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


                 DEPARTMENTS OF LABOR, HEALTH AND HUMAN

               SERVICES, EDUCATION, AND RELATED AGENCIES

                        APPROPRIATIONS FOR 2001

_______________________________________________________________________

                                HEARINGS

                                BEFORE A

                           SUBCOMMITTEE OF THE

                       COMMITTEE ON APPROPRIATIONS

                         HOUSE OF REPRESENTATIVES

                       ONE HUNDRED SIXTH CONGRESS

                             SECOND SESSION
                                ________

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

                 JOHN EDWARD PORTER, Illinois, Chairman

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

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

           S. Anthony McCann, Carol Murphy, Susan Ross Firth,
             and Francine Mack-Salvador, Subcommittee Staff

                                ________

                                 PART 4B


                      NATIONAL INSTITUTES OF HEALTH

                              

                                ________
         Printed for the use of the Committee on Appropriations
                                ________

                     U.S. GOVERNMENT PRINTING OFFICE
 64-199                     WASHINGTON : 2000

                        COMMITTEE ON APPROPRIATIONS

                   C. W. BILL YOUNG, Florida, Chairman

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

                 James W. Dyer, Clerk and Staff Director

                                  (ii)

                            C O N T E N T S

                              ----------                              

                               LABOR/HHS

                               VOLUME 4B

                                                                   Page

National Institute of Nursing Research...........................     1

National Heart, Lung, and Blood Institute........................    61

National Institute of Environmental Health Sciences..............   177

National Institute of Neurological Disorders and Stroke..........   299

National Institute on Aging......................................   415

National Institute of Mental Health..............................   511

National Institute of Diabetes, Digestive and Kidney Diseases....   617

National Institute of Arthritis and Musculoskeletal and Skin 
  Diseases.......................................................   761

National Center for Research Resources...........................   845

National Institute of Allergy and Infectious Diseases............   921

National Eye Institute...........................................  1073

Office of the Director...........................................  1137

Buildings and Facilities.........................................  1389

National Center for Complementary and Alternative Medicine.......  1435

                                 (iii)

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

                              ----------                              

                                           Thursday, March 2, 2000.

                 NATIONAL INSTITUTE OF NURSING RESEARCH

                               WITNESSES

Dr. PATRICIA A. GRADY, DIRECTOR
DR. MARY LEVECK, ASSOCIATE DIRECTOR FOR SCIENTIFIC PROGRAMS
HERIBERTO RIVERA, BUDGET OFFICER
WILLIAM V. ROSANO, EXECUTIVE OFFICER
DR. RUTH L. KIRSCHSTEIN, ACTING DIRECTOR, NIH
DENNIS P. WILLIAMS, DEPUTY ASSISTANT SECRETARY, BUDGET, DHHS
    Mr. Porter. The subcommittee will come to order. We 
continue our hearings with the National Institute of Nursing 
Research. We are pleased to welcome, again, Dr. Patricia Grady, 
the Director. Dr. Grady, it is wonderful to see you. You always 
do such a fine job before our subcommittee, as well as at the 
Nursing Institute.
    You are the institute that had the single largest 
percentage increase of all last year. So you have special 
responsibilities to tell us how you spent the money, or are 
spending the money, I should say. So please, introduce the 
people with you, and then proceed.

                           Opening Statement

    Dr. Grady. Thank you, Mr. Porter.
    Good afternoon, Mr. Chairman, and also members of the 
committee. It is a pleasure to appear before you today.
    I would like to thank the committee for its strong support 
of NINR and nursing research. In this period of rapid 
technological and demographic change, it is incumbent upon us 
to ensure that nursing research grow to meet the present and 
future health care needs of our nation's people.
    Today I will discuss our achievements and goals for fiscal 
year 2001 that relate to these concerns, especially in the 
areas of chronic illness, end of life, and health disparities.
    The President's budget provides a 3.3 percent increase or 
$2,900,000 total AIDS and non-AIDS funding for NINR in fiscal 
year 2001.


                        CHRONIC ILLNESS RESEARCH


    With regard to chronic illness, NINR is committed to expand 
this research to help patients manage their conditions. 
Progress in this area is encouraging. In one recent 
accomplishment, nurse researchers have further tested and 
confirmed the value of a transitional care model using a 
multidisciplinary team and advanced practice nurses. This model 
involves comprehensive discharge planning for continuity of 
care from the hospital to the home setting.
    The results of this study, as shown on the chart before 
you, clearly indicate that at six months following discharge 
the intervention group, in this case older adults with common 
medical and surgical problems, spent 65 percent fewer days in 
the hospital and had 48 percent fewer re-hospitalizations, at a 
total savings of 48 percent or nearly $600,000 to the health 
care system.
    Widespread use of this model could save significant health 
care dollars and improve quality of care. This model is 
currently being tested in patients with congestive heart 
failure and also in a rural setting in Western Pennsylvania.
    Most nursing research is clinical in nature and may be 
carried out in settings that range from the hospital to the 
community. Another recent finding concerns the use of feeding 
tubes that are required to provide nutrition in many conditions 
of acute or chronic illness. Incorrect placement of the tube 
may deliver food to the respiratory system, which would have 
serious consequences.
    Currently, a stethoscope or x-rays are used to determine 
tube placement. Nurse investigators have discovered that simple 
rapid chemical test of aspirated feeding tube contents is a 
more accurate alternative to the use of a stethoscope, and a 
safer and less expensive one than x-rays. Clearly, it is also 
more convenient for use in homes or long term care facilities. 
This new method has identified the misplacement of tubes in 
lungs with 100 percent accuracy.


                          END-OF-LIFE RESEARCH


    Just as biomedical advances are changing the way we live 
with illness, they are also changing the way we die. The 
duration of both chronic illness and the dying process is now 
prolonged. NINR is the lead institute for coordinating end-of-
life/palliative care research at NIH. Last year's request for 
applications for research on end of life resulted in more than 
100 responses, an impressive result for a relatively new area 
of research.
    Those studies that were funded will form a basis upon which 
to build an important, growing effort. In fiscal year 2001, we 
plan to expand our focus on end of life to better understand 
and improve symptom management, decisionmaking, and also 
communication between the family, the patient, and the health 
team.


                      HEALTH DISPARITIES RESEARCH


    With regard to health disparities, our efforts are directed 
toward closing the gap. Historically, nursing research has 
focused on minority issues. Currently, about 20 percent of our 
budget is directed towards this area. In fiscal year 2001 we 
will focus particularly on diabetes self-management and the 
influence of ethnic and cultural differences on health.
    An example of progress in our efforts to reduce health care 
disparities is a study in which nurse researchers adapted an 
arthritis self help questionnaire. Hispanics with arthritis 
have had limited resources to help them manage their condition, 
and sometimes restricted fluency in English may have excluded 
them from certain health research projects.
    The researchers have developed and tested a successful 
Spanish language education program that includes how to better 
communicate with the health care team members and manage 
problems of mobility, pain, fatigue, and depression with their 
arthritis. Throughout a one-year period of follow up, patients 
experienced significant improvements in all of these areas.
    Another version of this program is currently being tested 
in Hispanic populations with other illnesses that are chronic, 
such as diabetes, coronary artery disease, and chronic 
obstructive pulmonary disorders. It has the potential to be 
expanded throughout our country.

                    TRAINING AND CAREER DEVELOPMENT

    Finally, we continue to emphasize training and career 
development. Building nursing research capacity remains an 
important challenge. In fiscal year 2001, NINR is reissuing its 
institutional program request for pre- and postdoctoral 
students with increased attention to two specific areas: 
reducing health disparities and incorporating genetics into 
nursing research.
    This year we are also launching the Summer Genetics 
Institute for extramural nurse researchers. A career 
development program, now in its fourth year, offers mentored 
research experiences for minority investigators. Examples of 
studies being carried out by these investigators include 
reduction of developmental problems of migrant infants, 
prevention of suicide in rural Native American youth, and 
improved screening for prostate cancer in African American men.

                               Conclusion

    In conclusion, continued growth of nursing research is 
vital to meet public demands and pressing national health 
needs. Our contributions to the scientific foundation for the 
work of health care practitioners, including the 2.5 million 
nurses across the country, are already making a difference and 
have further significant potential to do so.
    There is still much to be done. The base of knowledge will 
require considerable expansion in creative new directions as we 
face the health challenges of the 21st century. And we at NINR 
look forward to making a difference with research findings that 
will help drive those changes.
    Mr. Porter, we regret that you will not be here to hear the 
results of these studies in person. We also know that you have 
had a very important leadership role in making this research 
possible and we are grateful.
    Mr. Chairman, I am pleased to answer any questions that you 
and the committee members may have at this time.
    [The written statement of Dr. Grady follows:]



    Mr. Porter. Thank you, Dr. Grady.
    I am going to call on Ms. Lowey first, if she has 
questions.
    Ms. Lowey. Thank you, Mr. Chairman, and I do apologize, Dr. 
Grady, that I have to run to another appointment, so I will 
submit most of the questions for the record, and I thank you 
for your important testimony.

                             PAIN RESEARCH

    I just wanted to discuss one area very briefly, because you 
talked about the end-of-life care and the treatment of pain. 
There was an interesting story in a New York magazine recently 
that examined the issue of pain management, and the article 
discussed how patients' reports of pain are routinely 
underplayed by providers, and that treating pain is not only a 
problem at the end of life, it is not handled well for young 
children with terminal illnesses.
    I would be interested in an elaboration from you concerning 
the treatment of pain. But one quick question before I run out 
of the room.
    I would be interested to know if the research has shown a 
gender disparity on the reporting of pain.
    Dr. Grady. It is interesting. We have funded several 
studies that do show disparities on reporting of pain between 
what the patient reports, what the relatives report that they 
perceive the patient is experiencing, and also between what the 
health team members report having observed these interactions 
and observed the patients.
    As far as gender reporting of pain, first of all we did 
fund the study that you have heard about previously that showed 
a difference in response to certain pain medications, that 
women respond better to certain medications than men do. So 
that there are gender differences that are biological, in terms 
of responses. Whether it is the number of receptors or the 
density is still being determined, but certain specific 
chemicals work better with women and do not work with men.
    Originally there was an interesting anecdotal report. The 
study was thought to be a failure and the only persons who were 
responsive to these particular chemicals were women. And then 
the study was done in women and it was found that that, in 
fact, was a gender difference. This was a remarkable finding 
and precipitated a two-day workshop at NIH to look at other 
biological changes.
    But the studies also report differences in gender reporting 
in the types of pain, that both genders subjected to the same 
painful stimuli will report different levels of pain over 
different levels of stimuli and different types. We are still 
refining that, but evidently women mind certain kinds of pain 
more than men and men object to other types of pain.
    So there are some differences which are not clearly worked 
out, but we are working on it.
    Ms. Lowey. I have always been interested in the connections 
between knowledge and pain. In other words, for those of us who 
have given birth, if you know what is happening and you are 
getting briefed, you can deal with pain very differently than 
unexpected pain without any explanation.
    Dr. Grady. Yes, that is a very good point. And just as an 
aside, I am not sure if you were reading my mind. What I did 
not say in the earlier study--that the one instance in which 
the kappa-opioids, which were the substances effective in women 
and not men, were reported to be effective--was in labor. So 
one of my non-scientific staff said I wonder why labor was not 
considered as painful as other things.
    Ms. Lowey. It is just a delight.
    Thank you very much, and I would like to follow up with you 
on the research that you are doing in this area. I thank you 
again for your testimony.
    Thank you, Mr. Chairman.
    Mr. Porter. Thank you, Ms. Lowey.

                         EDUCATION LEVEL OF RNS

    As I explained, Dr. Grady, I have a meeting at 3:30, but I 
want to try to pursue one line of questions before I turn the 
chair over to Mr. Miller.
    You said there are 2.5 million nurses; is that correct?
    Dr. Grady. Yes.
    Mr. Porter. Are those registered nurses, RNs?
    Dr. Grady. Yes, those are registered nurses.
    Mr. Porter. How many of the 2.5 million, if you know, and I 
do not know if this is a question you would necessarily have 
the answer to, but how many of those RNs have four year degrees 
and what percentage have two year degrees?
    Dr. Grady. The Division of Nursing compiles these 
statistics, our partners in HRSA, but roughly about 50 percent 
of those have baccalaureate degrees. As time goes on, the 
percentage of baccalaureate is increasing over two-year 
degrees. There are also some regional differences as well.
    The statistics that we are learning about now, as the 
enrollment in nursing schools has been going down, indicate 
that we are seeing a resurgence in graduate education, higher 
education. So that there is more of an attraction toward 
baccalaureate and higher education.
    Mr. Porter. I know this is properly a question for HRSA, 
but we have already heard from them, so you are the target of 
opportunity here.
    Dr. Grady. I am perfectly happy to try and fill in the 
blanks.
    Mr. Porter. One of my educators came to me and said we 
offer a two-year degree in nursing. They believe that, in many 
instances, that is all that you need to be a competent nurse, 
yet the nursing profession is pushing that everybody has to 
have a four-year degree and they are basically going to put us 
out of business. What would you tell them? What should I tell 
them?
    Dr. Grady. That is a difficult question and it is a very 
controversial issue in the field. In this field, as in many 
other fields, there is a drive toward advanced practice and 
toward additional education. Typically when there is a nursing 
shortage, it has come upon us rather suddenly because although 
there is a cycle, for some reason it is difficult to predict 
exactly when it is going to happen.
    We are now predicting one for 2002, just so you can be 
ready.
    Mr. Porter. We are in one now, are we not?
    Dr. Grady. We are just approaching one and we predict that 
it will be fairly serious by 2002. So we are trying to do 
something about it up front. We are meeting with our partners 
in HRSA and the Department.
    But the issue is a difficult one. Historically, when nurses 
were in positions where they were assuming less responsibility 
than they are expected to assume now, there was more of an 
emphasis on a two-year degree. And now that they are expected 
to assume more responsibility and they are more independent, 
and in many settings where they are performing with a physician 
colleague who is miles away or at the other end of a computer, 
we are seeing more nurses with advanced certifications and 
advanced clinical experiences, masters degrees, nurse 
practitioners.
    So I would say that it is a way to get started, but that 
one would want to continue gaining new expertise and to keep on 
moving.
    Mr. Porter. Thank you, Dr. Grady. You are doing a fine job 
there. It is wonderful to see you again. I am going to turn the 
chair over to Mr. Miller.
    Dr. Grady. Thank you, Mr. Porter.

                       HEALTH CARE OF THE FUTURE

    Mr. Miller [presiding]. Dr. Grady, thank you. It is a 
pleasure to be here. My mother was a nurse. She was one of the 
old fashioned ones. She passed away two years ago at age 89, 
but she finished the hospital-based nursing school, the real 
old fashioned type.
    Dr. Grady. So did I, Mr. Miller. And so did my mother. Yes, 
about two years ago, I gave the graduation speech at that 
school and closed down the school as it transitioned toward a 
baccalaureate program. My mother and her twin sister, both 
graduates of the same school, were there as well. So 60 years 
later they were not practicing, but still active. So I can 
identify with your mother.
    Mr. Miller. When Mr. Porter was asking about the two-year 
program, we have a community college that generates that. My 
area is Bradenton, Florida, lots of elderly. I have lots of 
senior citizens. Health care is our biggest industry. We do not 
have much manufacturing, because of the hospitals, the nursing 
homes, the home health agencies, and such, all have tremendous 
demands.
    One question, and unfortunately during this process, Dr. 
Kirschstein, we have so many hearings going on at one time, it 
is so frustrating, and I have had to miss so many. That is the 
unfortunate part of these other challenges you have to try to 
balance your time. So a couple of the questions may be a little 
more general if you do not mind.
    One of the things I like to talk about is what health care 
is going to be like 20 or 25 years from now. I have been around 
a lot because of my mother. Our family used to be in the long-
term care business, although we are no longer. And I was 
chairman of a hospital for 10 years, in our community. So I 
kind of have been around it. It was a volunteer job at a 
community hospital.
    I have seen it change dramatically, as you have. You talk 
about the reason you need baccalaureate degrees is the 
technology is amazing. Though I think, in many ways, the 
technology has been slow going into patient care, compared to 
what has happened in other areas of industry.
    And then we have gone through all the NIH research. Dr. 
Collins was here yesterday. We are just on the verge of such 
changes. Newt Gingrich used to like to talk about that health 
care 20 years from now would be a replacement business. That is 
real futuristic, but you have seen it change. How do you see it 
20 or 25 years from today?

                   SELF-MANAGEMENT OF CHRONIC ILLNESS

    Dr. Grady. We have been seeing a number of changes. The 
technology will impact on us because of making certain things 
easier and making many things possible. One of the things that 
we are noticing and we are expecting and preparing for, and you 
can see in the studies that we are funding in our areas of 
emphasis, is that as we are living longer and living better we 
hope, that people will be living longer and will be 
experiencing chronic illnesses, but in general will be learning 
to better manage those themselves.
    So we are focusing a great deal of our efforts on helping 
patients in self-management of their disorders, whether it is 
diabetes, whether it is arthritis. These will be chronic 
illnesses that one will be able to manage and keep on with 
activities of daily living and living a fulfilling and rich 
life.
    So we are directing a lot of our focus on that area, 
through the use of prevention, exercise programs, dietary 
modification, trying to get, for example, the elderly to remain 
active and to remain in the community. To test out programs as 
to whether or not, for example in South Florida on the other 
coast, we are testing out a program of exercise in older 
individuals, whether or not the resistive exercise program 
versus the walking program versus just ordinary lifestyle that 
they would live. Which of these is most beneficial and why? We 
are looking at outcomes such as increased aerobic capacity, 
decreases in body weight, and so on.
    One of the risk factors for falls in the elderly, in 
addition to the bone density issues, a study that we have done 
that has identified that the problem of balance is one of the 
more difficult ones in the elderly is related to weight. It is 
not perhaps a surprise, but people who are thinner have a much 
better balance. People who have extra pounds, even a small 
percentage of body fat, tend to have balance problems and tend 
to be more vulnerable for falls.
    So we are doing a number of studies in this area.
    Mr. Miller. It is not out of the question, 10, 20, 15 years 
from now, that cancer, Alzheimer's, some of these things that 
are the dread diseases of today, I know you do not want to say 
that is going to be the case, but it is not far-fetched to say 
that. We are making progress all the time.
    I was fortunate with my mother, my mother-in-law just 
recently, and my father, they were all up in their late 80s, 
early 90s. So old age eventually got them.

                         PREVENTION OF ILLNESS

    Dr. Grady. We are rapidly approaching what we call the 
post-genomic era. The genome will be identified and we will be 
in a time when genes for certain disorders, or as Mr. Porter 
and Dr. Olden were talking about earlier, a propensity for a 
disease will be identified. Then only about 5 percent of genes 
will be one gene/one disease. But the others will identify the 
risk factors or people who are at risk.
    So then it will be up to those of us in the health 
community, particularly the nursing community, to identify and 
to help modify the other risk factors. For example, in the case 
of lung cancer or even a respiratory disorder, that the other 
factors of the environment, factors of smoking, factors of 
occupational choices will be risk factors that would be 
identified for increasing your propensity to develop that 
disease since you already have the gene, or would decrease your 
propensity.
    So we are already starting to look at some of those areas.

                         TELEHEALTH TECHNOLOGY

    Mr. Miller. I made a comment in my opening statement about 
technology. I have not been as close to it in recent years, but 
technology really has not come to the bedside as quickly in 
health care as you would have expected it. It is in the 
laboratory. It is there.
    Now the bedside is the nursing area. Maybe we are getting 
ready to see a rapid movement in that direction. What is 
happening in that area?
    Dr. Grady. Let me, if I might, take that question and 
approach it from a slightly different tack. We have a small but 
growing program in telehealth. We are using technology, putting 
it to work in a somewhat different way. So that we have 
programs directed in several areas.
    We have several studies using telephone monitoring and 
telephone touching bases with patients to determine how they 
are following a particular program of prescription of 
activities or how they are doing. We are also using that 
technology for screening programs and monitoring.
    A second way that we are testing technology is that of home 
monitoring for patients who have certain chronic illnesses. One 
population of patients that we are following is a patient 
population who are post-transplant, lung transplant. Using a 
home monitoring system, including spirometry, electronic diary, 
et cetera, those patients are being monitored. The chance of 
infection or rejection is very high during the first year. So 
in the patients who are being tested, there is a high rate of 
compliance and we have been able to detect some early changes 
using this technology and report that and attend to them.
    Another way that we are using technology is in children 
with asthma. As all of those of you in the room who are parents 
know, children do a great deal of learning at a very early age 
through the use of computers, much more than we did as 
youngsters, and even some of us as adults. But there is a 
computer program that was designed for adults with asthma that 
is being adapted for children and tested by nurse researchers, 
in fact, at Johns Hopkins University.
    This computer program, working with the children, helps the 
children to identify allergens in the home and how to modify 
their behavior to decrease the number of asthma attacks. For 
example, bedroom allergens and things of that sort. It is being 
tested out, and the early preliminary studies do show a 
decrease in the number of asthma attacks in those children. We 
cannot say what the final outcome will be, but it is very 
promising so far.

                             MEDICAL ERRORS

    Mr. Miller. There has been publicity about the medical 
errors within hospitals, and I do not know if this fits into 
NIH research but it--you know, it can fit into nursing research 
and it fits into the whole technology area. I mean, what 
about----
    Dr. Grady. We are actually funding three studies in this 
area that are looking at the relationship between nurse 
staffing and adverse outcomes, including medication errors. 
They are also looking, in addition to medication errors, at 
complications such as pneumonia, urinary infection, falls, and 
so on. These studies are being carried out--one is a multi-
site, multinational study which is being carried out in the 
United States, Canada, Scotland, and the United Kingdom--
specifically England. Another is being carried out in the 
Midwest, a multi-site study. And a third one is being carried 
out in 11 southeast States and D.C., including North Carolina, 
South Carolina, Virginia, West Virginia, et cetera.
    Those studies are four- to five-year studies and two of 
them are about halfway through, and a third one has just begun 
this last year.
    Mr. Miller. You are talking about technology, one thing 
that our economy that--you know, economics background is always 
intriguing. We do not have inflation in this economy and we 
have such low unemployment. I mean, that is basic economics 101 
does not explain that one away, except for the productivity 
increases in, especially because of technology. Are we seeing 
those in health care?
    Dr. Grady. We are in fact seeing----
    Mr. Miller. The productivity. I mean, you are able to 
deliver more for less?
    Dr. Grady. To some extent, yes. It is difficult to answer 
that with a straight yes or no because in some areas we are 
seeing major differences. In other areas where patients are 
very critically ill, even with the advent and the assistance of 
technology, those are still very labor intensive areas. So the 
answer is mostly yes, but it is somewhat situation and patient 
dependent.

                     NIH DEVELOPMENT OF TECHNOLOGY

    Mr. Miller. Does NIH do any of this technology--I mean, 
technology is everything in health care. Because it may not 
always be that basic. But I mean, it is kind of like I 
mentioned earlier I was visiting the Brain Institute at the 
University of Florida and as an institute it brings--the 
engineering school is there, and there is engineering 
professors involved in the meeting and things. So the 
opportunities become--you know, with the magnetic imaging 
capacities they were developing there was just so impressive.
    But one of the strengths is it is not strictly a medical 
school. It is an institute separate.

                            MEDICAL IMAGING

    Dr. Kirschstein. It has become a medical field, Mr. Miller. 
The NIH has for many years been involved in particular areas of 
technology development. A great deal of technology development 
is being performed in the National Heart, Lung, and Blood 
Institute such as activities related to pumping; all the 
technology that is involved in bypassing the heart during 
coronary bypass surgery, for example. And there is more and 
more of that.
    All the imaging technology that you have been seeing over 
the last few days has led to the fact that in fact we have 
begun to work very closely with engineers, physicists and 
mathematicians. We have had a committee, a coordinating 
committee among the institutes called BECON, Bioengineering 
Consortium, which will be and already is just about set to 
become an office of bioengineering and bio-imaging within the 
office of the director, to coordinate all these technologies. 
We have had two and will have a third this June, large symposia 
on the subject.
    The other thing about technology in hospitals, intensive 
care units, and particularly intensive care units for premature 
infants, are highly dependent on the most sophisticated 
technologies, most of which are handled by highly skilled, 
hardworking, on the job I do not know how many hours a day, 
nurses it is just a remarkable activity, which is all the more 
reason I believe that the nurses with the advanced degrees and 
bachelor's degrees are required, because the technology is 
very, very sensitive and one small error would really be 
catastrophic.
    Mr. Miller. Maybe I am wrong about this technology. Maybe I 
am thinking about the patient in the hospital that is still 
charting by hand a lot. I mean, in the specialized areas like 
in the intensive care--of course, most people it seemed like in 
a hospital are always intensive care anyway. I remember being 
told that back in the early 1980s, if you do not belong in 
intensive care, you do not belong in the hospital just about. 
And it has changed. I mean, our hospital in Bradenton was a 
500-bed hospital that I was involved in and you do not--well, 
you know the changes.
    Dr. Kirschstein. Yes, absolutely.
    Dr. Grady. Across the country.
    Mr. Miller. It is just a very different institution from 
what it was.
    I am glad to hear you are working on this end-of-life 
studies. Are you the only----

                          END-OF-LIFE RESEARCH

    Dr. Grady. No, actually this is trans-NIH. We are a lead 
institute for coordinating, but when we sent out the RFA last 
year, the request for applications, there were eight other 
institutes at NIH and the then-Agency for Healthcare Policy and 
Research that has been renamed Agency for Healthcare Research 
and Quality. So that we actually plan to move forward, it is 
one of our areas to emphasize in the coming year in 2001. There 
is a great deal we do not know, so we are collaborating with 
several others.
    Mr. Miller. I should not take so much time, but I do not--
--
    Dr. Grady. No, that is okay.
    Mr. Miller. If you do not mind. I hate to keep everybody 
here because we could just sit and talk----
    Dr. Grady. We can stay. My time is yours, sir.
    Mr. Miller. Well, I do not mean to--it is not fair to take 
advantage of the fact that I am sitting up here.
    Dr. Grady. We do not feel at all taken advantage of.

                  REGIONAL DIFFERENCES IN HEALTH CARE

    Mr. Miller. Okay. Now I forgot what I was going to ask. 
Regional differences. This is years ago, I remember in long 
term care is that in Florida, for example, the rate of 
institutionalization was significantly lower than the State of 
Minnesota. My impression was--correct me if I am wrong. This is 
30-year-old data.
    But in areas where we have these large retirement--we have 
mobile home parks that have thousands of people in one mobile 
home park. And they live right next--that is how my 
grandparents moved to my area of Florida. They were trailer 
parks back then, and they are actually called manufactured 
housing. But they are trailer parks. And they are very close 
together but they all take care of each other.
    I mean, to grow old in Florida is, I find, a lot easier 
than growing old--as my in-laws grew old in Baton Rouge, 
Louisiana. The doctors and nurses--I mean, if you not into 
geriatrics, you do not--you should not be practicing medicine 
in my area. So there is that regional difference.
    Dr. Grady. We would agree with you. When you look at the 
titles of the research that we fund, and when you look at the 
States that we fund it in, you can see a number of regional 
differences reflected in the types of research studies that we 
fund because of that.
    But we are, because of the growing age of the population, 
the mean age of the population, and consequently, the increase 
in chronic illness with that population, we are funding many 
more studies dealing with the elderly, and dealing with trying 
to help people with what we call symptom management. How do you 
carry on quality of life and how to you maintain your lifestyle 
despite these annoying chronic illnesses?

                   COMPETING AND NONCOMPETING GRANTS

    Mr. Miller. Let me do something, if I may. I want to kind 
of go through--I have been looking at these all day and I just 
want to ask a question. I am going to use as an illustration as 
I walk through what is on my page 14 or 15. I do not know who--
when we talk about the non-competing research--I mean, this is 
the same format for all the institutes so I am just, you know. 
How do you define non-competing? Because these are not the 
renewal. Or are these renewals?
    Dr. Grady. Actually they are in a sense, but when we make a 
grant, each year when we have an appropriation approximately 
three-quarters of that, up to 75 percent roughly--since the 
average length of grant is four years, we make a grant award to 
someone and it is for this year, but it is also for what we 
call outyears. So it would be for three more years. And those 
are the so-called non-competing renewals, because the idea is 
that the person, the trust is that they will do good work and 
they will report progress each year, so that there will be a 
continuation of their funding. But it is a non-competing 
continuation.
    Then at the end of that period of time, at a four-year 
renewal, the application will be renewed competitively. It 
comes in again with new goals and shows the progress that they 
have made over the total of the award. Then if it competes 
successfully it is called a competing renewal and an award is 
made to that individual for that year and X number of outyears.
    Mr. Miller. How often do you have to suspend or they do not 
complete their requirements? I would ask you that, and also for 
the other institutes too.
    Dr. Grady. That does vary across NIH and Dr. Kirschstein 
may want to comment. Our institute is a young institute, as you 
know, as we actually--we had a very large increase last year. 
It was our best year ever. So we had, prior to that, in 1999 we 
had funded about 14 percent of all the research that came in. 
We were able to fund 14 percent. So all the rest of 
appplications went back to be revised or whatever.
    Last year with this really very large budget we hope, we 
expect in the year 2000 to be able to fund up to 24 percent of 
all the studies that come to us. But those will be the 
competitive applications.
    Now because we are also new and young, we do not have as 
many of the competing applications where people write a grant, 
get a grant for four or five years, and then compete. Last year 
we funded four competing renewals. So we had four investigators 
who had completed the research, wrote a renewal, and came in 
and got more funding.
    Mr. Miller. How about not completing the four years because 
they are, you know----
    Dr. Grady. That is unusual in our institute. I believe it 
is unusual across the NIH, but I would defer to Dr. 
Kirschstein.
    Dr. Kirschstein. Mr. Miller, first of all when we make an 
award and it has been peer reviewed and the reviewers have said 
that the outline of the work that the individual proposes to do 
is very meritorious and needs four years to have real progress, 
we make the award for one year but we have a commitment to make 
continuing awards for the next three years. That is the non-
competing fraction of our budget: the commitment to those 
grants.
    Mr. Miller. Do those with individuals--it is a combination 
of individuals and institutions. When that individual, the lead 
researcher moves, which has to happen----
    Dr. Kirschstein. There are two possibilities. First of all, 
all awards are made to the institution in the name of the 
investigator who has described his or her work, and the 
institution has signed off that this investigator is on the 
faculty of that institution and will do the work. If an 
investigator moves, and will be active in research at another 
institution, there is basically a gentleman's agreement between 
the two institutions that the work will be transferred to the 
new institution.
    There are rare occasions where that is not true. For 
example, an investigator dies or an investigator leaves 
academia and goes to industry. That investigator often has left 
behind other individuals who are doing the work in the 
institution that he or she was in. And if the institution can 
justify to Dr. Grady's institute or one of the others that 
there is another investigator who is equally qualified to carry 
that work forward, then that can be left in that institute.

