a message inside the cell.
    There is enormous diversity in these systems. There are 
hundreds and hundreds of different kinds of receptors, many 
dozens of different kinds of G proteins and signal generators. 
And it does indeed form a very, very complex switchboard in the 
outer membrane of the cell.
    Before I go on and explain the practical significance of 
this research, I'd like to mention just one other aspect of the 
basic science. Several of the molecular players in these 
switching systems were discovered in lower organisms, in yeast 
or worms or fruit flies. Nature is extremely economical. If an 
effective molecular mechanism is created, it is retained and 
used over and over again in evolution.
    You may not be aware of the fact that there are two 
different kinds of sex of yeast, for example, and that yeast 
have a sex life. Mating between yeast is controlled by chemical 
signals or hormones. Each kind of yeast sends out a chemical 
signal to the other, a signal that says, get ready to mate. The 
yeast perceives and responds to this signal in exactly the same 
way that we do when we react to the hormone adrenaline or to 
add another example, exactly the same we do when light strikes 
our eyes.
    So believe it or not, sex in yeast and vision in humans are 
accomplished by essentially identical molecular mechanisms, the 
same three kinds of protein are used to get information from 
the outside of the cell to the inside. If there's a twinkle in 
your eye, it was indeed inherited from a yeast cell getting 
ready to mate. [Laughter.]
    Now a few practical consequences of knowledge of these 
systems. Over one-third of all known prescription 
pharmaceuticals work by either activating or blocking receptors 
that are the gateways to these G protein-regulated signaling 
systems. This includes drugs that are used to treat heart 
attacks, asthma, to alleviate pain, drugs that are used to 
control schizophrenia, drugs that have put the ulcer surgeons 
out of business, and many, many others.
    But importantly, we do not yet know the nature of the 
hormone or the neurotransmitter that acts in well over 100 of 
these G protein coupled receptors. Because we don't know who 
acts on them, they are called orphan receptors.
    This orphanage, this collection of orphan receptors, 
represents an enormous resource for the discovery of new 
biology and new pharmaceuticals. Almost all the major 
pharmaceutical companies and many biotechnology companies have 
discovery programs to find new drugs that work on both known or 
orphaned G coupled protein receptors.
    Thanks to this approach, a new hormone called orexin was 
just discovered a few months ago that may be a critical link in 
controlling human eating behavior. And effective control of 
this behavior will be of enormous value in the treatment both 
of obesity and diabetes.
    How are new drugs discovered for these receptors? There are 
several different techniques, and I'd like to mention just one. 
Armed with the very, very basic knowledge that I just 
mentioned, that these receptor systems work in yeast and 
control such fundamental phenomena as cell growth and 
replication, one biotechnology company in New York takes the 
cloned genes for human receptors and expresses these receptors 
in yeast. Thousands of chemical compounds can then be checked 
to see if they change simple behaviors in yeast. And this is 
the first step to discovery of a lead compound that acts on the 
desired human receptor.
    In fact, this discovery system encompasses most of the 
elements of modern drug discovery: the use of cloned human 
genes, high throughput, robotically based screening techniques, 
and new methods of combinatorial chemistry to synthesize 
chemical libraries with many, many thousands of novel chemicals 
that can be tested for activity.
    In some cases, with help from physicists, drug 
developerscan determine the atomic structure of these receptors with 
the new drug candidate bound to it. This provides invaluable 
information for optimizing the chemical structure of the potential 
drug, so it does its job as potently and as specifically as possible.
    The future for drug discovery looks incredibly bright to 
me. In the not too distant future, we will know the chemical 
structure of all products of the human genome. We will thus 
have many new targets for drug action. Greater knowledge of the 
biological functions of these gene products will point us in 
the right direction, telling us which targets to exploit in 
individual diseases.
    Collaborations with the chemists and physicists will 
ultimately lead to truly rational drug design, done mostly with 
computers rather than experimental animals. Drug specificity 
and efficacy will be optimized and toxicity will be minimized.
    Mr. Porter. Dr. Gilman, I'm sorry to interrupt, but they 
are informing us we're going to have to recess very briefly. We 
will pick up right where you are when we come back. We 
apologize.
    The subcommittee will stand in recess.
    Ms. Pelosi. Mr. Chairman, as you're leaving, may I just 
have 30 seconds?
    Mr. Porter. You may.
    Ms. Pelosi. Thank you. We're having a markup in the 
Intelligence Committee and I'm going to have to go over there 
to vote. I just wanted to welcome all of the Nobel Laureates 
here. It is truly a proud day for us when you are here.
    But I have to say, this is the way it is around here. As a 
Californian, I'm particularly proud to be so well represented, 
both from public and private institutions. Dr. Baltimore, I 
particularly wanted to acknowledge the outstanding contribution 
you have made to the AIDS Vaccine Research Committee. As you 
know, that's very important to us in San Francisco and in our 
country.
    Dr. Chu, I'm so pleased to hear your presentation. When Dr. 
Varmus was here, he talked about improved instrumentation and 
what that means to biomedical research. Thank you for bringing 
it all together for us today, and congratulations to you on 
what you've done.
    Of course, in San Francisco, we talk about ECFF around here 
all the time, any regular attenders of these hearings can tell 
you. We're very proud of your work. It's a sad subject, how 
some of our loved ones are taken from us even before they're 
taken. I am pleased to hear Dr. Lederberg's presentation on the 
effects of aging. It's becoming more and more important to all 
of us all the time.
    And Dr. Gilman, when you said you were passionate about 
biomedical research in the United States, I didn't know that 
was going to extend to the yeast. [Laughter.]
    But it got our attention.
    Dr. Doherty, I'll look forward to hearing you later. But I 
can tell you that all year we talk about what you tell us here 
today. So thank you so much for the time that you've taken to 
be here. It's very, very important to us.
    And forgive my chauvinism about California. Thank you all.
    [Recess.]
    Mr. Porter. The subcommittee will come to order.
    Dr. Gilman, you are in the midst of your statement. Please 
proceed.
    Mr. Gilman. I think I've just come essentially to the end 
of what I wanted to say, about the future of drug discovery. I 
will summarize that. I think it's going to be spectacular. We 
will have much better drugs than we have today.
    I just wanted to close with a few comments on my opinions 
about what makes American science great. Adequate funding is 
obviously necessary. But it's not sufficient.
    In the United States, we allow our brightest young people 
to become independent and to receive funding to pursue their 
own creative ideas at the most productive times in their 
careers, when they're in their late 20s and 30s. While this 
strategy seems obvious, it is nearly unique in this country. In 
effect, we give our scientists a franchise to go to the 
equivalent of Queen Isabella and say, may I please have money 
for ships, because I want to discover the new world.
    We strive to find the right balance between basic and 
applied research. Both are critical. I appreciate the fact that 
it can be difficult politically to fund the seeming esoteric 
when there are very many critical immediate needs. However, we 
often do not know where to find the best leads for practical 
problems. I certainly never envisioned a biotechnology company 
searching for new drugs using human genes expressed in yeast.
    My father was a scientist, and I vividly remember when I 
was quite young how incensed he was one day when a cabinet 
officer in the Eisenhower Administration said, who cares what 
makes the grass green. Believe me, we really do care. The sun's 
light, captured by chlorophyll in plants, is the source of all 
energy on the earth.
    Even great statesmen and intellects have sometimes had 
difficulty in appreciating these concepts. I found the 
following from Thomas Jefferson. In 1806, Mr. Jefferson said, 
Harvey's discovery of the circulation of the blood was a 
beautiful addition to our knowledge of the animal economy, but 
on review of the practice of medicine before and since that 
epoch, I do not see any great amelioration which has been 
derived from that discovery.
    Mr. Jefferson would be thoroughly embarrassed with that 
statement today. [Laughter.]
    While there are some graybeards like us at this table today 
that occasionally still have a good idea, the true engine that 
drives the system is our extraordinarily bright, creative and 
energetic young people who thrive on the thrill of discovery. 
There are thousands of really smart young graduate students and 
post-doctoral fellows and junior faculty members who are 
working 80 hour weeks and receiving very modest compensation, 
but who would not trade their jobs with anyone.
    One way that we can really impair scientific discovery in 
this country is to disillusion the individuals who constitute 
this extraordinary resource. Unfortunately, there has been some 
disillusionment in the recent past. And our laboratories are 
becoming filled with foreign students and fellows, rather than 
our own.
    But there is hope in the air at the moment, as the 
scientific establishment watches your efforts, and thanks you 
very much for your interest.
    [The prepared statement follows:]


[Pages 2979 - 2985--The official Committee record contains additional material here.]