                         AVERAGE SIZE OF GRANTS

    Mr. Miller. What is the average size in your institute and 
overall for the entire NIH?
    Dr. Grady. The average size in our institute is 
approximately $265,000 for RPG, research project grant.
    Mr. Miller. Per year? Or per four years?
    Dr. Grady. Yes, per year.
    Dr. Kirschstein. That includes indirect costs.
    Dr. Grady. Includes indirect costs. That is total cost.

                        COMPETING RENEWAL GRANTS

    Dr. Kirschstein. At the end of the four-year period, as Dr. 
Grady described, the investigator has developed a certain body 
of knowledge so that he or she is in a position to now move 
this forward and to ask a whole new series of questions related 
to what was done originally, and puts in what we call a 
competing renewal. It goes through the review process again. 
Now having proved himself or herself the first time, you would 
anticipate that they would be even more successful than the 
first time an investigator comes in.
    Indeed, when we talk about success rates and we say that 
the overall success rate will be 26 percent for all of NIH 
which is what we are projecting in fiscal year 2001, it is 
about twice as high for competing renewals than it is for new 
applications. The new would be, in this projection, 21 percent; 
competing renewals, 45 percent, for an averaging out, because 
there is a difference in numbers, of about 26 percent.
    Now that does not mean that the person who is coming in for 
a competing renewal gets a free ride. If, for one reason or 
another, the review group feels that either the promise of what 
he or she did during the first four years was not sufficient, 
or he or she has proposed something that really is not 
meritorious, they can be told they cannot have a competing 
renewal.
    So it is a process that has some self-renewal in it, but we 
are also very, very cognizant of the need to bring newly minted 
investigators into the field. And we work very hard and we made 
a promise, as you all were very generous with our budgets, that 
we would support year by year the same number or even more 
newly minted investigators because the lifeblood of our 
research is the new idea.
    Mr. Miller. What is the average size overall for NIH, 
about?
    Dr. Kirschstein. It is a little larger than what Dr. Grady 
funds in NINR--it is about $320,000 to $330,000. So it is a 
little larger. This is a small institute and the nursing grants 
do come in somewhat smaller than the average.

                       ADMINISTRATIVE SUPPLEMENTS

    Mr. Miller. What is administrative supplements?
    Dr. Grady. Administrative supplement is--there are two 
kinds. But the most common one that we use is when someone 
applies for a grant and they have this award, as Dr. 
Kirschstein said, it usually is about four years. During that 
time they may find a very interesting finding that would be 
small and they would like to have additional funds for. So they 
write a smaller grant and ask to compete for more funding, and 
that is added onto their award.
    Dr. Kirschstein. There is another type of administrative 
supplement as well. As we have been talking about this week, 
the pipeline for minority investigators, new young graduate 
students, new high school students who we want to inspire to do 
research is woefully small. We do provide what we call 
administrative supplements so that a professor can train some 
of these people. We provide money for that training as an 
administrative supplement.

                            RESEARCH CENTERS

    Mr. Miller. What are research centers?
    Dr. Grady. Research centers are typically aggregates of 
investigators who are gathered around a central theme. Now 
there are several types of centers. But typically they are the 
large centers where you have larger projects around a theme 
such as studying various aspects of stroke for a stroke center, 
or diabetes for a diabetes center, et cetera. That is a fairly 
large center typically. It is called a P-50 on your chart.
    Other centers that are smaller are the kinds of centers 
that we particularly use in our institute. One of these is what 
is called a P-30 on your chart. What that is, it is a core 
center, and it is intended to bring investigators together to--
--
    Mr. Miller. Specifically for nursing or is it----
    Dr. Grady. In our institute it is specifically for nursing. 
But ours are multidisciplinary. So we encourage nurses and 
others to work together in a multidisciplinary way and to 
provide, to share resources so that they can attract other 
investigators and get R01 funding. So it really is to form the 
infrastructure.
    There is yet another kind that we have used that our 
council has been discussing; that is what is called a 
developmental center. It is an even smaller amount of money for 
about three years and it is to get groups that are close to 
being competitive, to try to help them to be more competitive. 
And to do preliminary studies to show that they have a 
hypothesis that looks like it is worth testing, and to come in 
for a larger amount of funding.
    Mr. Miller. You have 10 research centers?
    Dr. Grady. Yes, we have 10, and those are the core centers. 
Those are all, they are basically about $300,000 apiece, and 
they are--actually one of these is in conjunction with the 
Aging Institute network of centers, research centers for aging 
minority individuals. So we are funding one of those. We also 
participate in the study of women across the Nation, which is 
with the Office of Women's Health and other institutes.
    Then the remaining ones are the core centers which are 
newly let out last year and seven of those have specific 
emphasis on health disparities. So that we are trying to build 
up the research in that area.

                   GEOGRAPHIC DISTRIBUTION OF GRANTS

    Mr. Miller. At the hearing that I had to leave the first 
day and Mr. Wicker was bringing up the situation and you 
discussed the geographic issue. I was a little surprised almost 
by it in a way, and how Mississippi--you know, his home State 
does not really get very much through NIH. I do not think you 
should target necessarily just for geography. That is not the 
way we want this to be done. But you also have a reason not to 
let it all concentrate in Boston, and Chicago, Los Angeles. How 
does that play into overall----
    Dr. Kirschstein. As Dr. Grady was answering your question 
about developmental centers I was thinking about that. Actually 
when I realized that the State of Mississippi was not receiving 
very much in the way of research grants I was surprised. You 
are from Baton Rouge, Louisiana. I went to Tulane Medical 
School in the late 1940s and early 1950s, before the University 
of Mississippi had a medical school. When they founded the 
medical school, which was about 1953, 1954, they took some of 
the very best faculty, many of whom I knew, from Tulane and 
they all went up to Mississippi. And by the time I went back 
there to visit this year or in the fall, many of them were no 
longer in practice.
    It was a very active medical school. I am not sure what 
happened in that period of time, but we are working actively 
with them again to try to develop research, and these 
developmental centers might be a way to do it.
    What was interesting to me was that the pharmacy school, 
which is on the main campus at Oxford, had a much more active 
research program than did the medical school. Now whether or 
not this was because Mississippi needed to do something about 
its health care system--in fact the medical students at Tulane 
who were from Mississippi when I went to medical school, were 
having their tuition and living costs paid by the State of 
Mississippi. And the State of Florida did the same thing at the 
time before the University of Miami and the University of 
Florida had medical schools.
    Mr. Miller. Yes, Florida just got a medical school at the 
University of Florida in 1958 or 1956.
    Dr. Kirschstein. Yes, and Miami was just a little bit 
before as I recall. So it may----
    Mr. Miller. This is not just Mississippi. I assume there 
are other States that have the same concern.
    Dr. Kirschstein. Yes, but we visited Mississippi. We have 
been working with them. We are planning to do the same thing in 
Oklahoma. We told Mr. Istook we would go to Oklahoma in the 
spring and we expect to be able to help these schools and these 
States to develop programs.
    Mr. Miller. Does that come into consideration in anything 
you are doing? I am not here to advocate for Mississippi. I 
mean, I want to take care of Florida. But I----

                              AREA PROGRAM

    Dr. Grady. Actually it is very interesting. We have a 
somewhat different situation in the schools of nursing--there 
is a very wonderful program at NIH that is the AREA program, 
Academic Research Enhancement Award. That is given to schools 
who receive limited NIH funding. And as it turns out, with 
schools of nursing across the country, there are only five 
schools that are ineligible for this program. So most of our 
schools across the country are eligible for these small funds. 
They are roughly $50,000 a year for two years. They are 
renewable.
    So we do fund in a number of States where there are very 
good schools of nursing and they are just beginning to be more 
research intensive.
    We are actually working with Mississippi because the 
Jackson heart study has started there. The school of nursing 
there is very active and very research oriented. They are 
actually coming up next month. We have met with them before, 
but we had an RFA that we let out, just in January actually, 
for attaching to clinical trials small supplements. We would 
give supplements to nurse researchers to be able to work with 
ongoing clinical trials, to ask specific questions related to 
symptom management or other issues that would complement the 
trial but might not be the central focus.
    The Jackson heart study group is very interested in it and 
we have been working with the Heart Institute and the group 
from Mississippi and hope that--they tell us that they will be 
responsive to that. We think it would be a good opportunity.
    We even have funded studies in Oklahoma.
    Mr. Miller. I have taken a lot more time than--so I really 
appreciate the opportunity to ask some clarifying questions.
    Dr. Kirschstein. We enjoyed it.
    Mr. Miller. Thank you very much. And thank you for being 
here.
    Dr. Grady. Thank you, Mr. Chairman.
    Mr. Miller. The meeting is adjourned.
    [The following questions were submitted to be answered for 
the record:]



                                       Thursday, February 17, 2000.

               NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

                               WITNESSES

DR. CLAUDE LENFANT, M.D., DIRECTOR
DR. CARL ROTH, PH.D., ASSOCIATE DIRECTOR FOR SCIENTIFIC PROGRAM 
    OPERATION
DONALD P. CHRISTOFERSON, ASSOCIATE DIRECTOR FOR ADMINISTRATIVE 
    MANAGEMENT
JOHN TIBBS, FINANCIAL MANAGEMENT OFFICER
DR. RUTH L. KIRSCHSTEIN, ACTING DIRECTOR, NATIONAL INSTITUTES OF HEALTH
DENNIS P. WILLIAMS, DEPUTY ASSISTANT SECRETARY, BUDGET, DEPARTMENT OF 
    HEALTH AND HUMAN SERVICES

                            Opening Remarks

    Mr. Porter. The subcommittee will come to order. We 
continue our hearings on the appropriations for NIH with the 
National Heart, Lung, and Blood Institute. We are very pleased 
to welcome once again one of our favorite Directors, Dr. Claude 
Lenfant.
    If you will introduce the people with you, and then proceed 
with your statement, Dr. Lenfant, we will then go to questions.
    Dr. Lenfant. Thank you, Mr. Chairman.
    On my far left is Mr. Don Christoferson, the Associate 
Director for Administrative Management. Next to him is John 
Tibbs, who is the Budget Officer; and Dr. Carl Roth, who is the 
Associate Director for Scientific Program. And, of course, you 
have met Dr. Kirschstein and Mr. Williams.
    Let me begin my remarks, Mr. Chairman, by saying that we 
are having a wonderful year, which gave us the opportunity to 
do much for the scientists that we serve and, most importantly, 
for the patients who, in turn, are served by the outcome of the 
science we support.
    In the next few moments, I would like to highlight some of 
the investments that we are making at the present time.
    [The information follows:]



    Dr. Lenfant. As you can see on this first chart, for the 
sake of simplicity I have grouped our investments into four 
categories, but I should tell you that each that you see here--
genomic/genetic medicine, clinical research, bioengineering, 
and other--each of them comprises a number of initiatives which 
I could describe if needed.
    The thing that I would like to underscore is that each 
initiative that we have is directed toward at least one goal of 
our programs; the first goal is to make maximum use of all the 
research opportunities and new technologies that are available 
today; and the second goal is to to ensure that the health 
practices reflect the best knowledge that we have today.
    Meanwhile, I would like to show you some specific examples 
of how research that began at the very basic levels contributes 
to better care of the patients.
    [The information follows:]



                        CONGESTIVE HEART FAILURE

    Dr. Lenfant. On the next chart you can see some data 
concerning congestive heart failure.
    As I trust you remember, Mr. Chairman, of all the areas I 
have discussed with this committee, the importance of heart 
failure, the prevalence of which today is increasing in 
epidemic proportions, is a condition which is very difficult to 
treat because of the unpredictability of its course. However, 
things are changing.
    What you can see here on this chart are two curves which 
show the course of congestive heart failure in two patients who 
initially had the same symptoms, the same characteristics, but 
what distinguished them is a different genotype, which is 
indicated here as ``variant A'' or ``variant B.'' These are two 
different mutations of the same gene that these patients have.
    The important thing is that, as you can see, the patient 
with variant B has a course and an evolution of his disease 
which is much faster than that of Patient A. And the value of 
that knowledge is that it gives us the opportunity to predict 
the course of the disease by knowing the genotype of these 
patients, and therefore it helps us to develop the appropriate 
strategies, which are very important for these patients.
    For example, in the case of Patient B, Variant B, you could 
predict that this patient would be in need of a heart 
transplantation much sooner than a patient with variant A, and, 
therefore, you could prepare for that and the therapeutic 
strategies.
    [The information follows:]



                                 ASTHMA

    Dr. Lenfant. The next case that I want to show you has to 
do with asthma. Asthma, as you know, is a very prevalent 
disease which affects lots of people in this country, 
especially youngsters, and most of them are treated with 
bronchodilator therapy. The problem is that a great number of 
patients do not respond well to this therapy.
    Here, again, what genetics teaches us is that we can 
predict--as you can see here by looking at different variants 
again of the same gene in these patients--who is going to 
respond to the therapy.
    Of course, the value of that is very important, because you 
can therefore select the therapy which you know is going to 
work, rather than spending lots of time and sometimes money 
administering to these patients therapies which eventually may 
not work.
    [The information follows:]



                       MAGNETIC RESONANCE IMAGING

    Dr. Lenfant. The third example that I want to show you is 
the application of engineering imaging in clinical medicine. I 
am referring to magnetic resonance imaging.
    What you can see on this chart here is the evolution of 
this technology during the last ten years.
    In 1990, it would take five minutes to get the picture that 
you see here. In 1995, we were able to reduce the time to 20 
seconds to get that picture. This year, we can do it in real 
time. What we can do with that, I am going to show you on the 
wall here with a video.
    Here is what you see, putting a patient in an MRI. In real 
time, the heart of this patient, you can see the contractions, 
the ejection of the blood into the aorta that you see here.
    Now, what you can do is take a cross section in this 
direction or that direction, whichever direction you want, and 
that would allow you to detect immediately any lesion in the 
heart of this person.
    Now, that is a normal heart. It could be yours, mine, one 
of any person in this room, I hope.
    [The information follows:]



    Dr. Lenfant. Now, I am going to show you, in the last chart 
that you see here, the importance of that.
    In this country, each year there are millions of patients 
who enter an emergency room with chest pain, and the question 
is: do they have heart attack or not? And if they have it, it 
has to be treated very quickly.
    The first thing that is being done when these patients 
enter the emergency room is to give them an EKG. Unfortunately, 
the electrocardiogram is going to give you definitive answer in 
only approximately 20 percent of the cases.
    Now, for these cases it is very good. You can treat them 
immediately, and within 15 minutes they would have their 
therapy, which is a life-saving therapy.
    Unfortunately, for 80 percent of them, the EKG is 
indeterminate. So in the past, the option that we had was to do 
some enzyme measurements, and these enzyme measurements may 
take from one to nine hours, during which time the damage to 
the heart may increase and basically leap to a much more 
serious heart attack or complication than would be otherwise.
    With the MRI, the magnetic resonance imaging that I showed 
you on the wall, within 35 minutes you can have a precise 
diagnosis and say yes, this patient is in the process of having 
a heart attack, or not.
    The advantage of that is very clear--better result for the 
patient, less expensive. If the patient does not have a heart 
attack, you do not need to keep the patient in the hospital. If 
the patient has a heart attack and it has been diagnosed 
quickly, therefore treated quickly, the patient will stay less 
time in the hospital.
    Finally, because the treatment has been given very early, 
the risk of this patient eventually evolving toward heart 
failure is much less than it would be otherwise.
    It is a considerable saving of time and money for the 
patient and for the society, as well.
    So these, Mr. Chairman, are a few examples that I wanted to 
show you of what we are doing today, and I will be pleased to 
answer any questions that you may have.
    Mr. Porter. Thank you, Dr. Lenfant.
    [The written statement of Dr. Lenfant follows:]



                             HEART FAILURE

    Mr. Porter. I have a question about what you just said.
    If you go into the hospital with chest pains and perhaps 
other symptoms of a heart attack, don't they treat you as if 
you are having a heart attack in any case, even before 
diagnosis, just as a precaution?
    Dr. Lenfant. No, you would not do that because this 
treatment, which is basically, by and large, blood clot 
dissolving therapies--most of these heart attacks are due to a 
blood clot--there may be some side effects and complications to 
which you would not want to expose a patient unless it is 
necessary. You need to have a definitive diagnosis before you 
do that.
    Mr. Porter. You would not even provide, say, aspirin or 
nitroglycerin or anything until you have done one of these 
procedures?
    Dr. Lenfant. Well, that may be done, but nitroglycerin is 
also a medication which is not free of side effects, and 
aspirin, it would take some time for it to get to do what it is 
supposed to do.
    Basically, any patient will not go into intensive treatment 
unless there is a firm diagnosis of the condition, and that is 
why, in most instances, the physicians in charge will want to 
have the results of an enzyme test, and that, depending on the 
magnitude of the damage to the heart, if there is lots of 
damage, the result of the enzyme measurement may be very quick, 
but if it is moderate damage it may take a long time. Of 
course, during that period of time the damage is increasing.
    So the prospect of the MRI diagnosis is a tremendous step 
forward in the practice of this emergency medicine.
    Mr. Porter. If you can do the MRI in real time, as you 
showed us, why does it take 35 minutes to get a diagnosis?
    Dr. Lenfant. Because you have to make some slices of the--
what I showed you is the view, if you want, but you have to do 
some slices and basically cut the heart, if you want, with the 
computer, in a number of slices so that you can determine, 
number one, where the lesion is and, number two, the magnitude, 
the importance of the lesion.
    Now, the reason you want to know where the lesion is, 
because you want to know which artery is obstructed so that you 
can go and open it up, if necessary, with angioplasty.
    Mr. Porter. Is there potential that these slices in the 
future, as technology evolves, can be made much more quickly so 
that you are not having to wait, because you have obviously had 
a great progression from 1990 to the present.
    Dr. Lenfant. We are confident that, indeed, this time will 
be reduced in time.
    The progression of that, as you can see, has been quite 
logarithmic. Ten years ago it was five minutes, five years ago 
it was 20 seconds, now it is real time.
    What we need to do now is to be sure that the computers and 
the orientation of the slices that you want to get from the 
heart can be done much faster.
    That is what we are doing. It is part of our program 
research, and it is done in the hospital across the street from 
the NIH at the Suburban Hospital.
    Mr. Porter. The last time I asked this question it was 
unclear what the answer was, but do we know if there are any 
side effects from MRI?
    Dr. Lenfant. No.
    Mr. Porter. Is there any test to----
    Dr. Lenfant. I am not aware of any. I am not aware of any 
side effects.
    Mr. Porter. Are there any studies that have been done to 
determine that?
    Dr. Lenfant. I am sure it has been done, but I must admit 
it is not my field so I do not know. All I know is that there 
is an effect on your watch and your credit cards if you were to 
go through with them.

                         RESEARCH OPPORTUNITIES

    Mr. Porter. You may have already answered this in an 
anecdotal way, but what research opportunities have you been 
able to pursue with the increases that NHLBI has had in the 
last two years that you would not have been able to pursue if 
the increases had not been there?
    Dr. Lenfant. That is certainly one.
    Mr. Porter. That is what I assumed.
    Dr. Lenfant. Another one is the application of the genomic 
research that has been supported by our colleagues in the 
Genome Research Institute.
    We also have initiated a number of clinical trials, 
developing actually a new approach to clinical trials which 
brings out results much more quickly, and the institute has 
multiplied the number of clinical trials, and more are in the 
process of being developed.
    So I think what has been happening--and I have a list of 
specific initiatives that have been started during that period 
of time. What we have done is to take full advantage of all the 
new technologies and new approaches which have been developed 
in other fields--in molecular genetics, in cancer research--and 
we have imported that into cardiology and pulmonary medicine 
and hematology when needs be, and we are really increasing the 
process of translating all that into clinical applications.
    One thing, Mr. Chairman, that I would like to comment upon 
is that in some fields we know a lot, but I have to say that 
the gap between what we know and what is being applied is 
widening, and we are aware of that and using all kinds of 
approaches--demonstration studies by way of clinical trials, 
demonstration studies at the community levels, and public as 
well as professional education. We are trying to compensate for 
that and to basically speed up the application of what we know.
    Mr. Porter. Thank you, Dr. Lenfant.
    Mr. Hoyer?
    Mr. Hoyer. Doctor, if I understand that answer, we have 
greater knowledge today, and the gap between that knowledge and 
the application of that knowledge to patients is greater today 
than it was ten years ago?
    Dr. Lenfant. That is correct. Yes.
    Mr. Hoyer. Presumably, that is because we have so much more 
knowledge today----
    Dr. Lenfant. Yes.

                       PATIENT INFORMATION ACCESS

    Mr. Hoyer [continuing]. But the practitioners are having 
difficulty keeping up with that knowledge and applying it.
    When I first went on this committee in 1983, I discussed 
with the National Library of Medicine--I do not know that I was 
certainly one of the first to discuss it, but it was of 
interest to me--about having computer access--which now, of 
course, is the Internet--computer access to information at the 
National Library of Medicine so that the most rural doctor 
would have on his or her desk the ability to access the 
information to which you now refer.
    It seems to me that we are spending a lot of money, 
properly so, coming up with, obviously, both diagnostic and 
treatment modalities that are far superior to what we had ten 
years ago and five years ago, apparently, and I am sure of real 
concern to those who are going to get sick, that they do not 
have all the information available in their practitioner's 
office or the hospital to treat them.
    How big a problem do you think this is?
    Dr. Lenfant. Well, first of all, I should tell you that 
there are many physicians today who have computer facilities on 
their desk or in the back room where they can go and get the 
information as needed.
    I think you have put your finger on what I consider to be 
the real issue, which is that research has been extraordinarily 
successful. We learn a lot and we learn fast what could be 
applied. And it is very difficult, and that requires some work 
and new approaches on our part, I think, to speed up the flow 
of that information from the physician to the parties.
    At the same time, we have to recognize information 
overload. In addition, the practice of medicine, for a variety 
of reasons which really I cannot comment upon, has become much 
more complex in terms of insurance coverage and this thing and 
that thing and all kinds of conditions which have made the 
practice of medicine a little bit more complicated.
    Mr. Hoyer. Doctor, obviously I have some questions that 
relate directly to your institute, but I am interested in this.
    Let us say I am a doctor practicing in a relatively rural 
area and do not have a lot of colleagues with whom to interface 
on a particular set of symptoms that confront me. Do I have the 
capability of, in effect, logging them in to my computer, or e-
mailing to a central site, either at NIH or some place else, or 
maybe even in my State society, and, in effect, getting help 
with that diagnosis, based upon these symptoms?
    Dr. Lenfant. Yes.
    Mr. Hoyer. Do I have that?
    Dr. Lenfant. Yes. NIH has the--Dr. Kirschstein can probably 
explain that much better than I, because it is a centralized 
function at NIH at the Library of Medicine.
    Mr. Hoyer. It seems to me, quite obviously, in terms of all 
this money we spend, ultimately it is an individual patient and 
their treating physician or physicians that we want to make 
sure have all that information to treat them with the best 
information possible.
    Dr. Kirschstein. Mr. Hoyer, the National Library of 
Medicine--and when Dr. Lindberg is here you can get more 
details from him--has a very wide set of abilities to provide 
information to physicians very quickly through PubMed Central, 
through MedLine and so forth. What it does is allow people to 
put in symptoms or drug names or something of the sort and then 
get the literature and search through the abstracts of the 
literature.
    This will be increased soon something that I described on 
Tuesday, which is going to be the clinical trials database, 
which was legislated through the FDA Modernization Act, and 
that has just been set up. It is about to be launched, and all 
clinical trials for various diseases, whether they be Federally 
sponsored or privately sponsored, will be eventually entered 
into that database for physicians to access.
    Mr. Hoyer. Thank you. I will pursue that further with Dr. 
Lindberg.
    Dr. Lenfant. May I add that I am sure each institute does 
its own page now. We have a great number of clinical trials 
which were supported. Each time the outcomes of these clinical 
studies are known, we put them on our home page, which is very 
well known and recognized in the country. I think we get 
thousands, tens of thousands of hits each month, so people see 
these things.

                                 ASTHMA

    Mr. Hoyer. Thank you.
    Let me pursue a little bit of your particular institute's 
focus.
    Asthma--I am somewhat perplexed by--somebody has come into 
our office to ask questions about this, and the background is 
this: according to the information I have, the recent 
situations on the prevalence of asthma reveal that 11,100,000 
people in the United States reported having asthma, which is 
then said to be a 25 percent reduction from a percentage of 
14,900,000 reported in 1995.
    Now, that was contrary to the information that I had, where 
I thought the incidence of asthma was increasing. Now, maybe it 
is increasing among a particular cohort, but in a more broadly-
based, where children are experiencing more asthma but adults 
are not.
    In any event, can you explain this reduction?
    Dr. Lenfant. Yes. What you are referring to is an 
unfortunate artifact, I would say, which results from the way 
the National Center for Health Statistics has changed the 
question in the first survey relative to the second survey.
    The second survey was somewhat more restrictive in the kind 
of answer that people could give, and that is what has led to 
the reduction that you just mentioned.
    The fact is that, irrespective of all that, we do know 
that, indeed, in this country and in other countries, mostly 
western countries, the prevalence of asthma is increasing.
    We do know it from other studies and surveys which have 
been done by other organizations or agencies.
    But what you are mentioning here is a very interesting 
phenomenon, which is a change in the definition of the 
question, and that, of course, always causes a problem when you 
look at trends.
    The World Health Organization, for example, each three or 
four years has a different classification of disease, and then 
you see the number go up and down for that reason.
    Mr. Hoyer. Thank you, Doctor. I have other questions, but I 
will wait for the second round.
    Mr. Porter. We will have a second round.
    Thank you, Mr. Hoyer.
    Mr. Jackson?

                        MINORITY DATA COLLECTION

    Mr. Jackson. Let me begin by thanking Dr. Lenfant for your 
presentation today before our subcommittee.
    The President's fiscal year 2001 budget for NHLBI is a 
little over 2,000,000,000, an increase of about 108,000,000, 
and 5.5 percent above the fiscal year 2000 level.
    Included in this total is 40,000,000 for the following NIH 
areas of special interest--I want to say NIH areas of priority, 
as opposed to special interest. Whenever I hear that word, I 
feel like it is a program that is about to get cut.
    Health disparities, $6,000,000; new avenues for the 
development of therapeutic, 16,000,000; new approaches to 
pathogenesis, 7,000,000; new prevention strategies against 
disease, 7,000,000; computers and advanced instrumentation, 
4,000,000.
    Before I ask my question, I want to first acknowledge that 
Dr. Lenfant has been quite a champion for addressing some of 
the central inquiries that I have raised thus far, Mr. 
Chairman, on the issue of disparities in his area of expertise, 
and I want to begin by congratulating you for the efforts that 
you have made and again to thank the acting director of NIH, 
Dr. Kirschstein, for her stick-to-it-ness and commitment in 
this area.
    My question, Dr. Lenfant, is a question about data 
collection. Obviously, your department, based upon its budget, 
has a commitment in this area. I am wondering, has your office 
collected any data on the prevalence of heart, lung, or blood 
diseases amongst Native Americans, Latino Americans, or 
geographical data on the prevalence of these diseases, let us 
say in Appalachia or in the south by region, or in, for 
example, the former rust belt of the Nation.
    Dr. Lenfant. Yes. We have several programs for data 
collection, and we have this information. I could provide it, 
if you wish, for the record. But we know pretty well where the 
highest prevalence and incidence of cardiovascular or pulmonary 
or blood diseases, as the case may be, are in the country, and 
we know also pretty well what the reasons for these variations 
between States, for example, might be.
    It is interesting, Mr. Jackson, that you asked this 
question. Just yesterday, I believe, there was a report that 
was published by the CDC and the University of West Virginia 
which addresses that very issue, which is the variation of the 
differences in prevalence of heart disease in women, especially 
African American women in various parts of the country.
    But the short answer to your question, yes, we do know this 
data and we use them for many of our programs.
    Mr. Jackson. Thank you, Dr. Lenfant.
    I am wondering, does your institute collect economic data 
on the prevalence of these type of illnesses amongst, for 
example, the less affluent in our society who might find 
themselves working in Appalachia in a coal mine or in southern 
Illinois in a coal mine, but, compared to, let us say, someone 
in Silicon Valley who might be into computer programming and 
therefore never come into contact with an environment that 
might create heart, lung, or blood type illnesses?
    Dr. Lenfant. No. We do not collect these data because, by 
and large, I would say they are well recognized and we know 
about these data.
    Our way to addressing that is somewhat indirect. For 
example, if we think that we need to have a demonstration 
project or an educational program, a special action, that is 
often where we target it, in these areas of low socioeconomic 
status.
    For example, just a few days ago we made the awards for a 
program on the control of asthma in communities. We made seven 
awards, and all seven awards are in low economic status areas 
in the country.

                          JACKSON HEART STUDY

    Mr. Jackson. I guess that leads very gracefully into my 
next question.
    I am wondering, in light of your own testimony today that 
there is an increasing prevalence of heart, lung, and blood 
type diseases amongst African American women, and that, based 
upon certain economic data where someone might find themselves 
economically situated in the society based upon their 
education, based upon what is available to them in terms of 
employment, I am wondering, in light of that information, does 
your institute then specifically look for research proposals 
that will study even further the prevalence, let us say, 
amongst that new data in those particular categories?
    Dr. Lenfant. We do that. An example that I mentioned is a 
study that we have initiated in Jackson, Mississippi, which is, 
I believe, a unique study where--you may have heard about 
Framingham, which is a national treasure--that is the way we 
like to look at it--because of all the information that has 
come from that study.
    Basically, Jackson, if you want, is a Framingham South, 
where the entire cohort is African American. We have a cohort 
of 6,000 men and women who are going to be followed for a long 
period of time. Our initial award is for seven years. I am sure 
that will be continued after.
    Basically, at the end of all that we will know a great deal 
about not only the status as it is at the end of the seven 
years, but also it will give us a tool to do something about 
it.