    Mr. Porter. Dr. Gilman, thank you very much for your 
excellent statement. I apologize again for the interruption for 
the votes.
    Finally, Dr. Peter Doherty, immunologist. Dr. Doherty was 
born October 15, 1940, in Australia. He's Chairman of the 
Department of Immunology at St. Jude's Children's Research 
Hospital in Memphis, and professor at the University of 
Tennessee Medical School. He won the Nobel Prize for Physiology 
or Medicine in 1996 for his work on immunity to viruses.
    Dr. Doherty, we thank you very much for your patience and 
for your willingness to be with us this afternoon.
    Dr. Doherty. Thank you, Mr. Chairman.
    I'll be fairly brief, because 90 percent of what I would 
have said has already been said by my colleagues. I grew up in 
Australia, and I'm still an Australian citizen, but living and 
working in this country as a resident alien.
    My initial training was in veterinary medicine, and I'm 
actually the first veterinarian to win the Nobel Prize.
    Last year, I was also made the Australian of the Year, and 
I've had a strangely schizophrenic existence over the 18 
months, trying to talk up the cause for basic science and basic 
biomedical research in Australia while also working in the 
United States. I can tell you that the situation is much more 
positive in this country than it is in Australia. But we're 
still working on it, and I leave for Australia again on 
Thursday.
    My first nine years as a research scientist were spent 
working on infectious diseases of the food producing animals, 
initially in Brisbane, the northern state where I grew up, and 
later in Edinborough in Scotland, where I did experimental 
neuropathology, studying virus infections and working on 
systems that are somewhat similar to those that were described 
so beautifully by Stan Prusiner.
    After that period, I returned to Australia, to John 
Kirkland School of Medical Research in Canberra. Canberra, of 
course, is Australia's answer to DC. My aim there was to do 
basic immunology, returning to my career in veterinary 
research. But I never made it back.
    A young Swiss colleague and I made a discovery which later 
led to the Nobel Prize some 20 years later. We found, working 
with a virus, a leukocytic cardiomeningitis virus, which is a 
little known virus that often affects mice, mice in the field 
and also affects humans. We found the way the cell media immune 
system works. That is, we found how the immunity, lymphocytes, 
killer T cells, kill off the virus-infected cells, the little 
factories that produce virus, and thus terminate an infectious 
process. This is a normal mechanism of recovery in any virus 
infection.
    It changed the way people thought about the immune system, 
because we discovered that how that operates is through the 
virus changing the transplantation molecule, the structure 
that's recognized when a graft is rejected. And the virus 
changes that molecule, and then the immune system sees it as 
foreign, and then turns on to destroy it. Just in the way it 
would turn on to destroy a graft.
    The reason we were able to work that out, and we worked it 
out very, very quickly, was because of some 20, 30 years of 
research that had gone on in this country and in Britain on 
transplantation in laboratory models. This is work that was 
done particularly at the Jackson Laboratory in Bar Harbor, 
Maine, that was NIH funded. These people had worked out the 
whole transplantation system, they mapped it in genetic 
breeding experiments in mice.
    And as two young scientists, we were able to pick up on 
that system, use it immediately to work out how these T cells 
work. So that is a very good example of how the serendipitous 
discovery builds on technology that is developed for a 
completely different purpose and provides a major illumination 
as a consequence.
    I left Canberra in the mid-1970s, went then to work at the 
Whistner Institute in Philadelphia, where I was also a 
professor at the University of Pennsylvania. During the time in 
Philadelphia, we discovered that the immune T cell response, 
the same sort of response the influenza viruses, which are 
extraordinarily variable in the way they survive in nature and 
continue to infect us, was highly cause-reactive.
    We realized for the first time what was being seen by these 
cells was very different from the things that are seen by the 
antibody molecules that people have been studying for a very, 
very long time.
    I returned again to Australia, didn't work out too well, I 
missed the United States very much. I missed the openness, I 
missed the access to funding, which is what drives all 
scientists, you've got to have funding. And I came back to St. 
Jude's Research Hospital some 10 years back, they made mea 
fantastic offer. And I now live on the muddy banks of the Mississippi 
instead of the Pacific beaches of Australia.
    I think the things I particularly would like to bring 
before the committee have already been mentioned. The danger of 
infectious disease, the enormous threat, particularly 
respiratory infections. Dr. Lederberg alluded to the massive 
influenza outbreak which followed the first great war.
    We still don't really know what happened there, but we 
think a swine virus got into humans and caused this enormous 
pandemic. It was called the Spanish flu, because the Spaniards 
acknowledged they had the infection, whereas the Germans and 
the English, who were still fighting the war, didn't admit it. 
So the Spaniards got blamed for it, but it crossed all 
barriers.
    It also probably had an effect on the peace process, 
because I believe one of President Wilson's key advisors, who 
was a moderate, died from the influenza before the Versailles 
Congress. And as a consequence, the people who were much more 
rigorous and much more determined to extract retribution from 
Germany played a much greater part in that process, which 
probably led to some extent to what happened in the second war.
    So infectious disease has had enormous effects on human 
history.
    The flu still is a major threat to us, the influenza 
viruses that have been circulating over the last 30 years or so 
probably come to the human population from birds. They're 
what's called the H3 viruses. As we heard earlier, the H5 virus 
that came across in Hong Kong, again came across from birds 
into humans, and with very good public health and 
extraordinarily good application of research, largely again 
funded in this country, my colleague Rob Webster, at the St. 
Jude Children's Research Hospital, a New Zealander whose 
specialty is the avian influenza virus, played a very, very 
prominent role, and the CDC also played a prominent role.
    So I think we have to be extraordinarily careful with these 
viruses. In the 1980s, there was an incident where a chicken 
virus mutated, killed millions of chickens very rapidly. Just 
one mutation or change turned this from a relatively mild 
infection to something that was extremely lethal, extremely 
deadly.
    And of course, as we know, with rapid air travel, we 
realize how quickly these viruses can spread.
    Also, I'd like to reinforce Dr. Baltimore's point about the 
AIDS vaccine. I think this is the greatest single challenge 
that we face in practical terms at the moment. We have to learn 
how to deal with this virus by vaccination procedure. We cannot 
hope to control it in the developing countries by any other 
mechanism. Therapies are very expensive. It's killing very 
large numbers of children. There's only one way to do this, and 
that is to make a vaccine.
    The thing that also worries me is that there is a related 
virus in sheep called visma, which spreads by a respiratory 
mechanism. It spreads by mucosal, oral, respiratory means. We 
are putting the AIDS virus under enormous selective pressures 
that we don't understand all that well with the drugs that have 
been used.
    And it does scare me. I don't think it's likely, but it's 
possible, that this or something like it could emerge as a 
respiratory infection.
    I think also when we think about infectious disease and we 
think about children, for instance, there are figures, five 
children a minute die of malaria. We have no vaccine for 
malaria. We have no very good vaccines against many of the 
respiratory infections that infect children in preschools, we 
all suffer from them. Respiratory and simple virus comes back, 
infects us as babies, comes back and can kill us in nursing 
homes.
    So I think there is enormous need for more research in this 
area.
    I'd like to close by saying that the NIH is, to my mind, 
the greatest enterprise that has been funded by any government 
on the earth. I think what you've funded through this committee 
may well stand as the single most positive contribution of this 
century and probably the next century. This is an 
extraordinarily enterprise for government to undertake.
    I also believe that medical research has enormous 
implications for world peace. To some extent I'm in contact 
with the international agricultural community and the work that 
people are doing to try to promote food production and so 
forth. But it's also through infectious disease, by controlling 
infectious disease, we can hope to persuade people to limit 
population growth, which will again, in turn, have an enormous 
effect on world peace.
    Finally, we need to keep in mind the international nature 
of science. I'm an Australian working in the United States, 
I've moved backwards and forwards between Australia and the 
U.S. We depend very much on the interchanges from young 
scientists, bringing people here, having them go home again and 
so forth.
    It's very important to keep that whole process open, not to 
close down that interchange in its most international of all 
human enterprises.
    Thank you very much.
    Mr. Porter. Thank you, Dr. Doherty.
    I want to tell you that I've had the pleasure of being in 
both Brisbane and Canberra some 10 years ago, at the 200th 
anniversary of the founding of Australia.
    Let me thank all of you for excellent statements. I know 
that you realize that our questions are going to be on policy 
and not on the technologies that each of you represent.
    I want to begin with Dr. Baltimore, by asking, of course 
you talked extensively about HIV/AIDS. We have had, over the 
last four or five years, a very strong impact on patient 
advocacy groups who say that we have been, while fighting the 
AIDS pandemic, neglecting research in heart disease, cancer, 
diabetes, diseases of aging. And that the priorities 
represented by the funding in NIH really ought to be changed.
    Have we been doing that? Can we now, with the progress that 
has been made in respect to AIDS, look at those diseases that 
affect broader populations within our own country? What are 
your thoughts in regard to those charges?
    Mr. Baltimore. I don't think this is a time when we should 
be pulling back on our commitment to solving the AIDS problem. 
This is a new problem, in the last couple of decades. It's a 
problem which has unknown dimensions to it, as Dr. Doherty 
pointed out, and we don't know what the future holds with a 
virus like that.
    The international dimensions are monumental. There 
areprobably more people dying of AIDS today internationally than any 
other infectious diseases, except maybe malaria. I don't think that 
it's a wrong priority, I think it's an absolutely correct priority.
    I think there's a scientific perspective that needs to be 
remembered. HIV is a small virus, as viruses go. It has about 
10,000 nucleotides, which is the measure of its information 
content. We know every nucleotide, and we know all the proteins 
it makes. We know everything about it.
    It's a target of opportunity. I think one of the reasons 
why funding for HIV has ramped up so rapidly over the last 
decade and stayed so high is because it is something that we 
know about and we can really make a difference.
    With heart disease, and other diseases, we need to study 
those in great detail, and do. But they're not so close to the 
sort of development edge as HIV is. The reason we got drugs so 
rapidly against HIV is because we knew the proteins, because it 
is a small virus. And being a virus, it's a particularly good 
target for research.
    So I think we need to maintain our focus on it. I think we 
need it from an international perspective, and we need it from 
our local perspective.
    Drugs are terrific. They're expensive, but I think worse 
than that, they're probably a stop-gap. Because the virus can 
become resistant to them. And one by one, I think we will find 
the drugs, as we are finding even with antibiotics today, less 
and less effectively. It's really only a vaccine that's going 
to put HIV back in the box.
    Mr. Porter. Let me ask a related question, and then anyone 
who wants to comment on either of these questions, please feel 
free to do so.
    To what extent do resources drive research opportunity? In 
other words, if we put more funding for AIDS, does this attract 
the kind of scientific interest that might not be there if the 
funds weren't there? And if we put more money in respect to 
cancer, let's say, or diabetes or heart disease, would that 
attract more of the scientific effort in those directions?
    Dr. Baltimore. To my mind, it depends upon the opportunity. 
The opportunity with HIV/AIDS is significant, because we know 
all the basic things we need to know, that is, it's a virus 
disease, we know the virus causes it, we know a lot about that 
virus. So the developmental opportunities are there, we can 
determine the structures of the genes, we can find the drugs.
    And that has attracted people. There's no question that 
having funds available has attracted many more people to 
working on this virus than would have otherwise. There are now 
more people working on HIV than any other virus in the world. 
Probably than all of the viruses in the world. And that is a 
consequence of the priority that we've put on the funding.
    So yes, you will attract people. And you will attract some 
very good people who can make a real difference.
    Mr. Porter. Would anyone else like to comment on that? Dr. 
Lederberg.
    Mr. Lederberg. Yes. I will second what Dr. Baltimore has 
been saying and add a few other particularities. If we could be 
confident, and we're confident that it's wrong, that AIDS would 
not move further in its march around the world than it's 
already done, one might take a cold-blooded examination and 
say, let's stack up our investment in AIDS versus other kinds 
of diseases, or other existing mortalities.
    One of the reasons it's extremely urgent to get after AIDS 
is it was a nascent, burgeoning situation. It's still open-
ended. We still don't know what the full global outcome of this 
epidemic is going to be. There are new varieties of AIDS we're 
seeing in southeast Asia that have a very different sex ratio, 
where heterosexual transmission seems to play a much more 
significant role. Dr. Doherty's also referred to the 
speculative prospect that it might find other modes of 
transmission.
    So it isn't just those poor people who already have AIDS 
that are the issue. Everyone else is in fact subject to the 
looming threat if this epidemic isn't controlled. So I think 
that's one reason it does deserve a disproportionate emphasis.
    Now, in fact, other diseases do take a larger toll. More 
people today die of tuberculosis, and more people today around 
the world die of malaria than of AIDS. If there were a 
comparable ratio of malaria and TB in the United States, we 
would see much more attention to those diseases than they get, 
and I think it's inappropriate that they be so poorly funded.
    But there's also a larger issue at stake. Yes, allocating 
funds with the headline of AIDS does attract people who are 
looking for various modes of opportunity. If you're interested 
in viruses, if you're interested in retroviruses, it doesn't 
matter very much for the pursuit of the more basic questions 
whether you use HIV or another virus as the medium for that 
inquiry. Even work more narrowly directed against HIV has a 
spillover into many other fields and vice versa.
    It's not an automatic reallocation of scientific resources, 
because that's where the scientific opportunities lie. In fact, 
almost all of the very early work in this country on the 
identification of HIV was done under the aegis of cancer, at 
the National Cancer Institute, because of the historical 
peculiarities of where retroviruses were first developed.
    So things don't come in such neat, tidy packages. That may 
be frustrating to someone who wants to see all resources 
devoted to a given diseases. If we knew enough and were able to 
do that. The fact is, we're groping around in the unknown to a 
very large degree. There's in any area enormous spillover into 
every other level.
    Mr. Porter. Would anyone else like to comment on that 
question? Dr. Prusiner.
    Mr. Prusiner. I'd like to comment on it from a slightly 
different perspective. I think that one of the things that we 
really need to do in the future is try and keep the NIH at 
steady growth and to bring more and more young, bright people 
into biomedical research.
    We've seen this constant worry about, is the NIH budget 
going to go up or down, each year, make a number of young 
people at various points in their career paths, some of them in 
college, others when they finish their Ph.D.s, others when they 
finish their post-doctoral training, say to themselves, I'm not 
going to go into biomedical research, it's too hard and too 
difficult.
    I think we have made remarkable progress in AIDS research. 
I would hate to see this change right now. We're on a wonderful 
path, a wonderful trajectory to get a vaccine eventually. And 
in the interim, to develop even more effective drugs to treat 
this disease.
    So I think it would just be very wrong to make mid-course 
corrections because we happen to put a lot of resources into a 
very important lead.
    The other side of the coin is, we should be putting these 
kinds of resources into many other diseases. Not that we should 
withdraw from what we've done. I think that would be a very big 
mistake.
    Mr. Porter. Let me very much agree with you, the best way 
to aim at all of these questions is to put more resources into 
all research and make certain that none is neglected.
    I have to say that over NIH's 50-year history, I don't 
think there has been a year when funding has not gone up. There 
might be one. And if you look at the inflation statistics from 
the same time frame, the rate of growth has been pretty steady, 
right around 3 percent in real terms.
    So that while it is subject to appropriations and there are 
decisions made every year in respect to the level of funding, 
the support has been through administrations of both parties, 
through Congresses of both parties. It's always been very 
strong and placed at a high priority.
    Mr. Prusiner. But I think what happens is very frequently, 
the Administration's budget for NIH tends to be a little lower. 
Congress tends to pull this up at the end.
    Mr. Porter. We don't pay any attention to them. [Laughter.]
    Mr. Prusiner. Right. But the rest of the community does, 
the research community does. And young people see this. And for 
10 months out of the year, it looks like the NIH budget is 
going to go down. Then at the end, the Congress saves it.
    This kind of, the politics of this, make the young 
investigators very weary of what's going to happen to them. 
They are constantly under this black cloud for 10 months out of 
the year. Then all of a sudden, the black cloud is lifted by 
the Congress only for a couple of months, then another black 
cloud comes over.
    This is something that psychologically has a bad effect. 
When I talk to various people around the country, whether they 
be older people or younger people, I hear this constantly from 
them.
    Mr. Porter. Dr. Gilman.
    Mr. Gilman. I was going to say very quickly that I think 
that black cloud of two or three years ago diverted a large 
number of people out of Ph.D. training programs in this 
country.
    Mr. Porter. Dr. Chu.
    Mr. Chu. I just wanted to turn the conversation a little 
bit and say that sometimes, I think Dr. Baltimore said this, 
and I really want to emphasize it, there are some times when 
things are ready for larger investments, and other times 
they're not really ready. You think of starting from an idea, 
to a start-up company, to where the start-up company needs, 
where are you putting infusions of capital. There are very good 
times to put it in, and other times when it would be wasted.
    If people are doing extremely exploratory things and 
they're not really sure what's going on, you have to keep it 
going. So not saying particularly, it appears that AIDS is at a 
time where continued strong funding will be well spent. Other 
times, when you think there may be some breakthrough coming 
along, but you don't see anything, perhaps not so wise to put 
it in there. Because that will raise a lot of opportunistic 
organisms that maybe wouldn't be there otherwise.
    So its' a very delicate thing in the sense that when you 
have this slow, steady increase, it's really how you apportion 
that in the wisest way.
    Mr. Porter. Mr. Wicker.
    Mr. Wicker. Thank you.
    Dr. Prusiner, thank you for acknowledging that the Congress 
provides funds for NIH for research. Let me also apologize for 
coming in at the tail-end of this hearing. We on the 
subcommittee have a lot of confidence in our chairman. And 
there are a lot of things going on today on the Floor. So I'm 
sorry if I missed most of the testimony.
    Who are the potential young investigators that might go 
elsewhere? And where is the best research done in this venture? 
Are the universities doing the job?
    Mr. Prusiner. I said earlier that I thought there were 25 
to 30 lead research institutions across the country who do 
wonderful biomedical research, as well as the NIH intramural 
program in Bethesda.
    I think that the young people who disappear from science 
disappear at all levels. They disappear when they're in 
college, and they don't perceive from their professors that 
biomedical research is an area where they can have an exciting 
career path and expect to get funded at a reasonable rate. They 
disappear in the Ph.D. programs. They disappear in medical 
school.
    One of the areas that really deeply concerns me is that of 
physician-scientists. Because we've seen a steady decline in 
the number of physicians who are scientifically trained and 
choose this as a career.
    Now, we may see this increase a little bit, because managed 
health care is becoming so brutal. We may see a few people come 
back in for that reason. But I don't think it's going to be 
significant.
    So we're seeing people at all stages of their training run 
because we have not had sufficient funding, enough funding to 
increase steadily year after year, to take account of these 
wonderful opportunities that are being created by new 
knowledge.
    So I think we have the manpower as it exists right now. 
What worries me is the future. Because we're not seeing, I 
think, all the best and all the brightest young people find 
biomedical research as an extremely attractive career.
    I would hope that we could do something about this, in 
terms of increasing the funding level for NIH to a point where 
we'll have a more reasonable number of new grants funded, and 
the esprit d'corps in the research community will increase 
sufficiently to where the message will be given to the young 
people that this is really a great opportunity for themselves, 
to devote themselves to a really worthy cause, to find causes 
and develop cures for some of these devastating diseases.
    Mr. Wicker. Yes, sir.
    Mr. Gilman. I think we'd be naive not to also acknowledge 
that perhaps we're not doing a very good job in science 
education in this country from first grade up. And we need 
major improvements there, we're not doing a very good job 
interesting the young people in this country.
    I think the numbers of people, I could easily get the 
statistics on this, I think the numbers of U.S. citizens going 
into Ph.D. training programs, at least in the biological 
sciences, has been quite flat for a long time, at least 
particularly the numbers of males. The situation hasbeen 
salvaged to a certain extent by a much greater number of women going 
into Ph.D. programs.
    But all in all, we are relying much more on foreign 
students filling our graduate training programs and filling 
post-doctoral training slots.
    Mr. Doherty. I think it's a real problem when the students 
who come through the universities complete their post-doctoral 
training, which has become a formal training process in this 
country, where often these people will be 31, 33, 35 years old, 
earning only $25,000 to $30,000 a year. They look at their 
colleagues who have gone to law school, who are now well 
established and have a straight career path in front of them.
    Many of these people don't have a straight career path, and 
they're earning at a low level. We need particularly to develop 
better mechanisms for taking the most promising of those people 
and giving them a career path. There's been a shortage of jobs 
in the universities with the health maintenance organizations 
causing turmoil in university hiring.
    So if we had a mechanism that was coming from NIH to 
support those people through the first five years of their 
research careers after the post-doctoral period, a stronger 
mechanism.
    Mr. Wicker. How do we develop that?
    Mr. Doherty. There was a mechanism called the Research 
Career Development Award earlier on. I think maybe we need 
something like that again. We're doing that to some extent at 
St. Jude Children's Research Hospital with our own resources, 
particularly the initial investigators, taking people who have 
had limited research, giving them a good situation where they 
can develop their careers and get themselves to the state where 
they can compete in science.
    And the good science is now extraordinary.
    Mr. Wicker. Let me just ask one other question. With all 
this new knowledge that has been referred to, how much time 
would you gentlemen spend on the ethical questions raised, and 
what are the ethical issues in the near future in terms of 
science and medicine?
    Mr. Lederberg. I think there's a great deal of ferment 
about that. I can hardly think of any except the scientists I 
know are very alert to the fact the work they're doing does 
have large implications for what we think of ourselves, as 
human life and so on. You'll get different opinions on where 
are the most urgent matters. I know that almost anything that 
has to do with genetics will raise a storm very, very quickly.
    But I think that may be missing the main point. The main 
point is that the termination of life is becoming more and more 
voluntary. People can be put on life-sustaining machines, they 
can be kept going more or less indefinitely. If all you care 
about is that kind of technical artifact. That's becoming a 
grim consideration, the voluntarization of death.
    We've had discussions about assisted suicide, one far 
extreme of that kind of consideration. We have trouble defining 
death, when the issues arise about when it's legitimate to take 
organs for transplant, and so on.
    The reason I put an emphasis on this is that the other 
matters are going to be sporadic. They're going to be just a 
few odd cases where we're talking about cloning or field 
research and so on and so forth. I think life termination 
affects everybody. I put that as the utmost ethical issue.
    Mr. Prusiner. My comment on this, in the world of 
neurology, we see this as a problem constantly. Because we see 
people who are brain dead and yet their bodies can function. We 
see people who become demented and we constantly are faced with 
choices that we have to tell families about, that the patient's 
becoming very profoundly demented, and now the patient develops 
a urinary tract infection or pneumonia. And you're forced to 
counsel the family about, should this be treated, should it not 
be treated. We see this constantly.
    Sometimes I'm surprised at some of the things that some 
physicians do who are, for lack of a better word, I think 
they're uninformed as to just how profound these conditions are 
in some of these patients. So I think people in medicine and in 
biomedical research are constantly thinking about these kinds 
of issues and what can be done.
    Of course, the simplistic answer with respect to dementias 
is to figure out how to stop them. But we're not close. We've 
made a lot of progress, but we need much more research.
    Mr. Doherty. I think it's very difficult for scientists to 
really address ethical issues in their actual work. I think we 
probably get it wrong. Rutherford, the great physicist, 
describing the atom, said there'd be absolutely no practical 
consequences of knowing anything about this, and so forth.
    So really the ethical consequences of what we do and how 
that's handled really has to rest at a level beyond the actual 
research scientist. It has to involve lawmakers, people 
associated with religious organizations and so forth. It has to 
be a much broader set of people than the actual scientific 
community as such.
    Mr. Lederberg. Could I add a further comment? Actually, the 
National Institutes of Health has taken this matter under very 
serious advisement. It is now substantially mandatory that 
every institution which receives NIH funding for graduate 
training institute formal programs, seminars and courses, 
discussions, on ethical issues as part of their graduate 
training.
    I think that's helped to ensure that there's a lively 
discourse on these matters on every campus that I'm aware of. 
It's not been neglected.
    Mr. Wicker. Thank you very much.
    Mr. Porter. Thank you, Mr. Wicker.
    Ms. Pelosi, I imagine you claimed Dr. Prusiner and Dr. Chu 
and Dr. Baltimore when I was out.
    Ms. Pelosi. And partially Doherty. He has some California 
connections. And I'm working on the other two.
    Mr. Porter. Ms. Pelosi.
    Ms. Pelosi. Mr. Chairman, I defer to you if you want, 
because we may have a vote soon, if you had some further 
questions.
    Mr. Porter. All right.
    Ms. Pelosi. I do have some, but I defer to my chairman.
    Mr. Porter. You may proceed if you like.
    Ms. Pelosi. Well, okay. I'm going to be a little 
controversial.
    Mr. Porter. No. [Laughter.]
    Ms. Pelosi. There are two issues that I wanted to put on 
the table for our distinguished panel. One is budgetary and the 
other is more scientific. In the budget area, it's moreof a 
comment. That is that certainly no one speaks more eloquently to the 
need for more funding for basic biomedical research than you all do, 
and from the vantage point of the successes that you have had, 
certainly, the investment is clearly worth it to the American people, 
to the extent that there are other Nobel laureates out there.
    But the problem is that we only have a finite budget 
appropriation here. As I've said so often, this is a ``lamb eat 
lamb'' committee. Everything in here is probably something you 
would not want to cut. You don't want to cut any assistance we 
have for public education or early childhood education, because 
that is your seed corn and I know others have testified to the 
importance of our educational system, developing our 
scientists, giving us candidates to be scientists, great 
scientists, as you are.
    But the fact is, somehow or other, we're going to have to 
mobilize these intellectual resources, along with the others in 
the universities and elsewhere, to increase the size of our 
budget. Because it's easy for all of us to say, as I do, I want 
to double the NIH budget for the next five years.
    But where does that money come from? So while it's 
wonderful to have this support, we have to understand that 
there's a bigger budgetary issue, a wall that we have to crack 
in order to get the resources. So I would hope that you 
understand that some of us who say the only way we have a right 
to say we're for doubling the budget in five years, is if we're 
willing to make the other spending decisions that are 
necessary. That means going beyond the 602(b) allocation that 
we have in this committee, figuring out a way.
    Our chairman has been a distinguished leader in this 
respect. He has not been one of those who has fenced off any 
other opportunities for the committee. Nonetheless, those who 
make these decisions at a different level here put us in this 
place.
    Then my controversial question is this. From your vantage 
point, if you're willing to, you can comment on the budget if 
you wish. But in our committee, when we come to full committee, 
this subcommittee goes to full committee, we will have an array 
of amendments that come before the full committee.
    At the same time, there will be, shall we say, well, that's 
precisely what it is, it's a Christian Coalition alert. 
Anything to do with fetal tissue research or embryo research or 
funding teaching hospitals that train physicians to perform 
every reproductive need that is there for, address the 
reproductive needs of women, the list goes on and on. And we 
are regaled by the scientific community of all the missed 
opportunities that are there because we're not able to venture 
down that path, even though some of the ethical standards were 
established during the Reagan Administration.
    Could you speak to that issue? Because I think that we're 
not going to be able to win that fight in the Congress unless 
the scientific community weighs in. Up until now, it's been 
sort of considered an abortion issue, so the pro-choice 
community and the rest has weighed in on it. But that's not 
anywhere near the fire power that we need, if indeed the 
scientists, scientific pursuit is worth the trouble. Do you 
think it is, and do you think there's the will in the 
scientific community to weigh in on it?
    Mr. Baltimore. Let me try to answer that. Just very 
personally, reproduction is one of the most important aspects 
of biology and human biology. We've allowed ourselves to ignore 
research in that area, because it touches on ethical issues, 
some very powerful political forces. I think that's a great 
shame. Because I think there's nothing you need to understand 
more than reproductive biology, there's nothing we need to 
understand more than early embryonic development. We should be 
making every effort to see that decisions about these very 
intimate and very important areas of life are made with the 
fullest possible understanding.
    We've basically given up the ability to do that kind of 
work in the United States because of the political forces that 
you alluded to. I don't know if you or any other members of 
Congress are in a position to change that. I suspect the answer 
is probably no.
    But I think personally that it is a great shame. Because 
it's such an extraordinary scientific area.
    Ms. Pelosi. Thank you.
    Mr. Prusiner. Might I just mention and amplify on what Dr. 
Baltimore said. It seems to me that he's correct, that many 
areas of reproductive biology have their ramifications extend 
far beyond the course of the fetus. There are many illnesses, 
particularly when we see young children who are, for instance, 
autistic, we have no understanding of autism, or very little 
understanding. It may well be rooted during a very early 
embryonic period.
    And we have other forms of nervous system dysfunction in 
children that undoubtedly occur during pregnancy. And we need 
to understand, we need to try to prevent these. I think we're 
being seriously hampered by having all these restrictions. So I 
think that the scientific community, medical community, the 
physicians who see these children, the pediatricians, the 
pediatric neurologists, the pediatric psychiatrists who become 
involved in the many kinds of care for these many children who 
create such pain for their parents, would be more than 
delighted to try to help with this.
    I think we've all become a little discouraged at times by 
the political forces that seem so overwhelming. And that don't 
seem to be based on anything actual, and are somewhat--I don't 
want to use the wrong terms, but perhaps self-serving.
    Ms. Pelosi. Well, I'm very respectful of the religious 
beliefs of my colleagues. But I do think that with proper 
ethical standards, which I heard you talking about when I came 
in, and the rest, there must be a way. Because beyond the 
important work that you're talking about, Dr. Prusiner, there's 
also the whole idea, what we're told anyway, that Parkinson's, 
in the fetal research area, Parkinson's and any array of other 
illnesses could reap some benefit, in embryo research, how 
cells multiply is very important to cancer research as well.
    So beyond children, well, that's our most important issue 
here, children, but even beyond that, the health and well-being 
of those children's families, their parents and grandparents, 
are of concern to them as well.
    Did any of the others wish to weigh in on this?
    Mr. Doherty. Just to say that I think we must study human 
development, but if for instance, the situation you alluded to, 
the Parkinson's, where potentially one could use fetal tissue 
to correct an abnormality, if we understand what it is that 
makes that tissue what it is, we may not have to usefetal 
tissue. We may be able to produce an equivalent cell.
    But unless we do the study, we're not going to know how 
that works. So I think it has to go forward. We can't ignore a 
great segment of human biology as we attempt to define disease.
    Ms. Pelosi. I'm sure you would agree, as I'm sure everyone 
here would, that we're not talking about producing any of this 
fetal tissue or any of these embryos strictly for science. But 
rather than squander what is available to us, for reasons other 
than science, that's really what we're talking about.
    Mr. Doherty. There's also the issue of gene therapy 
applications in the fetus, that it may be possible to correct 
some genetic abnormalities. It could be quite predictable on 
the basis of what's happening with the genome project. We could 
treat the fetus, but we need to know what's happening with the 
fetus if we're going to treat the fetus just as we would treat 
an adult. So if you stop that research, you won't have that 
process available.
    Mr. Gilman. I would like to come back to the budgetary 
issue. It seems to me that medicine touches the lives of the 
American people many, many times in their lives. Nothing, I 
think, is more painful than the loss of a loved one or to see 
loved ones suffer.
    Never before, I think, in the history of mankind, have we 
had so many opportunities to begin to really intervene. This 
new biology that has really occurred over the last 30 years 
places so many new technologies, so much new knowledge at our 
disposal. It hurts me to see every day that passes when we're 
not able to push forward as fast as possible the acquisition of 
new knowledge, which will make new therapies possible.
    What I think our government has to do is it has to have a 
vision which goes beyond the individual person. It is always 
remarkable to me that people in the prime of their lives who 
happen to be healthy give medical science very little thought. 
They never really think about the fact that one day they're 
going to suffer from one of these devastating diseases. 
Everyone does. Everyone dies.
    And they almost have this sort of immortal view of 
themselves, and they don't really want to face up to what's 
going to happen later to them or to their loved ones. It's 
been, I think, you know, great foresight of our predecessors to 
build the NIH, as we've heard others say already, and to start 
this really rich tradition of biomedical research to try and 
develop these therapies, and many of them very successful. 
Enormous numbers of advances have come out of the NIH program 
over the past 50 years.
    I just think it's incumbent on us, trying to look ahead, to 
do something which is dramatic, something which will take 
advantage of all that we've learned, so that doubling the NIH 
budget is a very reasonable target. It's not pie in the sky. 
The dividends will be enormous.
    Ms. Pelosi. Well, I appreciate that. It's not the price, 
it's the money, as you said. [Laughter.]
    Mr. Gilman. I had a little fantasy scheme a year or two 
ago. It's probably simply humor. But on the wild chance that it 
might not be, I'll risk embarrassing myself.
    Ms. Pelosi. We do that all the time around here.
    Mr. Gilman. It starts with the fact that we spend less than 
2 percent of the Nation's health care budget on research, which 
is a really disgraceful figure. And there is no technologically 
oriented industry that would survive such a level of 
expenditure.
    I think that fact was in no way better emphasized by, I 
believe it was Senator Hatfield's proposal that a 1 percent tax 
health insurance bills would do incredibly wonderful things. It 
would, since we only spend 2 percent of the budget.
    My joking comment on that is, I think they picked the wrong 
insurers. I have a tendency to open my mouth too much, and I'll 
do it one more time. The health insurers perhaps weren't really 
very interested in prolonging life. Maybe the life insurance 
industry would have been a better one to take a look at. I have 
no idea what the magnitude of life insurance premiums versus 
health insurance premiums are. But perhaps the life insurers 
would be much more interested in accepting a tax.
    Ms. Pelosi. If I may just say, Mr. Chairman, may I?
    Mr. Porter. Certainly.
    Ms. Pelosi. I appreciate what you're saying. Just harking 
back to what Dr. Lederberg said in the beginning about life 
expectancy going from, what, 49 at the beginning of the 
century----
    Mr. Lederberg. Forty-seven.
    Ms. Pelosi [continuing]. To 74?
    Mr. Lederberg. To 76.
    Ms. Pelosi. That's remarkable, in such a short span of 
time, such a remarkable change in light of all the years people 
lived on the earth before that.
    And so any family, one accident, diagnosis or growing old, 
people are raising their children, their parents, everybody is 
very, this is very immediate to many people in the country, as 
I said, it's an accident or a diagnosis away, or God willing, 
their parents are alive, they may have to be compromised to get 
coverage for their health.
    I think there is a big market for it, but I do think it's 
going to have some almost radical change in how we budget if 
we're going to get what we need. In my view, we have a moral 
responsibility, where we need scientific opportunity, 
tremendous need, almost a Biblical power to cure at the NIH, to 
put those resources there.
    Mr. Gilman. I sometimes also think that part of the problem 
in getting the public support to committing more resources is 
that our memories are a little too short. I believe the public 
thinks that progress has been rather slow. I'd like to point 
out that there's nothing that could be further from the truth 
on that.
    If you look back at drug therapy, for example, over the 
span of my lifetime, your lifetime, it is amazing. I was born 
the same year as the first edition of a major pharmacology 
textbook was published, it happens to have been written by my 
father, which is why I know that.
    In that book, there is a three-page table describing the 
``routine'' treatment of syphilis with a 123-week regime of 
treatment with bismuth and arsenic and mercury. The book 
contains no antibiotics. The second edition of the book, 
published in 1955, contains no treatment of any sort for anyone 
with a mental disorder.
    In my childhood, I remember hearing one of the big problems 
was, how could we possibly build enough mental hospitals to 
encompass all the schizophrenics in this country. A few years 
later, those mental hospitals were being emptied by the 
discovery of drugs called phenociazines.
    The progress in the last half of the century has been 
extraordinary. And the progress will accelerate. So the 
opportunity is huge. I don't think the public really realizes 
it.
    Ms. Pelosi. Thank you very much, Mr. Chairman.
    Mr. Porter. Thank you, Ms. Pelosi.
    I and members of the subcommittee have been talking a great 
deal and strongly advocating doubling the funding for NIH over 
a five-year period, I have to say, not counting the current 
year, because I think it's going to be a very, very difficult 
year this year to make the kind of progress that will lead to 
doubling the budget. And it will have to start next year.
    But we spend $13.8 billion at NIH, but the total funding of 
basic research by the entire Federal Government, all basic 
research is about $34 billion. And I don't talk just about 
doubling NIH, I talk about doubling all basic research.
    Dr. Chu, is this a wise thing to do? Or should we just aim 
in one direction that maybe looks more promising than others?
    Mr. Chu. With basic research, you don't really know where 
to aim. In the sense that surprising things come out, as I 
tried to indicate, in the line of physics, where the people 
doing that work didn't really realize, that was not their 
focus, they were not training to develop a new technique in 
medicine. Roentgen was playing with gaseous discharge tubes, 
and found a tool that diagnosed broken bones.
    So you have to realize that many of the scientific 
enterprises come from different areas, especially in terms of 
instrumentation, I think that physical scientists, by their 
very nature, love to tinker at some level, have contributed a 
lot to the development of various tools based on conceptually 
new ideas. You can take a developed idea, magnetic resonance, 
for example, and say, maybe I can use this idea.
    The step before that, I don't think, could have been taken 
by biologists. But once you have been there, who would have 
thought that fooling around with the magnetic nuclei would have 
told me how to do my advanced work.
    So I think, bear in mind that there are some areas more 
ripe for development than others. There is also another issue, 
that is, I'm predicting that biological scientists are going to 
get better and better, there are questions that are going to be 
asked, they are questions that don't seem so foreign to 
physical scientists any more.
    In fact, some of the questions I actually ask myself when I 
go to my colleagues in medical school and biology, I say, is 
this an interesting question. I don't want to think about 
something and have them say, I don't care. Because in the past 
couple of decades, I think physicists have done that. They've 
gone toying around with something and biologists say, well, I 
don't care.
    But nowadays, I go and they say, that's fantastic. Not only 
fantastic, I've been doing this for the last three years, we've 
been trying to go to that goal as well. So if you now see 
divergent goals, there is an increased swing of the physical 
sciences not to accidentally something that can see would be 
useful to the medical profession and just hand it over, but 
they say, you know, I've been playing with this, too, and I 
want to join you in the fun.
    In coming together with the biologists, then you bring 
something you didn't have before. Because you now have not just 
a formal handle, but let's work together now. All sorts of new 
information and synergies and things you just couldn't have 
before.
    Mr. Porter. Dr. Lederberg.
    Mr. Lederberg. I'd like to give some validation and 
perspective about what the options are for useful results from 
these budgets. I'm a little surprised this has not been done, 
as far as I'm aware, I've been making this proposal for quite a 
few years.
    I was taught in high school economics to talk about the 
last dollar rather than the first dollar when you're talking 
about the merits of different kinds of expenditures, the 
marginal expenditure.
    My specific proposal is that you get your staff to get the 
cooperation of all the other science agencies, give you the 
panorama of the grants that are at the margin, the ones that 
were just not funded, and do it right across number of fields. 
Because that's what you're losing by not increasing your 
funding capability.
    You'll find it variable from one discipline to another. But 
pay lines run around 15, 20 percent. That's the fraction of 
proposals which are intrinsically quite worthy that end up 
being funded.
    If you could actually see what's being left out because 
there wasn't enough money to go around at the 23rd or 24th 
percentile on the pay line, you'd get a much more vivid picture 
of what it is that could be remediated by enhanced funding. I 
urge you to do that.
    Mr. Porter. I think we're running now, according to Dr. 
Varmus, at something close to 30. And the intention is to push 
that up higher as we go.
    Dr. Baltimore.
    Mr. Baltimore. Let me take a perspective that looks more 
broadly at science. I'm now the president of an institution 
that really focuses on the broad scale of science. So I've been 
exposed to people working in a whole range of fields and 
talking with them.
    I am impressed that the other sciences intrinsically, never 
mind their relationship to biology, but the other sciences are 
in general as vibrant, as exciting, as full of opportunity as 
the biomedical sciences. Astronomy, astrophysics, cosmology, is 
giving us a view of the universe with parameters we have never 
before imagined.
    The earthquake, seismologists and earthquake engineers are 
coming together to try to understand the forces at work in the 
earth, both from a practical point of view in trying to 
ameliorate the consequences of earthquakes and from the very 
scientific point of view that an earthquake is a remarkable 
probe into the earth's structure. And in fact, a prize was just 
given to two scientists, one from CalTech, who had studied the 
structure of the earth using earthquakes as a probe.
    Physics, chemistry, and I can go on, are all in a position 
now to take advantage of increased levels of funding. So when 
you talk about increasing the funding across the board in the 
sciences, I don't think the reason for that need be that it 
helps biology, although I certainly personally think that's a 
terrific opportunity. But because of the intrinsic power that 
the sciences have today.
    Mr. Porter. Let me add to what each of you has said. 
There's two other reasons I think are important. One is, we 
don't want to set disease against disease, which is what you do 
when you keep a static amount of funding. Neither do we want to 
set one science against another. I think they haveto all be 
valued and brought along at a relatively equal pace. Or you do set them 
one against the other.
    And while we have, over the last three and half years, 
increased funding for biomedical research rather dramatically 
compared to the rest of the budget, a lot of basic science 
funded by the Government has not done nearly as well. That 
worries me, from a political standpoint, a strategic 
standpoint.
    Secondly, it seems to me that from an economic standpoint, 
the future of our country lies in education and technology. If 
we don't make the investments now in both of those areas, we're 
going to have serious problems in the future.
    So from the standpoint of the economic quality of life, 30 
or 40 years from now, I think the investments have to be made 
now. With the economy doing as well as it is doing, this is 
obviously a very good time to engage in the debate as to how 
this money ought to be spent.
    And just to lobby all of you, your speaking out on the 
importance of investment in basic science and research is very, 