                MINORITY MEDICAL SCHOOL RESEARCH PROGRAM

    Mr. Jackson. I also understand, Dr. Lenfant, that there is 
some discussion at NHLBI about a minority medical school 
research program. I am wondering what the scope of the concept 
is and how will it work.
    That is my final question.
    Dr. Lenfant. That is correct. It is something that we 
intend to initiate in the year 2001. The issue, Mr. Jackson, is 
really two-fold. First of all, there is plenty of evidence in 
all areas that if you want to address a health issue which is 
specific to a group, it is better to have physicians and 
researchers which are part of that community to work on it.
    Therefore, one of our goals is to be sure that there is a 
program for all the same minority schools and universities of 
individuals who will become interested in biomedical research.
    The second thing is that we talk here about clinical trials 
and clinical studies. One of the great difficulties that we 
have at our institute--and I am sure it is shared by other 
institutes--is to recruit a number of participants from all the 
groups for which you want to get an answer, the different 
ethnic groups. That also requires the participation of 
physicians and researchers which are from the same community. 
So that is the second goal.
    And so the overall goal of this program is to develop a 
research interest, but also interest in this community and 
actually in these institutions and medical schools, and that 
actually is the second phase of a program that we started three 
or four years ago but which is reaching full maturity this 
year, and that is to establish a research base by providing 
resources to recruit very distinguished scientists into these 
institutions.
    We have six or seven institutions, historically black 
colleges and universities, which have been the recipients of 
this program.
    Mr. Jackson. Let me thank you, Dr. Lenfant, and also 
congratulate you once again for your very thoughtful approach 
to these issues and this area.
    Thank you, Mr. Chairman.
    Mr. Porter. Thank you, Mr. Jackson.
    Mrs. Northup?

                              GENE THERAPY

    Mrs. Northup. Yes. Thank you, Doctor.
    Doctor, I would like to talk to you specifically about the 
gene therapy approach that you talked about here, and also some 
other approaches to some of these problems.
    I am not objecting to the gene therapy. I just, in 
particular, have become increasingly aware that there are new 
approaches, for example, to sickle cell anemia, actual cures 
possible that are related to bone marrow transplants, reducing 
the mortality from those by not having 100 percent, not killing 
the patient's bone marrow 100 percent so that they are less at 
risk, and by, at the same time, using the donor's bone marrow 
that may not be perfectly matched, because there are ways that 
maybe, instead of six exact matches, you can have four exact 
matches.
    This has shown to be so successful in the early trials that 
I am concerned about two things: one of them, continuing to 
pursue mostly just a gene therapy approach to it instead of the 
bone marrow transplants; and, number two, whether we are 
funding the clinical trials necessary so that we can, as 
aggressively as possible, make this treatment widely available 
if it proves to be as successful as the initial approaches to 
it.
    Dr. Lenfant. Yes. Well, your question is absolutely 
fascinating and very important to us because these are 
activities in which we are very deeply involved.
    It is true, indeed, and I can confirm that the reports of 
partial ablation of the bone marrow works very well and has 
worked very successfully. In fact, in our internal programs we 
are pursuing that approach in a number of cases.
    The issue of bone marrow transplantation either with 
``mature cell'' or stem cell is also an approach and a 
technology which is really blossoming at this time.
    We do have clinical trials, but these are partial, small 
clinical trials, and we do recognize very well with, in fact, 
the Cancer Institute, that what is being done is not up to 
meeting the needs as we see them.
    Mrs. Northup. I think what my question is, though, is that 
gene therapy may, in the end, provide answers to things such as 
sickle cell, and I am glad we pursue that. But right now in 
front of us seems to be--I mean, as I understand the partial 
ablation, one of the reasons we did not use bone marrow before 
is because with full ablation the death rate was so high that 
children had to get so serious that we would take a chance, and 
then sometimes you could not reverse the damage the disease had 
done all along the way.
    But now, with partial ablation and the safety that that 
brings, there is a chance that right in front of us in the near 
term we could provide an alternative that would avert the 
strokes and the other damage to this population.
    And your very term, ``we have a few small clinical 
trials,'' I think is what worries me. My understanding is that 
they are under-funded, they are not at the level that pays for 
the cost of treating the patients that are actually in the 
trials.
    While we invest in long-term, fabulous biomedical research 
that will solve this, should we not, in the meantime, invest 
moving this apparent solution or possible solution ahead?
    Dr. Lenfant. Let me first reassure you by saying that I am 
not aware of any attempt to use gene therapy in sickle cell 
disease in this country or anywhere in the world.
    Mrs. Northup. Well, I thought it said in your 
presentation--when it talked about programs, excellence in gene 
therapy, I thought it said for cases such as sickle cell.
    Dr. Lenfant. To explore the avenue to eventually do it, but 
that is not being done. And I can also tell you that our 
commitment and investment in bone marrow transplantation is 
very large.
    I was about to tell you that, jointly with the Cancer 
Institute, we are, at present, exploring or pretty much 
deciding how to conduct and develop a network for bone marrow 
transplantation in this country. We do it with cancer because 
clearly malignant blood diseases are the prime target for this 
therapy, but there are also a number of non-malignant diseases 
which would benefit, one of them being sickle cell.
    I would like to say, though, if I may, that the major 
answer, sometimes reports on bone marrow transplantation here, 
another there, on sickle cell patient with great fanfare. What 
needs to be known is that it is still a very dangerous therapy, 
even with the caveat that you have mentioned, partial ablation 
and the ability to have a match for four or five antigens 
instead of the six.
    Mrs. Northup. Well, of course, just the fact you have 
sickle cell is very dangerous----
    Dr. Lenfant. Yes.
    Mrs. Northup [continuing]. Because it results in death.
    I point out to my colleagues, it is 100 percent African 
American.
    Dr. Lenfant. Yes.
    Mrs. Northup. And the occurrence of the other diseases that 
are similar that could benefit from this include--well, I am 
drawing a blank, but there are a number of other ones.
    Dr. Lenfant. Cooley's anemia, for example, or Fanconi 
anemia.
    Mrs. Northup. Lupus? Would lupus be an example, or would 
that be too removed?
    Dr. Lenfant. No.
    Mrs. Northup. Well, there are a number of other diseases. 
The incidence, I believe, in African Americans is much higher 
in these areas, and the fact that there is a possibility of a 
breakthrough that even healthy children with sickle cell would 
maybe begin to opt for it--as I understand, they actually have, 
in certain cases, in certain families, or asked for it--seems 
to me that, rather than look way down the line at gene therapy, 
we should move these studies ahead, so that if they have the 
benefits that they seem like they might have, they are within 
reach.
    Dr. Lenfant. I really wholly agree with you. I can only try 
to reassure you by saying that that is what we are doing.
    Mrs. Northup. Okay.
    Dr. Lenfant. We are working very hard to bring bone marrow 
transplantation and stem cell transplantation to where it is 
needed. But at the same time, I want to underscore that it is 
not an approach which is free of very, very serious 
complications.
    Mrs. Northup. Well, I look forward to seeing the review of 
the statistics that show what the success and failure rate is, 
what the level of danger is, especially as we begin to reduce 
the percentage of ablation that--you know, whether it is 90 
percent or 60 percent also might be the difference between the 
patients making it through. But my understanding is we have 
gotten it low enough with good results that it is possible that 
it will be a safe procedure.
    Mr. Porter. Thank you, Mrs. Northup.
    Ms. Pelosi?

                    PUBLIC ACCESS TO DEFIBRILLATORS

    Ms. Pelosi. Thank you very much, Mr. Chairman.
    Doctor, welcome. Thank you for your good work and for your 
testimony today, to all of you.
    Dr. Lenfant, clearly large Federal investments in health 
care research and prevention can improve health. We all 
stipulate to that. In your testimony, you discuss the 
effectiveness of installing automatic defibrillators in public 
places to rescue victims who need the assistance. Could you say 
a little more about the cost and the benefits of this approach, 
including the financial investment that would be required? And 
if we were to identify fatal arrhythmias through T-wave 
alternans and young athlete screening, what would be the cost 
and the benefits if we targeted that way?
    Dr. Lenfant. Let me first speak about the defibrillators 
and public access to defibrillators.
    There is, indeed, a program which is being set up and some 
research, as you put it, to establish the efficacy or lack of 
efficacy, whichever it is going to be, from this approach, 
which basically is to put defibrillators in public places. Our 
study is focusing on retirement homes and assisted living 
facilities because that is where you have the largest number of 
individuals who may experience a sudden cardiac arrest.
    The efficacy is not known because it has not been done in 
systematic ways. We have anecdotes of that being done on an 
airplane, and sometimes it works, sometimes it does not work. 
Just a few days ago there was a report in the national news of 
a case some place--I forgot where it is--where it did not work. 
The patient did not recover.
    The issue is largely one of the training and the experience 
of those who administer the electric shock.
    I cannot tell you either about the cost effectiveness nor 
the efficacy of that.
    With regard to the cost effectiveness, I can, however, say 
that if it was to work, if it was demonstrated that it works, 
there will not only be a great social but also financial 
benefit from that because if you have an individual who has a 
sudden cardiac arrest and whose heart is not made to work very 
quickly, but eventually it is done, meanwhile, the patient may 
develop some cerebral damages and we find ourselves with a 
terrible situation which, of course, is very heavy in 
consequences.
    You mention in your questions two approaches which are 
being now developed and, in fact, have been demonstrated to be 
quite effective to predict individuals who may be at risk of 
developing a cardiac arrest.
    The return to regular, normal heartbeat after exercise is 
extremely important for young individuals who engage in very 
active sports and things of that sort. It is an unfortunate 
case that very often we hear of basketball players or football 
players or whatever who literally drop dead during a 
performance because nobody knew that they may be at risk.
    That approach that you mentioned may be a way to detect 
these individuals and keep them from engaging in such 
activities.
    The other approach that you mentioned, which is to be able 
to detect abnormalities in an electrocardiogram reading is also 
quite effective. It has been demonstrated to be working well. 
However, at this point in time it is not generalized.
    But there is great prospect here.
    Ms. Pelosi. What does a defibrillator cost?
    Dr. Lenfant. I think they go for maybe a couple of thousand 
dollars, I think.
    Ms. Pelosi. But you said the key is the ability of the 
person?
    Dr. Lenfant. That is really the issue, because, you know, 
if you have somebody who, say, passed out, and people think 
that that is a cardiac arrest when it is not, and you start 
defibrillating the person, then you can cause the heart to 
stop. So you have really got to know what you are doing.

                             KIDNEY DISEASE

    Ms. Pelosi. I understand that hypertension is the second 
leading cause of American kidney disease, second only to 
diabetes. As you know, hypertension is more prevalent in the 
minority community.
    Last year you reported on the release of the clinical 
guidelines on the identification, evaluation, and treatment of 
overweight and obesity in adults. This report was a joint 
project of the NHLBI and the National Institute of Diabetes, 
Digestive, and Kidney Disease.
    Can you identify for the subcommittee specific joint 
research projects of the two institutes that relate to kidney 
disease? Are there any other plans for additional joint 
projects with the NIDDK ahead to discover more about linkages 
between hypertension and kidney disease?
    Dr. Lenfant. Ms. Pelosi, at this point in time we have no 
study which is specifically on kidney disease. However, it so 
happened that just a few days ago I was discussing the prospect 
of developing such studies with the newly-appointed director of 
that institute.
    However, the two institutes are supporting two major 
clinical trials in diabetic patients in whom, of course, kidney 
complications, kidney disease is a very serious complication, 
and these are huge clinical trials. The one, which the Diabetes 
Institute has the lead, focuses on a population of obese 
diabetics. The one that we have does not focus on obese 
diabetics, but these patients, as well as those from the 
clinical trial, supported mainly by the Diabetes Institute, are 
really candidates, if I may say so, for kidney disease.
    So there is work which is ongoing in diabetes patients.
    Ms. Pelosi. Thank you, Dr. Lenfant.
    Mr. Porter. Thank you, Ms. Pelosi.
    Mr. Bonilla?

                                DIABETES

    Mr. Bonilla. Thank you, Chairman.
    Dr. Lenfant, good to see you again. I have only one 
question this morning that relates to the things you are 
working on with diabetes. As you know, it is a problem that 
many of us on the subcommittee are trying to draw more 
attention to.
    I understand there are four major clinical trials on 
prevention of cardiovascular disease in persons with type two 
diabetes. Could you please explain how these trials differ from 
one another and what you might expect to gain from each one?
    Dr. Lenfant. Two of them I just referred to in my answer to 
the previous question. Let me repeat the essentials of this 
response.
    One of them is supported jointly by the two institutes--the 
Diabetes Institute and us. The Diabetes Institute is the lead 
institute, and that focuses on obese diabetic patients.
    Ours, where we have the lead, but there is a participation 
from the Diabetes Institute, does not focus on obese patients. 
The purpose of this one is to prevent the development of 
cardiovascular complications, which, as you know, are the main 
cause of morbidity in these patients.
    The third clinical trial, which is supported exclusively by 
our institute, is to prevent or interrupt the evolution of 
cardiovascular complications in these patients, and the idea 
here is to compare an intense medical approach with an 
interventional approach, which would be angioplasty in these 
patients.
    The fourth clinical trial, in which we are involved in a 
more advisory way than a financial one, is largely supported by 
the Veterans Administration. Here, again, it is on the 
prevention of diabetes in patients with elevated glucose.
    Mr. Bonilla. Thank you very much, Dr. Lenfant. It is always 
good to see you. I appreciate your hard work at the institute. 
Thank you.
    Dr. Lenfant. Thank you.
    Mr. Bonilla. Thank you, Mr. Chairman.
    Mr. Porter. Thank you, Mr. Bonilla.
    Dr. Lenfant, we have Dr. Slavkin following you today, and 
we are running low on time.
    I am going to ask whether any member of the subcommittee 
has one more question perhaps that they feel they would like to 
ask now.
    Mr. Hoyer?
    Mr. Hoyer. I will submit the questions. I know the time is 
short.
    Mr. Porter. Ms. Pelosi, any further questions?
    Ms. Pelosi. No thank you, Mr. Chairman.

                        CORONARY ARTERY DISEASE

    Mr. Porter. I am going to ask one, myself, so please feel 
free. I have a question that I find interesting that my staff 
prepared, and that is this one.
    Studies have suggested that relatively low bone mass tends 
to be associated with relatively high mortality from coronary 
artery disease and stroke.
    Yesterday we heard from Dr. Alexander that osteoporosis is 
a pediatric disease with geriatric consequences, because by age 
17, 90 percent of adult bone mass is established. It sounds 
like coronary artery disease and stroke could also be called 
pediatric diseases with geriatric consequences. Would you agree 
with that?
    Dr. Lenfant. Well, to that I will say that we know for a 
fact that coronary artery abnormalities or any artery 
abnormalities develop during the teens and some time before. We 
know that. We have done extensive studies. In fact, that 
started at the time of the Korean War, when many of these young 
soldiers who died and had autopsies, it was found that 
sometimes in their late teens and early 20s they had 
considerable lesions in their arteries, and that brought the 
focus on the early prevention of that state.
    So I think I would not go as far as the way it has been 
said, but I would certainly comment on the fact that it is 
critical that good healthy behaviors start very early in life 
to prevent further complications.
    Mr. Porter. Dr. Lenfant, what is the connection between 
bone mass on the one hand and coronary artery disease, or is it 
just a correlation?
    Dr. Lenfant. At this point in time, it is an association. 
It is true that a number of epidemiological studies have shown 
that there is, indeed, an association between osteoporosis in 
adults--not in middle-age individuals--and coronary heart 
disease.
    That is really what has triggered all the interest that you 
are hearing now, that if you treat coronary heart disease with 
statin--you know, this wonderful drug that really prevents the 
development and controls the evolution of coronary heart 
disease--if you treat patients with osteoporosis for the 
coronary heart disease with statin, you have a reversal of the 
osteoporosis.
    And so the mechanism at this time of that is not known yet, 
but we have an observation which is extremely interesting.
    In fact, one of the things that I believe I have in my 
testimony is that, jointly with the National Institute on 
Arthritis, Musculoskeletal, and Skin Disease, we do intend to 
develop a program next year to study the mechanisms--that is, 
the basic science--of that, but also the clinical implications, 
which are extraordinarily important.
    Mr. Porter. So the statin can both prevent further plaque 
in the arteries and maybe even reverse it, as well as reduce 
the osteoporosis?
    Dr. Lenfant. Correct, sir.
    Mr. Porter. Fascinating.
    Dr. Lenfant. It is. It is an amazing observation, which 
clearly has moved to the forefront this year.
    Mr. Porter. Well, Dr. Lenfant, thank you for the absolutely 
marvelous job you do at NHLBI. We very much appreciate you.
    I have so many questions I would love to ask, but 
unfortunately we just do not have time. We will have to submit 
them for the record. You are doing a marvelous job there, and 
we very much appreciate it, sir.
    Dr. Lenfant. Thank you very much.
    Mr. Porter. Thank you.
    The subcommittee will stand briefly in recess.
    [The following questions were submitted to be answered for 
the record:]



                                           Thursday, March 2, 2000.

          NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

                               WITNESSES

KENNETH OLDEN, Ph.D., DIRECTOR
SAMUEL H. WILSON, M.D., DEPUTY DIRECTOR
FRANCINE V. LITTLE, ASSOCIATE DIRECTOR FOR MANAGEMENT
LAURIE JOHNSON, BUDGET OFFICER
RUTH L. KIRSCHSTEIN, M.D., ACTING DIRECTOR, NIH
DENNIS P. WILLIAMS, DEPUTY ASSISTANT SECRETARY, BUDGET, DHHS

                       Introduction of Witnesses

    Mr. Porter. The Subcommittee will come to order. We 
continue our hearings on appropriations for the National 
Institutes of Health with the National Institute of 
Environmental Health Sciences, and I am pleased to welcome Dr. 
Kenneth Olden, the Director.
    Dr. Olden, it is always good to see you.
    Dr. Olden. Thank you.
    Mr. Porter. How many years have you been Director now?
    Dr. Olden. Soon to be nine years.
    Mr. Porter. I was going to say----
    Dr. Olden. It has been a long time. [Laughter.]
    And I have enjoyed every one of them.
    Mr. Porter. Not that long.
    We think that what you do is very, very important and we 
are always pleased to have you come and tell us the progress 
that you are making and how you are spending the public's 
money.
    Dr. Olden. Thank you very much.
    Mr. Porter. So, why don't you introduce the people that you 
have with you and then proceed.
    Dr. Olden. All right. To my extreme left is Ms. Laurie 
Johnson, and she is the Director of the Budget Office; and Ms. 
Francine Little, who is a new member of our staff and who is 
the Associate Director for Management; Dr. Sam Wilson, Deputy 
Director; and you know Dr. Kirschstein and Mr. Dennis Williams 
from the Department.

                  ENVIRONMENTAL HEALTH DECISION MAKING

    Mr. Chairman and members of the Committee, there has never 
been a more exciting time in environmental health research, so, 
I hope that today I can convey the urgency and talk about the 
opportunities and the enthusiasm in the field. All of this 
excitement and enthusiasm has been generated because we now 
have the technologies and tools to answer many of the important 
problems in environmental health research.
    Our products are used for two purposes, not only to make 
public health policy decisions in terms of prevention, 
diagnosis and treatment of human illnesses, but our products 
are also used by regulatory agencies to make environmental 
health policy decisions--two very important activities.
    Over the years as I have appeared before this Committee, I 
have consistently been an advocate for better science for 
better environmental health decisions and better science to 
prevent chronic diseases such as cancer, Alzheimer's and 
Parkinson's.
    Today I want to continue in that vein. I want to comment 
again on the state of the science that we use in environmental 
health decision making, and about the opportunities that we 
have to change that scientific base. Now, when we go to buy a 
car or a house the one thing that we spend a lot of time doing 
is gathering information. So, information is important in our 
personal lives and it is also important to the Government in 
terms of making sound public policy. For example, if we are 
going to buy a house or a car we consider things like 
reliability, safety, and resale value and the investments that 
we are making are very small compared to the kind of investment 
that we make when we set an environmental health regulatory 
standard.
    Also, the consequences of buying a house or a car are much 
less significant than the decisions as to what is the right 
level of exposure to allow the American people to be exposed 
to. So, the decisions that we make about environmental health 
cost the nation hundreds of billions of dollars in terms of 
regulatory compliance and it also could cost the nation in 
terms of human suffering and in terms of the health of the 
American public if we do not make the right decisions.
    Now, when I appeared before this Committee over the past 
couple of years, I have indicated that there are nine critical 
investments that we need to make to improve environmental 
health decision making. Now, on the exhibits that I have over 
here in the corner I have identified only four of those areas.
    [The information follows:]



    Dr. Olden. Now, you can visualize that scheme in that 
exhibit as having nine boxes, Scheme A, as being nine boxes 
with nine question marks. In other words, issues that we do not 
know. Usually, in environmental health decision making, we have 
information on environmental quality that we can associate with 
specific diseases. Usually we have very little information on 
the toxicity of those chemical, physical and biological agents. 
We almost never have information on the mechanism of action of 
those chemicals. We know very little about exposure and we know 
very little about susceptibility and there are a number of 
other issues that we also don't have information on that are 
not shown.
    Now, the debates about risk assessment usually revolve 
around one's confidence in Scheme A versus Scheme B. In other 
words, to what level must we fill in all of those question 
marks before you are satisfied, what is your level of comfort 
that we are making the right decision based on Scheme A versus 
Scheme B.
    Now, no matter what that is, I maintain that all of us 
would be much more comfortable if we had eliminated many of the 
uncertainties and many of the question marks that are evident 
in Scheme A versus Scheme B. So, what we are trying to do at 
NIEHS is to generate the data base to fill in the information 
that exists between exposure and human diseases.
    Even though we don't have the information, regulatory 
agencies must still make decisions, so they resort to the use 
of default assumptions. Default assumptions, because there are 
uncertainties and there is an absence of data. They also use 
the precautionary principle in arriving at a regulatory 
decision. So, we want to generate the science so that we can 
make decisions without doing that.

                       INDIVIDUAL SUSCEPTIBILITY

    Now, it was okay 10 years ago for us to make decisions on 
the basis of default assumptions and the precautionary 
principle and we should still use them in cases where we have 
to. However, I maintain that we now have a sufficient knowledge 
base. We know how to ask the right questions and we have the 
tools to provide answers to those questions. I am told by my 
friends who are practicing physicians that one of the most 
common questions that they are asked is. ``Why me, Doc?''
    [The information follows:]



    Dr. Olden. In other words, why do I have lung cancer, 
berylliosis, or asbestosis, while my friends who had similar 
exposures don't have these illnesses? Well, one answer may be 
differences in an individual's susceptibility.
    You will recall a few years ago, two years ago in 1997, we 
introduced at this hearing the development of the Environmental 
Genome Project to determine the genetic basis for differences 
in susceptibility to environmental exposures. Now, even though 
we know that we all are not identical, we still regulate as if 
one size fits all.
    [The information follows:]



    Dr. Olden. You can imagine a manufacturer of shirts, for 
example, who made the assumption that one mold, one size fits 
all. There would be no opportunity for that person to reinvest 
profits or to consider expansion because there would be none. 
So, we are in the same bind in environmental health decision 
making. So, what we are trying to do with the Environmental 
Genome Project is to determine what is the genetic basis for 
differences in susceptibility to environmental exposures.
    Since we announced the Environmental Genome Project in 
1997, we have discovered many genes--as a matter of fact they 
were being discovered prior to our announcement but the pace 
has been greatly accelerated--we have discovered many genes 
responsible for differences in susceptibility and I can say 
this is now probably one of the most exciting areas in 
biomedical research.

                       ELIMINATING UNCERTAINTIES

    Today I want to announce two new initiatives. Both 
initiatives will help us in eliminating some of those 
uncertainties or some of those question marks that you see in 
Scheme 1 in the first exhibit. First, we want to expand the 
Environmental Genome Project by developing university-based 
mouse genomic centers to construct animal models to mimic the 
susceptibility genes that we will discover in the Human Gene 
Resequencing Initiative. These genetically-modified animals--
they would be models of human susceptibility--these 
genetically-modified animals will be made available to 
scientists and investigators worldwide so that we can finally 
conduct the experiments to clarify the role of genetics in 
environmental susceptibility. The results from these studies 
will profoundly alter the practice of medicine and 
environmental health decision making in this country.
    Secondly, I want to announce the expansion of our efforts 
to develop high throughput technologies for carcinogenicity and 
toxicity testing. In my testimony before this Committee in 
1997, I updated you on our efforts to develop and validate 
transgenic animal models for use in carcinogenicity testing 
using high throughput approaches. In other words, I said the 
current approach using rodent bioassay is too costly and it 
takes too long to perform. Well, we have had a lot of success. 
And, again, there are now many papers and it is an intensive 
area of research in many laboratories to use these transgenic 
animal models to identify carcinogen and toxicants in a much 
more rapid manner, fashion.
    The cDNA microarray technology is really the second 
generation of high throughput approaches. I mentioned two years 
ago that even though I was excited about our success with 
transgenic animal models, that new high throughput approaches 
would be on the horizon very soon. Today we believe that that 
approach is here. And that is the use of cDNA microarray 
technology.
    [The information follows:]



    Dr. Olden. Now, the expectation is that each class of 
toxicants will alter the expression of genes in the cell, 
generating what we call a gene expression pattern. So, if you 
expose cells to a given class of toxicants there should be an 
expression pattern unique to that group of chemicals. So, by 
development of a signature data base, which is of all known 
toxicants--this is comparable to the FBI fingerprint data 
base--we can screen the universe of chemicals to identify 
agents whose signature patterns match one that is already in 
existence in the data base, just as the FBI can identify an 
offender from a population of 200 million with a very high 
degree of certainty. We believe that we can use a similar 
approach using a signature pattern of gene expression to 
identify those chemicals that are going to be toxicants.
    The data base will not only contain all the chemicals in 
commercial use in the United States and the world, but it will 
also contain the signature patterns of chemicals that failed in 
industry pre-market testing, because those are also important. 
So, we formed a partnership with industry and the Food and Drug 
Administration to get access to those chemicals that never made 
it to the market place because of toxicity. If we have the data 
base on the 85,000 chemicals in commercial use that are 
toxicants, as well as those from the various pharmaceutical 
industries then we believe that we will have an appropriate 
data base so that we can match an unknown.
    Now, what are the advantages of this approach? First, it 
can be automated so we could screen chemicals 24-hours a day, 
7-days a week using robotic technologies. We could screen 
thousands of chemicals and we could involve thousands of genes 
and we could do it at low-cost, in fact, dirt cheap compared to 
what the 2-year rodent bioassay costs. It probably would not 
require the use of animals and the mechanism by which the gene 
expression signatures are generated also reveals something 
about mechanisms. So, already we would know a lot about 
mechanism. Also, the interpretation of the results would be 
less subjective. In other words, it would be less dependent on 
pathological examinations of the tissues.
    So, we believe that we can compare the signature pattern of 
an unknown toxicant or suspect and match that with the 
signature pattern of a known and identify with almost absolute 
certainty that this chemical is a toxicant and operates by a 
specific mechanism.
    In closing, Mr. Chairman, let me say that we have the 
opportunity to fundamentally change toxicology as we know it 
today. And I hope the Committee shares my enthusiasm for doing 
so.
    Now, Mr. Chairman, let me finish by congratulating you on 
20 years of distinguished public service and I wish you good 
health and happiness in the years ahead. The President's budget 
request for NIEHS for fiscal year 2001 is $460,971,000. And I 
would be pleased to answer any questions that you might have.
    [The written statement of Dr. Olden follows:]



                       CDNA MICROARRAY TECHNOLOGY

    Mr. Porter. Thank you very much, Dr. Olden.
    What do we call this new--it is high throughput?
    Dr. Olden. It is cDNA microarray technology. It has been 
around.
    Mr. Porter. All right. We will just call it what it says 
there.
    Dr. Olden. Yes.
    Mr. Porter. All right, you are not yet doing this now; is 
that correct?
    Dr. Olden. We are doing it.
    Mr. Porter. You are doing it.
    Dr. Olden. Yes. It was developed in the Human Genome 
Project in the NIH and the entire NIH enterprise is interested 
in this technology for a number of reasons. We are interested 
in it from a toxicological point of view. We realize that this 
is a very powerful tool for toxicology to advance our capacity 
to identify toxicants and carcinogens in a very fast, 
economical way. So, we have taken the lead in the NIH to 
develop it for that purpose but other institutes are investing 
this technology for other purposes and we are doing it in 
partnership with other institutes.
    But we are focusing on the toxicology aspect of the 
technology.
    Mr. Porter. All right, now, would you do this by grants or 
by contract or intramurally or----
    Dr. Olden. Well, what we are proposing at this point, 
Congressman, is to create a resource center some place. This 
technology is very expensive and also you don't need one in 
every laboratory and at every university. You do need centers 
that know how to do it because it is also a very difficult 
technology and you need to have expert people who really know 
informatics and other aspects of the research.
    So, what we are proposing at this the moment is to provide 
this to the scientific community as a resource. We are 
proposing to create centers, one at NIEHS, which we already 
have up and running. Our hope is that we will also have four or 
five around the country, such as in California, so that all our 
investigators who are interested in this toxicology would have 
access to it.
    We are, however, going to have a national data base. The 
only place that the national data base will exist is in the 
NIEHS because we have the partnership with industry and Food 
and Drug Administration and we have access to many chemicals 
that an investigator in a university would not have access to. 
So, it is important that we develop the national data base.

                           TRANSGENIC ANIMALS

    Mr. Porter. How are you doing this now except for this? In 
other words, haven't you used some kind of transgenic rodent 
experiments?
    Dr. Olden. Yes, we have. That was the technology that I 
described to you last year or two years ago when we gave you a 
progress report.
    Mr. Porter. Yes.
    Dr. Olden. And we started that effort five years before 
1997.
    Mr. Porter. Right.
    Dr. Olden. And I promised you when I came on as Director 
that I thought that we could develop test systems that were 
faster and cheaper, indicating at the time, that a rodent 
bioassay costs us $2,000,000 to $6,000,000, and it takes 2-to-5 
years to do and it uses lots of animals. That is too long, too 
costly and uses 800 animals per test.
    Mr. Porter. Especially if you have 80,000 different 
substances to test?
    Dr. Olden. Right.
    Mr. Porter. Now, with the new technology, assuming you have 
it up and running and you have the 4, 5, or 6 centers going, 
does this obviate the need to prioritize among the substances 
you are testing because you can do it so quickly you don't have 
to? You can do them all?
    Dr. Olden. I think that is exactly where we are moving to. 
I think we can. Of the 85,000 chemicals in commercial use in 
the U.S. most of them do not need testing. We know, based on 
our experience, that many of them, most of them in fact, are 
not going to be toxic at all. If you narrowed that down and 
said, well, maybe 10,000 do need testing, we could do a general 
screen for every chemical, every suspect toxicant that was in a 
given class, and we could do it in a very short period of time 
once we had the technology up and running and perfected. The 
investment is going to be developing the technology and that is 
going to require a huge data base and that is why we have got 
to work together with industry and other Government agencies, 
but developing the data base is going to take time.
    Mr. Porter. You are going to put yourself out of business 
here.
    Dr. Olden. Well, the estimates are though, Chairman Porter, 
that it is going to take really 10 years to put this thing in 
place. But once we have got it--in other words, we have a data 
base like the FBI's fingerprints--we are home free.
    Mr. Porter. This is not all you will have to do though?
    Dr. Olden. This is not the only thing that we have to do 
but the opportunity to revolutionize toxicology is in hand and, 
so, that is what I am really talking about; not doing 
toxicology the way we have done it in the past. This is 
exciting and it is doable.
    Mr. Porter. It is certainly exciting and certainly 
something that you have been looking for, for a long time.
    Dr. Olden. Exactly.