very important. We've got a lot of priorities being argued for 
here. Protecting Social Security and Medicare and building more 
roads and bridges, and cutting taxes and paying down the debt. 
It's hard to argue that those aren't important priorities.
    But I think if we don't make the case for science, we can 
easily be left behind. The problem is that it did not needed to 
be made in the past, because we were doing a fairly good job of 
funding the available science that was there, the good science 
that was there. But now there's so much more good science 
there, that even with the kinds of increases we've had over the 
history of the NIH, we're funding too little of it to bring the 
young investigators to the table and keep them there.
    So this is a time when we really have to make a case for 
biomedical research and all basic research, more than ever 
before, in a certain sense, which is strange but I think true.
    Mr. Prusiner. Can I give you an example, that takes us all 
the way, I think, from physics and chemistry right to the 
patient? I think this is very illustrative of what we need.
    When we are able to use molecular biology and get at the 
gene, we now have a protein. The next thing we want to know 
from translating the gene to the protein sequence is how this 
protein folds up. We want to know its three-dimensional 
structure.
    The reason we want to know that is so that if that protein 
is involved in a disease process, we can develop a small drug 
which will modify the structure of that protein and make the 
bad form of that protein harmless and cure the disease.
    The problem, the biggest problem that faces us is really 
very similar, prior to the wonderful gene cloning technology 
that was developed. Before that, we could do very little in 
genetics. All of a sudden, with gene cloning, recombinant DNA, 
the whole science of molecular genetics evolved before us. It's 
very simple to access the sequence of genes. Then from that to 
translate that into amino acid chains, the protein.
    But what we don't have are very good techniques at 
determining the three-dimensional structure of proteins. We 
only have really two of these where we can know this in detail. 
One of them involves x-rays and the other one involves, as Dr. 
Chu said, magnetic resonance.
    We need desperately much better techniques, much better 
technology. And when we get it, it will revolutionize our 
ability to rationally design drugs for illnesses, just the way 
recombinant DNA technology revolutionized genetics.
    So I think there, biologists really need the help of 
physicists. They really need the help of chemists. And we don't 
have good ideas on the horizon. That's why we need a lot of 
basic research in an area like this, which is so fundamental to 
moving medicine forward and coming up with new therapies.
    We're beginning also to learn, particularly from my own 
work on prions, that where we thought that each protein had 
only one three-dimensional structure, we're finding out it can 
have more than one. It can be two, it can be many more. We just 
don't even know the limits, because our technology is so 
primitive.
    Mr. Chu. When I was speaking, I was addressing you as the 
chair of the appropriations subcommittee for NIH. I applaud 
your wisdom regarding the physical sciences. There are no 
hearings like this in DOE, the NSF, that I know of, and I 
inquired around a little bit.
    The whole structure of the scientific community, the whole 
enterprises, it toggles back and forth. If one could see a 
doubling at the end, where it will be money well spent, the 
time is right. I also agree that the time is also right for 
large increases in other sciences as well. It's just fantastic 
what's happening.
    And the two are coming together in very strange ways that I 
find both fascinating and exhilarating. People working on 
better and better transistors, we're going to smaller and 
smaller scales. Making things at the scale of a dozen atoms 
wide, developing technologies to see what they're seeing at 
this scale.
    And those same technologies are now being transferred over 
into the biomedical sciences. I myself am beginning to work on 
these things. Again, as a different type of imaging technique.
    So here you have something pushing transistors in 
electronics, which is a huge industry, where the United States, 
fortunately, is the inventor and remains the leader. And all 
the scientific energy and engineering energy being put into 
that area can now be used in another area.
    And likewise, I think the solid state engineers, chemists, 
physicists, can learn a lot by studying things that have been 
engineered over roughly a billion years. [Laughter.]
    Mr. Porter. Let me give you some reassurance on this. 
Because we're about 10 months into the time when the Speaker of 
the House was convinced that we have to address this in a very 
broad way. He's brought together the appropriations 
subcommittee chairmen that fund research, and fund it in a lot 
of different places in our Government. It covers maybe 8 of our 
13 subcommittees.
    He's also set up a task force that will work through the 
Science Committee, the authorizing committee, to look at all 
science funding across all departments of Government, and bring 
together an overview of what we should do in respect to all 
that funding.
    The commitment's already made, though, to double funding 
for basic research throughout the Government. The question is, 
where do we get the resources to do that, obviously.
    Let me ask a question before I call on Ms. Pelosi, let me 
ask a question of Dr. Doherty. I understand you have to catch a 
plane.
    You raised an issue that might seem in a way not relevant 
to our discussion regarding population growth and world peace, 
stability. I'd like you to expand. This is one of mine and Ms. 
Pelosi's very strong interests. I wonder if you could expand 
your thoughts in that regard for us.
    Mr. Doherty. I think the perceptions of those who work with 
infectious disease, and especially the perceptions of the group 
that put together the methods to vaccinate all the world's 
children against the common infectious diseases, the initiative 
that was launched two years ago, in fact, it was called the 
year of the vaccine.
    I believe that's gone ahead. It was a very broadly based 
coalition that involved physicians and involved Rotary, who 
provided all the polio vaccine, for instance. Something like 10 
million children in India were vaccinated in one day.
    Now, part of that perception is that the only way we're 
going to be able to see people in developing countries limit 
family size is if we can ensure them that children will 
survive. There are no social security systems. Your only social 
security system in a country of that type is to know that your 
children will be there to care for you when you're old. And of 
course, the children are also in many ways involved in the 
economic health of the group.
    So unless we can do that, we can't expect the process of 
rational reduction that we've seen happen in all western 
societies will occur.
    Now, that's no guarantee. There are some signs, I think in 
Pakistan, it's a bit disturbing, that as disease is being 
controlled that it hasn't necessarily resulted in more control 
of family size. But I think it is the only way we can see 
forward to deal with these issue.
    Mr. Porter. My understanding is that it takes a while to 
adjust.
    Mr. Doherty. It does.
    Mr. Porter. That it won't happen in a generation.
    Mr. Doherty. We were talking earlier about broad ethnic 
considerations. I think various of the groups that have a great 
ethical say in our society haven't yet even taken on board the 
consequences of the medical revolution in antibiotics, and so 
forth, for population size. We've disturbed, if you like, the 
natural order of things, by stopping children dying. If you 
lived in the 1920s or 1930s, or in the 19th century, death of 
your children was common. Much of the children's rhymes of that 
period reflect this sort of thing, the fact that children did 
die.
    We don't expect children to die any more. St. Jude 
Children's Research Hospital gets an enormous amount of money 
to work on childhood cancer, which actually kills relatively 
small numbers of children. But it's just seeing a child die, it 
seems so incredible.
    Mr. Porter. I don't think the scientific community often 
speaks out on the question of what the effects of a population 
growth that we're seeing now in the world has on our future.
    Mr. Doherty. It's been stabilized in a lot of countries. I 
think what we saw in Rwanda was clearly a situation 
exacerbated, that where you have a bad political situation, 
exacerbated by the fact, I think, in that state, was the most 
overpopulated country on earth. And now in areas of Kenya we're 
also getting to the stage where we're seeing rural economies 
with 1,000 people pre square mile.
    These are not cities, these are people supporting 
themselves in a rural environment in the density of 1,000 
people per square mile. Kenya is becoming substantially 
destabilized from what I can see recently. Partly it's 
political, because of the situation with the president.
    But partly, it's due to the fact that the population's been 
growing extremely rapidly, both by natural growth and by 
refugees coming down from sub-Saharan Africa. And also by the 
number of arms that have been coming down from the north of 
them, particularly.
    Mr. Porter. There are also obviously environmental effects 
from overpopulation.
    Mr. Doherty. Environmental effects are disastrous, yes. 
Denudation of forests, and so forth. And there's also the 
effect of course that in general, AID dollars, particularly in 
Africa, are being pulled, as aid is going more into central 
Europe, people have given up on some of the African 
governments. There's a general tendency in international aid 
communities now to only want to give money for very, very 
short-term type of results that will look good politically. 
It's understandable that it is having that constant response.
    Mr. Porter. Ms. Pelosi?
    Ms. Pelosi. Thank you, Mr. Chairman.
    I think it's appropriate that we went down the 
international path for a moment, anyway, because so many issues 
know no borders. Dr. Doherty, I was thinking about what you 
said about the need for, the concern about population.
    That's one of the reasons why we're going more in this 
direction, not just talking about family planning, but talking 
about saving of children. Because if we can say, says I, who 
had five children in six years,--but if we can say to these 
mothers that if you want two babies, have your babies two years 
apart, there's a better chance for them to survive, in the 
environment these people are in, it may be a little more 
accessible to them, that they will be able to have children, 
that they will continue to have children, but that they're 
spacing them in finite lengths of time, that will produce fewer 
children.
    Mr. Doherty. The international agricultural research 
community has a major concern with the empowerment of women. To 
give women economic power can make an enormous difference. That 
gives them the power to make their own decisions. For instance, 
there's a very interesting program in India, where, funded 
through international aid, they are encouraging women to sell 
milk. Women control the cows, the cows produce the milk. If 
they sell the milk, they get an income. If they get the income, 
they get certain other status with their husbands and so forth.
    So empowerment of women is part of this whole thing.
    Ms. Pelosi. Chairman Porter and I also serve on the Foreign 
Operations Subcommittee Appropriations where many of these 
international family planing-child spacing, empowerment of 
women and economic development, all those issues are important 
to us and what you're saying is music to my ears. I know it 
would be to Mr. Porter also if he were in here.
    We were both actually declared champions by the Eradication 
of Polio Coalition just a couple of weeks ago. So we're very 
familiar with that wonderful effort. I know you have a plane to 
catch, so I will not dwell on that. But perhaps another time, 
you could come before our Internationalsubcommittee.
    Mr. Doherty. I'd look forward to it.
    Ms. Pelosi. Our scientists, I talk to Dr. Varmus when he's 
here, and I talk to USAID when they're there, to tell Dr. 
Varmus that we're interested in international collaboration, 
then he tells the USAID, to share what they are finding here.
    To get back to the Chairman's point, though, about the 
other physical sciences impact on the biomedical research, I 
recently attended a conference put on by the Council of 
Competitiveness that was at MIT. Perhaps some of you were 
there.
    But over and over again in the workshops, and in the 
general sessions, etc., they talked about the fact that there 
was such a little bit, such a small amount of heavily-funded 
R&D in those other sciences. Not that they were--Dr. Varmus was 
there, he heard people say how it wasn't pitting one science 
against the other, but the message is clear, there isn't enough 
money. That sometimes is the case.
    It made such a, there is such a strong argument for us 
doing much more R&D. Because I believe, Mr. Chairman, that in 
addition to expanding our industrial and technological base, 
we're also increasing our revenue base. So I don't even think 
it's going to cost us anything to make those investments. I 
don't think it costs us anything to make the investment in 
biomedical research, because it increases our competitiveness 
internationally as we move these products along.
    I had the occasion to ask Andy Grove about the possible 
synergy between the physical sciences and what's happened to 
ECFF. Perhaps you were at that meeting with him, it was an ECFF 
meeting. We asked about any marriage between the ECFF type 
research and what was happening in Silicon Valley. He thought 
the cultures were very, very different. He pointed out what the 
challenges would be there.
    Nonetheless, as with many of the business people that have 
come before our committee, what they need most from the Federal 
Government is investment in biomedical research, so too, in 
order for us to remain competitive on the technological side 
investment is needed there as well. Over and over again we were 
hearing from the captains of the technology industry that they 
need the government to help fund research. And we have dropped 
off.
    I'm interested to hear what the chairman says, with this 
leadership that he's proposing. Because under this leadership, 
of course, we've lost other sources of funding for this 
research. I see this on the Intelligence Committee, as a member 
of that committee, where we have had some attrition in the 
funding of the other sciences.
    So I'm very encouraged to hear what you say about the 
intention. I'll be interested to see how they're paid for as 
well.
    But we keep saying, in the Intelligence Committee, we want 
that science that we have for imaging, for satellites to 
photograph the earth, to be available for mammograms. We see a 
translation from that kind of research to help us in biomedical 
fields, as you have so eloquently testified to. It's all 
related.
    Again, I'm pleased to hear what the Chairman had to say 
about it.
    I don't have any further questions, Mr. Chairman, except to 
say thank you once again for making this wonderful opportunity 
possible for our committee to have this excellent panel. I 
thank all of you.
    Mr. Porter. Ms. Pelosi, let me say, I think I've learned 
that what I must do is have, to ask the Nobel laureates to come 
early in the year, before we have votes to interrupt us, and 
members that have so many responsibilities outside. We'll try 
to, I hate to say this, try to plan it for January, maybe, 
rather than this time of year. And while Washington isn't 
nearly as pleasant as it is now, we hope that you can also 
attend at that time.
    Let me ask, we talked a little bit ago about life 
expectancy and how it has grown. Ms. Pelosi highlighted that. 
We've also talked about the research enterprise in this country 
being so much stronger than it is in other parts of the world.
    But life expectancy has grown in other parts of the world 
even faster than it's grown here, apparently. Have they simply 
adopted our technologies to their health care systems, or why 
is that true?
    Mr. Lederberg. Well, the short answer is yes. The knowledge 
that we can use for health is fungible and exportable to other 
economically advanced countries. We're about a year behind 
Japan, which I think is the world leader. Part of the other 
European countries.
    You have to look very carefully, because obviously 
different economic and social strata within our own country 
benefit to different degrees from these advances. They're all 
progressing, but some are further behind than others.
    One that's worth remarking on is that men aren't doing as 
well as women, by a long shot. That's been true for many, many 
years. Life expectancy for women in the United States is 79, 
and it's 73 for males. That gap, if anything, is widening. 
Women are experiencing a more rapid advantage from improvements 
in health inputs than men.
    Now, they may be making up for it as more women take up 
smoking and things of that sort. They may be equalizing the 
balance to some degree.
    But one should also look at these numbers as an 
opportunity. If we more thoroughly understood the difference 
between the outcomes in males and females, I think there may be 
ways of--I hope there's no objection to this--of removing some 
of that differential advantage.
    Whether this is intrinsic to the two Xs, there being two X 
chromosomes in the female and only one in men, so there's less 
buffering against genetic adversity, or whether it's direct 
effects of estrogen, there are some pretty strong hints that 
estrogen can be an important protective factor against 
atherosclerosis. And that might be a significant element of 
these distinctions.
    But the short answer to your question is, yes, other 
countries get advantages, some within their own social systems, 
not having the heterogeneity we do in this country, be able to 
provide them even more quickly to a broader advantage. But a 
rising tide is floating up all the boats in this arena.
    Mr. Porter. Perhaps on the male and female difference, 
we're spending too much money on diseases affecting women. Is 
that the case? [Laughter.]
    Mr. Lederberg. Whether you like it or not, there's a 
spillover that affects the health of males as well.
    Mr. Porter. I'd like to raise with you the question of 
personal reward of scientists. And by that I mean, I think it 
was Dr. Prusiner who said that we have to be concernedabout 
attracting, well, I think all of you touched on this, but Dr. Prusiner 
in particular, that we have to attract young people to come to 
scientific research.
    I wonder if you could delve into the more practical side of 
personal reward. Obviously, people are motivated by more than 
economics. But the economics plays a role in this as well.
    Are we providing the kind of support that leads people who 
might be inclined to a career in science and research by the 
economic rewards, or are we failing in that area? In other 
words, is it a tough thing to put all this investment in and 
see not much ahead in terms of your family, educating your 
kids?
    Mr. Prusiner. Well, I think to begin with, we are under-
investing at the level of post-doctoral training fellowships. 
There are proposals to increase these by 25 percent. We are so 
far behind in terms of making this attractive. We certainly 
need to do that.
    The second thing we need to do is to provide, as talked 
about earlier, perhaps reinstituting these research career 
development awards, which were so successful. I myself had one 
of these from the NIH in the beginning. So this helps create 
the kind of early funding which is needed.
    And of course, we need to increase the size of those 
awards, not just reinstitute what they were 15, 20 years ago.
    I think scientists, on the other hand, are not people who, 
they of course need to be able to earn a respectable living. 
But I think that's not what's driving a lot of people away from 
science. What drives them away from science is the uncertainty 
of having their research proposals funded.
    When the numbers have gotten very tight, at the 10 percent, 
15 percent level in some institutes at the NIH, and the 20 
percent level, not only do they see their mentors having 
enormous problems, but they can't imagine themselves being able 
to survive in such a system.
    So they don't see this as a kind of life they want to take 
on, because they see it as being so uncertain, so difficult. 
And of course, their ability to gain research support and do 
this consistently is directly related to their ability to 
advance within a university system. If they aren't able to 
acquire research support and then get their grants renewed, 
they're not going to be promoted.
    So again, the personal economics is tied to that. But I 
think it's more than personal economics. It's really the 
grueling and very stressful nature of the competitive grant 
process. We need to make it just a little less competitive by 
having more funding available.
    I think we also at this edge, as Dr. Lederberg was talking 
about, the grants that aren't funded, that's probably where 
most of the most innovative grants are. It's very hard for 
people, for that scientist, to step back and judge what's going 
to be successful five years and ten years down the road and who 
the very best people are going to be who emerge. Because just 
by the nature of science, we don't know what the very best 
science is going to be. None of us have a crystal ball.
    So I think it's extraordinarily important that those grants 
at the margin, so that we increase from 25 or 30 percent up to 
40 percent, which is what doubling the NIH budget will do for 
us, that those grants be funded. That will then increase, I 
think, the excitement among the established investigators for 
continuing their work. It will bring the young people into 
this. And people, I think, on all levels, all stages in the 
system, will find careers much more attractive.
    Mr. Porter. Dr. Baltimore.
    Mr. Baltimore. Let me address that perhaps from a slightly 
different perspective. Training in biomedical science today is 
a long process. People go through as undergraduates, they go to 
graduate school, they get post-doctoral fellowships. It's not 
unusual for somebody to start their first independent position 
in their mid-30s.
    We ask those people to live on pittance during that time. 
Many are willing to do it. Not many, but the ones who do it are 
willing to do it, they have no choice. Almost none of them have 
resources of their own.
    They tend to be immigrants to the United States, or born of 
immigrants. They see it as a way to find a place for themselves 
in the American firmament.
    That's terrific. But we really do have to ask why so few 
people born into second, third generation, later, American 
households, are willing to go into this kind of field. One of 
the reasons, I believe, is because the ability to earn a living 
up to age 35 is so limited, that it's really impossible to 
imagine having a balanced life of any sort on the amount of 
$21,000 a year, or $23,000. Impossible to imagine having a 
family.
    So I think we put a very high bar up to a career in our 
field.
    Mr. Porter. Dr. Chu.
    Mr. Chu. I just also, in addition to this suffering when 
you're young, people are amazing. They're willing to put up 
with a lot of things when they're young, if they see a light at 
the end of the tunnel. So you can pack all sorts of students in 
dormitories, if they know five years or ten years down the road 
that they're going to hit a point.
    In fact, when I was flying here, I was flying next to an 
airline pilot, a pilot for United Express. Well, United Express 
means you go up and down many, many times every day. He's a co-
pilot. But the light at the end of the tunnel is, once you get 
into this program, he sees some days later, maybe 20 years 
later, or 30 years later, he will be piloting a 747-400, and 
getting $250,000 for it.
    What the young scientists remark to me, when I say, I'm 
worried about funding, I'm worried about where the next years 
of continuous funding are. They're saying, they literally have 
said to me, if you're worried about this, what chance will I 
ever have. And if you're stressed now, I mean, forget about 
getting started. If you're stressed now, how could I think of 
not being any less stressed 20, 30 years down the road.
    So there's no light at the end of the tunnel.
    Lots of people are willing to work for $25,000 a year for a 
few years. Look at insurance. Because there is a light at the 
end of the tunnel.
    And so it's the whole package. It's not actually the money. 
We're not talking about paying scientists $4 million a year. 
They don't need that. They don't even need half that, for the 
most part. What they need is less stress, and enough to make a 
comfortable living and see, okay, now I've arrived, I can do 
things I wanted to do, and I don't have to worry literally from 
year to year where the next meal is coming from.
    Mr. Porter. Dr. Lederberg.
    Mr. Lederberg. I'd like to concur, and I'd like to add 
aspecific remedy from which a rather botched experiment has been done. 
It was totally misunderstood. This has to do with relief of stress.
    It's quite typical for grants, when they are successful, to 
be for no more than three years, sometimes just two years. When 
you look at the dynamics of what this means, in terms of how 
long it takes to submit a proposal, have it reviewed and have 
the reply, from the time that you've received one award, you 
have about a year clear time between when you have to start 
preparing your renewal grant application. You're living in a 
guillotine.
    And I think that's just an absurdity. My simple remedy is 
simply to expand the typical term of grants from two to three 
years to four to five years. In fact, the great majority of 
those renewals will be satisfied, an enormous amount of 
commotion is generated in the process of that reaffirmation, 
they make you drop out before you come back again and so on.
    Unfortunately, the way the bookkeeping was done, in order 
to achieve, and there was an interim experiment some years ago, 
an extension of grants, it appeared as if it was going to be at 
the expense of new grant applications, which it was not at all. 
It was just the bookkeeping heart attack.
    I think a re-examination of that issue, about the merits of 
looking fundamentally about reducing the number of times you 
have to have your neck in the noose, so you could spend more 
time doing your research. Now, obviously, some accountability 
is important. You do have to have periodic revisits.
    But it's too much, too often, too severe. And I think it 
really burns up a lot of the energy that should be going into 
the research itself.
    Mr. Porter. Let the record show that Dr. Ruth Kirschstein 
was nodding yes as you were saying that.
    Dr. Kirschstein. I think the average length of a grant now 
is four years.
    Mr. Porter. I'm glad we corrected that.
    Dr. Kirschstein. We have increased the length and probably 
will try to continue to somewhat do so.
    Mr. Porter. Dr. Prusiner, when you said that if we double 
the funding for NIH, we will be funding hopefully at 40 percent 
level, that probably won't last, though. Because we will again 
increase the body of knowledge, and there will be more good 
science being offered, and probably driven down again, so we 
won't be funding as much as we want to at that point in time.
    That leads me to another question for Dr. Gilman. Dr. 
Gilman, you said we spent 2 percent of our entire health care 
costs on research, I believe, is that correct?
    Mr. Gilman. That's the number I've heard.
    Mr. Porter. Isn't part of that problem, though, that you've 
been so successful? In other words, aren't the discoveries 
outstripping our ability to provide the fruits of those 
discoveries to our population, costing us a great deal of 
money? When we learn to replace a liver or a heart, then 
obviously there are people who need those replacements, and the 
demand for them goes up, they're very expensive. We can't 
always afford to do everything that we know how to do.
    Mr. Gilman. No, we can't. I think when new technology comes 
along, it inevitably is going to cost quite a bit at the 
beginning. And I think those costs will come back down. I think 
also as a country, I would hope that we would be happy enough 
to pay for its success. And that if the problem is increased 
appropriations bringing us a great deal more of additional 
knowledge, we'll face the problem how to pay for even more with 
smiles.
    Mr. Porter. I agree with that, but I wanted to get your 
answer.
    Yes, Ms. Pelosi.
    Ms. Pelosi. I heard Dr. Gilman's statement quite 
differently. I was thinking when he said it that we don't spend 
enough on early intervention, on research on addiction, which 
leads to other health care spending. And I thought that if we 
spent more on research, with these new discoveries, we need to 
spend money to make them available to more people.
    But on the other hand, in terms of prevention, early 
intervention, knowledge that we gain in the genome project and 
the rest----
    Mr. Gilman. It clearly works both ways, just what the 
individual problem is. Some new technologies are very 
expensive. Some very cheap drugs eliminate entire classes of 
surgery. We can cite many different kinds of examples on both 
sides.
    Ms. Pelosi. Thank you.
    Mr. Chairman, I just wanted to comment that on other 
occasions such as this, we have, at the kindness of our 
Chairman, had this opportunity before with other Nobel 
laureates, we talked a great deal about the brain, in this 
decade of the brain. I don't know when I was at the 
Intelligence committee if much discussion went on about that. I 
think not.
    But it seems to me that must be a given, now, that that's 
so important, that the strides are so great that it almost goes 
without saying, when we've asked the scientists before, where 
is the area of the most promise in science, biomedical 
research, a number of them in earlier years said the area of 
the brain. By that, they did not mean psychiatry. Well, that's 
what they said.
    Not to put down psychiatry, but just in other areas of the 
brain.
    So I assume we are not focusing on that today, it hasn't 
been brought up. Actually, it has been brought up in your 
testimony, but not so much in the way it was before, because 
the benefits have been so overwhelming and so clear.
    Mr. Baltimore. I don't think it's so much that the benefits 
have been so extraordinary as that it is now widely understood 
that the greatest challenge we have is understanding the brain. 
But I think one could easily reiterate that. It's not that we 
learn so much that the problem's gone away, it's just that we 
widely recognize that that is our challenge.
    When we talk about new methodology coming in from physics, 
coming in from computational science into biology, one of the 
places that we look for the benefit is in neurobiology, 
neuroscience. Because the brain is still, by many orders of 
magnitude, the most complicated biological problem we have to 
face. We don't know how many different neurons there are. But 
we know that the number is enormous.
    We don't know what the codes are that neurons use, but we 
know that they're complicated. We need to answer questions like 
that, simple anatomical questions, very complicated questions 
in the information process. And we probably can't do that with 
the technology we have now, we are very much technology 
limited.
    So this is an area of tremendous opportunity, tremendous 
promise, should, in fact is receiving increasing consideration, 
increasing resources. And promises tremendous excitement, both 
in dealing with the kinds of problems that Dr. Prusiner 
emphasized, the diseases of the brain, and in understanding how 
the brain works, so that we can actually understand what 
learning is about, what memory is about, that we can teach 
people within the context of how the brain works, rather than 
just doing it the same way that our grandparents did.
    Ms. Pelosi. When I said the benefits, I meant we had 
inspiration that the prospects were clearer to us. I take it by 
your remarks that the cohesion of the sciences, biology, 
physiology, etc., together with medicine and the convergence 
that you referred to earlier----
    Mr. Baltimore. Very much is around neuroscience, yes.
    Mr. Gilman. Everybody talks about the fact that we're 
entering a new age in biology, which we are. It also means 
we're finishing an age in biology. I think over the last 
several decades, many of us have been real reductionist. We've 
been looking for the pieces, identifying the molecules, taking 
the system apart a lot and learning what it is made from.
    This reductionist age is going to soon be concluded with 
the human genome project, etc. We're going to know all the 
pieces, and all the millions of puzzle pieces are going to be 
on the table in front of us. That's going to be the time that 
we're really going to be able to start putting the puzzle back 
together. We've been trying to put the puzzle back together, 
but because we don't have all the pieces, it gets to be sort of 
a pain in the neck.
    Now we have all the pieces. And I think this is going to be 
one of the things that will be enormously profitable to 
concentrate on if more money becomes available, will be real 
interdisciplinary, multi-institutional consortiums of efforts 
to really begin to be truly integrated in the way all this 
information gets put back together. And there's no place like 
the brain where, that will require supreme effort there. But 
that will really be the ultimate goal, I think.
    Ms. Pelosi. Very exciting.
    Mr. Baltimore. Yes, it is.
    Ms. Pelosi. All we need is the money. [Laughter.]
    Mr. Chu. Let me also say that I agree, there are more tools 
we need in order to really get inside and look at what's 
happening. Before it was a matter of really, literally being 
wired to electrodes. Sometimes you just can't do that.
    So there are many new tools that are being invented now, 
being developed. There is the opportunity, when you speak of, I 
would say systems engineering now, as we get more and more, why 
is it the systems have been built this way, what are the design 
rules that made this engineering trade off.
    But finally, there is something else that I find 
fascinating, and that is, there are, I worked at the lab for 
nine years. There is one biology group that still lags, and 
that has to do with the neurobiology. Why? The brain is a 
wonderful computer. Based on what it can do, what it has and 
the fact that its internal switches are going very slowly, it 
actually can process many, many, especially visual information 
and pattern recognition, in ways that our biggest investigators 
can't do.
    So here again we have the engineering experience, let's 
find out how this thing works, and maybe we can do that, use 
some of these ideas and things we build from scratch. So again, 
some of the driving forces in neurobiology, on the physical 
sciences and engineering side, are also taking us closer. But 
ultimately, on the biological side, we need much better, more 
powerful tools.
    It really is an area where many scientists and biologists 
are realizing the opportunities.
    Ms. Pelosi. Any of the tools necessary for cosmology 
helping us in the lab?
    Mr. Chu. It's hard to say, but I would say, surprisingly, 
some of the mathematical models have a way of popping up here 
and there.
    Mr. Baltimore. The imaging technology that's used to gather 
information with the most powerful telescope does have its 
application in gathering information.
    Mr. Chu. Pattern recognition actually, in mammography, that 
type of imaging technology is now in use. That was developed by 
NASA.
    Mr. Prusiner. Let me just respond in a little more 
practical sense. I made a list, I'll try to be very brief, 
seven areas where I thought in the nervous system, there were 
real opportunities just around the corner in terms of horrible 
brain disease. I touched on the neurodegenerative diseases, so 
I won't go back over those. But for instance, in alcoholism and 
drug addiction, we're learning a lot about signaling.
    I think a lot of that new information is not far away from 
being able to really intervene in a meaningful way in these 
conditions. And of course, coming back to what was said before, 
I think you raised that, the benefits from being able to treat 
alcoholism, in terms of cutting down on the number of criminals 
who occupy our jails, and the benefits from treating drug 
addiction, cutting down the crime that goes on all the time, it 
would be just enormous to our society. The savings would far 
outweigh the research monies that would be spent.
    If we look at stroke for a moment, we're all very excited 
about PTA, using this protease to treat early stroke. But it's 
really pretty primitive in the fact that we have to recognize 
the stroke, do a scan of the brain and in three hours institute 
the therapy.
    We need much better therapies. It's the third leading 
killer in America, stroke. The devastation in terms of chronic 
illness that's created by stroke is just huge.
    We go on to another area, schizophrenia, bipolar disorders. 
Neurologists are fond of saying, well, you know, some day, 
hopefully in the not too distant future, these will be 
neurologic diseases, not psychiatric diseases, because we'll we 
understand the chemical balances that go on, and we'll 
understand why they go on.
    And I think we're just very close to having some meaningful 
genetic studies that will tell us something about this. There 
have been some results and they haven't been confirmed. That 
tells me that we're not far away.
    And we look at a disease like multiple sclerosis, the 
greatest crippler of young Americans in the prime of their 
lives. And we're still struggling with this. We need 
desperately more investment and more young people to get into 
this field and try to figure out what is going on. It's been 
such a roller coaster. People thought they had therapies, 
people thought they had a cause or causes. And we still have 
tremendous numbers of questions.
    And in the field of cancer, we've been making a lot of 
progress, obviously, but brain tumors have been increasing at 
an alarming rate. And we don't understand why this is. We have 
no idea.
    I think all of us look at traumatic damage to the nervous 
system, spinal cord injuries, injuries to the cranium, and 
there's such a need for drugs to promote regeneration of 
nerves. This would be so wonderful.
    So there are so many areas that are just right or close, 
and a few that just need enormous amounts of research. We just 
can't tell where these breakthroughs are going to come at any 
moment. But I think there are so many opportunities, we're 
losing the opportunities by not pushing harder.
    Ms. Pelosi. We've had big changes, don't you think?
    Mr. Prusiner. We've had big changes, but I think we've had 
more of a sort of an enlightened period, where many studies in 
neural biology are beginning to catch up to some other areas. 
We're just really at the beginning. We're sort of at the 
beginning of the decade of the brain, after spending a decade 
thinking about it, seeing the progress.
    Ms. Pelosi. I thank all of you again.
    Mr. Porter. I know several of you have to catch airplanes, 
and Dr. Doherty slipped out before I could thank him, but I 
think if all the members of Congress could hear what we've been 
privileged to hear this afternoon, they would flock to the 
concept of increasing funding for research in the way that we 
hope they will be inspired to see all the opportunities that 
are lost if we don't provide that kind of increased funding.
    Let me ask each of you who want to comment on this, and I 
hate to talk about practical things, but I think it's 
necessary. Our scientific research infrastructure, something 
that Dr. Varmus has put at a much higher priority this year 
than previously, what do you think we need to do in that area 
to provide the kind of structures and equipment that is needed 
to conduct research, and are we doing enough?
    Mr. Baltimore. I think there's no question that the future 
of biomedical research will depend to an increasing extent on 
the quality of the instrumentation that exists in laboratories. 
We are more and more able to take advantage of very high 
resolution machines, of whatever sort.
    But with those increased resolutions come increased costs. 
And increases to the point where you can't put things like that 
onto a grant. They just are so out of scale with the size of 
the rest of the grant.
    So they need to be separately funded. Nothing has been 
knocking on my door as the President of CalTech more in the 
last six months than needs for equipment. For chemists, many of 
them working on biochemical problems as well as the biologists. 
New methods of visualizing molecules and methods of visualizing 
cells, there are tremendous microscopic advances in looking at 
cells, live cells in real time. But they're very expensive 
techniques. Because you can't put much energy into frying the 
cells, so you've got to be able to work at very low energy.
    I think Dr. Varmus is correct in making infrastructure a 
very serious issue.
    Mr. Gilman. That's absolutely true, and I'll second what 
David said about large instrumentation, the shared 
instrumentation programs in particular. I'm not sure how many 
of them cross institutes at NIH, but they should cross 
institutes. These are absolutely critical.
    I'll just put in a little pitch for more mundane 
instruments, too. I think budgets have become so tight over the 
last several years, the institutes have been trying to stretch 
the pay lines, that even replacement of modest equipment has 
been extremely difficult. We've had a grant for 10 years, 15 
years, we've got something as silly as a broken freezer that 
has been difficult at times to replace, a $5,000 equipment 
replacement.
    So both small and medium equipment on individual grants, 
and major equipment on shared grants is really very important.
    Mr. Chu. Also, I would say in terms of beating some of the 
stress, sometimes principal investigators have to run the whole 
show. They have the instruments, whether they're large or 
small. When they break, they're constantly worrying about this. 
Quite often, in many departments, schools, whatever, 
institutes, you're beginning to see people getting together and 
saying, okay, someone, something is going to run the cold room, 
run this or that.
    And in physics, there would be similar sorts of things, the 
electron microscope. So you take your sample and you give it to 
someone and say, here, look. Take care of it. It's very hard to 
get funds for this continued maintenance work. It's impossible 
to get endowments for that type of work. And if I look at the 
contrast between what I had at the laboratories, it just took 
your mind off a lot of things, you could concentrate on the 
science, not having to maintain something you needed, but had 
no desire in becoming professional across spectrums.
    Mr. Baltimore. Could I just comment on that? The other day 
I was talking to a young scientists who had been interviewed at 
the Whitehead Institute. The Whitehead Institute is an 
institute that I helped Mr. Whitehead found in affiliation with 
MIT. It's a quite wealthy institution. It initially had a $100 
million endowment.
    This guy who had just visited the Whitehead Institute said, 
you know, the atmosphere there is terrific. Of course, I 
remembered that, I tried hard to help that develop. He said, 
people are not stressed.
    I thought back to it, and I said, you know, that's really 
true. And it's true because we had sufficient money to do the 
kinds of thing Steve was just talking about, to provide help 
for people who need help, to provide resources so that if 
somebody finds themselves without a grant, they know that the 
ceiling is not going to fall in on them.
    Those kinds of institutional resources that make for a more 
effective research environment and a less stressful environment 
also make for a much more creative, productive and effective 
environment.
    Now, I don't know what you can do about that. Because we're 
talking about really institutional infrastructure. But there 
was at one time grants from NIH basically focused on 
institutions rather than individuals. I think those things can 
make a huge difference.
    Mr. Chu. One addition to that. Sometimes we are asked the 
question, how much time do you spend writing grants. That's not 
the right question. How much time do we spend worrying about 
grants. [Laughter.]
    Mr. Porter. Dr. Lederberg, when you were making your 
statement at the beginning, I wrote down virus wars. You were 
talking about death being an unintended consequence of microbes 
trying to survive, I think is the way you put it.
    And the question, then you talked about antibiotic-
resistant microbes, and the problem we face by their becoming 
resistant to the drugs that have been developed. If you look at 
the whole picture, is there a way that we will ever win? In 
other words, will we ever overcome all the afflictions, or will 
they simply metamorphose into a different form and keep us 
battling on into eternity?
    Mr. Lederberg. I think the latter is closer to the 
likelihood. We share the planet with a lot of species. We can 
be quite successful in eliminating some of the endangered ones. 
But these are the fish and the birds and the mammals, and we do 
that inadvertently. We're certainly never going to eliminate 
microbes. And God forbid that should happen. They are truly 
part of the balance of nature.
    I think we have to face up to the fact that some of the 
most grievous infections might be controlled, or in a rare 
number of cases, eradicated. Polio is well on the way, smallpox 
has been.
    But there's also the reservation that you then put yourself 
in a state of great vulnerability if they should ever come 
back, if you can't maintain, it's not as if we can drop our 
continued vigilance and have preparations to be able to deal 
with these issues if there should be a recurrence.
    Right now, for example, our stocks of vaccinia that might 
be brought into play if there should be a resurgence of 
smallpox are down to a few hundred thousand doses. And there's 
no manufacturing facility, there's no industry ready to back 
them up. I don't know whether I'd recommend investing a lot in 
that or not, but it is something to worry about.
    For the microbes, it will be ongoing trouble. We'll take 
the edge off, we'll learn how to live with them more 
successfully. We may be able to blunt the disease that they 
cause if we understand better how they moderate themselves and 
how that moderation is broken through, that will be a path 
through it. Learning to live together, rather than eradication, 
I think will be the outcome for a great majority of infectious 
diseases.
    Mr. Porter. Anyone else want to comment on that? No.
    There's been a lot of discussions about whether we ought to 
be having more directed research rather than more basic 
research. I wondered if I can get your insights and thoughts on 
that whole question.
    Mr. Baltimore. It's a very sticky issue. Because the ethic 
of the scientific community has been that research should be 
investigator-initiated. And there is no question that creative, 
inventive ideas come from investigators, they don't come from 
people who are thinking about how to do research, they come 
from people who are in the trenches doing research.
    And if you want the best of research, you certainly want to 
support an investigator-initiator. But there comes a time when 
you really want to focus resources on it. And it's not a time 
when necessarily you want to give up creativity. But when you 
have an idea where the goal is and you want to get to the goal, 
and I've seen this in particular with the fight against HIV. 
Because there was a problem that presented itself, and we very 
quickly understood its dimensions.
    It still poses extremely difficult basic questions. And 
those ought to be investigated by investigator-initiated 
methods.
    But it also posed some pretty straightforward questions, 
like what's the structure of the protein. Those kinds of 
questions really should get intensive investigation in a way 
that's coordinated from some central place.
    So I think as research comes closer to development, in a 
sense, it certainly comes closer to focusing on the solution of 
a problem, rather than gathering information, there is a place 
for direction in research. That's something that I think NIH 
has to come to grips with. Because NIH has not been well 
organized to provide that kind of research.
    Mr. Gilman. In addition, I think it's become really obvious 
over the last 15 years or so that very basic scientists are not 
averse to doing translational research if they see how to do 
it. Molecular biology really brought that to the fore.
    As soon as this whole area opened up and practical 
applications became clear, the joke was that there wasn't a 
full professor in California without his own lab techniques. 
Even very basic people have been very quick to translate when 
it's been obvious how to do it, or not necessarily obvious, but 
when it's been possible to do it.
    Mr. Porter. Dr. Lederberg, you have the last word.
    Mr. Lederberg. I think it can be said that for most 
circumstances, market-oriented mechanisms provide the best way 
for direction. The directed research, in a sense, I think you 
meant, has to do with the developmental stages of bringing 
concepts to market in the form of drugs. The large majority of 
that can be done very well by the private sector. And there you 
have issues of allocation resources that are driven by 
competition, potential markets and so on.
    I think once in a while the Government has to step in, but 
there will be market failures. These kinds of applications are 
just not going to be supported, there are too many risks, 
questions of identification and so on. But I think those 
generally speaking are the exception, not the rule. I think Dr. 
Gilman was hinting at that, because I think a lot of the 
technological translation he's talking about goes on in an 
entrepreneurial setting which professors and others may be 
consultants or may be indirectly involved.
    So it does need some balance. But most directed research, I 
think, can be done by the private sector.
    Mr. Porter. Thank you, Dr. Lederberg. This is another 
series of votes, unfortunately. You have been very patient, and 
gentlemen, I can't tell you how much I appreciate your taking 
your valuable time to come here today and talk with us. It has 
been, and I think I speak for all of us who have had an 
opportunity to talk with you. We've been inspired by what you 
tell us, and we're going to do the best we can to provide 
dramatically increased resources for research, and to do those 
things that are necessary to bring the best minds to science 
research and to keep them there, and see some light at the end 
of the tunnel, which I think is terribly, terribly important.
    So thank you all very much for being with us today.
    The subcommittee will stand in recess until notice of the 
Chair.
                                       Wednesday, October 29, 1997.

                           CHILD HEALTH HEARING

                               WITNESSES

DR. DUANE ALEXANDER, DIRECTOR, NATIONAL INSTITUTE OF CHILD HEALTH AND 
    HUMAN DEVELOPMENT
DR. ALAN LESHNER, DIRECTOR, NATIONAL INSTITUTE OF DRUG ABUSE
DR. STEVE HYMAN, DIRECTOR, NATIONAL INSTITUTE OF MENTAL HEALTH
AUDREY NORA, M.D., ASSOCIATE ADMINISTRATOR FOR MATERNAL AND CHILD 
    HEALTH, HEALTH RESOURCES AND SERVICES ADMINISTRATION
JAMES S. MARKS, M.D., DIRECTOR, NATIONAL CENTER FOR CHRONIC DISEASE 
    PREVENTION AND HEALTH PROMOTION, CENTERS FOR DISEASE CONTROL AND 
    PREVENTION
ERNST L. WYNDER, M.D., PRESIDENT, AMERICAN HEALTH FOUNDATION
    Mrs. Northup [presiding]. The subcommittee will come to 
order.
    Today the subcommittee is venturing into new territory 
about conducting hearings on a topic that is not specifically 
related to the budgets of the agencies that we fund. We wanted 
to spend more time looking at the issue of child health both 
from a research and a services and prevention perspective.
    Improving child health is a key objective of many of the 
programs we fund, and we have selected from a broad range of 
activities three witnesses for this morning and three for this 
afternoon.
    The subject of child health clearly merits much more 
extensive treatment than we have been able to give it in just 
two hearings, and we will not be able to deal with these issues 
such as health insurance coverage and a new children's health 
initiative.
    This morning, we will hear from three NIH witnesses who are 
very familiar to the subcommittee: Dr. Alexander from the Child 
Health Institute, Dr. Hyman from the Mental Health Institute, 
and Dr. Leshner from the Drug Abuse Institute. I am confident 
that our three witnesses will bring us up to date on the latest 
research and findings in the area of child health and describe 
the scientific opportunities that exist to generate knowledge, 
improving the health and the well-being of this Nation's 
children.
    Gentlemen, I think we will have each of you give us your 
statement and then proceed with questions. That way, the 
members will have a chance to direct questions to anyone of the 
three of you upon completion of your three statements.
    As members of the audience know, the Congress is in the 
final weeks of the session. With members pulled away in 
different directions, we are all here at the same time. We may 
have some interruptions this morning and members may not be 
able to spend as much time at these hearings as they would 
like. Nevertheless, we are all vitally interested in the 
questions before us today.
    Dr. Alexander, why don't you start first.
    Dr. Alexander. Thank you, Mrs. Northup, members of the 
subcommittee. I am pleased to have this opportunity to address 
child health research at the NIH.
    My colleagues join me in expressing our appreciation to the 
subcommittee for holding this hearing to focus on some of the 
most exciting achievements and promising opportunities in our 
efforts to improve the health of our children.
    We all agree our children are our Nation's greatest 
resource and that the quality of their health and well-being 
will greatly shape the future of this country. What we will be 
like as a nation 25 years from now and what our health care 
costs are going to be 40 to 50 years from now are being shaped 
by how today's children grow and develop and learn, by the 
kinds of health problems they experience as children, and by 
the kinds of social and health-related behaviors they develop 
in childhood.
    A recent Government report on ``America's children: Key 
National Indicators of Well-Being,'' pointed out our children 
are as important to our Nation's future as is the economy and 
that we should pay as much attention to indicators of how our 
children are faring as to how the economic indicators are 
doing.
    The picture presented by that report was a mixed one. On 
the positive side, we have achieved an all-time-low infant 
mortality rate and an all-time-high infant immunization rate, 
with virtual disappearance of numerous infectious diseases of 
childhood. Unfortunately, at the same time, cigarette smoking, 
drug abuse, and alcohol use by our children are all increasing 
and deaths from handgun violence among black adolescents have 
risen to alarming heights.
    Most of the improvements and positives cited in the report 
are traceable to advances from research, and most of the 
problem areas identified need research to guide corrective 
intervention efforts.
    The importance of investment in research in child health 
and development can't be overstated. The direct and immediate 
benefits to our children's health are obvious, and we owe it to 
them to focus the same effort in protecting and improving their 
health that we devote to the health of adults. But there are 
other benefits from investments in research on children as 
well.
    Actions to improve health in childhood have the longest-
term impact. There is nothing to equal the 75-year cure or 
prevention. In the area of health behaviors, childhood is the 
time that lifelong patterns are formed, and it is far easier to 
establish healthy behaviors in the first place than it is to 
change unhealthy behaviors in adulthood. Witness the difficulty 
adults have in stopping smoking, losing weight, changing 
dietary patterns, or even increasing exercise. Patterns 
established in childhood are likely to be permanent and be 
transmitted to the next generation when today's children become 
parents.
    The long-term benefits of interventions in childhood to 
prevent adult disease are enormous. The time to prevent 
osteoporosis, a devastating problem for the elderly, is in 
childhood, by providing the dietary calcium intake necessary 
for maximum bone calcification. Research has documented the 
amounts needed but now must help to show effective ways to 
achieve this intake.
    The time to establish healthy food choices and exercise 
habits to prevent adult cardiovascular disease and obesity is 
in childhood. The way to prevent cancer and lung diseasethat 
develop as a consequence of cigarette smoking is to stop initiation of 
smoking in early childhood.
    In all these areas we are obviously failing in part in 
whatever we are doing or not doing now. Only by investing in 
research on how to influence these behaviors successfully in 
childhood do we have any hope of preventing adult diseases that 
result.
    Fortunately, those of us who are involved in child health 
research today are both proud of our accomplishments and 
optimistic about the array of challenging opportunities that 
are emerging in this field. Many new biomedical research 
technologies will enable us to develop the ability to prevent, 
cure, or better treat many of the diseases that affect our 
children today or may affect them when they become adults.
    The prospects for significant breakthroughs in the field of 
child health research have never been brighter. These exciting 
new opportunities in child health research are emerging across 
the broad range of NIH institutes and centers, most of which 
support some research related to child health. Let me cite just 
a few examples of what that research has accomplished.
    Cancer is the chief cause of death by disease in children 
under age 15. Since 1960, children's cancer mortality rates 
have declined 62 percent. When I was a pediatric resident 30 
years ago, children diagnosed with acute lymphocytic leukemia 
had an average life expectancy of less than a year, and less 
than 5 percent survived 5 years. Our most recent data show that 
75 percent of such patients are surviving at least 5 years past 
diagnosis and may be considered cured.
    Pediatric AIDS is a relatively new problem. A major advance 
in preventing transmission of HIV from mothers to their babies 
was the NIH-supported development of the use of AZT treatments 
administered to HIV-infected mothers during pregnancy, labor, 
and to their newborns. Development and testing of this 
treatment was a collaborative effort at NIH and has proven to 
reduce such transmission by two-thirds.
    Among the most pervasive advances in our children's health 
has been the remarkable decline in incidence of dental caries 
through a combination of fluoridation of water, fluoride 
toothpastes, dental sealants, and improved oral hygiene, all 
developed through research. We have progressed from nearly all 
children having dental caries to 55 percent of 5- to 17-year-
olds having no caries at all.
    As the lead NIH institute for child health research, NICHD 
has supported and conducted research that has significantly 
contributed to improving the health of children. Since our 
institute was established in 1962, the U.S. infant mortality 
rate has declined by 70 percent. Much of that decline is due to 
improved survival of premature infants as a result of research 
advances. One of those is the development of surfactant for 
respiratory distress syndrome.
    Another advance in lowering infant mortality is our 
progress in reducing Sudden Infant Death Syndrome. After 
research demonstrated that back sleeping position reduced SIDS 
risk, NICHD initiated a ``Back to Sleep'' public information 
campaign. Over the 3-year history of the campaign, deaths from 
SIDS have declined 38 percent.
    Difficulties in learning to read affect 10 million children 
nationwide. NICHD research has developed inexpensive 
assessments to identify which kindergarten or first grade 
children are likely to have difficulties learning to read, and 
classroom interventions that have been very successful in 
helping the children to overcome their reading difficulties. 
While reading ability may not seem at first glance to be a 
child health issue, it is a key determinant of future life 
opportunities as well as a predictor of health risk-taking 
behaviors such as smoking, drug abuse, and alcohol abuse.
    Perhaps most striking of all is success of research in 
preventing mental retardation. Thanks to research, we have 
eliminated congenital hyporthyroidism as a cause of mental 
retardation in this country; we will have no more children 
retarded from having PKU.
    The development of Rhogam through research has eliminated 
RH disease as a cause of mental retardation and cerebral palsy. 
New vaccines have nearly wiped out measles encephalopathy and 
congenital rubella as causes of mental retardation, and 
development of the Hemophilus influenzae type B vaccine by 
NICHD's own intramural scientists has brought to near total 
elimination the meningitis that was once the leading cause of 
acquired mental retardation in the United States.
    All these diseases are gone as a source of fear for parents 
for causing mental retardation in their children, thanks to 
knowledge gained from research and its speedy application in 
our health system.
    Even with these dramatic advances, more remains to be done 
in these areas, as well as many others. Examples of special 
opportunities and needs and steps being taken to address them 
include autism, where there is a special initiative to 
stimulate promising new research, focusing on neurobiology and 
genetics of this order, and asthma, one of the most common 
chronic diseases of childhood where the number of affected 
children has actually been rising.
    Major advances in vaccine development are continuing to try 
to prevent some of our most common childhood diseases that 
threaten the health of children. These efforts take on 
increasing importance as antibiotic resistance becomes a 
greater problem. NIH researchers are developing new or improved 
vaccines for such conditions as tuberculosis, diarrhea caused 
by such pathogens as salmonella, shigella, rotavirus, and E 
coli, Group A and B Streptococcus, several forms of pneumonia, 
and otitis media, and even dental caries.
    Birth defects are the Nation's leading cause of infant 
mortality and a major source of lifelong disability and 
morbidity. Advances in developmental biology and genetics, 
especially from the Human Genome Project, hold great promise 
for understanding causes of birth defects and providing 
possible means of prevention or correction.
    Diabetes is a major chronic disorder of children, with 
long-term health consequences, and a major clinical trial is 
now under way to try to prevent or delay the onset of diabetes 
among children.
    For many years, child health professionals and clinical 
investigators have stated that the needs of children have not 
been adequately addressed by many clinical research practices. 
Because of this gap, many of the medical treatments applied to 
children are based solely on testing done in adults. For 
example, the large majority of drugs have no pediatric 
specifications, although physicians can and do prescribe them 
for children.
    To address the problem of testing medications in children, 
NICHD established a national network of pediatricpharmacology 
research units. These units provide sites with expertise in pediatric 
pharmacology, experience in the conduct of drug studies in children, 
and access to a pediatric population to encourage industry to do the 
studies in children necessary for pediatric labeling.
    This approach is working, and NIMH has recently built on 
this experience to establish a comparable network for studying 
psychoactive drugs in children in collaboration with several of 
the NICHD units.
    Beyond this approach, the appropriate inclusion of children 
in research is a topic of great interest and importance to the 
NIH. A year ago, NIH and the American Academy of Pediatrics 
convened a workshop on inclusion of children in clinical 
research. Workshop participants concluded that there is a need 
to enhance the participation of children in clinical research 
and that NIH should take the lead in changing the climate for 
inclusion of children and set the expectation that 
investigators should include children unless there is a good 
reason not to do so.
    Last January, NIH published a notice apprising the 
scientific community of its intent to develop and implement a 
policy in which applicants would be expected to include 
children as subjects in clinical research unless they justified 
exclusion, and encouraging investigators meanwhile to 
voluntarily include children in their clinical research 
projects.
    NIH will continue to involve the scientific and 
professional communities, as well as patient advocacy 
organizations, as it moves forward with efforts to develop, 
implement, and oversee policy in this area.
    While child health research is a major focus of NIH 
activities, this subcommittee's interest in this important area 
is beneficial to its continued growth and development. My 
colleagues and I are committed to a strong and comprehensive 
child health research program to better serve the health needs 
of our Nation's children and youth and focus on the 
opportunities in childhood to prevent adult disease.
    I will be pleased to answer any questions you and the 
members of the subcommittee have.
    [The prepared statement of Dr. Alexander follows:]


[Pages 3024 - 3037--The official Committee record contains additional material here.]



    Mr. Porter [presiding]. Let me apologize to our eminent 
witnesses this morning. When we originally scheduled this 
briefing, we thought we would be clear. We put it over, as you 
know, because we thought we would be clear. We are still 
working on our bill. We are supposed to go to conference this 
afternoon. There are major differences that remain.
    I had a meeting this morning that began at 9:40; I thought 
I would be here by 10:00. I apologize to each of you for my 
inability to do that, and I thank Anne Northup for chairing and 
our members for being present, and I just want you to know that 
we tried to schedule this in an appropriate way and it just--
you know how these things work; it did not work out.
    Dr. Hyman, we welcome you this morning and look forward to 
hearing what you have to tell us.
    Mr. Hyman. Thank you, Mr. Chairman, and thank you to the 
members of the subcommittee. I am delighted to be here in the 
company of my colleagues, Dr. Duane Alexander and Dr. Alan 
Leshner.
    I am particularly grateful to you for convening a hearing 
that will permit me to highlight the extremely pressing 
problems created by our as yet limited understanding of mental 
disorders of children and by our all too common failure as a 
nation to apply what we know.
    Dr. Alexander has just reviewed for you many extraordinary 
triumphs in the area of child health. I am instead going to 
focus on a number of challenges. I think the area of child 
mental health is an area that has come along a bit more slowly, 
partly because of the difficulties of understanding the 
developing brain but also because of the inappropriate stigma 
that has been attached to childhood mental disorders--indeed, 
all mental disorders--and the shame experienced by families in 
coming forward to report these kinds of problems.
    It is obvious that for a child with an unrecognized or an 
untreated cognitive or emotional disorder, it is impossible for 
them to live up to their potential. Children with these 
disorders cannot learn adequately in school or readily form the 
kinds of healthy peer or family relationships that undergird 
the emergence into adulthood of healthy or productive citizens. 
We know the children, moreover, are at heightened risk for 
school failure and dropout, drug use, risk behaviors for HIV, 
and many other difficulties.
    Perhaps the most dramatic evidence of ongoing problems is 
the steady increase in the suicide rate of both our 
preadolescent and adolescent populations, a suicide rate among 
adolescents which is now equivalent to that among adults, 
despite targeted attempts to lower the rate of suicide deaths 
in this age group. We also know there is severe stress and 
extraordinary disruption and interference in the productivity 
of their parents and for their families.
    Brain and behavioral research offers increasingly firm 
ground for confidence that we can correct our scientific and, 
in turn, our current clinical limitations with respect to 
children's health needs. The yield of our investment in 
research has enormous implications, enormous for any child who 
benefits and enormous for our Nation, and I think Dr. Alexander 
made these points very well indeed.
    Before briefly describing exciting lines of research 
focusing on the development of the brain, I would like to 
acknowledge the enormous distance that we must travel. The 
diagnosis of childhood mental disorders lags behind 
capabilities of diagnosing adult disorders. Significantly, we 
have an inadequate ability to distinguish the early symptoms of 
disorders that portend lifelong difficulties from the still 
serious dysfunctions that might be due to passing problems 
during development.
    Our lack of information denies rational treatment to our 
children, leaving some children's problems unrecognized or 
undertreated, including many who are disabled by severe 
disorders such as depression, childhood manic-depressive 
illness, severe attention deficit disorders, anxiety disorders, 
and eating disorders.
    We are aware of substantial benefits of some 
pharmacotherapies for these children but at the same time lack 
an adequate understanding of the long-term effects ofdrug 
treatments on the developing brain.
    The point has been made many times but remains critical, 
children are not simply small adults. In the case of both 
psychotropic drugs and psychotherapies, different stages of 
brain development and the change in handling of drugs by the 
body mean that specific developmentally appropriate information 
is needed at every stage of child development.
    While there persists a dearth of skillful researchers in 
the area of childhood mental disorders, NIMH is committed to 
building that infrastructure. In addition, we must address and 
resolve difficult ethical challenges in conducting clinical 
research on children, mindful of the fact--and the point was 
made to me by a parent of a child with autism--that the least 
compassionate and least ethical option would be to remain in 
our current state of ignorance.
    Mr. Chairman, to me as a neuroscientist, the process of 
brain development really borders on the miraculous. More than 
100 billion nerve cells, and, in aggregate, maybe a 
quadrillion--I don't even know what that number means--a 
quadrillion connections among many possible alternatives. How 
are these connections chosen? How are they right?
    This complex miracle, the brain, is built by an equally 
complex interaction of genes and environment. It is true that 
single defective genes have been identified that can cause 
serious brain disorders like Huntington's disease, but we know 
normal emotional and cognitive development as well as 
vulnerability to the brain disorders, that have traditionally 
gone under the moniker of mental illnesses, is the work of a 
large number of genes, most likely acting in different parts of 
the brain at different times of brain development.
    Perhaps two-thirds of the genes that are being identified 
by the Human Genome Project are involved either in building the 
brain or in its subsequent functioning. As complex as the gene-
gene interactions are proving to be, they do not explain 
everything. Equally complex and important are gene environment 
interactions. How might the environment cause our brains to 
develop in one possible way rather than another?
    The environment produces biochemical changes in nerve cells 
within our brains. When such biochemical changes are large 
enough, of enough magnitude, they turn genes on and off inside 
those cells as part of the normal processes that get the name, 
brain plasticity. During development, as these little tweaks of 
experience accumulate, our brains get wired up. New connections 
are built, useful connections are strengthened, and connections 
that go unused are actually eliminated.
    Neuroscience has made the greatest headway in understanding 
plasticity in the developing visual system. Genes are largely 
responsible for the initial wiring up of the brain, but the 
fine-tuning is dependent not simply on genes but on use, in 
this case, visual experience. As light excites nerve cells in 
the retina and they signal to the brain, those connections that 
are used effectively are strengthened, those that are not used 
are pruned away. This use-dependent sculpting of the brain is 
illustrated by the condition of congenital cataracts in which 
an opacity in the lens blocks the light from entering the eye.
    It has been found that if such a cataract is removed, an 
optically perfect eye can be restored, but the success of the 
surgery in actually restoring vision, the ability of the child 
to see, is highly age dependent. If the surgery has begun too 
late in childhood, after the age of 4, even though you restore 
an optically perfect eye, the child will be blind in that eye, 
and that is because there is a critical period for plasticity 
in which light, and the use of these nerve cells, is required 
to strengthen these synapses. After a certain period of time, 
this is no longer possible.
    This is a particularly interesting time in clinical 
neuroscience because we are beginning to obtain information 
beyond things like the visual system, about the cognitive and 
emotional development of children, and it again points to the 
remarkable plasticity of the brain in response to environmental 
influences.
    Researchers have demonstrated, for example, that rearing 
rat pups in a complex or enriched environment, as opposed to 
the normal laboratory conditions--a rather boring, narrow 
cage--dramatically alters brain function as measured by 
improved performance on behavioral tests.
    I think more remarkable is that one sees a different 
cortical thickness, different rich dendritic arbors in the 
brains of the rats raised in an enriched environment; recent 
research has actually shown, in some smaller areas of the 
brain, there are even additional cells.
    In addition, research published only last week in Science 
magazine shows that early experiences can have lifelong effects 
on how the brain subsequently handles stress and elaborates 
stress hormones with, I think, pervasive implications for 
health.
    Now let me emphasize, these studies are conducted in animal 
models. It is a long leap indeed from these studies to specific 
interventions for humans. What we can say for humans is that 
deprivation and neglect may produce long-lived and even 
permanent alterations in the brain, with serious functional 
consequences.
    For example, consider the plight of the Romanian orphans, 
many of whom spent their first crucial years in environments 
marked by extreme emotional deprivation and even abuse. Even 
after adoption, often in the United States, many children are 
growing up highly vulnerable to stress, and they exhibit marked 
difficulty in coping with normal human interactions. It is a 
dramatic example, but I think these kinds of things can go on 
all the time in our children.
    What basic science is telling us is that our cognitive maps 
and our emotional maps of our worlds are plastic in response to 
the environment. We are just at the beginning of knowing how 
the brain produces these maps and at what periods of 
development their plasticity begins to wane. There is much 
research needed to translate these basic science ideas into 
effective and deliverable clinical interventions.
    We recognize that the eventual application of this 
information to preventive and clinical interventions requires 
that the interventions be shown to be efficacious, deliverable, 
affordable, and useful in the real world, and free of serious 
harm.
    If we fail to recognize the cognitive and emotional 
disorders of childhood, we will be permitting a kind of malign 
plasticity. A congenital cataract that is neglected and leaves 
a child blind is now an avoidable tragedy.
    Less well understood but far more pervasive, I believe, are 
the unrecognized and as yet untreated mental disorders of 
childhood or situations of abuse and neglect. These situations 
also impact the developing brains of our children, with 
devastating consequences.
    Thank you, Mr. Chairman. I will be pleased to answer 
anyquestions.
    [The prepared statement of Dr. Hyman follows:]