                            CHILDREN'S HEALTH

    Mr. Porter. And you have obviously found it, so, it is very 
exciting to know that you have arrived there.
    Can you describe the children's health research agenda that 
you are pursuing and what you hope to accomplish by that?
    Dr. Olden. Yes. We started a children's health research 
agenda in 1993 when the Academy of Science first released a 
report on the diets of infants and children with respect to 
pesticide content. We started that year to invest in research, 
first of all, with animal models, exposing animals--these are 
rodents--during the first few weeks of life, phases that 
compare to in utero exposure and embryonic and fetal 
development, as well as the adolescent years. We exposed 
animals to a number of chemicals, pesticides, a number of 
chemicals that have estrogenic activity and asked, are there--
and we do this at low-level exposures--and ask, do we see 
adverse health effects at low levels in either young children 
or in utero that we would not see in an adult? That is one set 
of experiment studies.
    And the other is we have been supportive for a long time--
long before I got there--of research in air pollution and 
pulmonary and asthma and respiratory conditions. We continued 
that research. We developed 8 children's health research 
centers in collaboration with the CDC and the Environmental 
Protection Agency in 1998. And the focus of those centers is on 
development and asthma mostly, not on cancer, and also on 
cognitive and neurocognitive issues.
    We are also collaborating with the National Institute of 
Allergy and Infectious Diseases with respect to these diseases 
and also an inner-city asthma project and this is the second 
phase of the project. The first phase was to identify allergens 
in inner-cities and we have identified some--cockroach 
allergens, cigarette smoke and dust mite allergens. Now what we 
are trying to do in New York City and 8 cities around the 
country, is to develop intervention strategies based on 
physician or health care provider education as well as 
environmental remediation.
    We also, with the National Institute of Allergy and 
Infectious Diseases, have a project concerning asthma 
intervention again, but it is also based on education and that 
is based in Atlanta, Georgia.
    We have supported for a number of years research on lead, 
and we just completed a clinical trial, looking to see if we 
could prevent the cognitive loss that kids experience with 
blood lead levels in the range of 20 to 40 micrograms per 
deciliter of blood and that has come to an end.
    Mr. Porter. Would this technology tell us about the 
chemicals and the exposure levels that would be toxic to 
children? I mean would this lead us----
    Dr. Olden. Well, in our rodent bioassays we can't test at 
low doses. In other words, the doses which we are exposed to we 
cannot test at, because it would take just too many animals and 
cost too much to do. So, we typically test at very high doses. 
So, the answer to your question is, yes, we could test at very 
low doses. We could finally do low-dose exposures to see if we 
got a read-out in terms of a signature pattern that would match 
a given toxicant.
    So, yes, indeed.
    Mr. Porter. Thank you, Dr. Olden.
    Mr. Hoyer?

                         LOW LEVELS OF EXPOSURE

    Mr. Hoyer. Thank you, Mr. Chairman.
    Doctor, like the other institute heads, your enthusiasm and 
excitement, I think, is infectious in the best sense of the 
word----
    [Laughter.]
    Mr. Hoyer [continuing]. To all of us.
    Dr. Olden. Thank you.
    Mr. Hoyer. The threshold on which all of you seem to think 
we are, in terms of making very major steps forward and the 
interconnectedness and interrelationship of your work, I think, 
is very evident.
    In your statement and just now, you were talking about low 
doses. One of the issues, of course, that confronts us from 
time-to-time on riders on this bill is whether or not we ought 
to have various regulations that deal with low-dose exposure.
    In your statement you seem to indicate that low-dose 
exposure may be more dangerous than we think it is or 
historically have thought it to be. Am I correct in 
interpreting that from what you said?
    Dr. Olden. No. I think the point I am trying to make is we 
don't in most cases have the data to make that determination.
    Mr. Hoyer. Okay.
    Dr. Olden. I think that is unfortunate. We now have the 
technologies to make those determinations and, so, I think we 
ought to get the information in place so that we stop flying 
blind basically.
    Mr. Hoyer. Now, of course, as a practical matter, you well 
realize that at Federal, State and local levels those who want 
to do things that may have low levels of exposures of certain 
toxics. That may indicate that we, in Government, are crazy and 
are costing jobs and economic opportunities with almost--
because we are sort of relying on a no-risk environment--
objective. I guess environment is too precise a word--in terms 
of your objective.
    Dr. Olden. Well, I come back to the fact that I think you 
can argue anything you want in the absence of data.
    Mr. Hoyer. Right.
    Dr. Olden. And, so, I can cite examples of where low-dose 
exposure is a problem, for example, methylmercury. 
Methylmercury accumulates in the body until it reaches a 
threshold and there are probably a number of other chemicals, 
that are lipid soluble chemicals that dissolve in fat tissue 
which also do the same thing.
    So, just because the exposure is low dose does not mean 
that a chemical cannot bioaccumulate in humans to the point 
that it does, in fact, approach the levels that we use in our 
rodent models. So, low-dose, by itself, does not ensure that 
there is no harm. However, I probably could cite other examples 
where low-dose is not a problem.
    But the issue is we don't have information to make that 
determination and I think that is, in a sense, dangerous and it 
is not the way that you and I would buy a house or a car. We 
would want the information to make that important decision.
    So, my plea is to get the information so that you and I can 
be sure that the policy that you put in place is, indeed, 
protecting the health of the American people, protecting the 
environment and is not harming the economy because, as I 
mentioned, these decisions cost hundreds of billions of 
dollars, either in terms of public health or the economy, in 
terms of competition for American industry. So, let's do the 
experiments to answer the question.

                     TIME FRAME FOR NEW TECHNOLOGY

    Mr. Hoyer. Remind me of what you think our time frame is in 
terms of using the new technology to get it?
    Dr. Olden. Well, we are using the technology now. So, we 
know. In other words, we have done proof of principle. We know 
that the technology will work for the objective that I 
indicated.
    What we don't have in place, though, is the data base. In 
other words, if I wanted to screen an unknown--a suspect--I 
don't have a signature pattern that is good or bad to compare 
that with.
    So, we first have to develop and put in place a data base 
based on all of the known toxicants that we can get our hands 
on and that will take a while to put in place. And, so, that is 
what we are doing.
    We got together with industry. We had something like 20 
industry representatives around the table like this and that is 
what the conversation was about. They want the very same thing 
as we do.
    So, what we decided to do is to partner and let's generate 
this information together as soon as possible so that industry 
can save money and they can get their products to the market--
these are pharmaceuticals--faster and that is in the best 
interest of all of us.
    And, hopefully, we can screen and they will not be toxic.

                       INDIVIDUAL SUSCEPTIBILITY

    Mr. Hoyer. And your mouse genetic engineering will help us 
get there.
    Dr. Olden. Yes.
    Mr. Hoyer. That may be an imprecise way to describe it.
    Dr. Olden. We have a number of genomic projects in the NIH. 
Almost every Institute, and we have a number of trans-NIH 
projects; the single nucleotide polymorphism project that is 
operated out of the National Human Genome Research Institute is 
one example. What we are doing is we are identifying those 
genes where there is a variation that will increase lead-to 
susceptibility and/or resistance--both are important--to an 
exposure to an environmental pollutant. Once we have those 
genes identified, what we want to do is create animal models 
containing those variations.
    Mr. Hoyer. Am I correct in concluding that there may be, on 
certain products, a warning at some time in the future that 
states: exposure to low doses of this product will not be 
harmful to 90 percent of the population?
    Dr. Olden. Exactly.
    Mr. Hoyer. But if you fall into this category----
    Dr. Olden. Right.
    Mr. Hoyer [continuing]. It will be.
    Dr. Olden. Exactly.
    Mr. Hoyer. We will be able to segregate, if you will, those 
at risk and those not at risk?
    Dr. Olden. Exactly. Take the beryllium workers. We now 
know, in hindsight that 90 percent of the people who have 
berylliosis also have the beryllium susceptibility gene. There 
is a susceptibility gene that has been isolated and identified. 
We now have identified the gene, for example, that protect us 
against organophosphate pesticide toxicity. We have identified 
at least one gene that we know protects, and there are people 
who do not have that, and if we knew who those persons were.
    That is an important one because we know that gene is not 
expressed early on in children. So children and animals, like 
rodents and mice both, are much more susceptible to 
organophosphate pesticide toxicity because of the absence of 
the expression of one gene. Now, it is later expressed in 
children, but it is turned on much later.
    Mr. Hoyer. Conceptually, 25 years from now, or it may be 
even sooner, at birth, we would get a book all about ourselves. 
This is what you need to watch out for?
    Dr. Olden. Well, I think Dr. Kirschstein and others would 
say here, clearly, medicine is going to become more predictive 
and preventive, rather than diagnostic and treatment. And 
probably what we are going to do is a stage where we get some 
sort of bar code at birth, like one that you use when you go 
through a check-out counter at a grocery store. A physician 
could just print it out and find out what your susceptibilities 
are, and they all are not going to be just environmental. There 
are other susceptibilities like breast cancer 1 and 2 genes. 
There are different kinds.
    Mr. Hoyer. But it is not only your physician, but your 
parents.
    Dr. Olden. Yes.
    Mr. Hoyer. To guard against exposure to things that you are 
uniquely susceptible to; IA, IE and the asthmatic.
    Dr. Olden. Yes. What we really need, Congressman, is a 
comprehensive database that includes a lot of things. All of 
the nine issues that I mentioned, if we had information on all 
of those issues, then that is exactly what you need to set and 
sell environmental health policy to protect the health of the 
American public. And so that is what we need.
    Mr. Hoyer. Dr. Kirschstein, do you want to make a comment?
    Dr. Kirschstein. I wanted to make a comment, that as Dr. 
Collins said yesterday, we need to be deeply concerned about 
the privacy of that information in terms of discrimination, and 
insurance and other aspects that might affect an individual's 
life.
    Dr. Olden. Right. Absolutely.
    Mr. Hoyer. I think the more we can predict the future, the 
more complicated it becomes in trying to make decisions about 
what our predictions say. I think that we may ask questions we 
do not want to know the answers to.
    Mr. Porter. Thank you, Mr. Hoyer.
    Mr. Jackson?

                        COLLABORATIONS WITH NCI

    Mr. Jackson. Thank you, Mr. Chairman.
    Thank you, Dr. Olden, for appearing before our committee 
today.
    Dr. Olden. Thank you.
    Mr. Jackson. I am pretty sure you are familiar with the 
line of inquiry that I have been raising amongst NIH directors 
over the last couple of hearings.
    Dr. Olden. Yes. Yes, I am.
    Mr. Jackson. Since you are so familiar, I think I am going 
to approach yours just a little bit differently then. 
[Laughter.]
    As the head of the National Institute for Environmental 
Health Sciences, my understanding is that you are charged with 
Environmental Health Science is primarily devoted to disease 
prevention through understanding and minimizing adverse 
environmental effects on human health and that you are the 
Nation's premier research organization at NIH. The NIEHS has 
been a leader in the area of understanding how poverty, 
environmental pollution and health interrelate. The NIEHS has 
developed a number of projects and grants programs designed to 
define health disparities issue and to arm policy makers with 
necessary information to reduce these disparities.
    So I was just wondering since prostate cancer, for example, 
is very high amongst African-American men and breast cancer is 
reportedly twice as more lethal amongst African-American women 
than any other ethnic group or even the majority population, 
and that incidences, for example, of cancer in our community 
are higher, I am just wondering does your Institute, at least 
it is my understanding that Institutes are supposed to better 
coordinate across the entire NIH, that that is the purpose of 
being an Institute, has your Institute worked out any kind of 
grant proposals, RFPs, RFAs with Dr. Klausner that you would 
like to share with the committee?
    Dr. Olden. Yes, we have. We collaborate with the National 
Cancer Institute on many projects, including breast cancer and 
prostate cancer, not only with prostate cancer and not only 
with NCI, but with the National Institute on Aging as well. We 
co-fund a program with NCI--as a matter of fact the bulk of the 
support is NCI dollars--called the Agricultural Health Study. 
The purpose is to look at exposures to pesticides and breast 
cancer, but also many other cancers, as well as diseases like 
Alzheimer's and Parkinson's. And many of the pesticides have 
estrogenic activity, and most of the exposures, 90 percent of 
farm-workers in the United States are minorities--mostly, 
today, Latinos, not African Americans, but African Americans 
certainly, as a population, are second in terms of being 
agricultural workers.
    This study has been conducted in Iowa and in North Carolina 
to bring in the African-American population. In addition to 
that, we created a specialized Environmental Health Center. We 
have three of them that deal solely with agricultural 
chemicals, and two of those are in California. So we have a 
number of projects that we are working with NCI on. We also 
fund the Long Island Breast Cancer project with NCI.
    So the answer is, yes, we share a lot of information with 
NCI and work very closely together on both breast and prostate 
cancer, and certainly estrogens are also thought to play a very 
important role in prostate cancer.

                FINDING MINORITY BIOMEDICAL RESEARCHERS

    Mr. Jackson. Dr. Olden, the Chronicle of Higher Education 
wrote an article on November 10th of 1993 that said that the 
National Cancer Institute was having a problem finding minority 
researchers. Do you share that opinion?
    Dr. Olden. Finding minority researchers? Yes, I do. I have 
problems finding minority biomedical researchers. I used to be 
director of a cancer center at Howard University, as you 
probably know, and when I was there, I had a problem finding 
minority biomedical researchers. The truth is there is a 
pipeline problem, and we are doing something to address the 
pipeline problem.
    Mr. Jackson. You will have to forgive me. You have taken me 
aback a little bit here. You had a problem finding minority 
researchers at Howard?
    Dr. Olden. Yes.
    Mr. Jackson. Really. Could you care to explain where at 
Howard you were looking for them?
    Dr. Olden. Well, I think I used every possible mechanism. I 
was director of an NCI-funded cancer center, and the 
requirement of maintaining an NCI-funded cancer program is that 
you have to recruit investigators who are nationally 
competitive in terms of being able to secure independent 
research dollars. And if you do not do that, you do not exist. 
So we had a problem of finding people who had that kind of 
experience, and it is a pipeline issue. If only 600 or so have 
graduated in ``X'' numbers of years, there is no way that many 
of them are going to have the kind of experiences that are 
necessary to compete for a grant with the National Cancer 
Institute or the National Heart, Lung and Blood Institute or 
even my Institute.
    So, yes, I did have the problem there, and I still have it 
at NIEHS. I have a position open now, and I would be very happy 
to have a minority candidate for the position. The position is 
my scientific director.

                            OUTREACH EFFORTS

    Mr. Jackson. It is kind of hard for me to, well, and maybe 
it is me. I went to North Carolina A&T, and it is really hard 
for me to imagine that Howard University, with all of the 
funding that this committee and this Congress gives to the 
university, has a problem creating a pipeline of minority 
researchers for an organization that is like right around the 
corner from----
    Dr. Olden. Well, Howard is certainly----
    Mr. Jackson. Stay with me for a second, Dr. Olden. Stay 
with me for just one second. Let me move from that question to 
another one.
    Then, if you could explain to me, since there is this 
dearth of finding minority researchers, maybe you can help me 
understand whether or not you share the view that--well, let me 
rephrase that.
    Maybe you can help me understand what is your assessment, 
generally, of the outreach efforts by the NIH to try and find 
minority researchers? Sufficient? Could it be better?
    Dr. Olden. Well, I think there is no program, no activity, 
I have never seen anything, Mr. Jackson, that could not be 
improved, and I think NIH is very concerned about improving its 
outreach activities to minorities and underserved populations. 
But can it be improved? Everything in my Institute can be 
improved, and I suspect that effort in the NIH could also be.
    Mr. Jackson. Well, towards that very generous spirit, what 
recommendations for your own Institute are you moving towards 
to improve it?
    Dr. Olden. Well, for one thing, I am supporting a number of 
programs. I am supporting a Meyerhoff Program at the University 
of Maryland Baltimore Campus. It was created and developed by 
an African American, who is the president of the university.
    Mr. Jackson. I am sorry. Did you say Baltimore, Maryland?
    Dr. Olden. Yes.
    Mr. Jackson. But not like, let us say, Howard University, 
where there would be a natural pool of----
    Dr. Olden. I am sorry. All of the students in this, I think 
close to all of the students are African Americans, and this 
program is recognized as the best program in the Nation at 
producing minorities who go on to become biomedical 
researchers. And so I have invested in that. As a matter of 
fact, we contribute $600,000 per year, and we are now in the 
seventh year, I believe. And, in fact, it was co-funded, at the 
outset, by the Office of Research on Minority Health.
    We are making investments other places, as well. I do not 
know if you know about our ARCH program, which is also a 
program that we developed, which is a partnership between 
research-intensive universities and HBCUs, and we are 
reannouncing that to include other minority-serving 
institutions.
    So we have programs, a number of them, in fact.
    Mr. Jackson. Let me just ask one last question, and let me 
also thank you very much, Dr. Olden, for your candor.
    Are you aware of the persons who are in charge of the 
better coordination of addressing these disparities across NIH?
    Dr. Olden. You mean the trans-NIH working group?
    Mr. Jackson. There is a committee that Dr. Kirschstein has 
been----
    Dr. Olden. Yes. Yes, Dr. Tony Fauci and Dr. Kirschstein's 
deputy director. Yes, I am aware.
    Mr. Jackson. Thank you very much, Dr. Olden.
    Thank you, Mr. Chairman.
    Mr. Porter. Thank you, Mr. Jackson.
    Ms. Lowey?

                             BREAST CANCER

    Mrs. Lowey. Thank you very much, and I do want to 
apologize, Mr. Chairman, and our distinguished panel for being 
late and missing most of the testimony. As you know, we are 
pulled in so many directions. But I have such great respect for 
the important work you are doing, and I look forward to 
continuing to work with you, Dr. Olden.
    I know there has been some discussion, and you addressed 
the funding of the Long Island Breast Cancer Study.
    Dr. Olden. Yes.
    Mrs. Lowey. As you know, I have been working with Fran 
Visco and the National Breast Cancer Coalition for many years 
towards our shared goal of truly understanding breast cancer.
    Dr. Olden. Yes.
    Mrs. Lowey. While many believe that a link between our 
environment, drinking water, soil, and air quality, pesticides 
and the incidence of breast cancer in our community can be 
readily identified, there has not been very specific research 
on these factors. In fact, every year when we bring up the 
issue, we really do not get conclusive evidence, and it is 
either because the research has shown there is no conclusive 
evidence--as Dr. Kirschstein is shaking her head--or perhaps we 
have not done sufficient work in this area and maybe some of 
each.
    There are, to the best of my knowledge, a limited number of 
studies, and in many cases these studies have raised, rather 
than settled, important questions. And I really do feel that we 
have got to get some more information. So I have introduced a 
bill to create Centers of Excellence, very much like the 
Centers on Children's Health within NIEHS, because I believe 
that this kind of focused research would complement programs at 
the National Cancer Institute, at the Department of Defense and 
at academic medical centers around the country.
    What this bill would do is establish cooperative 
relationships between institutions so that researchers working 
on Long Island would share their findings with colleagues in 
New York City, Westchester, Connecticut, Northern New Jersey, 
as well as with other areas around the country.
    Perhaps most importantly, the proposal would also create a 
role for breast cancer patients, their families and advocates 
in giving their experiences to the scientists, which we hope 
would shed light on the whole issue. I do feel that the 
experience of women and families in their neighborhoods should 
provide some important information for the investigation. And I 
just feel this kind of joint effort could be very, very 
critical.
    Could you comment on this approach.
    Dr. Olden. Well, we would be very pleased to work with the 
National Cancer Institute, and I guess if you brought this up 
with Dr. Klausner, he also indicated that he would be very 
pleased to work with us on this issue. We worked very well with 
NCI on a number of issues, and this would be one that I think, 
again, that we would be very pleased to get advisers to look at 
and develop an appropriate research agenda to address your 
concerns.
    Mrs. Lowey. I appreciate that, and I hope, as the bill 
moves along and the process moves along, that we can continue 
our dialogue because I certainly have a great respect for the 
important work you are doing.
    Dr. Olden. Yes.
    Mrs. Lowey. Thank you.
    Dr. Olden. We think that is very important work.
    Mrs. Lowey. Thank you.
    And thank you, Mr. Chairman.

                                MIXTURES

    Mr. Porter. Thank you, Ms. Lowey.
    Dr. Olden, getting back to the cDNA microarrays.
    Dr. Olden. Yes.
    Mr. Porter. In many cases, a worker, for example, is 
exposed not just to one chemical substance, but a number of 
them at the same time, let us say hydrochloric acid and 
ammonia. Will this kind of technology assay two at the same 
time or three or four?
    Dr. Olden. Yes. That was why we got excited about it day 
one, Congressman Porter. It is one of the nine areas that I 
identified last year that has been crucial for environmental 
health decision making. An area where we had very little 
information is on mixtures. Almost all of our studies over the 
years in environmental health research and in toxicology have 
focused on one chemical or physical or biological agent at a 
time, and that is not consistent with the real world. We live 
in a world where we are going to be exposed to thousands of 
things during the course of this day. So it is the mixtures. 
But we did not have the tools to answer the question. That is 
one thing that the cDNA microarray approach, we believe, will 
allow us to do.
    Mr. Porter. If you look at all of the environmental factors 
that might affect health, and you begin with synthetic 
chemicals, and you said, well, we do not have to look at all 
85,000, we can look at just 10,000.
    Dr. Olden. Right.
    Mr. Porter. And then you add to that the byproducts of 
combustion and industrial processes, you look at foods and 
nutrients, natural substances, and we talked to Dr. Straus this 
morning about an interaction between a natural substance and a 
drug if you took them at the same time, prescription drugs, 
other pollutants.
    How, with so many possible environmental factors, can you 
again prioritize or separate out which ones to look at, and are 
you looking at real-life situations where you might be exposed 
to certain ones and saying, ``Those are the ones that we better 
look at''?
    Dr. Olden. That is exactly right. That would certainly be 
at the top of our list of priorities. We look at the real-world 
exposures. I think you can get a panel of 20 people in a room, 
and we can pretty much agree on the top 20 or 40 or 100 most 
common pollutants to which you and I are exposed to as 
mixtures. Automobile exhaust is clearly one. Second-hand smoke 
is clearly one. So we can identify them. So I think you can 
generate a list of priorities, maybe not narrow it down to ten, 
but you do not want to do that. But I think you could get a 
consensus on what the top----
    Mr. Porter. And will this technology allow you then to 
study a group of them?
    Dr. Olden. It will, yes. That is what we expect.
    Mr. Porter. That is very impressive technology.
    Dr. Olden. Right now we are not trying it with mixtures, 
but that is the objective because we had no technology for 
looking at mixtures. And the technology that we do have is 
simply too expensive to take into account all of the different 
possible combinations that you just referred to.
    If it is going to cost you $2,000,000 to $6,000,000, and 
you are only testing ten chemicals a year anyway, you cannot 
test all of the different permutations of chemical, physical, 
and biological agents. It is not just chemicals. Biological 
agents also interact with chemicals and vice versa. So it is 
complex, unless you have the right tools.

                            HERBAL MEDICINES

    Mr. Porter. Well, we were, as I say, talking to Dr. Straus 
this morning about his mission, and he was talking about all of 
the substances that are on the market already and more going on 
every day. But if you think of your job, it is even much more 
complex than his is.
    Dr. Olden. Well, we are collaborating with Dr. Straus 
because you remember I believe last year I mentioned our 
interest in testing herbal products.
    Mr. Porter. That is my next question.
    Dr. Olden. All right.
    Mr. Porter. You can go ahead and answer it. What progress 
have you made there?
    Dr. Olden. Well, we have not done any chronic tests yet, 
but we have done some pre-chronics on four. We do plan to start 
probably as many as two this fiscal year 2000. So it is 
important, and that is why we are interested. It is not only 
whether this mixture, which they are, is toxic in itself, but 
it could interact with pharmaceuticals, which people are also 
taking.
    So it is a difficult and complex issue that certainly will 
require the best of all of the Institutes in the National 
Institutes of Health to answer. And so we are very interested 
in collaborating with Dr. Straus to help us, in terms of 
expertise and advice as to what we need to do.

                          PARKINSON'S DISEASE

    Mr. Porter. There are some studies that suggest that over 
90 percent of late-onset Parkinson's disease may be due to 
environmental factors. Can you tell us what you are doing in 
that area.
    Dr. Olden. Yes. We are collaborating. As a matter of fact, 
the National Institute for Neurological Diseases and Stroke is 
the leader in the NIH, and they brought together three other 
Institutes--Aging, and Mental Health and my Institute--together 
in partnership, and we have identified a research agenda to 
address Parkinson's. There is both a genetic and environmental 
component. So we put in place an agenda to address those 
issues.
    NIEHS is looking at four things. We are looking at 
industrial chemicals, agricultural chemicals, which all have 
been reported to be risk factors, exposures to industrial 
metals--that is, occupational exposure--and finally we are 
supporting research on the basic biology of exposures to these 
agents. There is evidence that the whole biological cascade has 
something to do with protein degradation. And so we are 
supporting research at the Parkinson's Foundation to look at 
how the proteins that are involved in Parkinson's, they are 
also involved somehow in the protein degradation cascade. And 
so those are the four.
    Another area we are looking at is susceptibility. A number 
of our investigators are looking at the genetic bases of 
susceptibility, focusing on various enzymes that are involved 
in the metabolism of environmental genome biotics.
    Mr. Porter. Thank you, Dr. Olden.
    Mr. Jackson?

                           HEALTH DISPARITIES

    Mr. Jackson. Mr. Chairman, I have no further questions at 
this time. Thank you, sir.
    Mr. Porter. Ms. Lowey?
    Dr. Olden. May I just respond on one thing to Congressman 
Jackson?
    Mr. Jackson. I would be happy to engage.
    Dr. Olden. When you asked me did I know Dr. Yvonne Maddox 
and Dr. Tony Fauci, not only do I know them, I am working with 
them on the committee along with all of the Institute 
directors. They chair the committee, but Dr. Kirschstein asked 
all of the Institute directors to be active and involved, and I 
am interested in this issue and have been my whole life, 
obviously. When I came on in 1991 as director of the Institute, 
I immediately put in place a program to address environmental 
justice, which is our piece of health disparities, and I did so 
because of having served as director of a cancer center in 
Washington, D.C., I was well aware of the fact that many of the 
cancers are probably related to the environment, and people do 
not control where they live and work. They are there because of 
their educational level and poverty.
    And so I was very sensitive to issues related to poverty, 
race and ethnicity, and we developed a research program that I 
am proud of, that responds to these issues.
    Mr. Jackson. Let me say, Dr. Olden, I appreciate hearing 
that from you. But at least appreciate it from my perspective 
that oftentimes it is not so obvious. And when I look across 
the money that this committee is asked to appropriate for 
various Institutes, Centers and offices at the NIH, it is very 
clear that the absence of minority researchers who are not 
performing substandard research are absent, and I am trying to 
get to the bottom of that and find out what we can do to 
increase the likelihood that those who are interested in 
research might, indeed, be able or willing and have the 
opportunity to do that research with the NIH.
    And so I appreciate your interest and obviously your 
commitment. I thought very interesting that most of your resume 
has Howard University accolades associated with it, various 
fellows and various types of honors that the Howard University 
had bestowed upon you. But while at Howard University, you sat 
before this committee a few minutes ago and said that you were 
at Howard, in the middle of Howard Medical School, and could 
not find part of the answer to the pipeline problem. You looked 
outside of Howard.
    And then when I asked you now, as the director of the 
Institute for Environmental Health Sciences, what are you doing 
about it, and you said, well, you did not see it at Howard 
University's campus, you saw it somewhere out in Maryland, 
which I, you know, respect. I just think that oftentimes when 
we say we are trying to address some of the pipeline issues, we 
may not necessarily be looking in the right place. And I am 
sure if Dr. Louis Sullivan were here today, he would say that 
he has a sufficient amount of pipeline students at Morehouse.
    Dr. Olden. And we are supporting two programs at Morehouse 
to deal with the pipeline problem. I think we are supporting 
about $300,000 worth of pipeline problem issues at Morehouse.
    So we are going a number of places, Mr. Jackson. Morehouse 
is one of them.
    Mr. Jackson. I appreciate that, Dr. Olden.
    Thank you, Mr. Chairman.

                        EDUCATION OF PHYSICIANS

    Mr. Porter. Dr. Olden, I am going to ask you a question 
about DES and the need for education of physicians and 
patients. But I would like you to answer it in a broader 
context about any other similar types of problems.
    NIH estimates that almost 5 million women took DES, which 
is diethylstilbestrol, between 1938 and 1971. Apparently, this 
was a drug to prevent premature labor. Preliminary results from 
a national research and education program that was started in 
1992 points to potential health problems throughout life for 
those exposed to DES, not just as adolescents and young adults 
as once thought. Also, new findings from animal research 
suggest that DES may affect the granddaughters of the original 
DES mothers, as well. These findings highlight the need to 
educate the medical community that women who were exposed to 
DES and their families need to be watched more closely.
    What are you doing to educate physicians and patients about 
these findings and what are you doing to educate the physician 
community about the findings that your Institute makes in 
regards to other toxic materials and substances?
    Dr. Olden. Thank you. The studies you cite about the 
granddaughters were done at NIEHS by an investigator named Dr. 
Retha Newbold. And that is a very interesting study because we 
thought that it was only the first generation of women who were 
exposed in utero that would be at increased risk for certain 
cancers. But clearly, her studies with animal models suggest 
that the granddaughters may also be at increased risk for 
cancers.
    We started a number of years ago--in fact my predecessor 
started--an environmental and occupational health training 
program for physicians. What we tried to do through that 
program is to get incorporated into the training of physicians, 
while they are in medical school, information about 
occupational and environmental medicine. That program is still 
ongoing.
    So it is okay, but it is not adequate, probably. When we 
started the program, I think the estimate was that physicians 
were getting roughly four hours of occupational and 
environmental medicine training. The last time we did a review 
of our program, it had increased some and it was something like 
six hours rather than four hours. That is not enough.
    So the other thing that we are considering is to have 
continuing medical education for physicians who are in 
practice, to bring these issues. And certainly we have been 
talking with the Association for Physicians for the 
Environment, to see if we could develop that kind of activity.
    But there are so many physicians who were already in the 
practice of medicine--were out of medical school by the time we 
initiated our training--and so they clearly did not get much 
training in occupational or environmental medicine, unless they 
chose that as a specialty.
    So we have training programs in medical schools, but we 
probably need to do more. In other words, develop continuing 
medical education training courses.