[Pages 3042 - 3051--The official Committee record contains additional material here.]



    Mr. Porter. Thank you, Mr. Hyman.
    Dr. Leshner, nice to see you.
    Dr. Leshner. Good morning, Mr. Chairman, members of the 
subcommittee.
    I, too, am very pleased to be here with my distinguished 
colleagues to discuss a topic of tremendous importance to every 
person in this country, and that is the health of our children. 
But I have to say I am also very sad to have to tell you that 
drug use and addiction are becoming more and more issues of 
children's health. Drug use is beginning at earlier and earlier 
ages, and overall drug use has continued to increase among 
youth at all ages. Moreover, children are being dramatically 
affected by the drug use of other people, particularly their 
parents.
    It is for these reasons, NIDA has made children and 
adolescents one of its highest priority areas and why we are 
dedicating a large portion of our research portfolio to the 
study of the effects that drug abuse and addiction have on 
infants and on children and adolescents.
    Drugs can affect the health of children in three 
significant ways. The first is exposure through maternal use 
during pregnancy; second, by growing up in a household where 
drugs are used; and the third is by using drugs themselves. And 
I am going to speak a little bit today about each of those 
topics.
    Our best estimates are that in any year about 221,000 women 
used an illicit drug at least once during their pregnancy. That 
means 221,000 babies were born drug exposed. Cocaine was used 
by 1.1 percent of women, or 45,000 of them. Babies born to 
mothers who abused drugs during pregnancy are often prematurely 
delivered; they have low birth weights and smaller head 
circumferences.
    But determining the precise effects of maternal drug abuse, 
per se, is very difficult, and determining the dangers of 
specific drugs to the unborn child is even more problematic, 
given most drug users use more than one substance.
    Factors such as inadequate prenatal care, poor maternal 
nutrition, and poor postnatal parenting are just some examples 
why it is difficult to determine the exact effects of prenatal 
drug exposure. This complexity is why we believe we need to be 
very cautious in drawing any causal conclusions about prenatal 
drug exposure effects.
    Two weeks ago, the New York Academy of Sciences, with 
support from NIDA, just held a very important conference that 
brought together for the first time all of the major basic and 
clinical researchers to discuss what they know and what they 
don't know about prenatal cocaine effects.
    A decade ago, crack babies, or babies born to mothers who 
used cocaine while pregnant, were written off as a lost 
generation. They were expected to suffer from severe 
irreversible brain damage, including reduced intelligence and 
social skills. And of course we now know this was a gross 
exaggeration. Most crack babies appear to recover quite well. 
However, the fact that most of these children appear quite 
normal also needs to be interpreted cautiously.
    As we continue to study prenatal cocaine exposure effects 
on later behavior, as our cohorts of crack-exposed babies are 
just now entering elementary or middle school, we are finding 
some, though not all, children are in fact affected, although 
perhaps more subtly.
    Under the leadership of our colleagues from the National 
Institute of Child Health and Human Development, we have 
cosponsored the Maternal Lifestyles Study that has been 
examining the health and developmental sequelae of 1,400 
infants and children exposed to illicit drugs during pregnancy, 
and this is one of a series of studies we are using to follow 
large cohorts of drug-exposed children through their school 
years, and researchers are looking not only at the children's 
intellectual status but at their behavioral, emotional, and 
social development as well.
    We are now seeing exposure to cocaine and other drugs, in 
addition, during fetal development can lead to subtle but 
significant deficits later on, especially with behaviors that 
are crucial to success in a classroom, such as blocking out 
distractions and concentrating for long periods of time. Some 
prenatally exposed children are also showing subtle cognitive 
and learning problems as they enter middle school.
    Because effects can be subtle and only expressed as 
children develop, long-term follow-up is needed, and that is 
why we have a number of long-term longitudinal cohort studies 
going on. To best understand the biological mechanisms by which 
prenatal drug exposure can affect later behavior, scientists 
need to rely heavily on animal models, and those models are 
providing important hints about the mechanisms of these 
effects.
    As just one example, most people, for a long time, believed 
that most prenatal drug effects resulted from the effects of 
drugs on the mother's circulatory system, and that meant that 
drug use was altering the amount of nutrients and oxygen 
getting to the babies. But a recently published study at the 
University of Massachusetts has shown the actual presence of 
cocaine receptors in the brains of fetal rats and showed that 
cocaine is able to bind directly to these brain sites.
    And that is what this poster on my left is showing you. It 
is showing in yellow and in red the high distribution of 
cocaine receptors, actually on something we talked about during 
the hearing, the Dopamine reuptake joints border, showing 
presence in a fetal rat brain--this is a ratbrain--presence in 
fetal rat brain of a high concentration of cocaine receptors in the 
base of the brain but also in areas important for later memory like the 
hippocampus and later cognitive function, if you look at the bottom at 
the right at the cortical plate area.
    The point is that we are now beginning to understand that 
these effects are not just generalized effects of drugs on the 
mother being passed to the baby but, rather, are modifications 
in the brain that might be expressed later on as the brain is 
more fully developed.
    Another aspect that affects the overall health of the child 
is the family environment in which he or she is brought up. A 
variety of studies, including a major research center we 
support at the University of Miami, are dedicated, first of 
all, to understanding the family effects and, second, to 
developing family-based interventions that might be useful in 
preventing the expression of some of these effects.
    There also are a whole series of issues surrounding initial 
drug use by youngsters, and of course there is no single factor 
that is responsible for abusing drugs; drug use evolves from an 
interaction of complex biological behavioral and social 
environmental determinants, or risk factors.
    It is also important to remember that we have identified 
many of the protective or resilience factors, such as parental 
involvement in the life of a child, that typically reduce the 
chance of even those children with many risk factors from 
actually becoming drug users. And a major focus of current 
prevention research is understanding how specific risk factors, 
like unstable family environments, can be offset by increasing 
the impact of protective factors, like surrogate parenting or 
mentoring programs.
    We have been working hard at night to make sure the 
principles of effective prevention we are learning from our 
research will be used in real life programming, and I would 
like to mention two products of which I am particularly proud. 
One is preventing drug use among children and adolescents.
    This easy-to-read brochure is the first ever research-based 
prevention guide that a school or community can use to develop 
prevention programs specifically tailored to meet their own 
community's particular needs. This user-friendly guide provides 
practical guidance that can be applied by a community and lays 
out some of the principles and the criteria that should be used 
in evaluating prevention programs.
    The publication of this has resulted in an initial 
distribution by request of over 100,000 copies, and we are 
getting additional requests at about 20,000 a month, which 
shows the tremendous need and the tremendous interest.
    The second set of materials I want to mention is this 
colorful new ``Mind Over Matter'' series that I unveiled 2 
weeks ago at the annual meeting of the National Association of 
Biology Teachers. This is a set of drug education brochures, 
based on science, developed for students in grades 5 to 9, to 
spark their curiosity and to inform them with specific research 
findings of the effects of drugs on the brain.
    This series also includes a teacher's guide with suggested 
activities to encourage students to become engaged in 
discussion and thinking about the issues, since the other one, 
the prevention guide, pointed out that the only effective 
prevention programs engage students in thinking about the 
issues. Simply lecturing to them, as I am doing a bit to you 
this morning, in fact is not a very effective prevention 
technique at all.
    I want to mention that we are also working in the important 
area of treatment of drug abuse, particularly among 
adolescents, and I am sad to tell you we don't know a 
tremendous amount about that, but we have been working on a 
number of topics, including, along with our colleagues at NIMH, 
co-morbid child and adolescent mental disorders like depression 
or attention deficit hyperactivity disorder.
    We have been working on techniques to help match young 
people to the most appropriate treatments, and of course we are 
trying to help develop better and more appropriate treatments 
that will help young people become engaged in treatment, which 
of course is the most difficult problem, and, secondly, how to 
handle aftercare.
    All of these activities are a part of what we are calling 
our child and adolescence research initiative. The outcome will 
include much better understanding of the roles of risk and 
protective factors and what to do with and about them. They 
will also include the development of improved targeted 
treatment approaches that are tailored to the unique needs of 
young people.
    We will also conduct additional research to prevent or 
diminish the health and developmental consequences associated 
with direct or indirect, through their parents and other 
people, exposure to drug abuse and addiction. We are very 
encouraged that some basic but extremely important questions, 
such as what works in prevention, have been at least partly 
answered and that this information is now being disseminated to 
communities.
    However, there remain unanswered many important questions 
about how to move from these general principles of prevention 
to their application in specific ways in a diverse array of 
real-life settings, and there are many unanswered questions 
about how drug abuse and addiction affect our children.
    It has only been within the last few years that our 
understanding of basic neurobiology has matured enough andonly 
with the emergence of new noninvasive technologies we have become able 
to study intensively underlying biological responses of humans to 
various drugs of abuse.
    And I will remind you of a question Mrs. Northup asked me 
during the Appropriations Subcommittee hearing about the 
differential effects of drugs on a young adolescent's brain 
versus an older adolescent's brain. And, sadly, I still don't 
know the answer to the question, but we are working on it.
    To the extent there are differences among children and 
adolescents and adults, this new knowledge will provide an 
infrastructure from which we can develop more appropriate 
prevention and treatment strategies so that our children can 
live healthy, productive, and drug-free lives.
    Thank you very much.
    [The prepared statement of Dr. Leshner follows:]


[Pages 3056 - 3067--The official Committee record contains additional material here.]



                    healthy behaviors and lifestyles

    Mr. Porter. Dr. Leshner, thank you very much. Let me thank 
all of our witnesses.
    Unfortunately, I didn't get a chance to hear any of Dr. 
Alexander's testimony, and perhaps he has already discussed 
this, but I want to take my question time to ask really one 
question, because the thesis of this briefing is a little bit 
outside, in fact--you might think substantially outside--some 
of your responsibilities and your roles, and that is, how we 
can address early in life the matters of life-style that may 
determine the health of children and how we can translate the 
knowledge that we have into action that can change those and 
channel those into a positive experience for each individual, 
and talking about diet and exercise and alcohol and drug use, 
and societal interaction and the like, that can lead to a 
better health throughout the adult life of that individual.
    So what I want to ask each of you, and ask you to respond 
to it--and, again, I realize this is outside, in some degree, 
your role, and Dr. Leshner did touch on this in a very positive 
way a moment ago. But how can we take this knowledge that we 
have and translate it into action in such a way that we are 
helping people prevent the kinds of problems that they may have 
in their health throughout their lives, both mental health and 
physical health and, in the process, obviously, save a great 
deal of the money we spend today on treating disease by 
preventing disease.
    If each of you can respond, Dr. Alexander, how can we do 
this? How can we get from where we are to where we want to go?
    Dr. Alexander. First of all, I don't think it is outside 
our realm of research interests and responsibilities at all, it 
is very central to what we are trying to do. Today, we really 
know what healthy behaviors are and what healthy life-styles 
can mean long-term to people's health. And I did touch on this 
a little bit at the beginning part of my testimony.
    What we don't know is how to shape those behaviors most 
effectively. We know what should be done, we don't know how to 
get it done, and we are working on that, in a wide variety of 
areas.
    Let me mention one that NICHD is doing, and that relates to 
prevention of osteoporosis. We don't think of osteoporosis when 
we think of kids. This is a late adulthood disease for the most 
part, but the prevention of this disorder is primarily the 
responsibility of childhood. If we get adequate calcium into 
our bones when we are children, the chance of our developing 
osteoporosis as adults is markedly diminished. The problem is, 
we stop putting calcium into our bones by around age 21, and 
shortly after that a long slow process of loss of calcium 
begins. The more calcium we have in when the loss process 
begins, the longer it will take us to get into difficulty from 
osteoporosis.
    So we know exactly how much people should be taking in, in 
terms of calcium, at different ages in their diet; we know the 
best source is dairy products, milk; what we don't know is how 
we can achieve the intake that is necessary.
    We also know children are not getting anywhere near the 
dietary intake of calcium they need for appropriate 
calcification of their bones. If you look just in adolescents, 
about 15 percent of adolescent girls are getting adequate 
dietary, and they are the ones that are going to get into the 
most trouble when they become adults.
    We are working with research of our own, in looking at ways 
to encourage milk consumption, ways to encourage use of calcium 
supplements included in diets and other means to try and 
promote calcium intake by children. We are working with the 
National Dairy Council, the Milk Processors Association, on the 
milk mustache campaign, for example. You have seen some of the 
pictures of celebrities with a milk mustache. This is one way 
we are trying to get the message across to children and 
families about the importance of appropriate dietary intake of 
calcium.
    We are also working with the health care providers, 
especially the American Academy of Pediatrics in trying to get 
pediatricians to get the message across, that, you never stop 
milk as the drink of choice at a meal for children. This is an 
extremely important part of the message and the way to do it.
    So that is the story with osteoporosis as just one example. 
Another is smoking cessation or smoking prevention. Prevention 
is a lot easier to achieve than is cessation, as many people 
know. Here again, if you talk to kids, they very clearly know 
that they shouldn't be smoking, but 22 percent of 12th graders 
are now smoking on a daily basis, and the numbers, 
unfortunately, are going up, not down. So clearly we need to 
find and develop better ways of getting that message across and 
getting these healthy behaviors adopted and avoiding unhealthy 
behaviors.
    Very similar issues pertain in the areas of drug use, of 
alcohol use, and other areas, and maybe Dr. Hyman and Dr. 
Leshner would like to address those.
    Mr. Porter. Thank you, Dr. Alexander.
    Dr. Hyman.
    Dr. Hyman. Well, you have heard my diatribe on brain 
development, and in some ways it is exactly analogous to the 
story of osteoporosis.
    What Dr. Alexander told us is, even though osteoporosis is 
a disease of older years, calcification of bones occurs during 
childhood. What I told you is, increasingly we recognize that 
the brain, while its sort of coarse wiring may be set up by our 
genes, it is fine-tuned by experience, and it is literallythe 
hard wiring that is fine-tuned during childhood.
    We know a great deal about simple sensory systems like the 
visual system, which is the first obvious place to begin 
scientifically. But we are now recognizing that childhood, 
including early childhood, is a time when the wiring of the 
brain, in some sense, gets finalized and therefore greatly 
influences our talents and our abilities to function, first in 
school and then at work, and interpersonally. While I am not a 
pessimist, I believe insofar as we all learn, brain plasticity 
continues throughout life.
    I think we all recognize, both based on science and common 
sense, a great deal happens in early childhood. Therefore, I 
think it is really critical that we translate what we know 
about useful interventions for healthy development into action 
and early childhood. Let me give you some examples where I 
think we really know something. And here I am not talking about 
massive social programs or anything of the sort.
    What we recognize is that, tragically, the age of onset of 
serious depressive illness in our society is going down; it is 
getting younger and younger. The reasons for this are not fully 
understood, and this is partly reflected in the increasing 
suicide rate in preadolescence and adolescence. We are fully 
aware that serious depression is often not recognized by 
families, it is not recognized in school settings, and often, 
unfortunately, is not recognized by pediatricians. Now why is 
this?
    First of all, mental disorders, although they are disorders 
of the brain, have long been misunderstood and stigmatized; 
families are ashamed. Schools don't want to stigmatize children 
with mental health labels, and so sometimes it is almost 
perverse, sometimes you almost feel it is better for a child to 
end up sort of in the bad box instead of in the sick box 
because of the risk of labeling them. Of course, then they 
don't get treated, and the consequences are obviously 
problematic.
    Pediatricians increasingly are trained to recognize mental 
health problems, but in the current health care delivery 
setting, they have a short time with the child and may not have 
the opportunity to ask the kinds of questions about mental 
health and functioning that often take a bit more time. I have 
a great deal of sympathy for them. Now how can we change this?
    First of all, we have to disseminate information not only 
to families and schools, but also I think we have the 
responsibility to educate health care providers.
    Secondly, in the area of mental disorders, it is critical 
that we destigmatize, because without destigmatizing, I think 
no amount of disseminating cold facts is going to make a 
difference.
    The other thing, just to take this example, is we have to 
acknowledge what we know and what we don't know. For example, 
we know that untreated depression has dire consequences with 
respect to ability to learn, with respect to ability to form 
peer relationships, and of course the most dramatic negative 
outcome is suicide. But, as I told you, we also have to be 
concerned about the long-term effects of psychotropic drugs on 
the brain. So while we know enough to intervene now, we have to 
continue our research so that we develop age-appropriate 
knowledge about interventions. We know enough to be 
disseminating the information better than we are, but we 
continue to need to really understand what is going in the 
brain in childhood.
    I don't want to take too long. We could talk about many 
other areas, again, the controversial area of attention deficit 
hyperactivity disorder and Ritalin, where, again, there is an 
imbalance between knowledge and practice. In some school 
districts, Ritalin is overprescribed; in others, particularly 
in inner city minority neighborhoods, it is never prescribed; 
and these kinds of irrational patterns, I think, have set up 
lifelong problems for our children down the road.
    Mr. Porter. Can I interject a question that your answer 
touched on for me? It seems to me that, increasingly in our 
country, we are going to see great concentrations of wealth in 
private foundations, and we are already seeing the effect of 
that, and private efforts are going to mean a great deal, in 
addition to government efforts, in addressing serious problems 
for our country.
    Right now Rob Reiner, who is the chairman, I think, of 
Castle Rock Productions, has undertaken an early childhood 
initiative on his own and has put together a number of high-
profile people and a lot of resources to emphasize to the 
American parent or parent-to-be the importance of childhood 
development from birth to age 3, which is exactly what you are 
talking about.
    I wonder if any of you have had any contact with him in 
respect to this and whether he is drawing on your research and 
your talents to help his efforts.
    Dr. Hyman. I think Duane helped organize that.
    Dr. Alexander. Mr. Reiner was very much involved with the 
White House Conference on Early Learning and Brain Development 
in April and also had some involvement with the one last week 
on child care. And he has drawn, in his videotape presentations 
that he has made, as well as the activities of his 
organization, very heavily on NIH research, some from NICHD, 
some from Mental Health, from Drug Abuse, from the Neurology 
Institute, all of which Dr. Hyman summarized very nicely in his 
testimony about the importance of early brain development.
    All these neural connections that are established, unless 
they are reinforced, disappear; thus the importance of this 
zero to 3 age time in establishing these connections and 
establishing patterns of brain development.
    So, yes, Mr. Reiner has been very much involved with the 
NIH in gathering information from research and translating it 
in a way that the public can grasp its importance.
    Dr. Hyman. I think it is a wonderful beginning, but we 
should remember that brain development, fortunately, does not 
stop at age 3, so while that focus is critical, we also have to 
consider all of childhood.
    The other thing is that we have to also be careful to 
recognize the steps it takes to go from this basic science 
knowledge into any really effective, cost-effective, and 
deliverable intervention, whether it is medication or 
psychotherapy or some other intervention.
    Mr. Porter. The intervention we want to have is into the 
minds of parents so we don't have to make the clinical 
interventions later on.
    Dr. Hyman. I agree, absolutely.
    Mr. Porter. Dr. Leshner, you largely answered the question 
I posed, but if you want to add to that.
    Dr. Leshner. I will just make a brief comment, which is, we 
are all saying basically the same thing. The answer is 
straightforward but difficult, and that is public education,and 
we produce tons of material; we have been holding town meetings around 
the country trying to educate the public. I am off to the health 
professionals; I am speaking to a group of pediatricians over the 
weekend.
    But the problem we have--and this is true in any of our 
domains--is to make sure not only that the messages are 
persistent, that is, over and over again, but that they are 
consistent across the variety of people who speak about this. 
And in the drug abuse business, it is particularly important 
because you have many people who think that they are experts 
and need to expound it.
    One of the things we have learned from people who study 
what works and doesn't work in public education generally is 
that the messages have to be scientifically accurate, as we 
have said, they have to be science based: That is what worked 
to get people to stop smoking.
    And third--and this is much more difficult--we need to 
figure ways that we fail miserably at of getting nuance into 
the discussion. The world likes medical answers to be a yes or 
no, but the truth is, almost nothing is yes or no. The crack 
baby example I gave you is a good one. When we thought the 
situation was horrendous, everybody was nervous. Then the 
pendulum swung in the other direction, everybody was relieved. 
Now we have a different problem. The problem is, the effects 
are subtle and it is on some kids, and we need to figure out 
how to talk to the public about that without stigmatizing all 
of the kids and without getting in the way of actually doing 
something.
    Mr. Porter. Because your responsibility is mainly on 
developing the science, but you also help to disseminate that 
science, should we have a separate government corporation or 
foundation, because the Government can marshal more resources 
than anyone, to do the further effort of taking this body of 
knowledge and bringing it out into the consciousness of the 
American people and really working on sending messages on not 
using tobacco or moderate use of alcohol or not using drugs or 
proper diet or exercise, all of the things that can affect 
health later on?
    In other words, are we putting too much on your plate for 
you to accomplish and not giving you either the time or the 
resources to do that, and should we do it in a different way?
    Dr. Leshner. Let me say that NIDA is in a somewhat unusual 
situation. Since we support 85 percent of the world's research, 
we feel a tremendous obligation to get that out, and we are 
sort of the holders of it, and we feel we need to get that out 
to everybody. And I think every NIH institute has major 
campaigns that they are engaged in, and we are all concerned 
about public education and public understanding.
    There are other agencies of the Federal Government that do 
these things as well, and, candidly, I think the Federal 
Government can't do it by itself. I think unless we get 
partnerships with other sectors, we are not going to be able to 
do it. We cannot mount the massive educational enterprises that 
have to be mounted. We need private foundations, but we need 
private groups of citizens.
    We in the drug business have the Partnership for a Drug-
Free America. I could never mobilize the advertising industry 
in the way that they do it. But I think it is a complex set of 
players that have to get brought into it.
    Dr. Alexander. It is also an issue, Mr. Porter, of 
developing the knowledge of how to do this. Part of our role 
and responsibility in this effort, I think, is research to 
learn how to effectively deliver this message and have it 
translated into behavior change. In some areas we have done 
this relatively well, but in many of these areas we don't know 
yet how to deliver that message and have it believed, adopted, 
and taken.
    Maybe the Government is not the best source of the 
information, of delivering of that message, and in fact the 
foundations and the private organizations may be better at 
delivering it than we are, but we have to help develop the 
information on how to deliver that message most effectively.
    The partnership that Dr. Leshner mentioned is important. I 
mentioned with osteoporosis and calcium intake, the partnership 
with the Academy of Pediatrics, the Milk Processors, the Dairy 
Association. The resources and the message delivery capability 
of those organizations is far bigger and better than we have or 
could mount. Our role is trying to develop means, effective 
means, of delivering that message.
    The same applies if you are looking at cardiovascular 
disease and obesity and diet and so forth. Again, we know a lot 
of what the message should be, we don't know how best to 
deliver it, and we are testing that partly in the Government, 
partly in the private sector.
    We have a study in a school system in a local area looking 
at ways to deliver health-related messages on health behaviors 
to middle school students. When Dr. Wynder testifies this 
afternoon, he will probably talk to you about their efforts in 
the public schools also, a ``Know Your Body'' program targeted 
toward elementary school students, when the message needs to be 
delivered. That is the time we need to get started, not later 
on, with these health messages, and we need to study this and 
learn how more effectively to deliver this.
    The school population and the schools are in an area where 
we have not been successful in utilizing that resource to 
deliver this message. Health programs and health messages in 
schools are notoriously ineffective, but the population is 
there, the kids are there; they are a captive population, if 
you will; they are easily targeted, if we knew how to deliver 
the message most effectively, and that is what we need to work 
on.
    Mr. Porter. I am delighted to hear you are working on that, 
because I think that can make a huge difference in the future.
    Let me apologize in advance; I have been called to another 
meeting with the Senate and House leadership at 11:30, so I 
will have to leave at that time.
    Mrs. Lowey, you have been very patient.