                        OCEANS AND HUMAN HEALTH

    Mr. Porter. Dr. Olden, thank you. Finally, are you doing 
any research in the area of oceans and their relations to human 
health?
    Dr. Olden. Yes, we are. We have been very interested for 
years in the interrelationship between human health and the 
health of other plant and animal species. One of the first 
indicators that there are pollutants in the environment that 
may represent a threat to human health is often obvious in 
marine and freshwater environments.
    So we have been supporting research for a number of years. 
As a matter of fact, we have five marine and freshwater 
biomedical research centers. The main purpose of these centers 
is to develop alternative models. Many of the marine species 
make excellent models for toxicity testing and evaluation. So 
that is one objective.
    But the other one is also to use them as sentinel species, 
as biomarkers for changes in the environment. For example, the 
pfisteria outbreak that happened in this region about two or 
three summers ago in Congressman Hoyer's district, I believe, 
in Maryland along the Eastern Shore, and also in North 
Carolina.
    So we supported most of the research that has been used to 
prevent further outbreaks in subsequent years. And now we have 
a major project at the University of Maryland in Baltimore, in 
fact, to clone the genome of pfisteria because the problem was 
that we did not recognize when the numbers were increasing, 
because pfisteria has 24 different disguises and it is only one 
that we recognize, and that is the one that is harmful. It 
would be helpful if we had a DNA fingerprint to identify that 
microorganism.
    So now we are generating that through a grant at the 
University of Maryland. It is a partnership between Johns 
Hopkins and Maryland.
    Mr. Porter. Dr. Olden, thank you for the outstanding job 
that you are doing at NIEHS. It has been a real education and a 
real pleasure to have you up here before this subcommittee. I 
have luckily been here the entire time that you have been at 
NIEHS and have been able to hear you each year.
    We can tell the enthusiasm that you bring to your work. It 
is very evident the knowledge that you bring to your work. We 
are very thankful that you are in that position and doing so 
well for NIEHS.
    Dr. Olden. Thank you very much and I have enjoyed appearing 
before this committee.
    Mr. Porter. Thank you for appearing.
    We will stand briefly in recess.
    [The following quesitons were submitted to be answered for 
the record:]



                                        Tuesday, February 29, 2000.

        NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

                               WITNESSES

GERALD D. FISCHBACH, M.D., DIRECTOR
AUDREY S. PENN, M.D., DEPUTY DIRECTOR
KEVIN E. KIRBY, EXECUTIVE OFFICER
ANDREW C. BALDUS, BUDGET OFFICER
DR. RUTH L. KIRSCHSTEIN, ACTING DIRECTOR

        national institute of neurological disorders and stroke

    Mr. Porter. The subcommittee will come to order.
    We continue our hearings on the budget for the National 
Institutes of Health with the National Institute of 
Neurological Disorders and Stroke. We are very pleased to 
welcome Dr. Gerald D. Fischbach, the Director.
    Dr. Fischbach, it is wonderful to see you. We hear so many 
good things about the job you are doing within NIH. We are 
anxious to have you tell us what your Institute is doing; and, 
in that process, I would ask you to give us some understanding 
from your perspective as to how we can show that the increases 
at NIH are being well spent, are justified, and are being spent 
for good science.
    Dr. Fischbach. I will try. Thank you, Mr. Porter.
    I would like, before beginning, to introduce Dr. Audrey 
Penn on my left, the deputy director of NINDS; Mr. Andy Baldus, 
our financial officer; and Mr. Kevin Kirby, who is the 
executive officer of the institute. Ruth has already been 
introduced.
    I just want to add that for years before I came to the NIH 
I thought of Ruth as the soul of the NIH in many ways, and she 
is demonstrating now that the brain and the soul are actually 
more connected than many people might think. It is a pleasure 
to have her here.
    I will try to pay attention to the issue that you raised.
    I am pleased to present the President's 2001 budget which 
for NINDS amounts to $1,085,000,000, an increase of $55 million 
over last year.
    I became director of NINDS about 18 months ago with great 
respect for the institution and enormous enthusiasm. My 
enthusiasm has grown every week on this job because advances in 
neuroscience have continued at an incredible pace with direct 
impact more than ever on the burden of brain disorders. My 
enthusiasm has grown because of the generous support of the 
public, largely steered there by this committee and your own 
efforts, Mr. Chairman; and I think the entire scientific 
community is grateful for that. Although your term is coming to 
an end, I do hope you will not be far from the biomedical 
enterprise.

                           STRATEGIC PLANNING

    My enthusiasm has also grown because we have a wonderful 
staff in the institute, and many of them are here, who have 
initiated a very productive and powerful and, in my view, a 
very successful planning process.
    I discussed last year the reorganization of our institute 
into planning panels and clusters and announced our first 
strategic plan, Neuroscience at the New Millennium, which 
stated very clearly what our vision was, what our goals were, 
and now I want to add to that, this supplement, which is the 
implementation update as of this month. It is rather rewarding 
to review that implementation program. We don't want to just 
develop plans and leave them alone. We want to implement them. 
The degree of progress, which I will mention a little bit, has 
been remarkable.
    We planned on a level of basic science, based on a need to 
translate basic science into clinical, patient-oriented 
research. We have taken into account the changing nature of 
science, that it is moving towards more consortium 
arrangements, new funding mechanisms, and we have responded to 
a need to coordinate our efforts within the institute, between 
NIH institutes--and I will mention some of the collaborations--
and between agencies within the government.
    We have initiated programs with the VA on Parkinson's 
disease and with the Department of Defense on 
neurofibromatosis. We had a meeting yesterday with the National 
Science Foundation for a growing program in neurocomputation 
and with the FDA working on new problems in implantable devices 
and in stem cells for neurological research. So I think the 
planning process is well underway.

                        USE OF FUNDING INCREASE

    Before describing our plans for fiscal year 2001, I would 
like to review a little bit about how we spent our money in the 
past year and why I think it has been wisely spent. We had a 
large increase 2-years-in-a-row in our budget of about 15 
percent. We have used that in several ways.
    In the first instance, we increased the number of new 
grants that we funded by a total of 202 in 1999, and in 2000 it 
will level off a bit to an increase of 24. Our success rate has 
increased from 28 to 35 percent. We have decreased the cut in 
each grant, and the cost of each grant has gone up to about 
$335,000 per grant. That sounds like a big number, but when you 
subtact the indirect cost and subtract what an investigator 
needs to pay in salary support, it leaves about $50,000 maybe 
$70,000 for animal costs, supplies, and crucial small pieces of 
equipment, barely enough to support a lab of three or four 
people, let alone a lab of 10. So while the funds are 
increasing, I feel that we are catching up from several years 
of real shortfall.
    My thought is that in these new grants we are funding 
superb science. The evidence I can offer comes at different 
levels. First, my own reading and I think the reading of 
experts in the field, of the grant applications, is that they 
are better now than they have ever been before and informed by 
many new techniques. So the success rate increasing to 35 
percent is justified certainly in the area of neuroscience.
    You can see it in the quality of research publications at 
both the basic science and the clinical levels. The number of 
journals has increased, and the quality of the reporting is 
actually breathtaking. You can see it in the growth of the 
biotechnology industry. You can see it in the fact that we are 
attracting the very best and the very brightest people in all 
of undergraduate science to come into biomedical science and 
into neuroscience in particular.
    The Society of Neuroscience continues to grow from 500 
people in the early '70s at its founding to over 28,000 today. 
I think the U.S. now is the envy of the world in terms of its 
biomedical science. Half of our research population and our 
meeting participants are from abroad. Most of our trainees are 
here from abroad. Hopefully, they will take what they have 
learned through NIH funding back to their own countries.
    I think in the long run we also see an improvement in 
health care. If it was me--and I know this sounds like a bald 
statement--I would rather have a stroke today than 5 years ago. 
I would much rather have my diagnosis of multiple sclerosis, or 
intractable epilepsy, or Parkinson's disease made today than 5 
years ago mostly because of very recent advances in each one of 
those fields.
    I think we are seeing the payoff. You can't see it year by 
year, but over the course of 5 or 10 years I think it is very 
clear. I think we are spending our money well.

                          PARKINSON'S RESEARCH

    In addition to the grants, the increase in our funding 
allowed us to fund eight new Morris K. Udall Centers of 
Excellence in Parkinson's disease research. We were initially 
scheduled for four, but we funded eight. That brings us to a 
total of 11. That group is meeting on March 3 in Atlanta to 
plan together in a newly collaborative effort ranging from 
basic science through new clinical trials. Eighty investigators 
will assemble, and I think they represent a significant force 
in the field of neurodegeneration, research which I will say a 
bit more about in a moment.
    We have had new initiatives in exploratory grants in 
pediatric neurological disorders including Friedreich's ataxia, 
Rett's syndrome, and a number of others. We have instituted a 
very novel call for proposals and a remarkable new therapy 
involving deep brain electrical stimulation which has proved so 
effective in selected cases of Parkinson's disease and which 
appears to have applicability in cases of intractable epilepsy 
and in other disorders as well. Although it seems successful, 
there is a tremendous amount to be learned about electrode 
design, exact placement of the electrodes, and the limits of 
use of this technology in conjunction with more traditional 
medical therapies.

                   INFRASTRUCTURE SUPPLEMENT PROGRAM

    We have instituted an infrastructure supplement program 
which all of our advisors and our council suggested that we do. 
We funded that at the level of $20 million last year where we 
replaced desperately needed pieces of equipment, outmoded 
microscopes and centrifuges, which are crucial for the entire 
enterprise. We had 1,800 grantees, and we received 1,500 
applications. I suspect that means everyone because people 
doubled up on some of them.

                           PLANS FOR FY 2001

    As for our plans for 2001 I want to emphasize four areas 
before the questions.
    First, we want to maintain our efforts in 
neurodegeneration. We want to mount, as we say in our plan, an 
attack on neurodegenerative disorders over the entire life 
span, from birth to old age. The scope of neurodegeneration I 
don't think is generally appreciated by the public. Certainly, 
the classic neurodegenerative disorders of Alzheimer's disease, 
Parkinson's disease, amyotrophic lateral sclerosis, and 
Huntington's disease are included. The neurodegenerative 
disorders of childhood, Friedreich's ataxia, cerebral palsy, 
and many others are in that category. But neurodegeneration is 
ubiquitous. The same processes occur, although they are not the 
primary cause, in epilepsy and in multiple sclerosis. Even 
disorders traditionally thought of as mental disorders like 
depression and chronic stress are now clearly associated with 
ongoing debilitating neurodegeneration.
    I believe there are reasons for hope in this series of 
intractable disorders, not the least of which is we understand 
much better now than we did 2 or 3 years ago how cells die in 
the nervous system. Regardless of the inciting cause, many of 
them follow a single common pathway of enzyme activation and 
self destruction. Cells dying in the spinal cord of patients 
with ALS die in much the same way as cells die in substantia 
nigra of patients with Parkinson's disease, or as they do in 
the cerebellum of children with Friedreich's ataxia. We just 
have to intervene in that process to make enormous gains.
    Now, there is a crucial need for early diagnosis. I think 
there is hope in this regard, too, from two fronts. One is the 
genomics. The completion of the genome project is providing 
tools for us to make diagnoses on blood samples. But also the 
expanded use of modern, sophisticated imaging techniques should 
allow us to detect neurodegeneration before it is clinically 
evident.

                           MULTIPLE SCLEROSIS

    I want to show you in three posters an example involving 
multiple sclerosis--this is not a new finding, but this year 
its wide applicability in following treatment and early 
diagnosis has become manifest.
    These are two MRI images. On the left is a normal MRI, and 
on the right is one that has been enhanced by gadolinium, a 
rare earth element. What is striking here is that gadolinium 
crosses the blood brain barrier and stains--makes white--new 
lesions which are either invisible or barely detectable by the 
usual MRI image. This ability to detect very early lesions has 
revolutionized therapy in multiple sclerosis.
    The next slide shows that we do have an effective therapy 
in this disorder. There are several interferons now, without 
becoming proprietary about it, these interferons can reduce the 
number of gadolinium-stained new lesions to a very, very low 
level. That is a very dramatic curve, repeated now in many 
different studies.
    The payoff is in the next diagram where you can see the 
course of typical multiple sclerosis, which is called a 
relapsing and remitting disease. There are pulses of activity 
when patients are severely debilitated followed by periods when 
they seem to be in remission. It is now clear using the 
gadolinium scan that even those patients in remission are 
developing new lesions even when not symptomatic. Clinical 
practice has changed so that people in remission are being 
treated now with interferon with the clear result that severe 
disability is postponed and reduced. I have used this as an 
example of the need for early markers before the disease has 
worked its damage so that early intervention can minimize the 
effects of neurodegeneration.

                          PARKINSON'S DISEASE

    Parkinson's disease remains--still on the topic of 
neurodegeneration--one of our top priorities, and we have 
completed a report requested by Congress on a 5 year strategic 
plan for Parkinson's disease which is due March 1. I would be 
glad to answer as many questions about that as possible. The 
planning process involved extramural and intramural scientists 
and virtually every advocacy group in the Parkinson's 
community. I think we are all gratified with the process.
    In addition to degeneration, we want to emphasize 
regeneration and repair of the nervous systems. Our programs in 
prosthetic devices have developed exciting new ways of 
stimulating the nervous system to produce hand grasp in spinal 
order injured patients. There are, as I am sure you know, 
extremely promising results in animal studies of stem cell 
biology which offer promise in many areas of regeneration and 
repair.

                           HEALTH DISPARITIES

    One of our areas of emphasis has been for some time the 
issue of health disparities. This is a huge problem, and I 
think Ruth and others have recognized it. It requires the 
coordinated effort of the entire NIH, but NINDS has a long 
history in this area. We are proud of a new Office for 
Specialized Programs in Neuroscience, established in November 
of 1998 that is headed by a very talented program director, Dr. 
Al Gordon, to focus on increasing the number of scientists at 
predominantly minority institutions. The budget for this 
program, with the help of John Ruffin, has grown from $6 
million in 1998 to $23 million this year; and we project an 
increase under the President's FY 2001 budget of up to $26 
million. If possible during the question and answer period I 
would like to discuss these programs and other areas of 
outreach.

                 NATIONAL NEUROSCIENCE RESEARCH CENTER

    I would like to end by talking about an effort now under 
way at the NIH to create a National Neuroscience Research 
Center. This is stimulated by the realization of several of us, 
especially Dr. Steve Hyman of Mental Health and myself, that 
neuroscience has advanced to the point where these fields are 
coming together. The difference between traditional neurology 
and psychiatry is disappearing. The basic science underlying 
disorders of mood and movement is exactly the same, and studies 
of motivation and addiction are converging in the same 
direction.
    We feel that the field would be served by bringing 
scientists together across Institute boundaries and across the 
disciplines of clinical research and basic science research 
into one facility to focus on translational and patient-
oriented research. It is an extraordinary time in the history 
of the NIH. We are discussing this with several Institutes 
interested in contributing to the Center.
    I remember we discussed this at the very first meeting I 
had with you when I first arrived on the scene. You wondered 
whether the excellence of the intramural program could be 
restored to its tremendously significant history of the early 
'70s, late '60s, when it seeded programs throughout the 
country, certainly in the area of neuroscience. I am convinced 
that it can. I think the excellence can be raised. I think we 
can put the brain back together and in the process save 
enormous amounts of dollars in the intramural programs. This 
comes along with the hope for a new physical structure to jump 
start all of the reorganizational efforts.
    I am optimistic about the intramural program in setting an 
example, being a role model for programs throughout the 
country, actually. There should be much closer interaction 
between neurology, psychiatry and the basic neurobiology 
departments in the extramural community. I am optimistic that 
the field of neuroscience will move in a much more coordinated 
way. I would be glad to answer any questions about any of that.
    Mr. Porter. Thank you, Dr. Fischbach.
    [The written statement of Dr. Fischbach follows:]



                       FROM DISCOVERY TO PRACTICE

    Mr. Porter. Earlier you had alluded to the movement of 
discovery into practice. I think you said that today, for 
multiple sclerosis, a new imaging technique is being used. Can 
you give us an overview of what you see in general regarding 
the movement of discovery and bringing it into practice and how 
we educate practitioners to use new techniques and new 
approaches that you--that have been discovered through NIH?
    Dr. Fischbach. The education question is a very interesting 
one. The movement of discovery into practice I really do 
believe is a critical issue. It is much harder than we first 
imagined. We have developed new grant mechanisms by which 
individuals can travel between labs and collaborate with each 
other on a much more intimate basis than ever before. People 
working on spinal cord circuits can interact with those 
interested in rehabilitation and repair so that they can 
develop rehabilitation strategies based on what we know of the 
circuits. You can repeat that in every area.
    In Parkinson's disease, the need for stimulating the brain 
is based on years of experimental work in subhuman primates to 
understand the basic circuitry in the basal ganglia. The need 
now is to get the circuit and cellular neural science together 
with neurosurgeons in the operating room who can think more 
clearly about the unique features of human circuits. I think I 
can repeat that in virtually every disease that we study.
    In every step of the way there is a need to educate 
physicians. We have a remarkable success story in the area of 
stroke therapy. Tissue plasminogen activator, injected 
intravenously within 3 hours of the first signs of a stroke, 
can reverse the symptoms of an ischemic stroke. There is a 
small subpopulation of hemorrhagic strokes in which that 
doesn't occur. In fact, the TPA is a real threat and a danger. 
So physicians must be educated to recognize those symptoms, and 
we have a large public education effort under way to try and do 
that.
    Mr. Porter. There are, I think, something like 145 medical 
specialty societies. Is there a direct program between NIH and 
its various Institutes with going to those medical societies 
and educating their members? What do we do in a formal way--
because that seems to me where they meet and have their ongoing 
education programs as often through these societies, and it 
seems to me that would be a way to get discovery more quickly 
into their minds.
    Dr. Kirschstein. Yes. Most of those medical specialties 
have special societies and special conferences. Our staffs 
attend all of the meetings. They have exhibits with the newest 
findings. They talk to them about the newest activities, and 
they participate in the continuing medical education aspects of 
the speciality. Most medical specialties require that their 
physicians take continual medical education and pass their 
boards on repeated occasions now so they keep up with the new 
things that are going on.
    Dr. Fischbach. Going on, Audrey and I have spent a lot of 
time with the American Academy of Neurology and the American 
Neurosurgical Association to attempt to inspire them to move 
beyond the traditional notions of how they practice their 
medicine to reach out and adopt these techniques. I think that 
is a major issue.

                      REPLACEMENT OF LAB EQUIPMENT

    Mr. Porter. You said something about replacement of lab 
equipment, and I am not sure whether you meant that 
intramurally or extramurally. If you meant it extramurally, why 
wouldn't that be done by the Center for Research Resources at 
NIH?
    Dr. Fischbach. The NCRR has been wonderful in sponsoring 
programs for large pieces of equipment, $250,000 on up to a 
million dollars, very vital for new technologies. But our 
infrastructure program last year focused more on everyday 
pieces of equipment. People who had 10- and 15-year-old 
microscopes or outdated rotors for centrifuges could apply for 
one-time-only supplements to their grants. It has been hard in 
past budgets, given the numbers that I gave you with $70,000 
left for supplies, to apply for and receive equipment on our 
R01 grants. I think more often than not the equipment was cut 
from grants, and now more often than not the parent 
institutions have not been able to provide the funds. So this 
is a more grassroots infrastructure.
    Mr. Porter. Is this done in every institute?
    Dr. Fischbach. I think it is a growing interest, but I 
don't think so.
    Dr. Kirschstein. Over the years I think many institutes 
have done this. In the days when I was the director of the 
National Institute of General Medical Sciences we did a good 
deal of that for just the types of instruments that Dr. 
Fischbach has mentioned. I think different institutes feel that 
the needs of their particular grantees are different. There is 
not an across-the-board program. It really should be 
individualized to the needs of particular types of grant 
applications and grants that are made.

                         BRAIN CELL REPLACEMENT

    Mr. Porter. This is a question designed to simply let me 
understand what you were telling us earlier. I think we know 
that, for example, brain cells are continually growing. It used 
to be thought that from the time of birth we had a finite 
number brain cells, and now we believe that we actually grow 
new ones. Am I correct so far?
    Dr. Fischbach. So far.
    Mr. Porter. Basic knowledge. You talked about cell death in 
enzymes and interventions. Is this part of the same process--in 
other words, presumably, if we can prevent cell death, then we 
have done something that obviates any problem with cell growth 
or cell regeneration. Are we talking about the same thing?
    Dr. Fischbach. We are. It is like an equilibrium. The 
number of cells you have is a balance between the number you 
are producing and the number that you are losing. Simple 
kinetics.
    The notion of cells replenishing the store in the adult 
brain is a brand new concept. There is some evidence for it. It 
has been known for some years in rodents and subhuman primates 
that one region of the brain, a very critical region for memory 
called the hippocampus, had a population of cells that could be 
replaced, as does the olfactory system. Cells in the epithelium 
of the nose and in the first relay of the brain seem to be 
replaced on a scale of every 120 days; about half of the cells 
are replaced. But it was not thought and it is still very 
controversial whether the cells are replaced anywhere else in 
the huge universe of the brain. It is hoped that that is true.
    There is some evidence that there are stem cells in the 
adult brain, very rare though. So I don't think that the battle 
in our lifetime is going to be won by promoting the formation 
of new nerve cells. I think the battle is going to be won by 
preventing the degeneration of the ones that we have. But it is 
true that there is an increasing interest in the production of 
new nerve cells in our adult human brain.
    Mr. Porter. That is exactly what I wanted to know. Thank 
you, Dr. Fischbach.
    Ms. Pelosi.

                          ALZHEIMER'S RESEARCH

    Ms. Pelosi. Thank you, Mr. Chairman.
    Thank you all for your testimony and your excellent work.
    Dr. Fischbach, I was struck by your testimony and 
accompanying material that there really wasn't a great deal 
said about Alzheimer's. Is that the Institute of Aging or is 
that yours, too?
    Dr. Fischbach. No, that is ours, too. We have a large 
program in Alzheimer's disease basic research. This is an area 
of interesting and I think very productive overlap and 
increasing cooperation with aging. It does happen that 
Alzheimer's disease increases in prevalence with aging. But 
Alzheimer's is not directly caused by aging. In fact, 
Alzheimer's disease can begin quite early in life, in the 40s 
and 50s. So we have a very large commitment in grants. Indeed, 
there are many scientists who feel there is a spectrum between 
Alzheimer's disease at the one end and Parkinson's disease at 
the other--Parkinson's alone, Parkinson's with dementia, 
Alzheimer's disease with certain movement disorders, 
Alzheimer's disease and memory loss in isolation. So we are 
interested in the whole spectrum.
    Ms. Pelosi. I thought maybe there was not as much reason to 
be helpful in the Alzheimer's investigations because you didn't 
mention it that much in your testimony.
    Dr. Fischbach. The reason we have been focused a lot on 
Parkinson's disease is that starts in a locus of the brain that 
we know a lot about and there are promising medical and 
surgical therapies. Alzheimer's disease is more global. I don't 
mean to sound less hopeful, but if I were pushed I would say 
prospects for advances in Parkinson's disease are more 
immediate.
    Ms. Pelosi. I have no complaint of what you are doing in 
Parkinson's, and I commend you for it. Of course, all of us who 
served with Mo Udall saw firsthand the impact of it.
    As far as Alzheimer's is concerned, we have had people 
testify who were 45 years old, breadwinners of their family, 
children going to college, and now afflicted with Alzheimer's 
disease in their middle 40s in a crucial time of life for 
themselves, but especially for their families. I appreciate 
what you are saying, it not being so directly associated with 
aging.
    Let me start at another place. When we had the Wise Persons 
Panel any number of times here in the Decade of the Brain, we 
were told over and over again that the greatest area for 
scientific opportunity was the area of the brain, is that not 
correct, Mr. Chairman? And I was hoping that would also apply 
to Alzheimer's, seeing as how it affects so many families in 
America. I was on the plane last night coming here, and a young 
man was coming back from a conference from a pharmaceutical 
company and said that they were on the brink of finding a cure 
for Alzheimer's, which I found to be quite interesting. I 
assume that you don't know anything about any hopeful 
opportunities?
    Dr. Fischbach. I do. I believe that there have been a lot 
of advances in understanding how a dreaded protein, beta 
amyloid, is produced and how it accumulates in the brain. In 
the last year a long-sought mythical enzyme that destroys this 
protein, which forms clots in the brains of Alzheimer's 
patients, has been discovered and purified. A lot of that was 
done in private industry based on NIH-funded research. There is 
hope now that that enzyme has been identified to develop 
inhibitors and prevent the deposition of amyloid. So I think 
there are reasons for hope. Five or 10 years ago Alzheimer's 
disease was unthinkable as a therapeutic target. Now there is a 
lot of hope.
    Ms. Pelosi. Do we have sufficient resources as far as grant 
applications in this area?
    Dr. Fischbach. There are a lot of opportunities. There are 
Alzheimer's disease research centers. The area of Alzheimer's 
research is well funded. It could always use more. I want to 
reiterate that I think some of the very best science in 
neuroscience now is being driven by the disorders much more 
than in the past. People are entering the field of protein 
chemistry because of an interest, the passion that was 
mentioned earlier and interest in Alzheimer's disease.

                          STROKE IN MINORITIES

    Ms. Pelosi. When we talk about stroke, again we could have 
this question of almost every institute administrator who comes 
before us. Obviously, there is a high incidence in the minority 
community, for a wide variety of reasons. Could you talk a 
little bit about that to the committee?
    Dr. Fischbach. Stroke is----
    Ms. Pelosi. I am glad to hear that you would rather have 
one now than 5 years ago. Hopefully, no one has to have any, 
but this disparity has been of concern to the committee for a 
long time.
    Dr. Fischbach. The disparity is enormous. It is probably 
the most glaring and one that we must understand in the next 
few years. My numbers show that, even in the stroke belt and 
the buckle of the belt, the disparity between minorities and 
whites is probably between two- and fourfold. If I have the 
opportunity I will talk about our specialized neuroscience 
programs in that area at Morehouse College.
    Ms. Pelosi. That stimulated my questions, actually, as to 
the work of Morehouse College.
    Dr. Fischbach. Several years ago I initiated a program for 
building research capacity at Morehouse College, whereby we 
established a cooperative agreement to help that school build 
in the area of neuroscience, recruit faculty, write NIH grants 
and grow in size and influence the entire medical school. Based 
on the success of that program, we issued an RFA and are doing 
it at five other predominantly minority schools around the 
country.
    The interesting thing at Morehouse is we are beginning to 
move beyond building capacity to addressing this issue of 
stroke. And in collaboration with the Heart, Lung and Blood 
Institute, which also has a program at Morehouse, we developed 
a challenge to Morehouse to develop programs dealing with 
stroke in the population, prevention, novel methods of 
treatment involving the community, and many more 
epidemiological and clinical trials. We now have seven clinical 
trials funded around the country addressing the issue of stroke 
and the minority population. We feel that the involvement of 
the local community of minority scientists would be an enormous 
help in bringing fresh ideas and methods to the study. But it 
is a beginning.

                            HEALTH DISPARITY

    Ms. Pelosi. It is a long overdue beginning, I must say. We 
have known for a while about the disparity, but I am pleased to 
hear about the initiatives and that Morehouse School of 
Medicine is playing such an important role.
    Mr. Chairman, as we saw the charts on multiple sclerosis 
and the impact of improved instruments and the genome project 
and also the need for early intervention that was mentioned in 
terms of multiple sclerosis, I think it drives home the point 
even more clearly, the need for access to quality health care 
for all Americans even more strongly, because to the extent 
that we can catch these things early--and if you are not in the 
loop of health care, they are not going to be caught early. And 
if you can catch it early, the early intervention, as you said, 
is crucial.
    But the moral responsibility that we have is even greater 
since we have so much more opportunity with the genome project 
and the instruments, improvements in imaging that we have, that 
while we will take these strategies that you have talked about 
at Morehouse School of Medicine and all of those discrete 
initiatives, it is very positive initiatives, we have to back 
up and look at access to quality health care if we are going to 
address those disparity issues in this country. If you would 
like to comment----
    Dr. Fischbach. I absolutely agree. I think it is becoming 
even more acute as new therapies, which are going to be limited 
initially, surgical therapies, cell implantation therapies, 
therapies that depend on very sophisticated technology are not 
going to be widespread initially. We have to be sure right from 
the beginning these are equally distributed and people have 
equal access and an equal voice in deciding about which 
therapies can go forward and which can't. So I agree.
    Ms. Pelosi. Thank you, Dr. Fischbach, Administrator 
Kirschstein, and Dr. Penn. Thank you for your leadership and 
for your testimony.
    Thank you, Mr. Chairman.
    Mr. Istook [presiding]. Thank you, Ms. Pelosi. Obviously, 
when you weren't looking, we pulled a little switch on you. 
Chairperson Porter had to go on.
    Dr. Fischbach, Dr. Kirschstein, Dr. Penn, gentlemen, I am 
pleased to be with you. But I believe Mr. Jackson is next. Mr. 
Jackson, you are recognized.
    Mr. Jackson. Thank you, Mr. Chairman.
    I thank you, Dr. Fischbach, for being present today.
    The President's fiscal year 2001 budget for NINDS is 
$1,100,000,000, an increase of $54,300,000 and a 5.5 percent 
increase over fiscal year 2000. Included in this total is 
$20,800,000 for the following NIH areas of priorities: biology 
of brain disorder, $7,400,000; new approaches to pathogenesis, 
$2,000,000; new preventive strategies against disease, 
$1,900,000; new avenues for development of therapeutics, 
$3,200,000; genetic medicine, $2,000,000; bioengineering, 
computers, and advanced instrumentation, $3,100,000; and health 
disparities, $1,200,000.
    You indicated that in your opening remarks that was an 
increase to $24,000,000, which at some point in time in the 
not-too-distant future you hoped to move that number to 
$26,000,000. My calculation in math--and I may be wrong; I 
didn't do very well in math when I was in school--it took us to 
24. $26,000,000 is about 2.4 percent of $1,100,000,000.

                            STROKE RESEARCH

    I was reading--I went to a used bookstore this weekend and 
bought a number of books on family medical prescriptions--which 
I would imagine would be medical school 101 for a lot of 
people--because a lot of the language that is used in this 
committee are very difficult for me, but I am learning a lot 
about the sciences in this examination period.
    I was reading under stroke. It said, ``Those at risk, 
people who have hypertension and atherosclerosis, are the most 
likely to suffer a stroke since both diseases weaken and damage 
the arteries. Hypertension probably also encourages hemorrhage. 
Heredity may play a role in stroke since the tendency to 
develop both hypertension and atherosclerosis appear to be 
inherited. Black persons, it says, are more susceptible to 
stroke because of high blood pressure, about twice as common in 
the black population as in the white population.''
    You mentioned some of the work that you are doing at 
Morehouse College. While the committee is considering an 
increase in your institute for the outstanding work that you 
all are doing, I am wondering if, since it is clear that high 
blood pressure, for example, is a factor, for example, in 
African Americans, what percentage of that increase is being 
used for addressing the education associated with high blood 
pressure. And since it is clear also that fatty acids or fatty 
materials are also a function in slowing down the amount of 
blood that gets to the brain, I am wondering if any studies or 
RFPs have been issued on the impact of fried food or fried 
chicken or fried fish or fried anything and the likelihood that 
certain communities are more likely to have their food fried 
than baked and, as a result of that, increase the likelihood 
that they may one day have a stroke.
    Dr. Fischbach. One reason we are focusing on the 
predominantly minority schools is we believe these issues are 
tremendously important. The best way to intervene in the local 
community is by using the local community in trying to 
understand these issues better, always emphasizing the quality 
of the studies and the investigators involved.
    We are proud of the Morehouse program and the five other 
programs that we are funding. Several of the epidemiological 
studies now underway are addressing issues of diet and genetics 
relating to hypertension. The education component of that is 
going to be critical. It is going to involve the entire 
community outside the medical school.
    First, we have to document what we all suspect is the cause 
of the hypertension. It is a lot of rumor and innuendo, but we 
have to document it with hard data. I think a large fraction of 
the studies in our stroke programs will focus on identifying 
these factors.
    We are also very interested in prevention. Black people do 
not only have a higher incidence of strokes, they do worse with 
them. If you have a stroke, a black person is more likely to 
die with a stroke than a white person.
    We have to intervene at all levels and understand the 
prevention, the intervention, and the treatment of stroke and 
getting that more widely disseminated. All of those account for 
big fraction of our increase.
    The $23,000,000 and $26,000,000--I just want to add a 
note--are related only to this office of specialized 
neuroscience programs. We have other programs outside that 
office which are also focused on these issues and on other 
disparities, including diabetes, trauma, HIV infection. You 
know them as well as I do. There are many others.

                       DIETARY FACTORS AND STROKE

    Mr. Jackson. I guess I have one final question. I was 
wondering whether or not you were aware of any RFPs that go to 
the issue of these fatty foods and a study of diets in various 
parts of the population to find out what differentiating 
dietary factors might be a factor in incidences of stroke. And 
where is the stroke built? You mentioned in your remarks about 
stroke built----
    Dr. Fischbach. I think many institutes, not so much yet the 
neurology institute, have been very interested in diet and the 
impact on health. This is a problem that transcends NINDS, and 
it is a huge one in the American population. The stroke belt 
extends through Atlanta, the Carolinas, Tennessee, through the 
southeast. It is most intense--it is called the buckle of the 
belt--in and around the Atlanta, Georgia, area. That is the 
stroke belt where stroke mortality is 1.5 times as high as for 
the rest of the country among whites and blacks. Within the 
belt, stroke mortality is 1.4 times higher among the blacks 
than among the whites. If you take blacks living in the stroke 
belt there is an enormous disparity compared to the rest of the 
country.
    Mr. Jackson. Thank you. Thank you very much.
    Dr. Kirschstein. Mr. Jackson, I have something to add about 
studies and activities related to fatty foods. The National 
Heart, Lung and Blood Institute in particular has had a very 
active program of hypertension outreach and atherosclerosis 
outreach with education about diet. They produce a large number 
of books about not using fatty foods and perhaps not frying 
foods. There is a great deal of work there.
    Mr. Jackson. Thank you.

                      DISSEMINATION OF INFORMATION

    Mr. Chairman, if I could add one thing just for the record 
to hear, I was shocked to hear that there is a gulf between the 
research that these outstanding doctors are doing at NIH and 
actually being able to provide that information to surgeons. I 
don't know what it is that we can do or what it is that NIH can 
recommend on helping us to find a way to help bridge the gap 
between the information that you find about--I thought you were 
talking about neurological transmitters or something like 
that--and how we can actually close that gap, either through 
the certification process or the recertification process of 
surgeons so that they are current on current information so we 
can make their job a little easier.
    Mr. Istook. Thank you, Mr. Jackson.
    Mrs. Lowey.
    Mrs. Lowey. Thank you, Mr. Chairman.
    Mr. Jackson, I would just like to say--I don't want to take 
time because I wanted to focus on some other areas, but 
Secretary Glickman just had an interesting hearing on the 
Atkins diet et cetera. This committee and several members on 
both sides of the aisle, including myself, have been obsessive 
about this issue for a long time. I still wonder why at least a 
dozen of my colleagues have gone on Atkins and lost weight, 
cholesterol has gone down and they feel great, but I can't 
discuss it now. But another time.
    I just want to welcome you. As a native of New Rochelle, it 
doesn't surprise me that you are a star since it is my 
district. I thank you very much for the great success of your 
area of expertise.

                     DUCHENNE'S MUSCULAR DYSTROPHY

    Dr. Fischbach, I have in my district a number of families 
whose sons are affected by Duchenne's muscular dystrophy, the 
most common fatal genetic disorder striking children. As you 
know, a child with DMD, like Ben Sernau in my district, 
measures his life in months. The parents are, I believe, 
understandably frustrated and anguished about the pace of 
determining the cause and treatment for DMD. My staff and I 
have been researching ways in which we might encourage better 
progress. Frankly, we have become frustrated as well. Some say 
adding study groups with reviewers who study these disorders 
would advance the research. Others point out the lack of 
research in choosing to pursue this disorder. How can we 
increase the motive and opportunity for DMD research?
    Dr. Fischbach. This is something that is actually very 
close to my own research and Dr. Penn's before, so I am very 
understanding and empathetic.
    The gene that is mutant in DMD was discovered 14 years ago. 
It was greeted with a tremendous enthusiasm and a sigh of 
relief for progress. It has been frustrating for more than a 
decade that knowledge has not yet led to improved therapies. 
There are many reasons for it. You, being familiar with 
families who are very knowledgeable themselves, are probably 
aware that it is a very large gene. It is very hard to correct 
this gene that can mutate in many different places.
    But I do think that in the last year there have been 
renewed efforts here by several groups in this country and in 
England and some success in introducing a modified healthy gene 
back into muscle. So I think there is renewed interest in a 
kind of gene therapy and less effort using blood cells as a 
source, stem cells, to correct the muscle defect. Muscle is the 
largest tissue in the body. So it is a good target for gene 
therapy.
    There is also some hope, on another front. You probably 
have heard of a rather serendipitous finding of an antibiotic, 
gentamycin, which seems to improve the outcome of animal models 
of muscular dystrophy, and we are sponsoring a trial now using 
gentamycin in humans. I think the field will begin to attract 
excellent scientists again now that these avenues are open.
    We in neurology have talked quite a bit about this in the 
last six months. We are re-emphasizing it. NIAMS has a major 
interest in muscle disorders. But we want to be better partners 
in this. We want to increase our portfolio in this area. I 
don't like that word ``portfolio.'' We want to increase our 
efforts in that area.
    We are co-sponsoring a meeting in May on Duchenne's 
muscular dystrophy just for this reason, to invigorate the 
field and to get people from outside the field to begin paying 
attention to it again. I am hopeful that we will know more late 
in the spring.

                              ALS RESEARCH

    Mrs. Lowey. I appreciate that, and I look forward following 
up with you on the issue.
    As you know, because we discussed it last year, I also have 
a great deal of interest among my constituents in ALS. Could 
you give me an idea what is the outlook of this terrible 
disorder?
    Dr. Fischbach. It is a terrible disorder. Right now, you 
know, the predictions are rather dire of a 3 to 5 year course 
following diagnosis. There is one drug approved by FDA on the 
market, an antagonist that seems to interfere with one of the 
triggers of the cell death program I mentioned earlier. It 
produces a modest prolongation of life.
    I think there has been a breakthrough in the genetics of 
ALS. A gene has been identified in a few families, less than 1 
percent of the patients, but that gene has pointed the way to 
defects that may be true of all patients with ALS. We are 
sponsoring an effort to develop new medicines based on that 
gene. It is a technique that is widely followed throughout the 
NIH called high-throughput drug screening. We have a conference 
on that in April. It is using large chemical libraries on the 
order of a million molecules to screen them for anything that 
might affect this mutant gene.
    I think now within the last 6 months assays have become 
available that make this approach of high-throughput screening 
reasonable. I think there is a new interest in new therapeutics 
in ALS. But, once again, just like in multiple sclerosis, the 
key is going to be earlier diagnosis before these motor neurons 
have degenerated too far.
    Mrs. Lowey. You also mentioned in your testimony that ALS 
and other neurological degenerative disorders have many 
features in common, and you have addressed some of them. Can 
you tell us a little bit more, or expand on what you have 
already told us, as to how these diseases relate and how 
research in one area can benefit disorders in other areas?
    Dr. Fischbach. It is a wonderful story of discovery in 
modern science. It has its home now in neuroscience. It began 
with the realization that some cells during very early 
development degenerate on cue. It is called a programmed death. 
It is part of the normal fate of these cells to degenerate. It 
has been discovered that the very same processes occur in the 
adult brain when they are challenged or threatened by disease. 
It leads to a process that has been named by scientists 
apoptosis.
    The fact is we know a lot about this process now. Among the 
hottest areas of drug development are enzyme inhibitors that 
can stop the process. So cells that have been insulted in one 
way or another don't necessarily have to go down this death 
pathway. The cell death pathway is common in stroke, ALS, and a 
number of disorders. We have to find out what is unique about 
ALS. Why do these particular nerve cells in the spinal cord 
degenerate?
    If you had a chance to look at the New Yorker 2 weeks ago 
there was an article on discoveries at Johns Hopkins about 
local factors that may trigger this death process. It is common 
to all of the diseases. That is why I believe, and this is my 
own thought, that we ought to declare war on neurodegeneration 
in the next 10 years and solve this problem of apoptosis and 
neurodegeneration. Even prolonging life by 2 to 3 years would 
have enormous impact, and give us enough time to look for the 
primary causes.
    Mrs. Lowey. I thank you very much and, unfortunately, my 
time is up. But I would like to say that many of us feel that 
war has to be declared on a lot of fronts. We would greatly 
increase the budget to the NIH as much as we possibly could. I 
am ready to declare war on that and obesity and a lot of other 
areas.
    Dr. Fischbach. I am a believer in that diet.
    Mrs. Lowey. Thank you.
    Thank you, Mr. Chairman.
    Mr. Istook. Mrs. Lowey, tomorrow in the defense 
subcommittee, we have the Secretary of Defense testifying and 
also the chairman of the Joint Chiefs. You may want to attend 
that hearing as well.
    I certainly appreciate--we know there is a lot of hearings 
we get into regarding NIH because there is such a great 
interest not only but by this panel and Members in Congress but 
by the American public in what is going on, medical research. 
We certainly appreciate your commitment and devotion to that, 
and I thank you for taking the time this morning.
    Mrs. Lowey, was there anything further?
    Mrs. Lowey. No. Mr. Jackson left, otherwise----
    Mr. Jackson. I have no questions, Mr. Chairman.

                          POOR DIETARY HABITS

    Mrs. Lowey. I would like to say that I am very serious 
about following up because I have personally participated in 
dozens of conversations, Mr. Jackson--as Dr. Kirschstein 
knows--on the whole issue of diet and health and disease. I 
think what is very puzzling and very troubling is that there is 
so much conflicting information. So for someone like myself who 
can start the morning on Atkins by the afternoon you have done 
something else and you neutralize the benefits of every one of 
them.
    Mr. Istook. It depends on what you want right then.
    Mrs. Lowey. Exactly. You know that. We have talked about 
that. I mean this very seriously, because we see the connection 
between poor dietary habits and health. I do hope that, 
although there have been dozens and dozens of studies and 
reports, that somehow we can gather this information and 
present it in a persuasive way. Because although the low fat, 
vegetable, et cetera, diet seems to be endorsed by the NIH, 
there is evidence--maybe it is circumstantial and anecdotal--
from those who are committed to the Atkins diet, and they walk 
around with high fat diets--I forget if that was the one you--
--
    Mr. Istook. No, no.
    Mrs. Lowey. So I look forward to additional research so 
that we all can become better informed, and then we have to 
deal with the behavioral issues so we can act on the knowledge 
that is available. Let me thank you again for the important 
work that you are doing. Thank you.
    Mr. Istook. Thank you, Mrs. Lowey.
    We thank you, and we stand adjourned.
    [The following questions were submitted to be answered for 
the record:]



                                      Wednesday, February 16, 2000.

                      NATIONAL INSTITUTE ON AGING

                               WITNESSES

DR. RICHARD J. HODES, DIRECTOR, NATIONAL INSTITUTE ON AGING
DR. TERRIE WETLE, DEPUTY DIRECTOR, NIA
COLLEEN F. BARROS, ASSOCIATE DIRECTOR FOR ADMINISTRATION, NIA
KARYN S. ROSS, FINANCIAL MANAGER, NIA
DR. RUTH KIRSCHSTEIN, ACTING DIRECTOR, NIH
DENNIS P. WILLIAMS, DEPUTY ASSISTANT SECRETARY, BUDGET, DHHS
    Mr. Porter. The Committee will come to order. We continue 
our hearings on the National Institutes of Health and its 
fiscal year 2001 budget. We are pleased to welcome this 
morning, Dr. Richard Hodes, the Director of the National 
Institute on Aging. Dr. Hodes, it is good to see you. More 
members will come back because we just had a vote on the House 
floor. Why don't you proceed and then we will follow with 
questions.

                           Opening Statement

    Dr. Hodes. Thank you. Let me begin by introducing those 
accompanying me. At the far left, Colleen Barros, the Executive 
Officer of the institute, Dr. Terrie Wetle, Deputy Director, 
and Karyn Ross, the head of our Financial Management Office.
    Mr. Chairman and members of the committee, it is a pleasure 
to have an opportunity to appear before you again. Since the 
inception of the National Institute on Aging some 25 years ago, 
there has been truly great progress in understanding the basic 
biology of aging, in developing interventions to avoid aging-
related disease and disability, and in understanding the ways 
in which the quality of life for older Americans can be 
improved. The pace of this progress has been impressive, and I 
welcome this opportunity to share with you some of the most 
recent progress as well as a description of current research 
opportunities.

                          ALZHEIMER'S DISEASE

    One of the very great threats to quality of life among 
older Americans remains Alzheimer's disease, a devastating 
disease which tragically affects some 4 million Americans at 
present. With the current projection for an increase in the 
numbers of individuals at highest risk, namely 85 and older, a 
population which will increase to an estimated 20 million 
Americans by the year 2050, the urgency of solving this problem 
has increased.
    The National Institute on Aging, as the lead Federal agency 
for AD research, has taken this impending public health crisis 
seriously. On the basis of recent research-based findings, 
enabled by the recent budget increases in the fiscal years 1999 
and 2000, the institute has announced the initiation of an 
Alzheimer's disease prevention initiative, consistent with 
congressional language and in partnership with other public 
agencies and the private sector.
    In 1999, the first large-scale prevention trial was 
initiated for Alzheimer's disease. In this trial, individuals 
with a diagnosis of mild cognitive impairment, that is 
individuals who suffer minor memory impairment but without 
actual dementia, will be treated with either vitamin E or 
Aricept, to determine whether it is possible to delay or 
prevent the onset of disease.
    This trial will take place in some 65 centers across North 
America and should offer an answer as to the efficacy and 
prevention rather than treatment of this devastating disease 
where it would appear that the most hope lies to arrest this 
disease at an early stage.
    Similar trials, funding permitted, will be initiated over 
this year and in connection with agents such as anti-
inflammatory agents and antioxidants and estrogen. In order to 
identify individuals at risk and to monitor disease at early 
stages, it is critical to develop means for detecting the 
changes that occur in the brain prior to the development of 
symptoms. Brain imaging that has developed over the last year 
offers enormous potential for this. One example shown on the 
first poster illustrates recent success in defining the area of 
the brain called the hippocampus, which is critically involved 
in memory and which is selectively affected in Alzheimer's 
disease.
    [The information follows:]



    Dr. Hodes. What you see on the panel at the left, in the 
normal 25-year-old brain, indicated in red, is the relatively 
large size of the hippocampus in younger adults. The most 
marked contrast is with the picture on the right, where 
individuals with Alzheimer's disease have much reduced volumes. 
If one looks at 75-year-olds who are normal, there is 
relatively little change in the size of the hippocampus 
compared to younger adults, and in the intermediate group, mild 
cognitive impairment, you can see there is an intermediate 
decrease in size. The quantification of that decrease is 
actually a strong predictor of the risk of subsequently 
developing Alzheimer's disease.
    In a research setting, we identify individuals at high 
risk, and hopefully use this information to monitor the success 
of therapeutic or preventive interventions. In order to enhance 
our approach to Alzheimer's disease, an important component of 
research is that which is focused on the basic underlying 
genetic and cellular mechanisms. In the past year, again, there 
has continued to be great progress in that area. Some of that 
is illustrated on this slide.
    [The information follows:]



    Dr. Hodes. From the time that Alzheimer's disease was first 
described by Professor Alzheimer in 1906, one of the 
characteristics of the brain was that of the so-called amyloid 
plaque. Up in the top right corner is an illustration of that 
plaque. What has developed over past years is strong progress 
in understanding what leads to the development of these plaques 
and their precursor and antecedent products. Illustrated here 
is the fact that discovered in the last year are two enzymes 
called beta secretase and gamma secretase, illustrated as 
scissors here because their action is to actually cut from a 
normal protein in all cells the beta amyloid. The result of 
that cutting is to generate the peptide which forms amyloid 
plaques.
    The promise of understanding the chemistry that creates 
these plaques now offers an opportunity to intervene in an 
attempt to arrest and prevent the development of amyloid 
plaques with a strong hypothesis being that this will, in fact, 
be directed at the most basic molecular underpinning of 
Alzheimer's disease itself. Basic science discoveries of this 
sort and others will be a primary priority of the institute in 
their translation into interventions to prevent and arrest 
Alzheimer's disease.

                            BIOLOGY OF AGING

    Similarly, studies of the basic genetic and molecular 
biology of aging have elucidated a great deal about the 
underlying mechanism of normal aging as well as its 
pathologies, as illustrated in the next visual.
    [The information follows:]



    Dr. Hodes. That is the identification of genes, which in 
experimental systems are capable of having marked effects on 
how long organisms live. In this case, the experimental 
organism is C. Elegans. In the graph shown on the right there 
are two lines. The first of them with the open circles 
indicates the survival curve of normal or wild types of C. 
Elegans, which show that they nearly all died by 20 days of 
age. In contrast, the results of a single mutation in a gene, 
aptly named age 1, results in an extension of life to a nearly 
doubling of life span.
    What is particularly interesting is that when one examines 
a panel of such mutations as discovered in experimental 
animals, they have close homologues or similar genes in the 
human. Moreover, the genes that have been identified as 
illustrated in this selective list on the left form an 
interesting pattern, in this case in coding the genes for 
insulin receptors and the molecules that are responsible for 
the metabolism of insulin and glucose. This suggests that 
longevity in experimental animals may shed a good deal of light 
on the underlying processes in disorders such as diabetes and 
control of weight and metabolism important to human aging as 
well.

                    REDUCING DISEASE AND DISABILITY

    These and other discoveries will be applied to the 
development of meaningful interventions to avoid disability and 
prolong the quality of life into later adult years. Until a few 
years ago, it was widely thought that the increased number of 
older people in our society was going to carry with it an 
inevitable burden of increased disability. I think it was in 
1997 before this subcommittee, we had the opportunity to first 
report initial studies which indicated that this was not true, 
and in fact, since 1982, there had been a marked decrease in 
the rates of disability among older Americans, age 65 and 
older.
    On the basis of more recent research, it is gratifying to 
be able to report that not only have these findings been 
sustained and supported by additional studies, but that the 
trend towards decreasing disability rates in older Americans 
continues through the present, and that it appears to be shared 
by both genders, men and women, as well as by minority and 
nonminority populations. A high priority of the institute at 
this point will be to further understand what factors have 
contributed to this decrease in disability and to use such 
information in designing strategies to sustain and accelerate 
that trend.
    It is increasingly clear that among the factors that are 
important determinants of quality of life and life expectancy 
are behavioral features that include physical conditioning, and 
the variable of exercise, which has now been shown to have 
positive effects in a remarkable spectrum of disease, 
including, for example, osteoarthritis and depression. Exercise 
has been shown in experimental animals to actually increase the 
number of brain cells formed in adult and even older adult 
animals. In humans, exercise has been shown to increase certain 
high-order cognitive or intellectual abilities.
    [The information follows:]



    Dr. Hodes. There also appears to be a strong connection to 
overall survival and risk of disease. Illustrated here is the 
result of a study that was reported last year in which nearly 
10,000 individuals, ages 20 to 82, were studied for physical 
fitness by measures such as treadmill performance, and then 5 
years later were reexamined by the same tests. Individuals, 
following that test, were studied for their subsequent survival 
and susceptibility to disease. What is illustrated here is the 
relative risk of cardiovascular mortality, that is, death from 
cardiovascular disease.
    If you look first at the higher light blue curve to the 
left, that bar indicates the high risk of disease in 
individuals who are noted to be unfit to unfit, meaning that at 
the first examination they were unfit and they remained so.
    In the right in orange, the lower bar, is the much lower 
risk of mortality in individuals who were fit at the time the 
study began, and were fit 5 years later. But perhaps most 
important of all is that middle bar in blue labeled ``unfit to 
fit.'' This is a group of individuals who were not fit at the 
time the study began but who, 5 years later, were fit. Remember 
these are individuals who were 60 years of age and older at the 
time of the study and who, as a result of this change in 
physical fitness, had a reduction of nearly half in their risk 
of cardiovascular mortality. This is an important suggestion 
not only that fitness can be protective against disease, but 
that it is not ever too late to start, and that changes in 
behavior, even late in life, can have important impacts.

                      REDUCING HEALTH DISPARITIES

    On the background of lessons being learned and their 
application to the quality of life in older Americans, the 
variable of health disparities is one that looms heavily for 
all of us. It has been found, for example in the past year, 
that on top of the very high quoted and identified rate of 
Alzheimer's disease among nonminority populations, that the 
risk of Alzheimer's disease in both African-Americans and 
Hispanic populations is higher still.
    Moreover, in trying to understand both genetic and risk 
factors for Alzheimer's disease, it appears that the risks for 
various minority subcomponent populations may not be identical 
to those in nonminority populations, so that it is critical to 
look at both genetic and environmental factors across 
components of populations to best understand the risks that 
people have, and to address them.
    More broadly, since about a year ago when we first had an 
opportunity to meet with Mr. Jackson to discuss our plans to 
initiate a widespread strategic planning effort for minority 
research, we have carried out, with the help of a panel of 
distinguished outside advisors, an assessment of current and 
projected research in areas of health disparities and minority 
research. We are awaiting in April the report from that study 
which we look forward to sharing with the public and with 
members of this committee.

                               CONCLUSION

    Mr. Chairman, overall, until a short time ago, there was 
little that could be offered by way of interventions to modify 
the diseases and disorders that accompanied aging. Over the 
past years the situation has changed dramatically and we look 
forward to similar opportunities in the future.
    It has been a privilege, I must add at this point 
personally, to have had the opportunity to testify before you 
as well as the rest of the committee over these past years. The 
President's proposed budget for fiscal year 2001 for the 
National Institute on Aging is $721,651,000, and it will be a 
privilege to respond to any questions that you may have.
    [The written statement of Dr. Hodes follows:]



                          ALZHEIMER'S DISEASE

    Mr. Porter. Dr. Hodes, thank you very much. Can you put 
your first chart back up there.
    As you were testifying, I was thinking as to how large your 
own hippocampus must be because you always testify a cappella, 
and I don't know how you do it. You cover so much ground 
without a single note, and it is very impressive, Dr. Hodes, I 
must say. I want to ask some questions about some of the things 
that you said. You said that you are going to have an effort to 
identify things that might prevent the onset of Alzheimer's 
disease, and there were three different compounds. One was 
vitamin E.
    Dr. Hodes. I referred to a study initiated last year in 
which two agents were being tested, vitamin E, which is in the 
category of antioxidants, and the drug Aricept, which is a now 
FDA-approved drug. I also alluded to the fact that there were 
future projections to take advantage of the fact that three 
categories of agents showed promise in the area of prevention. 
One of them is antioxidants which would have included vitamin 
E, another anti-steroidal, anti-inflammatories and the third, 
estrogen.
    Mr. Porter. How do you know that vitamin E might be 
something that would help? In other words, how did you get to 
the point of identifying this as one of the possible----
    Dr. Hodes. That is an interesting question. For each of 
these categories, the balance of evidence is somewhat 
different. In general, the two broad categories of evidence 
that one can conceive of are those which are epidemiologic, 
that is, clues as to what seem to be risk or protective factors 
from observational studies, and the other, the broad category 
of basic science that will look at molecular structural events, 
and from those, deduce what might be protective. So that, for 
example, in the case of estrogen, the primary drivers come from 
both categories. That is, epidemiologic studies suggested that 
if one analyzes women who either have or have not had a history 
of using estrogen replacement following menopause, the risk of 
Alzheimer's disease is about half in those women who have a 
history of having taken estrogen versus those who have not.
    I will have to quickly add that we don't know if that is a 
causal relationship or if it correlates with other factors that 
we are not able to identify. That is why we need to conduct 
controlled clinical trials to look for direct evidence of 
efficacy.
    Estrogen is also known to have trophic effects, meaning it 
can influence the growth of nerve cells in tissue culture. 
There are receptors for estrogen in the brain, so there is a 
convergence in this case of epidemiologic data and basic 
science data.
    For antioxidants, the data are more heavily from basic 
science studies where there is evidence that oxidated damage 
occurs in the brain, increasingly in Alzheimer's disease and so 
agents which could prevent that might have an effect.
    In the case of the nonsteroidal anti-inflammatories, again, 
there is evidence from both directions. So individuals who have 
taken drugs such as ibuprofen for a variety of reasons, 
arthritis and other diagnoses, also have something like a 50 
percent reduction in apparent risk of Alzheimer's disease, but 
once again, we don't know if that is causal. Similarly, there 
is evidence for inflammatory processes in the brains of 
individuals with Alzheimer's disease. So again, there is a 
convergence of basic science and epidemiologic data to suggest 
that this is a promising candidate, but one that is certainly 
not an established effective one until we have the results of 
direct clinical trials.

                       MILD COGNITIVE IMPAIRMENT

    Mr. Porter. When you look at the chart, what is normal at 
age 75? In other words, how many people at age 75 as a 
percentage of the total fall into the latter two categories?
    Dr. Hodes. The precise numbers, the prevalence, really 
cannot be given with accuracy, certainly in terms of imaging, 
which has not been done on a sufficiently large number of 
people to make it a population study, to determine what is 
``normal.'' Those data will be forthcoming as there is more and 
more experience applying these techniques.
    Mr. Porter. So it might be 10 percent fall into the other 
category? You might find this in 90 percent?
    Dr. Hodes. Possibly. I should note that the definition of 
mild cognitive impairment has been classified only recently. So 
this is a real element of progress and research. Only in the 
past years were definitive studies published, which indicated 
that criteria could be set that reliably identified individuals 
with mild cognitive impairment, and as a correlate of that 
demonstration was the realization that individuals in this 
category were at high risk for developing Alzheimer's disease.
    So if one looks at individuals with mild cognitive 
impairment, there is a risk that approximately 14 to 15 percent 
per year will go on to develop Alzheimer's disease versus a 
less than 1 percent risk in the same age group of the general 
population without mild cognitive impairments. This becomes a 
strong predictor of impending Alzheimer's disease.

                          LIFESTYLE AND HEALTH

    Mr. Porter. Much of what we are seeming to find about 
disease and about health comes back to us in a way that we all 
say well, that is logical. Having a good diet, avoiding toxins 
of one type or another, such as the use of tobacco, exercising, 
it all seems very logical. We ought to say, gee, that makes 
good sense. Knowing as much as we do about the effects of bad 
lifestyle, if you want to call it that, are we doing enough in 
prevention to keep people healthy long into their later years? 
Are we, with all of this knowledge, seeming to look into a lot 
of ways where we can develop pharmaceuticals of one type or 
another as substitutes for really good living?
    Dr. Hodes. That is a very important and insightful 
question.
    First, I think all of us, perhaps sometimes scientists 
above all, are too ready to indicate that something was obvious 
after the fact. But, as you pointed out, for example, in the 
area of exercise, until not so many years ago, the wisest of 
clinicians taking care of older people advised that older 
people were frail and needed to be careful and should not 
exercise too much. There are cases in which we thought that we 
knew what made sense, such as the use of antioxidant vitamins 
that remain an area of real controversy. As you know, there are 
studies that used some these agents in cancer trials. They 
turned out in particular studies to not only not have positive 
effects, but to actually be detrimental. There is reason for us 
all to be cautious about the basis upon which we make 
recommendations.
    But the real meat of your question is in those cases where 
we have things that not only make sense but where that sense 
seems to be sustained by the best objective evidence that we 
can muster, are we doing enough to translate that into changes 
in behavior? The answer is clearly that we are not, and that 
emphasizes a couple of points. One, I think, is that not only 
is the molecular biology and the hard bench biology that we 
stress a critical science, but so are aspects of behavioral 
science. It simply is not as easy as it would appear to let 
people know what is good for them and expect that they will be 
able to comply.
    That is the reason why across NIH and certainly within NIA, 
there is an important research program in the behavioral 
sciences trying to understand the most effective ways of 
encouraging people to initiate and then sustain productive 
changes in lifestyle. We have an obligation to communicate to 
the public in the case of exercise, for example. One component 
of our attempt to communicate the science base has been in the 
recent publication of an exercise manual which has received 
enormous demand from the public. In response to availability of 
this as a free document to individual requests by citizens in 
response to a phone call or postcard, we have now distributed 
over 300,000 copies of this publication and will continue to 
monitor not only its use but the impact that it is having on 
the public's behavior.
    Mr. Porter. Dr. Hodes, this is a comment for both you and 
Dr. Kirschstein. The 300,000 people that called are probably 
people that care enough to do the right thing in the first 
place and the ones who don't call are the ones that you really 
need to reach. It is hard to get from where you are to where 
you want to go. I know that NIH's primary responsibility isn't 
public health or changing lifestyles, but increasingly, it 
seems to me that we need to make a connect between the 
knowledge base that we are gaining all the time about that 
subject and getting people to change their lifestyles to be 
more healthy and save all of the health care costs that follow 
if they don't.
    I am in discussions right now with CDC, HRSA, SAMHSA, and I 
will be including NICHD to talk about what we can do to get a 
message in places where people can be reached about children's 
lifestyle. Getting kids started at a young age with good 
exercise, good diet, avoiding the toxins and all of the rest. 
But I think what I would like to see is a greater coordination 
between these public health agencies and NIH and a real effort 
made to broaden that, to reach older people who ought to be 
influenced by this knowledge base and change their lifestyles 
as well because as you said, it is never too late. You can pick 
it up even if you are 65 or 70 years of age and live a much 
more healthy and longer life.
    So I would like to really get NIH and the public health 
agencies, particularly CDC, working together on this and really 
try to impact people with the knowledge we have instead of, you 
know, putting it on the shelf and saying now we know it, but 
what are we going to do with it? That is just a comment.
    Mrs. Northup.