                            health education

    Mrs. Lowey. You have been very kind, Mr. Chairman, and I 
thank you.
    And I do apologize that I missed so much of your testimony.
    Before I get on to another area, I would just like to 
follow up, Dr. Alexander, on your comments, and I just wonder 
why, it seems to me that we have been--and I look forward to 
Dr. Wynder's testimony as well--we have been focusing on 
delivering these messages for a very long time.
    The health education courses in most of our schools are a 
disaster. I am very involved with Students Against Drunk 
Driving and Mothers Against Drunk Driving, and I got into a 
debate--and perhaps you can enlighten me--with some kids 
justthis last week: They said: Okay, so we will stop drinking; we will 
use marijuana because that doesn't affect our coordination as much. And 
I quickly said, read this.
    But I really provoked a major confrontation between the 
drinkers and the drug users in that room, and the drug users--
now this is Westchester County. I mean, it is not an area--I 
shouldn't say that; I don't want to insult anyone. But the kids 
were arguing with each other about, smoke pot because it 
doesn't impair your coordination, and the other kids were 
saying, yes, and then I said, I will send you more information. 
They thought they really knew the truth.
    I can remember 15 years ago, I was working with Matilda 
Cuomo on education, and many people in this audience have been 
working on that as well. We have done a terrible job of 
somehow, whether it is convincing them, I am not sure if it is 
the communication that is ineffective or the lack of 
information, but the kids don't believe drugs and alcohol are 
harmful, and then it becomes a situation of habits built, then 
they are addicted, then you have to get them off the cigarettes 
or the alcohol, the drugs.
    But even when we try and start early, we are just not doing 
a good enough job.
    Now maybe you answered, Mr. Porter, earlier. Don't you get 
enough cooperation? It seems to me a case of deja vu; we have 
been discussing this, I remember--grandchildren now, too--I 
remember, going back to my childhood, and we just can't seem to 
do a good job. Why not? And then I will get to another area.
    Dr. Leshner. Let me address this, just because you 
mentioned marijuana and driving.
    Mrs. Lowey. I would love that for the record, so I can show 
them what you said.
    Dr. Leshner. Yesterday, at the Society for Neuroscience 
meetings in New Orleans that both Dr. Hyman and I were at, I 
had a long discussion with one of our investigators who is, as 
we speak, refining what we know about it. And I can assure you 
that there is a large body of data, studies done over the 
course of the last 30 years, to demonstrate that marijuana, 
even a small amount of marijuana, interferes both with motor 
coordination and with perception, and therefore there is a 
large body of data to suggest that it is a problem for people 
driving.
    One of the problems we have had----
    Mrs. Lowey. If you can send that to me, again, if it is 
more recent, I would appreciate it.
    Dr. Leshner. Sure. I will.
    [The information follows:]

                         Marijuana and Driving

    Marijuana is the most commonly abused illegal drug in the 
United States, and it is of particular concern that this drug 
is abused by large numbers of adolescents. Cannabis is a term 
that refers to marijuana and other drugs made from the same 
plant. All forms of cannabis are mind-altering (psychoactive) 
drugs; they all contain THC (delta-9-tetrahydrocannabinol) the 
main active chemical in marijuana. Within a few minutes of 
inhaling marijuana smoke, the user will likely feel, along with 
intoxication, a dry mouth, rapid heartbeat, some loss of 
coordination and poor balance, and decreased reaction time. For 
some people, marijuana raises blood pressure slightly and can 
double the normal heart rate. This effect can be greater when 
other drugs are mixed with the marijuana; but users do not 
always know when that happens. As the immediate effects fade, 
usually after 2 or 3 hours, the user may become sleepy.
    Marijuana can be harmful in a number of ways, through both 
immediate effects and damage to health over time. For example, 
marijuana smoking affects the brain and leads to impaired 
short-term memory, perception, judgment and motor skills. The 
user may have trouble handling complex tasks. With the use of 
more potent varieties of marijuana, even simple tasks can be 
difficult. With regard to long term effects, research findings 
so far show that the regular use of smoked marijuana may play a 
role in cancer and problems in the respiratory, immune, and 
reproductive systems.
    As is the case with alcohol, marijuana intoxication is 
often associated with impairments in sensory, psychomotor, and 
cognitive functions. Marijuana has adverse effects on many of 
the skills needed for driving a car. These effects may include 
difficulty in judging distances and delayed reactions to sights 
and sounds that drivers need to notice. There are data showing 
that marijuana plays a role in traffic accidents. When users 
combine marijuana with alcohol, as they often do, the hazards 
of driving can be more severe than with either drug alone.
    Studies of insured drivers suggest that driving under the 
influence of drugs other than alcohol is a growing cause of 
traffic injuries in the United States. A study of patients in a 
shock-trauma unit who had been in traffic accidents revealed 
that 15 percent of those who had been driving a car or 
motorcycle had been smoking marijuana, and another 17 percent 
had both THC and alcohol in their blood. In Memphis, Tennessee, 
researchers found that, of 150 reckless drivers who were tested 
for drugs at the arrest scene, 33 percent showed signs of 
marijuana use, and 12 percent tested positive for both 
marijuana and cocaine.
    While the effects of marijuana on equilibrium and driving 
have both been studied separately, a critical gap in existing 
knowledge of marijuana effects on driving is the lack of a 
rigorous examination of these effects within the same group of 
subjects. NIDA is currently funding a study which is comparing 
the effects of placebo and two potencies of marijuana on 
equilibrium and simulated automobile driving. Adult volunteers 
are undergoing a battery of tests of reaction time, balance, 
nervous system activity, and risk-taking driving maneuvers at 
various potencies of delta-9 THC via smoked cigarettes.

    Dr. Leshner. One of the issues is, a lot of prevention 
efforts were initially based on intuition and common sense, and 
I myself believe that it is only in the last 4 or 5 years that 
we have begun, in the case of drug abuse, to know what doesn't 
work as well as what does work.
    A big problem we have is moving science to be the focal 
point, or the basis, rather than ideology, intuition, and 
common sense.
    I mentioned before, we actually have a science-based guide 
to how to do drug abuse prevention. Everybody wants a copy of 
it. Most or many programs don't use the principles that are 
derived from research. The problem is on both ends. It is on 
our end because we haven't disseminated it well enough, and it 
is on the other end because these are programs, some of which 
have been very longstanding. It is also a tough thing to do.
    Dr. Hyman. There is one very important thing that, often we 
have the assumption that any intervention is benign; whether it 
works or not, it can do no harm. But, indeed, we found there 
are a number of behavioral interventions that can be 
counterproductive, or even harmful. For example, at one 
university, an intervention against eating disorders, against 
bulimia in women, appears to increase the incidence of bulimia. 
So we have to take seriously studying the behavioral 
interventions.
    Something I say a lot, it goes for psychotherapy, for 
behavioral interventions: Anything powerful enough to dogood is 
also powerful enough to have side effects, and we actually have to be 
skeptical in the same way we are with a clinical trial with medication.
    Now, having said that, I think, as both Dr. Alexander and 
Dr. Leshner have focused on, we have used principles of basic 
behavioral science and other principles to develop a certain 
number of preventive interventions I think would be very 
useful. We have to study them in the real world.
    I think the arena of AIDS behavioral prevention illustrates 
the potential for making a real public health impact, but it is 
really serious business, getting these interventions in place.
    In terms of health curriculums--and here now I am afraid I 
am working on intuition--one of the things a lot of us have 
been talking about is where in a school program health 
education would be most effective. Given the fact we are all so 
concerned about science literacy in the United States, rather 
than separating health education, as something other or some 
less serious part of education, whether, in fact, shouldn't 
some of it be incorporated into science education, because 
children are absolutely fascinated by their bodies. And, again, 
this is something Dr. Wynder is likely to talk about, and it 
would be one way of getting accurate information to children 
that might be useful in the preventive arena.
    Mrs. Lowey. I will get to another area, but I would be very 
interested in pursuing this with you, because I think we have 
all been a real failure.
    And for those of us who have been involved in overeating 
programs, one can understand something about those who have 
addictions to more dangerous substances. I mean, cigarettes, I 
never smoked and I don't drink, but I have problems with food 
like ice cream, and we know a lot of that stuff is just no good 
for you.
    Dr. Alexander. Ice cream is. I am sorry.
    Mrs. Lowey. I am really very serious.
    Dr. Hyman. It is a serious point. People are differentially 
vulnerable, and this is the issue of nuance that Dr. Leshner 
raised. Everyone will say, I had a grandmother who smoked for 
90 years and she was fine, or, I know somebody who tried this 
or that and they didn't get addicted.
    The problem is, this is a game of Russian roulette, and 
while one person might be vulnerable to alcohol or nicotine, to 
starting or getting trapped, another might be vulnerable to 
poor eating habits, to obesity. A lot has to do with our genes 
and early gene-environment interactions, and the difficulty in 
the messages is precisely the issue of nuance. Everybody sees 
somebody who has gotten away with it, and we have to learn to 
say, ``but you don't know that you will.'' And, as we all know, 
any message that is nuanced in children is a very difficult one 
to deliver.
    Mrs. Lowey. In any event, I think it would be worth 
pursuing, certainly here, and I would be interested in any 
available scientific method that could be applicable, because 
we all know behavior modification is much easier when you 
address it early on to children.
    Another area that I know we touched on briefly before, 
several of the major mental illnesses, such as manic 
depression, schizophrenia, don't commonly appear in children 
until late adolescence.
    What have we learned that would enable us to predict 
earlier in a child's life that they had a likelihood of 
developing a major mental illness, and what is most important 
that would enable us to begin treatment early? I understand 
that some would rather be considered a bad kid, rather than a 
child who has a mental illness, but what really enables us to 
identify it and begin treating earlier that can help that 
youngster later on?
    Dr. Hyman. I don't think at the end of the day any child is 
happy that a kid gets put into the wrong system.
    I think, actually, before answering your question directly, 
there are many youngsters in the criminal justice system who 
actually have mood disorders and we would have been much 
happier identifying and treating them, and the fact that stigma 
doesn't permit us to do that is a disaster.
    Let me just say that these mental disorders--major 
depression, manic depressive illness, schizophrenia--are 
extraordinary scientific challenges and we do not yet know, as 
is the case for many of the serious chronic disorders that 
affect human beings, exactly what the risks are.
    Obviously, if we could identify, if we knew the precise 
risks, we might find modifiable risks where we could intervene. 
The fact is, we do know a few things. Especially for the mood 
disorders, we know there is great risk conferred by family 
history; that genes, unfortunately, have a lot to say about 
risk, not fate, but they have a lot to say about risk. And I 
think that what we could do, quite readily, if we again 
disseminated information correctly, is to make sure that if a 
child is behaving in such a way that is consistent with a mood 
disorder--and, here again, telling a passing stage from 
something that is serious is challenging but not impossible.
    Are the symptoms pervasive? Are they long lasting? Are they 
changing the ability of the child to function at school and at 
home? These should raise questions, and the presence of a 
family history, for example, should redouble our concern for 
early interventions. And I believe that with early 
identification of mood disorders, one potentially can initiate 
behavioral programs. But, again, I think we need to develop 
more age-appropriate psychotherapies, and if symptoms are 
really severe, to initiate pharmacotherapy, but, again, with 
the caveat, we have to observe carefully.
    While I am happy there is the first evidence that the 
Prozac-like drugs are effective in treating early adolescent 
depression, I am also keenly aware of the fact that we don't 
know when to stop, we don't know what the impacts are.
    So we know enough--we actually do know enough to identify 
the kids early; we are not effectively using that knowledge in 
a variety of settings. Schizophrenia is much more complicated. 
I don't want to go on for too long, but let me say that 
although there is an important genetic component, family 
history is often less strong.
    I think, once again, if we pay attention to really 
pervasive, disturbed behavior, unaltered behavior in children, 
and don't write it off, don't sort of see no evil, I think we 
will be able to make the diagnosis earlier and intervene 
earlier.
    I have to tell you, at NIMH we have just convened a whole 
expert panel to study our prevention portfolio and we are in 
the process of implementing some of their recommendations so 
that we don't have to know what all of the risk factors are to 
intervene early and get treatment started.

        safety and efficacy of drugs for mental health problems

    Mrs. Lowey. One other question, Madam Chair, following up 
on your last statement, and, in fact, in your testimonyyou 
mention the lack of adequate knowledge about the safety and efficacy of 
drugs for children suffering from mental health problems.
    Dr. Hyman. Yes.
    Mrs. Lowey. What is the institute actually doing to correct 
this lack of information? What can and should drug companies do 
to provide more information about the special needs of 
children, with regards to psychotherapeutic drugs?
    Dr. Hyman. As you know from appropriations hearings, when I 
arrived at NIH, now almost a year and a half ago, I was rather 
appalled at the knowledge base in pharmacotherapies and 
actually psychotherapies for children, and we have begun a 
concerted effort to initiate drug trials.
    Obviously, the pharmaceutical industry also has to be a 
partner in this, and we do talk to the pharmaceutical industry 
and also FDA. At the same time, we actually did not have the 
infrastructure; that is, we did not have the base of 
investigators who could actually go forward with these trials, 
and we have a number of programs in the works to increase the 
base of investigators. Perhaps the most exciting is our 
cooperation with NICHD which had an existing network of centers 
to study pharmacotherapies; NIMH has taken advantage of that 
with cooperation to piggyback on so that we can begin to learn 
some of these things.
    Mrs. Lowey. I thank you, Madam Chair, and I am sorry Mr. 
Porter left because, following up on his statements about the 
public-private partnership, I am honored to have in my district 
Connie Lieber, who has probably been one of the major leaders 
in the private sector contributions to this important field of 
research.
    Dr. Hyman. I have enormous respect for Connie Lieber. She 
is someone who really raised money from scratch, and her 
foundation, the National Alliance for Research in Schizophrenia 
and Depression, in the last year funded, I believe, 60 young 
investigators to get them to a stage where they would have the 
data to be able to apply for Federal grants.

                         challenges in science

    Mrs. Northup [presiding]. Thank you.
    We will move on, because we want to give everybody an equal 
chance.
    Let's see; Dr. Alexander--really, anybody can answer this--
I have listened to some of the questions that are posed, some 
of the challenges we have in front of us, and I think it must 
be a constant frustration to hear people promote certain 
remedies, or antidotes, to the challenges we face. And have 
those promotions run counter or certainly not been backed up by 
the science that you have seen? Is that a regular occurrence?
    Dr. Alexander. I think it occurs in children, it occurs in 
adults, it occurs pretty much across the board.
    One of the problems is that when we lack an effective 
treatment, all kinds of things jump in to fill that vacuum, and 
it is often not possible to test each of them in a trial that 
is able to prove one way or another whether they work. Some of 
them, just on the surface, are so unlikely that they can almost 
be dismissed.
    But one of our jobs is trying to sort out the ones that may 
be likely to work and pursue those and try to document whether 
they are effective or not. This applies in a wide variety of 
areas; it applies in the health scene, it applies in the 
learning area, it applies in drug treatments, it applies in 
many different areas; and one of our issues is to try and 
determine where to focus our efforts to test scientifically 
what may hold the greater promise and target our resources to 
those.
    Sometimes it is particularly important to try and 
demonstrate whether something that seems popular is effective 
or not, and then we have to invest resources in actually 
testing that, using a comparison with another treatment 
approach to see which is a preferred method and whether one of 
them actually works or not. So, as I say, this applies across 
the board in many of the areas we focus our research on.
    Mrs. Northup. Well, following up, particularly, you 
mentioned when there are diverse ideas on how to address them. 
On this committee, we have talked about learning. I think Time 
magazine and Newsweek both did an article about children and 
learning, and they talked about all the different models and 
schools that have been successful.
    They did, however, talk at great length about the seemingly 
increasing number of children that are not reading. One, I 
think, used a 60 percent figure, another used a 70 percent 
figure, number of children that seemingly will learn to read 
any way they are taught, and then the growing number of those 
that fall into the balance, that are not learning the way we 
are teaching. And I am reminded of just, with six children, the 
sort of different popular ideas that have come forth saying 
this is the way all children read.
    What ability do you all have to evaluate, for example, the 
research that is being done to determine whether or not it is 
legitimate research and whether it has been effective?
    Dr. Alexander. Well, the research that we have focused on 
in this area has been on the basic learning process and how 
children learn to do various things, reading being one of them, 
also mathematical function, how they learn other things as 
well, how they learn health behaviors. And probably, in this 
area, the most success we have had has been in reading, and we 
have had that success because we have started to go back to 
basic principles of how kids learn and whether all kids learn 
in the same way, and methods by which most kids learn. There 
are some who have that method blocked, and they use an 
alternative pathway to learn.
    But we have started off by, as I say, trying to use basic 
principles to examine how children learn, and learn to read, 
and then to develop means to apply those learning principles, 
scientifically demonstrated, to actual methods of teaching 
reading and, as a consequence of doing that, have been very 
successful in demonstrating methods and testing them in the 
classroom that actually are effective in reaching the vast 
majority of children, and relatively easy to apply by the 
teachers, succeeding in teaching most of the children in any 
given classroom to read.
    Some of these methods are more applicable to children with 
specific disabilities in reading that are identified, and then 
they can be applied in the regular classroom or with special 
assistance to these kids who have special difficulties.
    But what we have been able to do, as I say, by applying the 
basic principles in scientific evaluation of how children learn 
is to take that and translate it into teaching methods, and 
that is where we are at the present time with that research.

                       public-private partnership

    Mrs. Northup. To go further, though, we talked about the 
public-private partnership and we have talked about the 
importance of collaboration and so forth. I think that my 
concern is who can assess, when, let's say, if somebody says 
this is scientifically based, research based, or whatever--who 
can look at that research and see whether that is market 
research, or research that makes a difference in outcome, and 
what capacity do you all have to do that?
    Dr. Alexander. Well, we don't do it alone, we do it with 
the scientific community. We have a wide variety of experts out 
in the scientific community who are doing research, who 
understand basic research methodology, that understand how you 
do studies and ways that you can get appropriate answers versus 
inappropriate answers or misleading answers, and the things 
that go into study design, that lead you correctly or 
incorrectly down the path.
    And these people can work with us in evaluating--they do it 
all the time--in evaluating proposals to do research that are 
submitted to the NIH. Our whole peer review system is based on 
the scientific community evaluating proposals that are 
submitted to us to do studies, as to whether the research is 
set up appropriately to answer the question in the first place, 
and the research that passes that test is what we fund.
    We also have methodologies for looking at research that has 
been conducted and published, and assessing, again, in the 
judgment of the scientific community, a system of peer review, 
whether or not this research was conducted according to certain 
standards: Did it have an appropriate design to answer the 
question that was being posed? Was it conducted appropriately? 
Were the subjects selected in an appropriate way? Were the 
subjects appropriate to answer the question? How long did they 
follow up the subjects? And was it long enough to tell whether 
the test worked or not?
    So we can do that retrospectively as well in making 
judgments as to whether this research that was reported meets 
scientific standards of excellence and acceptability and should 
be considered to prove the point that was at issue.
    Mrs. Northup. And in other areas of NIH, are you aware that 
this goes on at this degree, at this level of assessment? Does 
the NICHD place where those sort of assessments take place any 
place else?
    Dr. Alexander. We do that in the health arena. The NIH does 
it, for example, with our system of consensus conferences, 
where we pull in an expert panel of people who have not done 
the research themselves but can serve as a jury, if you will, 
an impartial jury, to review what the state of knowledge is in 
a particular area, often a controversial area, and make 
judgments as to what has been conducted that is acceptable and 
what decisions should be based on.
    Mrs. Northup. But even in those cases, the assessment to 
research methodology is under the institutes of the NIH; is 
that right?
    Dr. Hyman. I think Duane has made a series of critical 
points. Let me illustrate with an example right now.
    NIMH is funding a very large trial of St. John's Wort, an 
herbal remedy for depression, and I feel we have a public 
health requirement to do that. St. John's Wort is, you know, 
flying off shelves at health food stores, and there is, 
``research'' to say that it works. This research was actually 
collected in what is called a meta analysis in the British 
Journal of Psychiatry.
    In looking at the studies, largely done in Europe, some of 
them funded by the manufacturers problems were evident. St. 
John's Wort, is an herb, so some of the product used in the 
study had flowers and some had leaves; the preparations were 
different; the duration of the studies was, by and large, too 
short. And, you know, we had concerns that people would be 
self-medicating. And, I mean, I am interested in anything that 
works and I am very open minded, but I was afraid this research 
was not exactly research, and I think that gets to the heart of 
your question.
    Mrs. Northup. Right.
    Dr. Hyman. And we selected this area to invest money 
appropriated by you precisely because we felt it was a public 
health necessity, so many people were using it, and we are 
going to compare St. John's Wort to both placebo and to Zoloft, 
the standard effective treatment.
    We can't do this in every arena. There are an immense 
number of claims made, not only for health but for educational 
methods, something you referred to, and this is well beyond our 
arena. But one of the reasons I think we all have concerns 
about the scientific literacy of our children is because 
eventually individuals do have to be able to read and somehow 
assess the kinds of claims that are being made for either 
health supplements or educational methods, and there is no one 
clearinghouse to help people through this maze or jungle of 
information.
    Mrs. Northup. Except you all.
    Dr. Hyman. Well, in biomedical science, except us, I think.

                        dissemination of results

    Mrs. Northup. And, finally, I would just like to ask you 
what you are doing in the area of disseminating the results of 
your information to other areas of the Government.
    In particular, I think there was a conversation in the 
earlier testimony, earlier in the hearing process, about, how 
research on how kids read was being disseminated to the 
Department of Education. You know, I would like to carry that 
forward--to talk about drug use and how research is being 
disseminated to SAMSHA and Health and Human Services. I think 
that there is a lot of focus.
    I still believe that cigarettes are the gateway drug, and 
that for psychological reasons and for social reasons, kids, 
when they are about 11 or 12, decide that maybe having their 
mom and dad's approval isn't as important as their fellow 7th 
grader. And a fast way to be somebody, if you are afraid you 
are going to be nobody, is to smoke cigarettes, and that is a 
step towards not doing what your track coach wants you to do, 
but hiding behind the garage or whatever.
    And I think we are talking a lot about regulation and 
changing the laws so that kids don't have such easy access to 
cigarettes, and I think that is very important. I have authored 
a number of those bills myself. But even if we made it very 
tough for kids to buy cigarettes in convenience stores, I don't 
think the use would go away.
    You can't buy marijuana across the counter, and they don't 
advertise it either, so you have to get to a kid's heart and 
mind--their heart by engaging them by not wanting them to smoke 
and their mind by educating them as to why it is bad for them. 
And it seems to me like, rather than you developing the 
delivery system for that, there is already one there and it is 
through SAMSHA or any other programs, CDC, and HHS.
    And I am afraid from the conversation that we had regarding 
how kids read, if you carry that forward, theconcern about, 
will the information on using cigarettes, using drugs, and so forth be 
communicated to the agencies that we already have, so that they may be 
able to incorporate that in their programs.
    Dr. Leshner. Let me just make a comment about that. Over 
the last few years, we have always had good relationships with 
SAMSHA because it is a sister agency and we all originally came 
from the same agency, but in the last 18 months, actually, a 
group of people from the Department of Education, the 
Department of Justice, and HHS have been meeting together, 
actually, under General McCaffrey's leadership, to talk about 
things like principles of prevention: You know, why don't you 
use it? And we have been very encouraged.
    The problem is, many programs everywhere are longstanding 
and therefore, for any program to change dramatically is not 
easy, but we do have communication links, at least in the drug 
abuse arena, that I think are working pretty well.
    Mrs. Northup. I know my time has run out, so I will defer 
now to Mr. Obey.

                          international travel

    Mr. Obey. Thank you, Madam Chairman.
    First, let me ask on a totally different question, as 
something you may remember, we had quite a scare a couple years 
ago when NIH was intending to send about 400 scientists to a 
conference in Florence, Italy at a huge cost. I have a number 
of questions I would like to submit for the record with 
reference to the international travel engaged in by your 
agency, and I would be interested in knowing what the responses 
are. I won't ask them now, but I will submit them for the 
record.
    [The information follows:]


[Pages 3083 - 3096--The official Committee record contains additional material here.]



               support for education policies and reform

    Mr. Obey. Secondly, I think everyone on this subcommittee 
recognizes your fine work with respect to research on child 
development, on cognitive development, and on reading, but I 
want to make certain that that expertise is not drug in, as 
Dizzy Dean would say, or doesn't fit.
    It is one thing to assess research on reading. It is quite 
another thing to assess how you fix screwed up schools. I 
appreciate receiving a letter from you which reads as follows: 
Because the NICHD's area of expertise relates to cognitive 
research on the development of reading and learning skills and 
to research methodologies, we believe comprehensive school 
reform which involves the development and school restructuring 
goes beyond NICHD in this area of expertise.
    I agree with that letter, and I would simply like, for the 
record, you to respond to the following questions, because I am 
interested in determining whether or not there is a significant 
overlap and duplication between you and the Department of 
Education which could enable us to save some money.
    So I would be interested in knowing what research grants 
and contracts have you awarded in order to determine how 
student performance is best raised in the areas of math, 
algebra, social science, study science, geography, or history.
    I would be interested in knowing what grants and contracts 
you have produced to determine effective school reorganization 
and governance, including decentralized and school-based 
management.
    I would be interested in knowing what grants and contracts 
you have awarded to help State schools and communities to 
design and implement policies and procedures that help raise 
student performance at the most effective cost to the taxpayer.
    I would be interested in knowing what grants and contracts 
you have awarded which relate to how you change the 
relationship between school administrators and teachers to 
effect better motivation.
    Also, as you know, there are lots of salesmen running 
around selling their version of technology reform, and a lot of 
them are good and a lot of them are turkeys, and a lot of them 
are very expensive and a lot of them are rip-offs.
    I would like to know what contracts and grants your 
institute has let that assess competing types of education 
technology. I would also like to know what contracts and grants 
you have issued which would help us to determine how to get 
greater accountability out of schools for the performance of 
students, in individual school buildings as opposed to school 
districts, because kids learn in buildings, they don't learn in 
districts.
    I would like to know what research and grants you have 
provided in the area of building effective high schools that 
discourage dropouts and what contracts and grants your 
institute has financed in order to strengthen community support 
for school reform efforts around the country.
    And if you have any general comments in response to those 
questions, I would be interested.
    Dr. Alexander. We will be glad to submit that for the 
record, Mr. Obey. I assure you, the answers will be shorter 
than the questions because in most of those the answer is, 
none.
    Our studies have focused on how kids learn, which has 
general applicability, and how children learn to read in 
particular.
    We are working in a small area on how children learn math 
skills, which is also important for us to study, I think, but 
in most of the areas you addressed in your questions, we have 
no studies whatsoever.
    Mr. Obey. I think that is a point that needs to be made. 
Thank you.
    [The information follows:]

               Support for Education Policies and Reforms

    In response to the questions asked, the answer is that the 
NICHD has funded no grants or contracts in the areas specified.