                 COMPLEMENTARY AND ALTERNATIVE MEDICINE

    Mrs. Northup. Thank you, Mr. Chairman. I appreciate your 
final comments, Mr. Chairman, and I think as a mom I am really 
good at nagging. I have gotten good over the many years that I 
have practiced it. I am always finding myself saying to my kids 
if tomorrow they invent a cure for diabetes, give everybody 
liposuction, hook you up to a machine and it exercises every 
muscle, you still won't be as well off as if you drag yourself 
out of bed, walk 2 miles, choose bran instead of pancakes and 
so forth. But it is not what any of us choose. I would just as 
soon hook myself up to a machine as go out and run or walk, 
too. So I think it is a real hard sell. And it is a lifetime 
sell. I think sometimes we hope that there will be the magic 
cure, as I certainly do for AD, and I want to ask you about a 
couple of magic cures right now, but I thought I would just say 
first of all, I know that there is no magic cure. I wondered 
how many of your studies have involved nonpharmaceutical 
efforts? For example, if you get any of the magazines, the 
health food magazines, there is another thing you are supposed 
to take every single month. And most--an increasing number of 
50-year-olds are taking.
    So I am wondering if memory enhancers, vitamins or gingko, 
if you study those? I know that you have like a nonmedical area 
or unconventional therapies now that thyroid is seen as maybe 
something that declines as you age, there are now thyroid 
enhancers. I wonder, first of all, about the safety of those 
and about the efficacy of them? Is your institute working in 
that area?
    Dr. Hodes. These are very important areas where we are 
certainly working very heavily. The general caution to the 
public in the face of a barrage of recommended interventions 
was, for example, the topic of a public service video that was 
produced a couple of years ago. I mention it because it 
actually won an Emmy, and this was a first for a product by a 
Federal agency winning such an award in that category. It was 
meant just to alert people to be cautious and provided them 
with phone numbers to access information facilities which the 
institute sponsored so we could provide what information was 
available. We work very hard to try to understand the merits of 
any potential interventions, whether they come from 
conventional or unconventional sources.
    In response to your specific question about ginkgo biloba, 
there is currently a controlled clinical trial underway that is 
carried out with collaboration between NIA and the Center for 
Complementary and Alternative Medicine. We certainly need to be 
very careful not to reject out-of-hand promising alternatives 
of any sort, but we are committed to making sure that they are 
assessed in the most objective way.
    We are confronted with circumstances in which many of these 
products are available without prescription in an unregulated 
way, and that puts a unique burden on us to provide 
information. That is sometimes difficult because the background 
use of some of these agents in the population confounds efforts 
to do systematic studies. We appreciate the importance and are 
very committed to looking at these nonpharmacologic 
interventions. Another whole category is that of behavioral 
interventions themselves, and there we alluded to studies on 
exercise, which is a very important example. There are others 
as well. For example, treatment of a very common and costly 
problem in older people, women predominantly, men as well, 
incontinence. There have been some recent studies, which 
indicate that behavioral interventions are actually somewhat 
more effective than pharmacologic interventions, are better 
received by the individuals with a problem, and now provide an 
important alternative to a drug or a pill.
    Mrs. Northup. But you don't recommend any of the non--or 
the alternative medicines for Alzheimer's disease? If you had 
a--parents in their 70s, would you recommend that they take any 
of the alternative medicines?
    Dr. Hodes. The only positive result from a controlled 
clinical trial that reached the level of statistical 
significance was one reported a couple of years ago. It was an 
NIA-sponsored trial which looked at vitamin E for individuals 
who had relatively advanced Alzheimer's disease. Vitamin E had 
a very modest effect on delaying, on average, the time until 
adverse consequences, such as death or institutionalization or 
loss of independence.
    Interestingly and sobering for investigators in the field, 
the same intervention had no detectable effect on measures of 
cognition. So all in all, there was a modest effect of that 
agent indicating that it would not be irresponsible for a 
physician or health care provider looking at such information 
to decide that the agent might have some efficacy. That is 
really the only one on which there is an equivalent such basis 
of data, and again, I emphasize the effects are very modest.

                       MILD COGNITIVE IMPAIRMENT

    Mrs. Northup. Let me ask you, when you say mild cognitive 
impairment can be a predictor of AD, is it that or is it just 
AD in the earliest stages? And let me say, Mr. Chairman, in the 
latest, or in a couple of old-week Newsweek Magazine or Time 
Magazine, the statistic was that 50 percent of all seniors, 85 
and older, currently have AD. From 75 to 84 it was 20 percent 
of all in that age group, 50 percent over 85.
    Dr. Hodes. Yes, those two numbers and the 3 percent in the 
65-to-74 age were numbers that were actually shared with this 
committee when they were reported some years ago. They came 
from the first study of that kind done in East Boston. Other 
studies would have quantitative differences in the numbers, but 
I think they all agree that it is a shockingly high percentage 
of individuals, 85 and older, who have Alzheimer's disease and 
who are at risk.
    The question that you ask about whether mild cognitive 
impairment is really just an early stage of Alzheimer's disease 
or not is an important one that many of us have asked. I think 
that the answer is not known. I quoted a figure that per year, 
14 to 15 percent of individuals with mild cognitive impairment 
develop Alzheimer's disease. Presumably, if one were to follow 
those individuals for enough years, either 100 percent of them 
would develop Alzheimer's disease, and that would support the 
suggestion that possibly it is just an early stage of 
Alzheimer's disease, or we would find that there is a subset of 
them that never go on to Alzheimer's. That, in itself, would be 
an important observation in trying to understand the difference 
between Alzheimer's disease and mild cognitive impairment. At 
this early stage of research, we don't know which of those two 
is the correct answer.
    Mr. Porter. Thank you, Mrs. Northup.
    Mr. Hoyer.

                       DECLINING DISABILITY RATES

    Mr. Hoyer. Thank you. Doctor, I looked at your testimony 
quickly and I apologize for being a little late.
    What should we expect as a society in dealing with old age? 
And by that I mean if you could describe the optimum attainment 
through medicine and lifestyles, behavior, what would that 
optimum be? Presumably we are all going to die. Now do we get 
to a point where we turn off the switch, we have been healthy, 
our minds are strong and everything or is there an 
inevitability about the deterioration of the human 
physiological being?
    Dr. Hodes. First, I would regrettably concur with your 
first conclusion that we are all going to die. And that does 
raise the issue then of what the optimum outcome is for aging 
research aimed at improving the condition of older people. And 
I think it clearly is to minimize the total amount of disease, 
disability, the amount of time spent until death in a condition 
of lessened independence. Is that realistic or not? Some of the 
data that I alluded to about observations of decreased rates in 
disability are very heartening. They suggest that having people 
live longer is not a guarantee that they are going to spend 
more time disabled. There are studies in progress that attempt 
to break down the increased life expectancy that we now enjoy 
into periods of extended life without disability and periods of 
life with disability.
    Again, part of the heartening news is that we are not only 
increasing life, we are increasing the years of life without 
disability. Certainly our objective is to minimize disability 
until the final stages of life and ending in death. The ability 
of behavioral interventions versus drugs, high technology and 
other factors to contribute to this is not at all clear. Part 
of the research that we need to pursue is what each factor 
contributes. Clearly behavioral aspects can, clearly high 
technology can. Public health measures, education, all are 
contributing.
    The precise mechanisms by which each plays a role are the 
subject of current study and are important priorities for what 
we continue to support.

                COLLABORATION WITH OTHER NIH INSTITUTES

    Mr. Hoyer. What impact do you believe that the research 
your institute funds and the results have on the other 
institutes? In other words, what is the cross-fertilization 
between your institute and the other institutes? My thought is 
if a lot of the findings that you come up with internally or 
externally do in fact impact on what, for example, Dr. 
Alexander is going to be thinking about, what are kids going to 
be facing? How perhaps--if they are bad consequences, do we 
avoid them? And, if they are good consequences, how do we 
enhance them?
    Dr. Hodes. I think you are absolutely right. I should say 
that the background level of collaboration across NIH is 
extraordinarily good. As you allude, in the Aging Institute, we 
have a yet higher standard and relevance of such interactions 
and collaborations. You are correct that with the Child Health 
Institute, there is the issue of life course in both 
directions, the ways in which events in early life influence 
the health status of older people, the way in which older 
people impact on the development of children.
    Many of the primary problems faced by older people are also 
very much at the center of the mandates of other institutes. 
Some of the studies that I was able to present in earlier years 
allude to the effects of controlling blood pressure on a number 
of outcomes. These studies were appropriate collaborations 
between the Heart, Lung and Blood Institute and NIA.
    In the area of cancer, we are collaborating with the 
National Cancer Institute because cancer is predominantly a 
disease of older people. In the case of diabetes and 
musculoskeletal disease and on and on, these are natural and 
compelling collaborations with other NIH Institutes. In many 
cases we are taking advantage of the collaborations in very 
explicit ways to conduct studies that neither institute could 
sustain optimally on its own, not only because of budgetary 
constraints but because the expertise that comes to bear on 
some of these problems is complex and the collaborations are 
far better than the impact of individual institutes.
    So you are absolutely correct that it is important that 
these collaborations occur, and I think in large measure they 
are. I am sure there is room for improvement and we are 
constantly looking for new opportunities.
    Mr. Hoyer. Doctor, I had questions on Alzheimer's disease 
but your statement was thorough and your responses to the 
chairman and to Ms. Northup have been pretty thorough so I am 
not going to repeat them. Let me make an observation, though. 
The name of your Institution, the National Institute on Aging, 
is appropriate--as opposed to the National Institute on Aged. I 
think we need to redefine when old is old, and maybe I have a 
personal interest in this, of course, as does the chairman. Not 
Mrs. Northup, of course, as she is much younger than the 
chairman and I.
    Mrs. Northup. Well, I can at least keep my hair brown.
    Mr. Hoyer. But I think our concept, as life expectancy 
grows, will fit in with fitness of the psychological, because I 
find that I have a lot of friends in my age group who think of 
themselves as pretty young, myself included. We do a lot of 
things, and there are other people who keep talking about 
themselves, well, I can't do that at my age. I frankly think 
that is the first step toward going downhill.
    What I am saying is that I think the concept of what old is 
needs to change. But it is a concept that is tied to my first 
question, which asked how long can our physical bodies sustain 
a healthy, active vibrant life? Obviously our own observations 
indicate that is very different. I had an aunt in England who 
wrote me regularly until the age of 96. In the last 6 months 
she went downhill pretty quickly and died just after she turned 
97. Up until that time, she was obviously both young of mind 
and fairly young of body. The psychology of what is old is 
something that we need to deal with as well. Thank you, Mr. 
Chairman.
    Mr. Porter. Thank you, Mr. Hoyer. I think we have time for 
one more question each if we would like to do that. I would 
like to ask a question. Can we go back to the chart that showed 
glucose metabolism.
    Dr. Hodes. That is the slide of genetic mutations.
    Mr. Porter. There has been a study that indicates that if 
there is a substantial reduction in caloric intake and I think 
it was done on mice, and I mean 30 to 50 percent, that that is 
something that leads mice to live longer and appear more 
vigorous and less prone to disease. Is that part of this 
approach and what does that tell us about the role of diet and 
weight in longevity?
    Dr. Hodes. That is an excellent question, Mr. Porter. Yes, 
you are quite right. The observation which has been consistent 
over some 30 to 40 years now has been in rodents, mice or rats. 
The one reproducible intervention which will extend maximum 
life expectancy, and that is an interesting distinction, not 
just avoid disease and let animals live to the usual life 
expectancy without dying prematurely, but actually extend 
maximal life expectancy, is caloric restriction.
    Typically, this has been done by comparing a group of ad 
lib-fed mice or rats, which means that they have all of the 
food that they want all of the time, with a group that has 
caloric intake restricted by typically 30 to 40 percent below 
that level while maintaining nutrition, so they are not 
malnourished animals. And the impact of this is to increase 
maximum as well as average life expectancy by some 30 to 40 
percent over a series of studies.
    Mr. Porter. What implications does that have for human 
beings?
    Dr. Hodes. That is precisely the question that we are now 
trying to address. Some have taken that evidence to mean that 
it must apply to humans as well, and the fewer calories one 
eats, the better, but it raises much more complex questions. We 
don't know, for example, whether the critical variable is 
maintaining an appropriate body mass, for example, low in fat 
and ideal weight, however you achieve that, or whether there is 
a distinction between whether one achieves weight control by 
exercising but perhaps eating more to maintain weight, or by 
simply reducing caloric intake. To translate those animal 
studies, then, to these important human relevant questions is a 
very specific initiative. In this year, we will be funding in a 
more extensive way studies to try to understand these 
calorically restricted mice and rats, and on the one hand, 
analyze biologically what is going on and what the impact is of 
this caloric restriction to see if we can understand the 
variety of ways in which they might be reproduced in humans. At 
the same time we will be trying to look at pilot studies that 
will compare exercise interventions with voluntary caloric 
restriction, not an easy study to do in humans, to determine 
whether in the human condition what occurs will mimic what has 
been observed in the rodents.
    There are also studies that are ongoing in nonhuman 
primates who are being subjected to caloric restriction as 
well. I have to stress that these animals are being well 
treated. They are receiving full nutrition and are under 
physically optimized conditions, but they are given a percent 
decrease in calories. Because of the life span of these 
animals, it will take some additional years before we know the 
final impact on life expectancy, but early suggest that calorie 
restricted animals are healthier. They have lower levels of 
lipids, lower sugar, better insulin responsiveness, which gives 
reason to have serious interest in seeing whether in nonhuman 
primates positive effects on longevity and health might be 
achieved.
    Mr. Porter. And they might outlive the scientists who are 
performing the experiments.
    Thank you, Dr. Hodes.
    Mrs. Northup.

                               NUTRITION

    Mrs. Northup. Well, I would like to follow up on that. Let 
me first of all make one statement, and that is, I hope that 
you will use multidisciplinary efforts beyond science, basic 
science, that you stretch out to the psychology department, the 
sociology department, in order to--but that is not the question 
that I have.
    I want to ask if you have looked at the Atkins diet in 
terms of what you are just talking about, because as you know 
the rage--first of all, it was my kids who came home from 
college, everybody on Atkins, and it made you sick watching 
them fry bacon and eggs and stuff for breakfast. Now it is the 
seniors. He has gone into the senior population and claims that 
it is sugars that age you and cause obesity, not fats. If you 
see the new books and everything, his claims and there are--he 
gives lots of examples, and I just wonder, if that is a type of 
approach that you've looked at, the high protein, low 
carbohydrates?
    Dr. Hodes. I am aware of the publicity and popularity, but 
the answer to your question directly is no, at least in the 
National Institute on Aging. We have not carried out studies 
trying to reproduce diets of that composition for their impact 
on an experimental system.
    Mrs. Northup. It worries me to see such a popularity of 
these types of things that we talked about--the ginkgo and so 
forth. While all of the people that we are seeking to serve 
are, in large numbers, pursuing sort of self diagnosis and 
treatment. It seems like science ought to at least try to keep 
up with that.
    Dr. Kirschstein. Mrs. Northup, nutrition is an area that is 
supported by many of our institutes as you will hear when the 
Heart, Lung and Blood Institute comes tomorrow, Diabetes and 
Kidney Diseases, the National Institute of Child Development, 
this afternoon. We set our course as to how we eat, as you well 
said, based on how we teach our children to find appropriate 
nutritional activities. A lot of this is coordinated through 
the nutrition coordinating committee. The lead institute is the 
National Institute of Diabetes, Digestive, and Kidney Diseases. 
There is also an Office of Dietary Supplements, and we will 
talk about that when we testify March 8. So there is a great 
deal of activity, and much of this is being looked at. I don't 
know the details, but the institute directors will be able to 
tell you.
    Dr. Hodes. Mrs. Northup, I will add that the ability to 
respond to areas of public interest which have promise and/or 
are advertised to have promise for so-called anti-aging effects 
as well as a variety of others creates an imperative that we 
realize. With funding which we have been fortunate enough to 
receive this year we will be able to initiate an infrastructure 
for the testing of such compounds in which we will have in 
place investigators most expert in rigorously carrying out the 
interventions and measuring impact on life expectancy and on 
disease at intermediate end points. Thus we can attempt, with 
as much scientific validity as possible, to be responsive first 
at the preclinical experimental level and ultimately at the 
level of human interventions to some of these myriad of claims.
    Mr. Porter. Thank you, Mrs. Northup.
    Mr. Hoyer.

                           NIA SUCCESS RATES

    Mr. Hoyer. Doctor, we talked about pay lines yesterday. 
What are your pay lines projected to be under this budget 
compared to this year or the year before?
    Dr. Hodes. If I could quote success rates, which you know 
are the parameter most widely used to reflect what you are 
using, last year in fiscal year 1999, our success rate was 
approximately 28 percent. This year it is projected to be 
approximately 22 percent, and next year under the President's 
budget it is projected to be approximately 17 percent.
    Mr. Hoyer. Now, that is quite a reduction. Yesterday we 
heard that one of the issues impacting that was the increased 
dollar value of the particular grants. Can you relate it, 
therefore, to the number of grants that are given and the value 
of those grants?
    Dr. Hodes. Yes. Certainly in the case of the National 
Institute on Aging one of the contributors to a projected 
decrease in success rate is an increase in average cost. As you 
heard yesterday, it reflects a number of variables, in part, 
the success of the research enterprise. As we are able to 
translate basic science studies to interventions in clinical 
trials and studies, those become increasingly expensive, as 
well as the fact that many of the costs of basic research are 
increasing at a rapid rate. The competition between supporting 
research that is expensive but valid, and weighing that against 
a success rate that is sufficient that it will not discourage 
investigators, particularly a new generation of investigators 
coming into the field, is a consideration that I think all of 
us across NIH are constantly engaged with.
    Mr. Hoyer. In terms of numbers, can you give me that or 
provide that for the record? 28 percent--do you recall in the 
ballpark how many grants that was? And how many 16.7 percent 
is? If it is 16.7 percent of 1,000 applications, that is better 
than 22 percent of 500 applications?
    Dr. Hodes. Yes. Although the denominator is going up 
slightly, it is not going up enough to maintain the number of 
successful grants. So 398 was the number actually funded in FY 
1999; estimated this year, 389; and next year's estimate is for 
a true decrease to 315.
    Mr. Hoyer. Now, I presume--I asked Dr. Kirschstein some 
questions with reference to the 3,000,000,000, and the 
7,000,000,000 and also to the incremental----
    Dr. Kirschstein. We are working on that.
    Mr. Hoyer. I didn't expect you to have that now. I didn't 
mean to imply that. I just asked it yesterday or the day 
before.
    But clearly one of the things--if Joe Early were still 
here, he would be appalled by this reduction. For Mrs. Northup, 
he was a member of this committee for many, many years and 
clearly was the expert on NIH, immersed himself deeply in NIH 
and knew a lot about it, and clearly was its most tenacious 
advocate on our committee. But he was always very concerned 
about pay lines because he thought it would have a direct 
impact on what you referenced, the discouragement or 
encouragement of young researchers to go--to believe that there 
was an opportunity for them in basic biomedical research 
because pay lines were going up and because the percentage of 
applicants were greater.
    Dr. Hodes. I think in that regard, one thing that all of us 
are doing in addition to generally paying attention to overall 
success rates is to, in particular, give close scrutiny to the 
status of new investigators entering the field. Dr. Kirschstein 
can speak to the NIH-wide profiling of that, but we have been 
very careful, and so far gratified to find that there has not 
been a substantial decrease in the number of new investigators. 
It is a critical trend that we need to continue monitoring.
    Mr. Hoyer. Also, one of the things that my friend Joe Early 
would have been concerned about was how much good science was 
not being funded. In other words, obviously at some level, and 
I don't know where that is, at 33 percent or 34 percent, at 
some level above that what peer groups are saying, this is 
interesting, but probably not worth the investment, but clearly 
I am presuming that you think that there is good science not 
being funded above 16 percent pay line?
    In other words what I am asking you, where could you go and 
still feel that we are investing our money well?
    Dr. Hodes. Despite the fact that it is difficult to give a 
high limit to this number, I think it is rather straightforward 
and easy to say that at 17 percent that number is clearly too 
low. In the range of recent success rates across NIH of late, 
in the 25 percent category, there is great confidence in the 
fact that the research being supported is uniformly outstanding 
as reviewed by the peer review process.
    Mr. Hoyer. Thank you. Dr. Kirschstein.
    Dr. Kirschstein. I agree with what Dr. Hodes has said and 
we have made sustained and strenuous efforts, and we will 
continue to do so to assure that in the cohort of individuals 
who receive our competing grants, there will be an appropriate 
number, in fact, the number equivalent to that which we have 
been supporting and probably higher, of new and young 
investors. This is a priority for all of the institutes and for 
the NIH as a whole.
    Mr. Hoyer. Thank you. Thank you, Mr. Chairman.
    Mr. Porter. Thank you, Mr. Hoyer.
    Dr. Hodes you are doing a marvelous job and I am sorry more 
members were not here because I find your presentation and the 
discussion of what you bring to us fascinating. We thank you 
for the work that you are doing at NIA.
    Dr. Hodes. Thank you all.
    Mr. Porter. I remind the subcommittee members that we have 
NCRR immediately after this vote and the committee will stand 
in recess briefly for the vote.
    [Recess.]
    [The following questions were submitted to be answered for 
the record:]



                                           Thursday, March 2, 2000.

                  NATIONAL INSTITUTE OF MENTAL HEALTH

                               WITNESSES

STEVEN E. HYMAN, M.D., DEPUTY DIRECTOR
RICHARD K. NAKAMURA, PH.D., DEPUTY DIRECTOR
WILLIAM T. FITZSIMMONS, EXECUTIVE OFFICER
J. RICHARD PINE, BUDGET OFFICER
GEMMA M. WEIBLINGER, SPECIAL ASSISTANT TO THE DIRECTOR
RUTH L. KIRSCHSTEIN, ACTING DIRECTOR, NIH
DENNIS P. WILLIAMS, DEPUTY ASSISTANT SECRETARY, BUDGET, DHHS
    Mr. Porter. The Subcommittee will come to order. We 
continue our hearings on the budget for the National Institutes 
of Health with the National Institute on Mental Health and we 
are pleased to welcome Dr. Steven E. Hyman, the Director, who 
probably has the most fascinating job of all, and as we have 
said many times, your area, mental health, is probably the 
frontier that we know least about and need to know the most 
about.
    So, why do you not introduce the people who are with you, 
Dr. Hyman, and then proceed with your statement.
    Dr. Hyman. Thank you for that very gracious introduction. 
On my far left is Gemma Weiblinger, who is my Special Assistant 
and Congressional Liaison; Mr. Richard Pine, our Budget 
Officer; Mr. Richard Nakamura, who is Deputy; Mr. William 
Fitzsimmons, the Executive Officer, who you have just actually 
met; and, of course, Mr. Williams and Dr. Kirschstein.
    Mr. Porter, this has been a really wonderful year for the 
National Institute of Mental Health on several counts. But it 
is not an entirely happy moment for me because I realize that I 
will be appearing before you for the last time and I just want 
to take a moment to say how important this Subcommittee has 
been but also, Mr. Porter, you in particular. I met with you, I 
think, my second or third day on the job and one of the things 
besides the support of this Committee, I think an important 
tone that you have set is that along with the healthy 
increases, we needed to be fully accountable and demand 
excellence. And it is something that has really helped me to do 
my job as well as I am able and I appreciate the support of 
this Subcommittee but I also really appreciate the integrity 
and the seriousness and the high standards that you have 
communicated to all of us and it is much appreciated.

                 GROWING AWARENESS OF MENTAL DISORDERS

    This has been a great year for mental health because based 
on the accumulation of scientific evidence, based on the 
recognition that mental illnesses are real, diagnosable, and 
treatable, based on evidence from the World Health Organization 
and World Bank that I actually heard Mr. Hoyer quote in his 
questions to Dr. Kirschstein, the Nation has begun to confront 
some of the issues that you alluded to in your remarks. There 
was a White House conference, for example, on mental health 
which was a very healthy way of getting the word out, again, 
that these are real, diagnosable and treatable illnesses; it 
also was a chance for the National Institute of Mental Health 
to work very hard in dissemination activities and every one of 
you has a copy of our ``Science On Our Minds Fact Sheets'' that 
we produced for the White House conference. They are in a clear 
folder. And we are keeping these updated. They are also on the 
Web and they are extraordinarily popular. In fact, our updated 
Web site (www.nimh.nih.gov), designed for the White House 
conference, now gets 5 million hits a month.
    In addition, based on this science, there was a first-ever 
Surgeon General's Report on Mental Health, which we might 
discuss further at length but, again, to have the Surgeon 
General, the chief public health officer, making mental health 
one of his priorities is really critical for us, again, getting 
the word out that these are real, treatable illnesses. In 
addition, the Surgeon General issued a Call to Action on 
Suicide. In all of these activities the National Institute of 
Mental Health was pleased to collaborate along with other 
Federal agencies as leads for providing the scientific 
background.

                    NEW APPROACH TO CLINICAL TRIALS

    But it was also a great year because of the healthy budget 
increases which we have used, I think, to do very exciting new 
things. Beginning two years ago and continuing vigorously last 
year, we began an entirely new style of clinical trials. You 
know, the standard clinical trials for an antidepressant or an 
antipsychotic drug were really based on the model that industry 
would use to get FDA approval, which is often a six-week trial. 
But for an illness like depression or schizophrenia, six weeks 
is but a moment in the course of a terrible illness. We 
recognized that with the healthy increases we had gotten we had 
the opportunity to initiate trials that were more true to life, 
that is, where people would be followed in larger numbers for 
greater lengths of time, helping us to understand the treatment 
of these chronic illnesses.
    In addition, what we recognized is that traditional 
clinical trials, in order to maximize the ability to see the 
effect of a drug, would often exclude lots and lots of people 
from the trial: in a depression trial anyone who was not say 
between 20 and 60 might be excluded, anyone with heart disease, 
anyone who had anxiety symptoms and probably anyone who drinks 
alcohol excessively.
    Well, in reality, of course, people who come for health 
care do not always meet textbook criteria, and we need 
information that is truly applicable to real populations in 
real health care settings to help both patients and doctors but 
also, frankly, to convince insurance companies and employers 
that the treatments are relevant and effective. In the last 
year we were able to initiate two new trials that more closely 
reflect reality: one is on the very important topic of 
depression that does not respond to initial treatment. 
Depression is very common, affecting 19 million Americans 
annually, and about 20 percent of them do not really improve 
with our current treatments and we need to know how to treat 
this very large number of people. A second trial that we 
initiated is on the best use of the new antipsychotic drugs.

                    ATTENTION DEFICIT DISORDER STUDY

    We had the release of long awaited results from a clinical 
trial called the Multi-Modal Treatment Assessment Trial for 
Attention Deficit Disorder and perhaps there will be questions 
about psychopharmacology in children given what has been in the 
news in the last few weeks, but this was a very interesting 
trial. Again, it took 600 children and followed them for what I 
think is really the ethical limit for a randomized clinical 
trial, which was 14 months.
    You know, you could not really ethically randomize a kid 
for 10 years, but it was 14 months and we compared Ritalin, a 
very, very rigorous behavioral therapy, the combination of the 
two, and ordinary community practice. Ritalin emerged in this 
age group, which was above the age of 6, as quite safe and 
effective, which is important information for parents. But one 
thing was really troubling. The children in the community 
treatment comparison group were also on Ritalin, but they did 
not do very well at all. And we recognized that the use of 
Ritalin or other psychopharmacologic interventions in 
children--this should be true of all of medicine--the 
effectiveness really depends on the quality of the evaluation 
and the interaction with the family. We believe that 
prescriptions were being written but side effects were not 
being ascertained, adherence to treatment was not being 
ascertained, there was not the right explanation and help, 
frankly, hand-holding, and, so, there were enormous differences 
in outcome that we, again, might come back to later.
    [The information follows:]



                   BASIC RESEARCH ON MENTAL DISORDERS

    Dr. Hyman. In basic science--and I will go quickly here in 
the interest of time--perhaps some of you have heard--and if 
you look at this chart on my left--that for severe depression 
we actually begin to see physical changes in the brain (Figure 
1). A critical part of the brain, called the hippocampus, a 
part of the brain that is required for conscious memory, may 
begin to atrophy in depression. This is due to the fact that 
about half of people with severe depression elaborate very high 
levels of a stress hormone, cortisol, which may be toxic to 
neurons. This is an MRI scan from grantees at Yale and what you 
can see, outlined in red, is the healthy control on my left and 
on the right you can see the person with severe depression--and 
outlined in red and blown up at the bottom is this hippocampal 
atrophy.
    Now, this, of course, is very worrisome, brain damage, 
could it be irreversible. And one of the issues, certainly 
something I learned as a dogma in neuroscience, is that the 
brain does not ever make new neurons. You know, you are born 
with your full complement of neurons and every kid on the 
school bus says if you bump your head you lose some and so on. 
In fact, this dogma has turned out not to be true and it is a 
message of hope for conditions like this.
    [The information follows:]



    Dr. Hyman. If I could have the next poster. A number of 
investigators, including an NIMH grantee, Elizabeth Gould, at 
Princeton has good evidence for the generation of new 
potentially functional nerve cells in the brain, including the 
hippocampus (Figure 2). Interestingly, this story started with 
the study of song birds. Sometimes people wonder why we study 
song birds. Canaries sing a wonderful song in the Spring and 
they do pretty poorly in the Fall and it turns out that they 
actually grow neurons in the Spring before they relearn their 
song and they atrophy in the Fall. Now, this wholesale 
development of an organ in the brain is very unusual. But it 
gave people the opportunity to begin to study the generation of 
new nerve cells in the adult brain.
    In rat brain, seen here, the blue is the background, the 
hippocampus, in red, is the part of the brain that gets damaged 
in depression. Staining for DNA, cells that have made new DNA, 
therefore, new cells, there are new neurons being made in the 
rat brain. Now, strikingly, if the rats get stressed the amount 
of neurogenesis decreases. And this could be because the stress 
hormone, cortisol is now up. It might have been what is 
attacking the hippocampus in people who are depressed. We do 
not know this yet. But--and here is something really 
interesting--if you train these rats in a hippocampal-dependent 
task, new object learning which uses their hippocampus, the 
rate of neurogenesis actually increases. So, it is really 
fascinating.
    So, we do not know yet whether these neurons are really 
incorporated into usable circuits. There is a long way to go. I 
do not want to oversell this but it is really exciting. It is 
the death of a false scientific dogma. The idea is that this 
could be happening in the brain. Fred Gage and colleagues have 
actually demonstrated this in human beings, in terminal cancer 
patients in Scandinavia, who were getting a DNA marker to 
follow their tumor size. When those individuals passed away 
their brains were looked at and there was actually new growth 
of neurons in humans. So, this is a phenomenon that is exciting 
and that will really potentially have an enormous impact on 
health. Again, we do not know just how far.