    Mrs. Northup. As a follow-up question, I would like to ask, 
while you have no grants or studies that you have done on how 
kids learn--I mean programs on geography and so forth--I think, 
what you said in your letter I was glad to hear said, is that 
your expertise is in evaluating the research that others 
submit, the research methodology, and if it is valid and if in 
fact the results are verifiable. Is that correct?
    Mr. Obey. Well, if I could simply observe, I don't think 
that is what the testimony indicated. I think the testimony 
indicated that they had expertise in the development of reading 
skills, but their area of expertise does not extend to many of 
the areas I just raised.
    So the research that you are qualified to evaluate is 
research that is related to your very specific and narrow 
mission of learning how children develop cognitively and how 
you can especially improve their reading performance, but you 
have no special capacity above that of anybody else to evaluate 
these other issues that I raised this morning. Isn't that 
correct?
    Dr. Alexander. Our area of expertise is in cognitive 
development and learning and research related to that. We do 
not have expertise in areas of school structure, organization 
systems, architecture, motivation of teachers, any of those 
areas. Our area of expertise has been in how children learn and 
cognitive development. That is the area where we have done 
research.
    Mrs. Northup. Again, I would like to follow up. I think Mr. 
Obey may have been on the phone, Dr. Hyman, when you were 
talking about evaluating other people's research and your 
ability to do that, even in areas where you haven't had the 
grants on your own.
    Dr. Hyman. That is true, but, again, that is in the 
biomedical arena. I think we have--this was in the case of St. 
John's Wort, where lots of people are taking a treatment, and 
so we felt that we had a public health responsibility to 
evaluate these claims because people with illness were self-
medicating. So we do evaluate these other areas of research, 
but as they pertain to our biomedical and behavioral mission.
    Dr. Alexander. The methodology for doing the evaluation is 
pretty much the same, whatever area you are looking at, in 
terms of evaluating the quality and caliber of research. The 
principles are the same.
    The area of expertise of the people who are doing that 
evaluation needs to be relevant to the area that is being 
evaluated, and our area of expertise really lies in cognitive 
development, learning how children process this information, 
how they can best learn, either on a one-to-one situation out 
in the world or in a classroom. And so the methods that we use 
to evaluate that area are fine and we know the people to do 
that.
    The methodology is the same if you are looking at 
organization structure or nuclear physics, dairy science, or 
whatever else, but the people who would do that would be 
different from us and our scientists.
    Mrs. Northup. When you have different programs that say 
they are research based and they work, who is able to look at 
their research and evaluate whether the research is valid, 
whether or not it has been done over a long enough period to 
give long-term results, whether or not the sample is sufficient 
size, whether it is anecdotal evidence or scientific? Who would 
be able to do that?
    Dr. Hyman. In the biomedical sciences, that is really 
fundamentally our job, and if there is an area of controversy, 
I think Dr. Alexander has already mentioned the consensus 
conference process where we bring in all the appropriate 
expertise.
    I think what we would all try to say is that we, however, 
have to have humility about the boundaries of our expertise. We 
can evaluate research, you know, within the diverse institutes 
within the biomedical arena, but as I think Mr. Obey's 
commented, as things start to extend well beyond the biomedical 
arena, for example, in the area of school buildings, Dr. 
Alexander or I or Dr. Leshner wouldn't even know what expert to 
call up to get an opinion.
    Mrs. Northup. That is right, but would you be able to 
evaluate whether or not children learned more over a long 
period of time?
    I mean, the whole point is not how we organize the 
financial arrangement and the governance relationship. The 
whole question is, at the end of fifth grade, do the children 
do better in school or worse in school, and is there evidence 
or testing or whatever to verify that the children have done 
better under one model than another?
    Dr. Alexander. If those issues had been studied, a panel of 
experts would be able to be assembled to judge the quality of 
that research and say what that research had shown, and whether 
the answers that had been obtained from that research were 
valid because the research methodology was valid and 
appropriate and the samples were large enough and so forth. A 
panel with expertise related to that area, using these general 
principles of research evaluation, would be able to do that.
    Mrs. Northup. So if you had 10 different groups saying, we 
have a research-based proven way of reorganizing schools where 
kids learn better, you could empanel a group of people that 
could evaluate that research as to its validity?
    Dr. Alexander. Someone could assemble such a panel.
    Dr. Hyman. We wouldn't know how to put together such a 
panel. Perhaps the Department of Education ought to do it. But 
the point is that the methodologies for that kind of rational 
evaluation are there.
    Mr. Obey. Aren't you really saying there is a scientific 
method that holds, regardless of what field you are talking 
about, and your field of expertise is biomedical research and 
not school reorganization and the school administrative 
reorganization, and don't you in fact stand by your letter 
which says that you believe that comprehensive school reform 
proposals which involve the development of effective schools 
and school restructuring go beyond your area of expertise?
    Dr. Alexander. That is what I wrote, and that is correct, I 
stand behind that.
    Mrs. Northup. Were you asked to write a letter?
    Dr. Alexander. Was I asked to write a letter?
    Mrs. Northup. Yes.
    Dr. Alexander. The NIH was asked to write a letter 
explaining what our position and capabilities were in this 
area, and that is the letter we wrote.
    Mr. Obey. Let me be clear about that. I asked the NIH to 
make clear what your area of expertise is, because a lobbyist 
came to see you and represented that she in fact was there at 
my behest when she was not. And so when I found out my staff 
was being quoted in order to provide insight to that meeting, I 
asked what is your area of expertise, and are you suggesting 
you can do researchthat is supposed to be done by the 
Department of Education? And your answer spelled out what your area of 
expertise is and is not.
    And what is going on here, very frankly, is Mrs. Northup is 
trying to drag you into the school reform controversy, where, 
as you know, you have no business being drug into it, except 
insofar as your expertise can be used to help us assess what 
kind of progress has been made in areas such as reading, and I 
welcome that evaluation, but I don't think that school 
organization is a charter of NIH.
    Dr. Alexander. Mr. Obey, let me try to make clear that our 
staff met with your staff purely with the intent and purpose of 
discussing our research related to how children learn to read. 
It was not our intent or purpose at that meeting to discuss 
school reorganization.
    We have done no research on school reorganization; we have 
no special expertise on school reorganization; we have no 
position on school reorganization. Our area of expertise is in 
cognitive development and how children learn, including how 
children learn to read. We are eager to do anything we can to 
get the information about that research out to the public, the 
Congress, to anyone else, and any way that we can be helpful in 
doing that, we are eager to do.
    I regret very much that our efforts in doing got 
misinterpreted in some way as carrying over into the area of 
school reorganization, where we do not have expertise.
    Mr. Obey. Well, the fact that happened is not your fault, 
it is the fault of people who have tried to make your comments 
into something that I don't think they were.
    Mrs. Northup. Well, with that said, since I may be the 
person referred to, I would just like to say I am very eager to 
see us find ways to make schools work better, and there are a 
lot of people that are talking about science-based methods, and 
I would like to see the science because I know I don't know the 
right methodology. The results I have seen have been anecdotal; 
they have been short lined instead of long lined.
    Many of your publications regarding this have talked about 
how important it is to have long-term benefits instead of 
short-term benefits. So I am not reassured by groups that want 
to sell their services and don't have any long-term results.
    And so, you know, I am very eager to ask which agency is in 
the best position to evaluate research, that has been done, and 
provide those answers to a Congress that really doesn't know 
what science-based research is either.
    So I thank you for the questions you have answered for me, 
both here and before, and if there are no more questions, we 
are adjourned until 1:30.
    Mr. Porter. The subcommittee will come to order.
    This afternoon, we continue with our second session of 
hearings focused on child health and the public health approach 
to prevention.
    This morning, we heard from the directors of three NIH 
institutes that have responsibility for developing the research 
base for public health prevention measures. This afternoon, we 
are pleased to have three witnesses, two from Federal agencies 
and one from a nonprofit foundation, to talk about health 
prevention and education programs for children and adolescents.
    We are pleased to have with us Dr. Nora from the Health 
Services and Resources Services Administration, Health Services 
and Resources Administration; Dr. Marks from the Centers for 
Disease Control and Prevention; and Dr. Ernst Wynder from the 
American Health Foundation in New York City.
    If each of you could give your statement, and then we will 
proceed to questions after that. And in that way, members who I 
think will be here will have a chance to direct questions to 
any of the three of you upon completion of your statements.
    As was mentioned at this morning's hearing, Congress is in 
the final weeks of the session, with Members pulled in many 
different directions. We may have interruptions this afternoon, 
and Members may not be able to spend as much time at the 
hearing as we would like them to have. And I want to apologize 
to the witnesses. We just had a vote, which is still on. We are 
hopeful that Members will come back and join us as time 
permits.
    And, finally, you should know that this subcommittee will 
have its conference with its Senate counterpart at 4 o'clock, 
right after this hearing concludes. So there is a lot going on 
behind the scenes to prepare for the conference in an attempt 
to resolve final issues that has occupied our time.
    So you will have to blame me for scheduling this at the 
wrong time. I had assumed originally that we would be past the 
conference by this date; in fact, by the original date; and 
then had to put it over. And we thank our witnesses for 
indulging us and apologize for the problems that this causes. 
But we are doing the best we can.
    Dr. Nora.
    Dr. Nora. Thank you. Good afternoon.
    I am Dr. Audrey H. Nora, director of the Health Resources 
and Services Administration's Maternal and Child Health Bureau 
(MCHB). I am a pediatrician with an academic and private 
practice background who made a career change to public health 
when I realized that children needed a much broader, family-
centered approach to care.
    I want to thank you for convening this hearing on child 
health. I am pleased to be here with my colleagues, Dr. Marks 
from CDC and Dr. Wynder from the American Health Foundation. 
The Maternal and Child Health Bureau has collaborated with 
their institutions around a number of issues such as infant 
mortality reduction, immunization, and health promotion, and we 
expect to continue working with them in the future.
    Today, I would like to discuss with you the child health 
activities administered by HRSA's Maternal and Child Health 
Bureau. The bureau has roots that go back more than 80 years to 
the creation of the Children's Bureau in 1912. Today, Maternal 
and Child Health (MCH) administers programs that 
comprehensively address maternal and child health for all of 
our Nation's mothers and children, stressing health promotion 
and disease prevention.
    In this regard, I would like to highlight an exciting 
recent bureau achievement, the publication of "Bright Futures: 
Guidelines for Health Supervision of Infants, Children and 
Adolescents." It provides state-of-the-art health guidance for 
children at four developmental stages: Infancy, early 
childhood, middle childhood, and adolescence. The services 
prescribed for each of these areas are designed to improve the 
overall health of children and families, enhance the way 
professionals practice, and foster partnerships among families, 
health professionals, and communities.
    For example, in ``Bright Futures,'' there is always 
interaction between the care giver and the family around 
healthy habits, around the social competence, around family 
relationships, and community interactions.
    More than 250 academic institutions that train health 
professionals are currently using ``Bright Futures'' as a 
required text. Many States are using it, as well as 
policymakers, families, health plans, and State health 
officials. With its recognition of the multiple social and 
cultural factors that impact children's development, we expect 
``Bright Futures'' to be the health supervision system of 
choice for the 21st century.
    The MCH block grant which funded ``Bright Futures'' is 
authorized under Title V of the Social Security Act and has 
provided national leadership in developing health care systems 
for America's mothers, children, and families for more than 60 
years. It links Federal, State, local government, and private 
resources to help improve health outcomes and is the largest 
bureau program at $681 million in fiscal year 1997.
    The maternal and child health block grant is a true 
Federal-State partnership with Federal Title V investments 
leveraging and facilitating local, State, and other Federal 
resources for maternal and child health services. The Title V 
partnership strives to assure mothers, infants, children, 
adolescents, and children with special health care needs a 
brighter future.
    The partnership developes systems of care to improve access 
and to deliver individual family and community health care, 
especially primary and preventive care. Examples of what the 
States use their block grant funds for include needs 
assessment, quality assurance, standards development, newborn 
genetic screening, lead poisoning prevention, injury 
prevention, SIDS counseling, outreach, transportation, case 
management, and services for children with special needs.
    Having affordable health care is a prerequisite for 
healthier children. But in order to guarantee that children 
actually receive the care they need, complementary public 
health services provided by Title V State programs are 
necessary to make the difference. Congress has recognized this 
relationship by legislating that State MCH programs play an 
integral role in the development and operation of State 
Medicaid programs. The Title V partnership stresses 
accountability for achieving ``Healthy Children 2,000'' 
objectives and interagency collaboration between Title V 
Medicaid and now Title XXI, the new State Children's Health 
Insurance Program.
    In addition, Title V provides needed supplementary services 
to children, especially those children with special health care 
needs, and supports for their families. Approximately 17 
million children and families, including pregnant women, 
directly benefit from such services.
    The Federal-State partnership is enhanced and strengthened 
by the two grant programs authorized under Title V. The Special 
Projects of Regional and National Significance (SPRANS) and 
Community Integrated Service Systems (CISS), these programs 
address the many high-priority needs that continue to exist for 
providing health services to mothers and children at the State 
and community levels.
    They support leadership for working with States and 
communities to more effectively deliver services to moms and 
kids. They allow rapid, effective responses to threats to 
America's children and families, as well as to such national 
policy health concerns as early hospital discharge of newborns, 
early childhood brain development, teen pregnancy, youth 
violence and suicide reduction, genetic diseases, and newborn 
genetic screenings.
    The Title V CISS program began in 1992 and is designed to 
overcome fragmentation and inefficiencies in providing maternal 
and child health services in community-based systems 
development. CISS funds, for example, were used in partnership 
with the Administration for Children and Families in 53 States 
and territories to develop family preservation State plans 
which integrate child health and child welfare services with an 
emphasis on home visiting.
    My State colleagues tell me that the seed money provided 
through our CISS funds has been the most effective way of 
assuring that health care people are at the table working with 
welfare workers to integrate these services.
    Of particular importance today to this hearing is MCHB 
support through our SPRANS program for new knowledge through 
research. The bureau's research program is different from that 
of basic research in that it applies biomedical knowledge, puts 
that knowledge together into clinical interventions that 
emphasize prevention and promotion, and then assesses those 
interventions for effectiveness and quality.
    Beginning with the first U.S. study on infant mortality in 
1913 and continuing to the present with studies and the science 
of caring for the neonate, MCHB research partnerships have 
yielded proven results and made significant contributions. The 
unique character of the bureau's research and our close 
collaborative relationships with our sister Federal research 
agencies help us avoid duplication. We currently maintain close 
contact with the National Institute for Child Health and Human 
Development, the Agency for Health Care Policy and Research, 
the National Center for Nursing Research, and the Centers for 
Disease Control.
    There are examples where the bureau has been supportive in 
collaborating with NICHD around pediatric pharmacology, and 
certainly around the ``Back to Sleep'' campaign. Our network is 
the way in which the ``Back to Sleep'' campaign materials are 
disseminated throughout the Nation.
    We also are funding interagency agreements to support 
research on early discharge of newborns from the hospital, 
nurse home visiting as a way to avoid hospitalization of 
children, and ways to improve preventive care in private 
pediatric practices through ``Bright Futures.''
    In addition to the MCH block grant, the bureau administers 
other related child health programs. The Healthy Start program, 
initiated in 1991, is an excellent example of how the bureau 
has addressed the ongoing need to improve infant health through 
research and through experience gained from Title V. Healthy 
Start has the objective of decreasing infant mortality in 
targeted urban and rural communities. In the past summer, we 
had a competition and awarded 40 new grants to communities 
which have infant mortality rates 1 and one-half times the 
national average.
    The Emergency Medical Services for Children program 
established in 1984 funds grants to States to develop or 
enhance emergency service programs for children who have been 
critically injured or who have life-threatening diseases. The 
program is designed to ensure that all children, no matter 
where they live or where they travel, can receiveadequate care 
in a health emergency. In the last decade, the EMSC program has 
assisted 47 States, the District of Columbia, and Puerto Rico in 
incorporating pediatric components into their EMS systems.
    In summary, I believe that we can improve the health of our 
Nation's children through health promotion and disease 
prevention, through partnerships, both public and private, 
corporate, foundations, professional organizations, and all 
entities who have an interest in the future of children, and, 
thirdly, through interventions based on good science and good 
judgment.
    Mr. Chairman, this concludes my remarks. I will be pleased 
to answer any questions you may have on the bureau's programs 
and activities.
    Thank you.
    [The prepared statement of Dr. Nora follows:]


[Pages 3106 - 3119--The official Committee record contains additional material here.]



    The Chairman. Dr. Nora, thank you very much.
    As you can see, we are having a series of votes, 
unfortunately, and what I am going to have to do is to recess 
the hearing until we finish that series of votes and then come 
back. Excuse me.
    But let me give you kind of a heads up, because what I 
really want to discuss with each of you are the broader issues 
of what we can do to intervene in childhood to establish good 
health habits, as I said this morning, dealing with diet, 
exercise, no use of tobacco, no use of drugs, maybe moderate 
use of alcohol, and good societal relationships that--in other 
words, the mental health side of a child's health; and how we 
can bring the minds of this country and the resources of this 
country to bear on preventing the kinds of diseases and 
negative outcomes that happen to too many of our young people 
later in life. In other words, giving up on the present 
generations, looking at youth and seeing whether we can start 
the country on a new track that will really make the difference 
and save, by the way, billions and billions of dollars in 
resources that we spend trying to cure diseases that afflict us 
because of our bad health habits.
    So I am going to have to ask that you, again, be patient 
with us. We are going to have to stand in recess, subject to 
the call of the chair.
    Thank you.
    [Recess.]
    Mr. Porter. The subcommittee will come to order.
    Dr. Marks, why don't you proceed.
    Dr. Marks. Thank you.
    Good afternoon, Mr. Chairman. Dr. James Marks, director of 
the National Center for Chronic Disease Prevention and Health 
Promotion, Centers for Disease Control and Prevention. I am 
pleased to be here to discuss our activities related to child 
health and pleased to be at this table with my colleagues.
    My written testimony provides many examples of the child 
health activities and programs at CDC, such as childhood 
asthma, disabilities, drugs and tobacco. I would like to have 
that entered into the record so that I can shorten my remarks 
for today.
    Mr. Porter. It will be received.
    Dr. Marks. Because of the limitations of time, I want to 
focus my oral remarks on the health behaviors among youth, 
specifically the increased opportunities that school health 
programs can offer to improve the health of our Nation's 
children.
    As you are aware, today's most serious and expensive health 
and social problems are caused in large part by behavioral 
patterns usually established during youth, including tobacco 
use, high-fat diets, inadequate physical activity, drug and 
alcohol use, violence, risky sexual behaviors, et cetera. These 
behaviors place children at increased risk for severe health 
problems both presently--that is, during their adolescent and 
youth years--but also in the future.
    Among 5- to 24-years-olds, only 4 causes account for nearly 
three-quarters of all deaths in that age group, principally 
related to issues of injuries, motor vehicle crashes, other 
unintentional injuries, homicides, and suicides. Additionally, 
the high prevalence of sexual intercourse among school-aged 
youth contributes to major health and social problems.
    Only three causes account for two-thirds of all deaths 
among adults 25 and older: Heart disease, cancer and stroke. 
Many of these deaths are caused by a limited number of health-
related behaviors that are established in youth. CDC works to 
monitor the prevalence of these behaviors, and, as you are 
aware, these health problems are widespread.
    For example, among youth surveyed from our youth risk 
behavioral surveillance system, 39 percent rode with a drinking 
driver in the past month, 33 percent had 5 or more drinks on at 
least one occasion, 53 percent engaged in sexual intercourse in 
the past month, and 35 percent smoked cigarettes in the past 
month. A number of these risk behaviors are worsening. Yet, all 
of these behaviors are preventable.
    Why schools? Every day, about 50 million young people 
attend over 100,000 schools across the Nation. School health 
programs are one of the most efficient means the Nation might 
employ to improve the health and education of Americans.
    With more than 20 years of research, we know that school 
health education programs can be effective. CDC has done 
several large-scale evaluations that show that comprehensive 
school health education curricula reduce the use of tobacco, 
alcohol, or drugs, among junior and senior high school 
students. Others have had similar results with their studies, 
Dr. Wynder here among those.
    Preliminary studies indicate that for about every dollar 
spent on comprehensive school health education, an estimated 
$14 are saved in avoided health care costs. Yet, comprehensive 
school health programs are not widely implemented. Ninety 
percent of States and districts require schools to offer some 
health education, but only about 2 percent of schools provide 
school health education programs of the types shown to be 
effective in research studies.
    What does CDC do? First, as I mentioned, we monitor the 
prevalence of the key behaviors among youth. We do this 
nationally, and we work with the States so that they can have 
information that allows them to compare themselves to other 
States and to the Nation as a whole.
    In addition, we look at the characteristics of policiesand 
programs that are in schools. For example, a study that we did of the 
school health policy and program study showed that less than 5 percent 
of teachers of health education majored in it. That is far lower than 
other academic disciplines. Further, despite all the effort in HIV, 
only 31 percent of teachers that taught HIV education had had training 
in it after college.
    We also conduct prevention research, compile the findings 
from the studies that we do and other studies about the 
effectiveness of interventions to influence behavior among 
youth, and we convert these findings into guidelines that are 
useful to school districts. This is an example of our 
guidelines related to physical activity. It grew in part out of 
the work for the Surgeon General's report, and we brought in a 
group of experts to work through what might be possible in a 
school based setting.
    We have developed other guidelines for lifelong healthy 
eating, prevention of tobacco use, promotion of HIV prevention. 
Our goal is to make sure that local and State school districts 
have access to the state of the science in ways that they can 
use to implement successful programs.
    We also help States and large cities plan and implement 
comprehensive school health programs, especially for HIV. We 
fund every State and 19 large city departments of education to 
help local school districts implement HIV prevention programs.
    In addition, we support 13 State departments of health and 
education to jointly work with their local school districts to 
implement school health programs. This support provides each 
State with the capacity and flexibility to determine and 
address its own unique needs.
    For example, in Arkansas they have set up a network of 
representatives from the State departments of education, 
health, and human resources to help schools implement effective 
programs. This network has been successful and serves as a 
model for some of the smaller rural districts. For example, 
Paris and Magazine, have duplicated this model to help 
implement programs in their districts.
    We also support national education, health, and social 
service organizations, most of which have working affiliates at 
the State or local level. For example, the National School 
Boards Association conducts workshops, with our support, for 
school policymakers and school district teams to develop and 
improve school health policies and programs.
    The Council of Chief State School Officers provides 
materials and technical assistance to State school officers and 
State education agencies. The National Association of State 
Boards of Education is developing a guide featuring model 
policies and programs for promoting healthy eating and physical 
activity and prevention of tobacco use for children in all 
grades.
    Lastly is prevention research and evaluation. We help 
constituents evaluate the impact of interventions over time by 
conducting prevention research, dissemination research, and 
evaluations of programs. This helps the State and local 
education agencies evaluate and improve their own programs and 
to learn what has been proven effective elsewhere.
    Given that these leading causes of death and disease in the 
U.S. have their roots and behaviors established in youth, 
school health programs can help young people develop the skills 
they need to engage in positive, health-enhancing behaviors 
rather than those that put them at risk.
    Even though I have had to shorten my remarks here, I do 
want to say I have focused on schools, but I want to be clear 
that changing behaviors of our youth to positive, health-
enhancing ones is not just a job for the schools. Families, 
health care workers, media, religious organizations, community 
organizations that serve young people, have to be 
systematically and consistently involved.
    I firmly believe that we cannot achieve the kind of results 
that we would all like to see without the schools being a key 
partner. We are firmly committed to working with the schools 
and communities to improve the health of our Nation's youth and 
the lives and well-being of our youth. Their future and our 
future depend on it.
    Thank you. And I will be happy to answer any questions you 
might have.
    [The prepared statement of Dr. Marks follows:]


[Pages 3124 - 3144--The official Committee record contains additional material here.]



    Mr. Porter. Dr. Marks, thank you very much as well.
    We have saved Dr. Wynder for the last witness because I 
wanted him to get a chance to hear the previous five witnesses 
and what is being done, and he has heard from NIH, from HRSA, 
and from CDC.
    Dr. Wynder is the president of the American Health 
Foundation, the man who conceived Child Health Day.
    And I would like to know, Dr. Wynder, what you think we are 
doing right and what you think we are doing wrong and what we 
can do better in a different way. Please.
    Dr. Wynder. Mr. Chairman, first of all, I would like to 
thank you for convening this particular meeting and for your 
leadership for the NIH. And being a member in NIH, I can tell 
you that the research community owes you a great deal of debt, 
you and your colleagues, for making so many funds available to 
the NIH and to institutions such as ours. We are a designated 
cancer center going from basic research to applied research.
    Historically, I have learned from a long time ago that I do 
not need to know the precise cause of a disease in order to 
prevent it. That was true for lime and scurvy, for smallpox, 
for Semmelweis of childbed fever, and it is certainly true for 
life-style-related-diseases today. You so aptly called our 
problem a problem of life-style medicine.
    What is life-style medicine? It relates to what wesmoke, 
what we eat, what we drink, our sexual behavior, our exposure to 
sunlight, our lack of exercise, in all the kind of things that, after a 
while, when you lecture about it, it makes you one of the more 
unpopular people in your city. But the fact is that these are the 
causes, and in terms of treating these diseases in adulthood, we make 
but very slow progress. Therefore, for academic and economic reasons, 
we must follow what you so aptly call the principle of life-style 
medicine.
    Now, in my written testimony I have said a few words about 
how we should do this as adults, and the key variables that we 
learn from adults that our life-style practices, to a large 
extent, relate to our education. So education is crucial for 
life-style medicine, with respect I have for myself.
    And if you look at smoking as an example, while smoking in 
the general population is 25 percent of adults; among less 
educated, it is 45 percent; among adolescents that drop out of 
school, it is more than 60 percent. So the more educated we 
become as a Nation, the healthier we will be as a Nation.
    So the good news is that we know many of the life-style 
variables. The bad news is, we have to do it ourselves. And 
here we could talk forever about the barriers of preventive 
medicine, there is no economics, the self-denial that we all 
have. And so what are we going to do? And the focus of our work 
at the foundation, what I call application research, is the 
realization that our life-styles begin very early in life.
    Dr. Hyman Eppley called attention to the fact that it is a 
critical curve of learning to which we not only learn our 
language--and as you have often said, and the audience behind 
me may wonder how come I still speak with an accent, I still 
speak with an accent because I didn't come over to this country 
on the Mayflower. And so what we need to learn, that for 
language, as for behavior and emotion, we are baked in the 
first 8, 9 years of life, and probably earlier.
    So we need to focus our search. Why is it so? Can it be 
corrected? It probably cannot be corrected. And therefore our 
strategies, not only for children, but for adults, we must 
focus on behavioral medicine as it relates to children. And 
then we divide children into teens and preteens.
    Now, we and others have learned that if you do antismoking 
programs, programs on sex education, programs on nutrition in 
the high schools, they are largely failing. And the reason they 
are failing, we are starting too late. And so we are working, 
and we need to work as a Nation, on educating our children from 
zero to 8.
    How do we do that? First, as parents. We talk a lot about 
parenthood, and as we look around today, we see many children 
born to a single mother. We have a high divorce rate. In 
certain population groups, as many as 67 percent of children 
are born out of wedlock. When we just look at a PTA meetings in 
some of our inner cities, we are lucky if 5 percent of those 
parents come to such a meeting.
    So to begin with, parents is where we need to start. And we 
know that if we have two parents, you smoke less. If you have 
one parent, you smoke more, or if you have no parent. If you 
have two parents who smoke, you smoke more than if your one 
parent smoked. If a parent is obese, you become obese. If a 
parent is on drugs, you are likely to get on drugs.
    So we need to recognize that parents are our first 
obligation. In effect, when I talk about parents and school and 
community and media, they all come together, and we need to 
recognize that, in prevention, like in therapy, it is a dose 
that makes the therapy. So first, parents.
    Secondly, as Jim said, comprehensive school health 
education, very, very important. It becomes age 2 or 3 or 4. 
Transition or universal education for 3- and 4-year-old of 
everyone in France. And I would encourage a Head Start program. 
In fact, all children need to be educated when they are 3 or 4 
years old.
    We have a major campaign that we ought to leave to our 
children. It is a very good campaign because the more we eat, 
the more our brain develops. The more our brain develops, the 
more we are likely to take care of ourselves. So this is a 
comprehensive program. I am against unifactorial education 
programs, be they drugs, be they smoking, be they alcohol, be 
they teenage pregnancy, because we know that they are all 
interrelated.
    It was said earlier that tobacco is often the gateway to 
other health habits, and, in fact, if you do a correlation 
between smoking and all other variables that are good behavior 
in children, they all correlate. So it has got to be 
comprehensive. It has got to be run what I call in this city a 
Vince Lombardi teacher. You have got to be a teacher with 
absolutely experience, interested, and almost emotional for a 
subject, because children relate to such teacher who is caring.
    And the third segment is a community, and within the 
community, I am particular calling on the television industry. 
I find it--I was going to say disastrous. If you look at the 
fare that we feed to our children today on television, 
including Saturday mornings, of violence, the sexuality, it is 
certainly misleading our children.
    So I am calling on the television industry, and perhaps you 
could help us there, at least on Saturday morning; give us a 
program that teaches children self-respect and self-esteem, 
because that is the crux of a comprehensive school education 
which we call ``know your body,'' self-esteem.
    So the American Health Foundation is developing a little 
character called Dr. AAAH. He speaks a little bit like me. He 
is the healthy people doctor. And Dr. AAAH has got one saying; 
he says, remember, nobody takes better care of you. And, you 
know, you could be rather humorous about this. And the children 
relate to humor and relate to care.
    Finally, in summary, let me make a couple of specific 
suggestions. I suggest the creation of an office or a czar for 
child health behavior that encompasses all the different 
activities that go on at NIH and elsewhere that deal with child 
health behavior.
    Secondly, I am calling for a health report card that would 
be issued each year on data that are only 1 year old. And on 
this data, we can see whether we fail or whether we succeed.
    Thirdly, I suggest, within the NIH, a study section that 
deals with behavioral research particular to young children.
    I call on all States to get involved in comprehensive 
school health education with proper annual evaluation, 
including attitude, knowledge, and behavior. And I call for an 
enhancement of Head Start to include comprehensive health 
education.
    We need, as Jim Marks said, to get the PTA, the workplaces, 
the places of worship, the medical profession, the community 
schools, television, health insurance company,HMO's, all 
together behind the move to enhance the health of our children.
    I believe, Mr. Chairman, that for children to grow up to be 
healthy with healthy behavior, it is not a privilege, it is a 
right. And for us, as adults, we need to recognize--and I 
cannot express it better than Confucius said many centuries 
ago: Tell me, I forget; show me, I remember; involve me, I 
understand. If we are a more involving society, all of us here, 
our children will become healthier and more educated and more 
productive for our Nation.
    [The prepared statement of Dr. Wynder follows:]


[Pages 3148 - 3164--The official Committee record contains additional material here.]



    Mr. Porter. Dr. Wynder, thank you for your very 
comprehensive testimony, including the things you think we 
ought to do in detail.
    The first thing I want to ask you is a little bit about the 
suggestions--the first thing I want to ask you is, have you 
ever talked to Rob Reiner?
    Dr. Wynder. No. But as you can imagine, a lot of people 
said, you ought to meet Bob Reiner. And I stand ready to meet 
him any time.
    Mr. Porter. Well, he was in my office last week, and I 
brought up the fact that he ought to meet you. So we have got 
you both in a mode to meet one another. I am going to set this 
up so you can talk, because he is doing a part of what you want 
to do and focusing on early childhood and its importance, which 
I think is very much a part of what you are attempting to do, 
but in a broader sense through zero to 8.
    You know, we often say to our schools, you have got to 
teach this or that. When I was in the Illinois General 
Assembly, we put a mandate on Illinois schools to teach private 
enterprise, and then it occurred to me, none of the people that 
teach in our schools are in private enterprise, and they don't 
know anything about private enterprise; they are government 
employees, like I am.
    How do we get people in our public school system to teach 
comprehensive health education who are qualified to do so and 
who can be effective in bringing these concepts into the minds 
of our children?
    Dr. Wynder. Well, in years gone by, many schools had 
nurses, we had physical education teachers who more or less 
could have been trained into this. But the American Health 
Foundation, through funding from the Department of Education, 
we are part of a National Diffusion Network where we trained 
several hundred teachers in health education, and as part of a 
lease and budget cut, the National Diffusion Network was cut 
out, and so therefore we can no longer train these teachers.
    We at American Health Foundation stand ready to launch a 
program to teach teachers. And there are sufficient teachers 
around the country who have an interest in health, who, with 
very little education, could be taught to be effective health 
education teachers.
    Mr. Porter. So you would teach the teachers--you said 
earlier we have 100,000 schools; or maybe that was Dr. Marks 
that said that. There are a lot of schools. Those are just the 
number of schools, not the number of classes. And, presumably, 
you have got to teach this every year, not just once for a 3-
week period or something.
    Dr. Wynder. Well, I believe that if we had one health 
education teacher per school, who again might be called the 
healthy people teacher, this teacher, by affecting parents or 
other teachers, by affecting school luncheon, by affecting 
exercise program, and by involving her or himself in all of the 
factors that we discussed today, would be one of the best 
expenditures this country could make, because if we create a 
healthier group of children early on in life, we do not have to 
pay for all these major disorders.
    I was just reading the other day the most common operation 
in the country is coronary bypass, 350,000 per year. And if 
your cholesterol is under 160, and you don't smoke, and normal 
blood pressure, we could send all the coronary bypass surgeons 
back to do something different than that operation. So that, 
economically, the best way to deal with life-style medicine, 
have one of those factors beginning in school, and particularly 
in preschool.
    Mr. Porter. What is the grade now? C minus, is it, or was 
it C?
    Dr. Wynder. Well, we gave it this year, Mr. Chairman, a C.
    Mr. Porter. C.
    Dr. Wynder. And the other day, when we had to celebrate a 
child health day in the White House, Mrs. Clinton said, can we 
make it a B, and I said this depends on what we as adult 
society provide as a motive for our children to do better.
    Mr. Porter. Okay.
    Well, Dr. Marks and Dr. Nora, Dr. Wynder is giving you a C. 
What do you say about that? And what should we be doing? And 
after hearing Dr. Wynder, what are we doing to head in his 
direction?
    Dr. Marks. In some ways, I think his grade is actually a 
little bit on the generous side for our country, because while 
the grade may be a C, I think in many ways we actually have 
been worsening as far as our health status for our children. So 
if it is a C, it is not as if we are heading towards our B.
    We have talked about what we can do with regard to school 
health education, where the data is, in fact, quite strong when 
it is done in the ways that we know work. But in fact, as you 
mentioned, it is very hard to get the schools to take this on. 
That is why we have said that it needs to be done jointly by 
the health departments and the departments of education working 
together.
    Where we have seen that this has happened, it is, I think, 
having an effect. It is not nearly as effective as it could be 
on an individual basis in the local schools.
    One of the things that Ernst talks about is also showing 
the impact. Any teacher, any school, any person providing care 
to children feels good when they see that they are making an 
impact, and we need to show that where it is happening and show 
that if they did things the way that we know work, they would 
have an impact, and they, I think,would in fact do that.
    The area of physical education is one that I did not 
mention in my remarks but is one example of what I am referring 
to Illinois is the only State that still requires daily 
physical education in the schools, and in fact in the last 5 
years, physical education has fallen; the number of students, 
the proportion of students participating, has fallen from 42 
percent to 25 percent.
    This past week in U.S.A. Today----
    Mr. Porter. Excuse me. Is that strictly budgetary?
    Dr. Marks. It is not strictly, but it is often largely 
budgetary. There are issues of trying to get in other events as 
well, other things that they are asked to teach, but it is 
often heavily budgetary.
    There is an article in U.S.A. Today about the Army 
increasing a 70 percent higher rate of washout because of 
physical condition alone. They have now remedial physical 
conditioning programs, and they say it is the first time in the 
history that the physical conditioning of parents is better 
than that of incoming soldiers.
    There is just a tremendous amount to do, and yet the 
science is there that says we know what we can and should do. 
We need to make sure that the science that I have gotten from 
NIH, and from other places, is disseminated and is translated 
out there.
    It is like we have a new computer chip that is better than 
anything we have had before, but we have not done any work in 
designing the programs that will take advantage of it. We don't 
have marketing to get it out to the States and communities so 
that they are aware of it. We don't have any technical support 
so, as they try to implement it, and they have glitches, they 
have backup and we don't have people looking at how to improve 
it for the next generation.
    Mr. Porter. If we are going away from teaching physical 
education and we are going away from having even a school 
nurse, in most cases, how can we go toward providing health 
education? I mean, we seem to be going in reverse. We don't 
even emphasize the importance of exercise.
    Dr. Marks. I think that with the kinds of support that we 
provide for the comprehensive states, they have been able to do 
this in a few areas as demonstrations. But it is not to the 
extent that they need to or that we need to as a country. But 
by starting to show this in, not just in university settings, 
by showing it in rural communities like I mentioned in Arkansas 
and other places in schools, the prevention research center we 
have in Illinois is working with inner city schools at the 
school of public health. By starting to show that we can make 
these differences in regular settings, I think that, in fact, 
we can generate the kind of momentum that is needed.
    We also need to do the teaching, though. As mentioned, less 
than 5 percent of health education teachers have majored in it. 
We have so far to go in getting those that are now trying to 
teach it to where they really know what they are supposed to 
teach.
    Mr. Porter. Before I call on Dr. Nora, I want to ask Dr. 
Wynder, Dr. Wynder, does the American Health Foundation have 
any Federal grant funds to teach health teachers, teach 
teachers to teach health?
    Dr. Wynder. No, we do not.
    Mr. Porter. You mentioned the National Diffusion Network.
    Dr. Wynder. The only grant we had was a very small grant, I 
believe, of $75,000 to train teachers around the country about 
health education. And the fact that so many people wanted to be 
taught indicates that there is a great need and interest.
    I believe a problem, Mr. Chairman, we have, we have the 
Department of Education, we have a Department of Health, but 
they don't interconnect in terms of health education. But 
Assistant Secretary Towaldy, with whom we are meeting next 
Monday could be asked, and of course the Department of 
Education could be asked, how this could be corrected, because 
I believe there is the interest, Jim, among teachers.
    Health education is at least as fun to teach as Greek 
mythology, I believe, and it has a lot of people out there, 
particularly among young women these days, who are very 
interested in physical fitness and in health who would make 
terrific teachers.
    Mr. Porter. Dr. Nora, are you aware of any programs that 
provide funding for educating teachers to teach health in the 
public schools? Or does the Department of Education, to your 
knowledge?
    Dr. Nora. Let me just share some of the things that the 
Maternal and Child Health Bureau is doing. Two years ago, we 
funded a distance learning project at the School of Nursing at 
the University of Colorado which did distance learning through 
a national hookup for all of the school nurses in Montana, 
bringing them up to speed on new developments in school health. 
This was a very, very successful program and is just one 
example of such a program.
    We have supported and funded training programs in 
comprehensive adolescent health including health education for 
health care providers. The behavioral and social changes that 
take place in adolescents really need to be addressed.
    In addition, we have also funded behavioral training 
programs where health care providers are trained in early 
childhood behavior--what to look for, how to intervene when 
children began acting out, that type of thing.
    We have mentoring programs that are particularly effective 
in minority communities and low-income communities. We work 
through our school health services programs to coordinate 
mentoring with school health education so that there is balance 
and a comprehensive approach. There is no question that more 
needs to be done.
    I would also like to point out that I think that health 
education really needs to begin earlier than at the school-age 
level. And that is one of the reasons why, in our ``Bright 
Futures'' document, we have promoted healthy habits from the 
prenatal period through early infant visits on up to early and 
late adolescence and encouraged discussion between the care 
giver and the family about the ``anticipated challenges'' that 
the family and the child are going to be addressing, whether 
this is bicycle helmet safety, smoking, drug abuse, any of 
those kinds of issues. This is a challenging area to try and 
improve.
    Mr. Porter. How long have you been doing that?
    Dr. Nora. Well, ``Bright Futures'' came out in 1994. Our 
behavioral training programs have been in existence for several 
years, and the adolescent training programs for about 15 years.
    Mr. Porter. And do we have any data on at least theolder 
ones telling us whether we are being effective, whether it is making 
any difference?
    Dr. Nora. Well, the information that we have is that we 
need more and that care givers really need to be comfortable in 
dealing with adolescence. By and large, parents aren't 
comfortable in dealing with their own adolescents, and many 
physicians are in the same dilemma, so there is a need for some 
educational programs in that direction.
    Mr. Porter. Dr. Wynder, are we doing enough in this area? 
What should we be doing that we are not doing?
    Dr. Wynder. Well, our problem among our scientists, you 
know, we have basic scientists in the American Health 
Foundation, behavioral scientists, and sometimes the behavioral 
scientists do not get the kind of credit that they really 
deserve from our scientific colleagues, because we are putting 
so much emphasis on gene and molecular research and so much on 
therapeutics that sometimes I feel the best among us do not go 
into behavioral scientists. So, clearly, we must do much 
better.
    As Jim properly said, probably the passport should continue 
on C minus, because obesity is worse, smoking is not getting 
any better; this morning, reported drug use in very young 
children has gone up.
    So we have, I believe, a very fundamental societal problem 
that can only be corrected if all of us, including all the 
corporations who make a large income on children, ought to put 
something back to provide better health education to children. 
We need professionals, as pediatricians, as physicians, put 
much more emphasis in talking to our young people.
    Our young people today feel kind of lost because of the 
disintegration of many families, because of television, because 
of the way we talk to one another as public figures. It is not 
easy to be brought up today as a young person and not succumb 
to these temptations that many risk factors develop.
    So I believe that we need to do much better, and we need to 
determine, CDC and your office, Dr. Nora, and the NIH, and all 
the associations that deal with children come together, because 
what our children need is a much more concerted effort, a much 
more coordinated effort. And, as Jim said, we must have these 
reports every year.
    Some of the data, Mr. Chairman, we have in here are 2 or 3 
or 4 years old, because we don't collect these data every year, 
and we must have them on 8-years-olds and 12-years-olds and 16-
years-olds, we have got to have them by different minority 
groups, because in certain subpopulations we do work than in 
others.
    And if these were made public to the American public every 
year, perhaps there would arise a concern among all of us who 
are in a position to make a difference to make a change, 
because if you ask me whether we can do much better, we can, 
and we must do much better, not only for the sake of our 
children but for the sake of all the diseases that will not 
only happen in their future but in the long future as they 
continue under this state of behavior they have today.
    Mr. Porter. Dr. Marks and Dr. Nora, Dr. Wynder suggested we 
have a czar of child behavior, a special, presumably assistant 
secretary. Is that a good idea or a bad idea?
    Dr. Marks. I can't really speak for the administration's 
position on this, but I think the key issue, in my professional 
judgment is, in fact, that the emphasis needs to be on the 
behaviors and disseminating what we are learning from the 
research more widely.
    And I think that--I can't speak for Ernst, but of course--
because he will tell me if I am trying to--we need to make sure 
that the science and the dissemination are hand in hand and we 
put as much effort in getting it out there as we do in doing 
the science.
    Whether or not that requires a czar, it certainly requires 
coordination. It requires more than Federal coordination; it 
requires it at the State and local level as well. A czar as a 
symbol is perhaps nice, but it is really what happens at the 
State and local level that is much more important.
    Mr. Porter. Dr. Nora, what do you think?
    Dr. Nora. Well, I have to agree with Dr. Marks that I 
really think it is a bigger problem to get the information 
disseminated. And we attempt to do that through all of our 
partnerships-- through State and local communities, through our 
relationships with professional organizations such as Dr. 
Wynder's or the American Academy of Pediatrics, and through 
corporate working groups, foundations, and all kinds of other 
mechanisms. And I think there really needs to be more emphasis 
in that direction.
    Mr. Porter. We have talked about that kind of dissemination 
and about the role of our public schools, all of our schools, 
in educating children. But isn't the most powerful medium 
television? And can't we reach their minds more easily there 
than perhaps anywhere else, if we can get there?
    What do you think, Dr. Wynder?
    Dr. Wynder. We need two things. You know, there needs to be 
less violence, less sexuality, on television. I am sure this 
has been said by many, many others. But obviously what guides 
our television industry is the Nielsen rating.
    Some time ago, I was in Europe and I saw on prime time a 
program on how the Dutch recovered land from the sea. I think 
this would get a Nielsen rating of minus 10 here, but in Europe 
it was on prime time.
    But what we can do, I believe, is get the industry, 
particularly on Saturday morning, to give us the opportunity to 
have half an hour to impact on children. And it must be done in 
an entertaining manner. And there are marvelous writers out in 
California who, in addition to writing a comedy on Seinfeld, 
could write a beautiful scenario for children to laugh at and 
be educated at the same time. This is what I am calling for.
    We are going to start with Dr. AAAH as a health minute. You 
remember in the Bicentennial, you had the Bicentennial minute. 
And Jim Burke, who collects a lot of money for the Partnership 
for a Drug-free America, tells me again and again it is through 
television that could be accomplished.
    So I would like to get the Bob Reiners of the world and 
some major industries to help us to establish these health 
minutes. And I believe what Dr. AAAH could do what little 
Bonnie is doing, what Big Bird is doing, to teach children 
early on, 2 or 3 years old, that, I am responsible for myself 
is only, of course, one step, but together with all the other 
things we have mentioned are very important, sir.
    Mr. Porter. Are you assuming that our television networks 
or industry is going to provide this time free? And if so, 
where does that assumption come from?
    Dr. Wynder. No. I would hope that initially they wouldgive 
us the 1 minute free as a PSA. In the long run, I hope that there are 
major companies who makes a living on children who would support such 
an activity as part of the advertising campaign.
    For instance, these writers in Hollywood came up with an 
idea--I was talking about glasses, and I said, give me a little 
minute on glasses, and they came up with the idea that Little 
Red Riding Hood goes to the forest to bring food to her 
grandmother, but she didn't want to wear glasses because she 
was ashamed to wear glasses. So she runs into Big Bad Wolf. 
Fortunately for her, he didn't wear glasses either, so he 
didn't recognize her.
    And that is the beginning of a little story in 1 minute 
that, by the end, the kid says, hey, ma, I don't see too well. 
You better buy me some glasses.
    So it is just one idea where--of course, it is easier on 
glasses, on dental hygiene, than it would be on drugs and 
smoking. But I believe we could--certainly, if I were Mr. 
Reiner, I could, and therefore I would be delighted to meet 
with him, because there are some people in Hollywood who have 
enormous power, and perhaps we could influence them to make 
programs that some commercial company might want to endorse.
    Mr. Porter. Dr. Marks.
    Dr. Marks. I would like to support Ernst on this but also 
to talk about what we know. We know that in some other 
countries they have used TV very effectively. In Mexico, they 
had a soap opera that was very popular that had as its story 
line a father who couldn't read and had--there were a lot of 
interpersonal problems, and eventually he comes to the 
conclusion that he is going to go to the literacy clinic and 
learn to read.
    The TV station let the Government know about this ahead of 
time. They (the Government) didn't do anything. The next day, 
and the day that the father--after the father made the decision 
to go himself, they were swamped. They could not handle the 
calls that they were getting, the numbers of people, men 
especially, that were signing up.
    We cannot just model and tell children what to do, but we 
can model the kinds of family behaviors in the stories that are 
already popular, and the shows that are already popular, the 
things that can encourage children and their families to have 
more positive behaviors.
    We know, for example, when we do a survey of children and 
their physical activity, the thing that predicts more than 
anything their physical activity rates, children now in their 
early adolescence, is whether their parents were physically 
active with them, played ball, took them for walks. It is not 
whether their parents told them to. It is not even whether they 
have school health education, physical eduction in the schools, 
it is whether their parents did something with them to be 
physically active.
    That is the kind of thing that could easily be modeled in a 
number of the popular shows, so that the time doesn't really 
have to be donated, the creativity does.
    Mr. Porter. Does the concept that Murphy Brown recently did 
in highlighting breast cancer--is that kind of a model for----
    Dr. Marks. That is a very good one, yes.
    Mr. Porter. Bringing this up to a level on TV where you can 
reach people's consciences with a positive message.
    Dr. Marks. That is a very good one, yes. I don't know how 
effective it was, but I do know, for example, when Nancy Reagan 
had breast cancer, you can see in the next month an increase in 
the number of women who signed up to get mammograms.
    These kinds of events have reached millions of people. And 
if what we are asking people to do is not so difficult, we can 
get them to start to make those changes. You can't get them to 
sustain it unless they like it, but we can start it.
    Mr. Porter. To what extent does HRSA use this kind of 
approach through television, I mean, as a medium to reach 
people with health messages?
    Dr. Nora. I would have to say that I agree wholeheartedly 
with what Dr. Wynder and Dr. Marks has said. As far as our use 
of television, we are certainly interested in trying to 
influence the development of programs. We have done a few 
documentaries with organizations like the National Parents 
Network, for example, that have focused on relationships of 
parents and children, trying to emphasize the importance of 
those relationships.
    We have targeted a national PR campaign on early prenatal 
care to young pregnant women through our Healthy Start program 
and through partnership with the State health departments, all 
of which have established a 1-800 number for people to call to 
find out where the closest prenatal clinic is to them and where 
they can go for their care. Our national information number is 
designed to roll over to the State and the local numbers. This 
campagin has truly been a partnership, one that has been very, 
very successful, with both the English- and Spanish-speaking 
communities.
    I would just like to add something to Dr. Wynder's comments 
about television. My own personal experience was that our 
children were watching too much television, and we, as parents, 
decided that it was important to limit the amount of time. We 
limited our children's TV time to 2 hours per week per child, 
that they could select. So the family had 6 hours of 
television.
    It was very interesting to me that suddenly these children 
were coming home from school and not sitting down in front of 
the TV. They were out interacting with other neighborhood 
children. And our decisions were influencing not only our 
children but the children of the neighborhood, because they had 
all been congregating at our house, and I said, no more. They 
were out riding bicycles, playing at sports, and being creative 
in what they were doing after school.
    I have to say that I really believe parents have to assume 
a role in this and that it is important that parents instill 
the values they want to share with their children at a very 
early age.
    Mr. Porter. We have talked about the role of parents. We 
have talked about the role of the school. We have talked a bit 
about television. We have talked about the role of the 
Government in influencing those sources. Are there any other 
ways, Dr. Wynder, that you can bring across the message of a 
healthy life-style, if you want to call it that, that need to 
be explored?
    Dr. Wynder. Well, if you look at the rest of our community, 
you certainly need to look at a place of worship that has a 
profound influence. And many studies have shown that 
churchgoers smoke a good deal less than those who do not.
    We need to look at a place of work where there could be 
work-related good health habits, including not smoking. One 
could look at the health insurance companies who could put 
afocus on good health behavior for which they might give some 
incentives. One could look at the health maintenance organizations who 
could give incentives for all the young people.
    I always say, if I were going to run a health insurance 
company, I would like to have people who don't smoke, who drink 
in moderation, who are normal weight, who exercise, who don't 
use drugs, and are happily married, and who go to church once a 
week. I bet I could make a lot of people compared to all the 
rest of the people.
    And you read in the papers the other day that our managed 
care organizations are running a deficit. And the deficits are 
probably relating to all these diseases that we are talking 
about which have their beginning early in childhood.
    So it seems to me also as a government--and I know we are 
concerned about Medicare and Medicaid; there only one reason 
that we need to die, and that is when the genetic time clock 
has run its course.
    The chairman has often heard me saying we should all die 
young as late in life as possible. Now, if we do that, we can 
take all the money we saved from Medicare and Medicaid and put 
it in the health education of young people. I don't know 
whether I could be elected to office on that agenda, but it 
makes a good deal of sense.
    Mr. Porter. Yes. Ideally, we should all live 100 years and 
die without being ill a day and save a lot, of course. I think 
it is possible, or something close to it. We may not see it in 
our lifetimes, but if you keep working on this, Dr. Wynder, and 
we give you a hand, perhaps it is; we can bring it closer to 
realization.
    I want to thank each of our witnesses today. We have, I 
think, focused on a very, very important subject. And I want to 
commend Dr. Wynder for the leadership he is providing to the 
Nation.
    I said this morning that I think, 20 or 25 years from now, 
a lot of what is accomplished in our country will be 
accomplished through--and it already is, but a lot more will be 
accomplished through private foundations, private money, that 
is directed to achieving specific ends.
    And yet, in the meantime, we are going to need government 
resources brought to bear on problems like this and the degree 
of government direction as well.
    And it seems to me, Dr. Wynder, you have given us some--not 
only some food for thought but some real suggestions as to how 
we can make changes here that will help in this endeavor. And I 
want to work with you to bring those to fruition. In the 
meantime, I am going to set up this appointment with Rob Reiner 
and get you two together.
    Thank you all for being here today. I thank each of our 
witnesses. You did a wonderful job. I think we have made some 
progress. Thank you.
    The subcommittee stands adjourned.
    [The following questions were submitted to be answered for 
the record:]


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