              APPLYING BEHAVIORAL SCIENCE TO PUBLIC HEALTH

    I just want to touch on two other things that, again, the 
healthy increases in budget have allowed us to do. One is the 
area of translating basic science rapidly and significantly 
into the clinical arena. Now, I have talked to you in the past 
about how we have done this in molecular biology and in 
pharmacology and it is obvious that this is an important goal 
for all of NIH.
    One area, however, in which this has been lacking is in 
basic behavioral science. In some sense we have not asked that 
basic behavioral science be translated into public health 
applications. And, so, after a National Advisory Mental Health 
Council report, and after a meeting that brought together 
psychology department chairs who were often sequestered off in 
colleges of arts and sciences and never have dealt with public 
health issues, with deans of schools of public health, we have 
come up with programs to bring what we know from basic 
behavioral science to bear on public health issues. Issues like 
treatment adherence. Very important in all fields of medicine, 
but in depression we know that the major reason for treatment 
failure is people do not go to their psychotherapy, do not take 
their medications. Clearly there are important behavioral 
advances but we need new ideas and new ideas we believe will 
come from bringing together basic behavioral scientists, people 
who really understand the underpinnings of human behavior, with 
people interested in public health applications.
    [The information follows:]



                             YOUTH SUICIDE

    Dr. Hyman. Finally, I want to talk a bit about youth and, 
in particular, youth suicide. And I am going to highlight this 
because there was a hearing in the Senate which was 
highlighting problems with youth suicide. What you see here 
(Figure 3) is that the rate of suicide among all youth 
increased three-fold from about 4 per 100,000, peaking at about 
12 per 100,000 a number of years ago and settling back just a 
little bit at really unacceptably high rates. And within this--
and you cannot see this--this suicide rate traditionally was 
really contributed to almost entirely by young Caucasian males. 
However, in the last few years, the rate of suicide among 
minority youth has climbed markedly. The rate of suicide among 
adolescent African American males doubled between 1980 and 
1996. In some Native American groups and Alaska Natives the 
rate for young males is a staggering 62 per 100,000. I had the 
opportunity to visit Native Alaska villages last summer and to 
see firsthand some of the problems.
    In order to to gain information about what exactly is 
happening, we have funded two studies. One is a very large-
scale epidemiologic study that is going to survey kids as young 
as the age of 13, really looking at mental health issues across 
the entire population but we are really going down into the 
young ages because we do not know what the correlation is in 
children between depression, other mental illnesses and 
suicide, as well as we know it in adults. But more to the 
point, we really do not understand what is happening in 
minority youth. And as part of this effort, which is being 
directed by Dr. Ron Kessler, at Harvard University, Dr. James 
Jackson, at the University of Michigan, is initiating a very 
large-scale study of the epidemiology of mental disorders in 
African American youth. We have been trying to organize similar 
studies to deal with problems in different Hispanic subgroups 
and in Native Americans. But we need this data to understand 
these suicide rates and the disparities among minority groups.
    That is a lot and I could go on but I think it would be 
best if I stopped here and I would be pleased to answer any 
questions.
    [The written statement of Dr. Hyman follows:]



                             YOUTH VIOLENCE

    Mr. Porter. Thank you, Dr. Hyman.
    I remember that the canary study was one that was 
disparaged by an NGO in Washington and then featured on ``Prime 
Time.'' It was, Sam Donaldson saying, wait a minute, there is 
something very valuable going to come out of this and, of 
course, it has.
    I want to start with a question that is on so many of our 
minds and that is how in the world a 6-year-old in a class in 
Michigan could come to school and shoot a classmate dead? We 
can say, well, this is something that is just a total 
aberration and dismiss it and say, obviously, it has no meaning 
but it seems to me that it does have meaning and that this is 
the first time it has happened at this age. I wonder if you 
could give us your insights on this specific incident and what 
kind of--what are we doing to address this problem and head-off 
these kinds of horrible incidents?
    Dr. Hyman. We are clearly not doing enough to head these 
things off. But, in fact, this does have meaning. It reflects 
very clearly on some data that may sound like common sense but 
is very, very well established and that data has to do with the 
role of families and family supervision. In the case where 
families are disrupted, data from a large study in Chicago 
being conducted by Dr. Felton Earls, suggest that neighborhoods 
can also play a role and that is in the appropriate supervision 
of children.
    Now, of course, we would assume that at the age of 6 a 
child would be very well supervised by a family but, clearly, 
in this case from what I understand--and I only know the news 
reports--this was a child who was growing up in very, very 
chaotic circumstances. But the bottom line is that in many of 
these tragic instances--and I am not saying it is easy for 
parents to know what is going on with their children--parents 
have not known what is going on with their children. In terms 
of prevention, and again, this is not generalizable necessarily 
to a 6-year-old, we know some really clear facts. Much of youth 
violence, in fact, the vast preponderance does not occur during 
school hours; it occurs between the hours of 3 and 10 in the 
afternoon and a lot of it would be stopped if there were 
appropriate supervision of youth with either school-based or 
family-based or church-based or any other sorts of programs. 
Secondly, we know there is a critical aspect to that 
supervision and that is that the aggregation of, let us call 
them deviant youth, is the final common pathway toward often 
criminal careers and violence.
    Parents really should not only supervise their kids but it 
is very important to know who their friends are. Peers have 
enormous power. And, indeed, it is not only parents.
    You know, as a society we tend to aggregate deviant youth 
in group detentions, group homes, in alternative schools and 
there are alternative models that we are funding. Models for 
kids who have already been in bad trouble include therapeutic 
foster care, for example, where the foster families are taught 
and supported. There is a 24-hour, on-call person. It is a lot 
cheaper than incarceration, even though it is labor-intensive. 
One of the key things that the parents learn is the need for 
supervising kids and the need for keeping them apart from, you 
know, bad friends. Again, it sounds like common sense, but we 
are not doing it and a lot of the way we are treating kids is 
to aggregate kids, creating, in essence, ``graduate schools for 
delinquency.''
    To return this discussion to this 6-year-old, it is clear 
in retrospect and tragic to have to say that this was not an 
appropriately supervised child. Whether this child had a 
serious emotional disturbance that could have been diagnosed 
and intervened with is anyone's guess. But what I will say is 
that one of the lessons we have learned from some of the 
horrific school violence is that disorders that we have not 
previously associated with violence, disorders like depression 
and anxiety actually may contribute to violence. Some of the 
anxiety disorders might actually come from exposure, witnessing 
violence. It turns out that a combination of depression and 
conduct problems is a really combustible mix because these 
depressed kids are sullen and withdrawn and often irritable and 
we do a very bad job of identifying these kids in school 
settings. You know, the sullen, withdrawn kid is sometimes 
mistakenly considered a good kid. They are not out of their 
chair, racing around like the kid with attention deficit 
disorder. And we really need to do a better job of identifying 
these kids and treating them.

                        STRESS AND MENTAL HEALTH

    Mr. Porter. Dr. Hyman, you mentioned a stress hormone, I 
think you called it cortisol?
    Dr. Hyman. Hmm-hmm.
    Mr. Porter. You said it was a stress hormone, so I assume 
there are many.
    Dr. Hyman. Yes, there are.
    Mr. Porter. There is a good body of information that leads 
us to believe that stress has a great role in health, 
generally, and one assumes also in mental health. Are there 
studies underway in your Institute or elsewhere to figure a way 
of preventing the hormone from doing its damage? In other 
words, we know that we all are going to be stressed throughout 
our lives, but is there a way of perhaps controlling the 
damage?
    Dr. Hyman. Yes. It is a very interesting and important 
question and it is an enormous area of research. So, first of 
all, these stress hormones, like cortisol, adrenaline, we have 
them because we need them in emergencies. You know, when our 
ancestors were faced with a saber-toothed cat, their body 
needed to be prepared, right? You need to get the blood away 
from where it was digesting lunch and into your thigh muscles 
so you can run. You need to do things to your brain. You have 
to stop mulling your prehistoric philosophy and start being 
vigilant and scanning and really alert. You, interestingly, 
have to suppress pain responses. You know, if you are running 
from this animal and you cut yourself it is not the time to be 
saying, ouch, you have got to keep going. You actually know 
this from ordinary life. You might be involved in a heated 
tennis match and you hurt yourself and you do not realize it 
until you cool down afterwards. And that is sort of a relic of 
our ancestors' response. You suppress your immune system. You 
know, you better not get a swollen knee at this minute, that is 
for later, that is for splinting the knee after you have 
finished the tennis match. So, your immune system is 
suppressed. Also, you need to produce energy. So, you are 
melting away fat and turning it into glucose and melting away 
lots of other things.
    Well, this is great in an emergency. The problem, of 
course, is if this system is activated chronically for no 
reason. We see this in people with major depression, we see 
this in people with post traumatic stress disorder, and we see 
this actually in some youth. It is very interesting, there were 
abnormal levels of this hormone, cortisol, in some of the 
Rumanian orphans who were brought to the United States and 
studied and found probably just ordinary interpersonal 
interactions very stressful.
    So, we are studying the biology of this to mitigate some of 
the damage, to understand how this process is controlled. Just 
to take one example: There is actually a medication that is 
going to enter clinical trials that blocks the machinery, 
upstream of cortisol release. It is another hormone called 
corticotropin releasing hormone, and it blocks the functioning 
of that master switch. The real question is whether it is going 
to do too good a job? You know, again, we need these stress 
hormones. We have lots of stressors--we do not meet saber-
toothed cats any more, but we get a viral infection, our body 
does have to mount a stress response.
    So, the hope is that we are going to find interventions, in 
this case a medical intervention but also potentially psycho-
social and behavioral interventions, that can get this stress 
response back to where it ought to be; that is responding 
briefly and acutely to real stresses, but not flooding our 
bodies chronically with these hormones, because you do not want 
your immune suppressed over the long-term and so on and so on.
    Mr. Porter. Thank you, Dr. Hyman.
    Mr. Hoyer.

                        TRENDS IN YOUTH SUICIDE

    Mr. Hoyer. Thank you, Mr. Chairman.
    Doctor, I have some questions but let me make an 
observation about your response to the question. Initially you 
said the child did not have proper supervision. I think that is 
such an understatement as to really almost not be accurate.
    Dr. Hyman. Yes. I agree.
    Mr. Hoyer. There was a story in the ``Washington Post'' 10 
years ago about a child named Doonie Waters, who lived in 
Prince George's County. He was 6 years of age and he lived in a 
crack house. He had no bed, the bathroom was not working, his 
bedroom was used to shoot up by his, presumably his mother, 
very similar situation. Doonie Waters did not commit a crime 
but Doonie Waters was left in that context for way too long a 
period of time.
    In 1978, we adopted legislation that had the premise that 
we needed to keep children with their parents. That was the 
primary objective of the system. It had a good premise, that 
children with their families that properly supervised them are 
better off than they are not. The tragedy is that not only did 
the suicide rate go up and I want to ask you about this 1968-
to-1978 spike----
    Dr. Hyman. Yes.
    Mr. Hoyer [continuing]. Because I look at your--there was 
a----
    Dr. Hyman. Enormous.
    Mr. Hoyer [continuing]. It is interesting the spike is not 
recently, the spike was 1968 to 1978, where it doubled from 4 
to 8.
    Dr. Hyman. That is correct.

                SOCIETAL ROLE MODELS FOR YOUTH VIOLENCE

    Mr. Hoyer. One of the things that I think in the context of 
you and Dr. Alexander and others, this child had no family. 
This child had a learning experience which was filled with 
violence. Every child in America, of course, has the 
opportunity to turn on the television and watch Jerry Springer 
that dramatizes and puts before us some of the most 
dysfunctional human beings in our society. The Worldwide 
Wrestling Federation puts on television activity that is not 
conscionable by a civilized society. The National Hockey League 
allows people to hit people with sticks and only in the most 
egregious events do we respond as we responded just recently. 
There ought to be criminal prosecution of somebody that hits 
somebody with a stick, I do not care what the game is. So, I 
mean it is something that we ought to be motivated as a 
society, we teach all of our children violence.
    Mr. Porter. Will the gentleman yield on that?
    Mr. Hoyer. Yes, sir, I would be glad to yield.
    Mr. Porter. You might be interested to know that in my 
district the grandson of my finance chairman was recently in a 
high school hockey game, and was hit from behind after the game 
was over, allegedly. He is paralyzed from the neck down, he is 
15 years old, and the State's Attorney of Lake County is 
prosecuting the individual who did it as a criminal act.
    Mr. Hoyer. Mr. Chairman, I am glad to hear that. Frankly, 
Abe Pollin is a good friend of mine and I have had discussions 
with him for the last 20 years about the countenancing of 
fighting in hockey. You know, they do not do that in the NFL. 
The National Football League, are there fights? Yes. It is a 
sport and they hit one another and people get mad and they take 
a strike. But they are ejected and they are separated 
immediately. You know, people do not stand around and watch and 
say, you know, the Christians are being fed to the lions, which 
is essentially what we have.
    So, Doctor, it seems to me that this is a systemic, broad-
based problem. Jerry Springer outrages me. We ought to, 
frankly, boycott every advertiser of the Jerry Springer show 
because what he is doing--and that is on at 4 o'clock in the 
afternoon. It is despicable that a civilized society would 
countenance that.
    He was going to run for the United States Senate and my 
party, I think luckily, was outraged by it and he did not run. 
But I mean, you know, the concept that somebody like this would 
be--so, I was--your answer was very mild in terms of my 
reaction as to why this 6-year-old child, why society did not 
rip him out of this context.
    I mean if he went to kindergarten, they had to have some 
knowledge of what was going on. A child does not live in a 
crack house with no bedroom of his own, probably no sanitary 
facilities available to him, nobody fixing him breakfast, lunch 
or dinner without the system knowing that we have got to save 
this child and bring him out and the consequences are not only 
that we lost this child, maybe the next child can be saved, but 
we lost another totally innocent child.
    Dr. Hyman. The tragedy is that one story gets in the 
newspaper but this is replicated infinitely across the country.
    Mr. Hoyer. And, again, in 1978 our theory was because we 
thought about families being functional and if families are 
functional, absolutely the children ought to be with them.
    Dr. Hyman. Right.
    Mr. Hoyer. But to leave a child in this context for very 
long is a national disgrace. And it happens in my county. This, 
you know, obviously, it was not in my jurisdiction but it 
happens in my jurisdiction and every jurisdiction in America. 
We need to raise that issue.
    Let me ask you some questions about the budget. Where do 
you stand relative to other institutes in the rate of grants 
submitted and approved?

                      RESEARCH GRANT SUCCESS RATES

    Dr. Hyman. Since my arrival three years ago, we have had a 
very healthy increase in the number of grants submitted. We 
have, in terms of historical success rates, been rather on the 
low side with a success rate in the last year of, I think, 
about 26 percent. You know, for me one of the things that has 
done my heart good as the director of this institute is that we 
have had an increase in very high quality applications. Before 
I arrived, as you remember, of course, NIMH was part of ADAMHA, 
and when NIMH rejoined NIH in 1992, one of the goals was to 
join the review of NIMH grants with the rest of NIH.
    Fortunately my colleague at the Neurology Institute at that 
time, Zack Hall, agreed with me that the best way to integrate 
neuroscience review--and, subsequently, we have done this for 
behavioral review at NIH--was to start with a blank sheet of 
paper. You know, the study sections were 20 years old, the 
science had changed, and we started with a blank sheet of 
paper, we involved the extramural community and we came up with 
a whole new set of review sections. In those review sections, 
grant applications referred to NIMH are doing somewhat better 
than would be expected against the rest of the league. So, I am 
very happy in the quality of grants. I, obviously, wish I could 
do better, given that quality, than a success rate of 26 
percent.
    Mr. Hoyer. How much good science do you think we leave on 
the table? I asked this question last time and I think Dr. 
Fauci answered in the neighborhood of 45 percent, which meant 
about half of the good science or a little more than half, 
probably 60 percent of the good science was funded.
    Do you think that is about right?
    Dr. Hyman. I think Dr. Fauci is about right. I would tell 
you that not being able to pay a success rate of 35 percent 
is--I mean if you look at the next 10 percent there is a lot of 
really good science there.

                    USE OF RESEARCH BUDGET INCREASE

    Mr. Hoyer. Now, the other related question is--and you have 
indicated in your statement that you have been able to expand 
some translational research----
    Dr. Hyman. Translational research in clinical trials.
    Mr. Hoyer [continuing]. You indicated in your statement you 
have been able to coordinate better and expand that. You have 
gotten generous increases. Are you confident that we are 
expending that money effectively and efficiently and can absorb 
it at the rate that it has been increased?
    Dr. Hyman. In NIMH I am absolutely confident and I am 
confident for several reasons. First, the brain sciences are 
maturing now at an astounding rate and we now have tools for 
really incisive and good investigations. Things like neuro-
imaging, things like you saw on the neurogenesis slide, are 
generating an enormous amount of good science.
    The second thing is--and I am actually quite proud of this 
as an accomplishment for the institute--I think that we were 
sort of at the leading edge of the recognition that many of the 
most common human illnesses and, indeed, the risk of all mental 
disorders is genetically complex. That means that more than one 
gene, plus non-genetic factors, all conspire to produce risk, 
not a single gene, as is the case for Huntington's disease. And 
by using, I think, some of the very best geneticists in the 
United States to help us think about how we would solve these 
problems, we have actually attracted people into our portfolio: 
People who had never had NIMH grants before. And that has been 
something that has really been something I have tried to do to 
get really the best possible scientists to get interested in 
our problems and that is becoming successful.
    So, I think that is another hallmark of good science. And 
then the clinical trials I described at the outset I feel are 
high-risk. You know, when you break out of the usual safe mold 
and you start doing trials that look at real people and real 
settings, the danger is that they will lose some rigor. Of 
course, the danger of having a rigorous trial that is 
irrelevant is that you have answered a question that nobody 
cares about. So, I think that is going to be very important 
science. But I think only in the context of the support that 
you have given us can we do good science that also breaks the 
mold, you know, where there is risk, where we are going to 
start to answer some important questions.
    Mr. Hoyer. Thank you very much.

                     RISK FACTORS FOR YOUTH SUICIDE

    I know my time is up, Mr. Chairman, but I would like to at 
some point in time pursue why the 1968-to-1978 period was such 
a spike because that would be very relevant--suicide is a 
critical problem, obviously, in our community. I do not know 
whether you want to let him answer that. But I think it is a 
relevant question.
    Mr. Porter. I think you snuck it in. [Laughter.]
    Dr. Hyman. Let me just say about----
    Mr. Hoyer. Thank you for your tolerance of letting me do 
so.
    Dr. Hyman. Let me say something about suicide, which I 
think the American people do not realize. There were 31,000 
suicides in the United States in the last year, I think 1998, 
for which we have good statistics. There were in contrast, 
19,000 homicides. So, people tend to read the newspapers and 
think that homicide is the leading cause of unnatural death. It 
is actually suicide by a long shot.
    This is an enormous public health problem. It is the 9th 
leading cause of death overall, for young women the second 
leading cause of death and for young men the third leading 
cause of death. And, of course, it leaves unutterable tragedy 
for families.
    We believe that this spike had to do with a number of 
things but a critical factor had to do with drugs. And we 
believe that the rise in African American youth also had to do 
with the rise of drugs. Drugs seem to be a lethal co-factor 
when mixed with a child who has depression. I mean drugs often 
push them over the top.
    There are other theories but one of the reasons we want to 
do this careful epidemiologic study is we really do want to 
understand these risk factors in more detail.
    Mr. Hoyer. Thank you, Mr. Chairman.
    Mr. Porter. Thank you, Mr. Hoyer.
    Mr. Miller.

              USE OF PSYCHOACTIVE MEDICATIONS IN CHILDREN

    Mr. Miller. Good morning.
    First off, there is something that you made a comment about 
in your statement and it has been discussed for children and 
all of that and it has been in the lay literature about the use 
of the Prozac and things like that.
    Dr. Hyman. Yes, yes.
    Mr. Miller. You know, what we are hearing, you know, what 
is your concern about that issue? Just, you know, the over-
medication. Does it lead to violence?
    Dr. Hyman. Yes, yes. Well, okay. So, there are a few 
things, Mr. Miller. It is a really important question. I would 
answer that the real problem is inadequate knowledge and it is 
not so much over-medication as over-medication and under-
medication. The wrong kids are often getting these medications. 
Now, what do I mean by that?
    First of all, there has been a dearth of studies in anybody 
under the age of 18 for psychopharmacology and, frankly, for 
psychotherapy as well. One of my enormous frustrations as NIMH 
Director is the lack of a research infrastructure to deal with 
children's problems and we have been working on that with 
career awards to welcome pediatricians into the field, 
neurologists, any good scientist who wants to come into this 
field, we will pay for their retraining and the initiation of 
their research.
    We have also, for the first time, brought the pediatricians 
on board as a critical group because they are the ones who are 
really seeing these kids. It is not the psychiatrist. We have 
data that for kids above the age of 6, as I was describing, 
Ritalin is safe and effective. But let me focus on this for a 
minute. What we recognize is that about 3 to 5 percent of 
children have attention deficit disorder and that, untreated, 
the outcome is bad. These kids, they cannot learn in school so 
they do not live up to their potential. They have a higher risk 
of eventually using drugs, and here is an anecdote: The number 
of kids with untreated attention deficit are so over-
represented in incarcerated populations that the Justice 
Department, the Office of Juvenile Justice, co-funds some of 
our ADHD treatment studies. So, I think that is testimony to 
how badly these kids do untreated.
    But here is the problem. In some neighborhoods, especially 
Caucasian, upper-middle-class neighborhoods 20, 30 even 40 
percent of the boys may be on Ritalin and this is a disorder 
that occurs in 3 to 5 percent of children. In contrast, 
actually in many inner-city neighborhoods there is no Ritalin 
used because the word is out on the street that this is a 
chemical restraint to, you know, to take away normal boyhood 
and a tool of discrimination. So, the problem is that there are 
lots of kids getting Ritalin who really do not need it and 
there are other kids who need it who are not getting it. And, 
you know, it is true that even for a kid who would not meet 
diagnostic criteria for attention deficit disorder, Ritalin 
will help them concentrate better, it will make them somewhat 
easier to teach and parent, but I would argue that there ought 
to be other behavioral means and we ought to reserve the 
medication because even though the safety record of Ritalin is 
much better than the media would lead you to think, any 
medication has side effects and raises concerns. You just do 
not want to be reaching for the pill instead of engaging in the 
kind of behavioral interactions that would be appropriate.
    Now, we know less about antidepressants in children. In 
fact, we know virtually nothing about SSRI's, Prozac-like 
antidepressants in children below the age of 12. We know very 
little about their use in teenagers. One of the things we were 
able to initiate, actually two years ago was one of these 
clinical trials that I was describing to Mr. Porter and Mr. 
Hoyer on adolescent depression, looking at Prozac, 
psychotherapy and the combination. We do not actually have 
enough researchers yet who could conduct such a trial in 
children under the age of 12. So, it is really very much 
needed.
    Mr. Miller. But how much is it being utilized right now?
    Dr. Hyman. A lot. But we believe that perhaps as many as 5 
percent of children under the age of 12 get an antidepressant 
at some point. Now, the most troubling thing to me was this 
recent finding of the use of two types of drugs, clonidine and 
tricyclic antidepressants, in preschoolers, age 2 to 4. This 
was in the media and on television.
    I have a particular problem with the use of the drug, 
clonidine and with tricyclic antidepressants in these very 
young children because these are drugs that actually have known 
side effects, including very rare cases of sudden death. 
Clonidine is being used probably to sedate kids who are really 
acting up a great deal.
    The tricyclics may actually be being used for bedwetting. 
You know, at low doses they are very useful for treating 
enuresis, or bedwetting. But, you know, I am a parent of a 
young kid. If a 2- or a 3-year-old is not ready to be toilet 
trained what is wrong with a diaper and a little behavioral 
therapy? I mean I would not be giving a kid a tricyclic 
antidepressant. And insofar as their being used for depression 
it is really an irrational practice because unlike the Prozac-
like drugs, these have been studied in young children and zero 
of 13 studies found efficacy.
    So, again, we do not know enough but what we know is not 
being appropriately applied and we really are going to need to 
somehow get the word out, you see, not to psychiatrists but to 
family doctors and to pediatricians.

                 DISSEMINATE BEST PRACTICE INFORMATION

    Mr. Miller. What is being done to get that word out? I mean 
obviously----
    Dr. Hyman. Well, we have been trying to actually engage the 
pediatric community in NIMH research. We are also trying to 
disseminate, again, you know, it is late, I admit, but in the 
context of these news reports, we have put together a fact 
sheet to disseminate on what is known and what the best 
practices are for primary care providers. We also have been in 
contact with the FDA about having a conference about what we 
can do in terms of really getting the word out appropriately.
    Mr. Miller. What other ways are there to get the word out 
besides your institute? FDA?
    Dr. Hyman. Child Health. Well, I think that the 
professional societies could have an enormous role.
    Mr. Miller. With all of this publicity.
    Dr. Hyman. We have had some--yes, actually ``U.S. News'' 
and ``Newsweek'' have helped disseminate this. And actually 
were very responsible articles.
    Mr. Miller. Were they good articles?
    Dr. Hyman. Yes. The ``U.S. News'' article----
    Mr. Miller. Good. I have got it sitting on my desk.
    Dr. Hyman. Yes, yes.

                   TRANSCRANIAL MAGNETIC STIMULATION

    Mr. Miller. Let me ask a couple of quick questions before 
my time is up. In January I was up at the University of Florida 
and went to the Brain Institute and I was really impressed with 
these magnets, you know, these gigantic ones that they have 
there.
    Dr. Hyman. Yes.
    Mr. Miller. The possibilities there--I mean the really 
powerful ones are not designed for humans yet.
    Dr. Hyman. Yes.
    Mr. Miller. But the ability, what they are talking about 
doing is exciting. I mean do you--I know you do some funding 
through there.
    Dr. Hyman. Yes, yes, a lot.
    Mr. Miller. But the potential for that whole magnetic 
imaging, you know, because you can really target exactly what 
you want in the brain without playing around.
    Dr. Hyman. Well, we have created a new psychiatric syndrome 
which is ``Tesla envy'' because you measure the strength of 
these magnets in Tesla and, you know, you can attract 
scientists depending on how big your magnet is. [Laughter.]

                     NEW BRAIN IMAGING TECHNOLOGIES

    The potential is enormous. Let me just give you one example 
of something that I have been really trying to facilitate, both 
within our intramural program and also extramurally to a number 
of sites. High field strength functional magnetic resonance 
imaging is going to give us the ability to really see with 
incredible spatial resolution the activity of the brain as it 
thinks, as it feels, as it performs motor acts.
    But one of the things about the limitation of this 
wonderful technique is that it collects data no more quickly 
than one second. Because what it is seeing is not the neurons 
firing, but when neurons fire or work they call for more blood 
and more oxygen. You know, they are busy. And what we actually 
can see in the magnet is the change in blood oxygenation; 
whether hemoglobin has oxygen on it or not, slightly changes 
its magnetic properties. But it takes about a second for that 
blood flow to arrive.
    There is another technology, however, called 
magnetoencephalography, or MEG. Neurons are electrical and 
every time you have an electric current you generate a tiny 
magnetic field. MEG devices are super-conducting devices that 
can detect the minute endogenous magnetic fields produced by 
human neurons. And they work on the millisecond time scale that 
the neurons are actually working on because they are detecting 
the results of the actual electrical change in the neurons.
    What we are trying to do computationally is put together 
FMRI, for its great spatial resolution, and MEG, for its great 
temporal resolution, and we are starting to see, obviously 
slowed down for us, real time movies of neural activity 
following cognition and emotion. And we are just at the 
beginning. I think we are going to have an incredible window on 
the brain which is obviously going to be very relevant to 
making diagnoses and developing new treatments for mental 
illness.
    Mr. Miller. Thank you.
    Thank you, Mr. Chairman.
    Mr. Porter. Thank you, Mr. Miller.
    Mrs. Northup.

                       RITALIN AND HYPERACTIVITY

    Mrs. Northup. Thank you, Mr. Chairman.
    First of all, I would like to go back the question about 
Ritalin and hyperactivty. I realize attention deficit disorder 
is not the same thing as being hyperactive but they often are 
assiciated.
    Dr. Hyman. Yes, that is correct.
    Mrs. Northup. Children that have attention deficit are 
often hyperactive. And, you know, as somebody that had that as 
a child and can remember in great detail that I could not sit 
in my seat in school. I learned through really wonderful 
parents, who helped me see this as a positive. Probably my 
husband thought it was great to marry somebody with so much 
energy but when we started having 2 year olds with this much 
energy it was not quite so much fun.
    Dr. Hyman. Right. [Laughter.]
    Mrs. Northup. And I was so determined I would not use 
Ritalin, no sugar, no artificial flavorings and colorings. You 
know, I did it all. Until finally, you know, when the oldest 
was 7 the doctor said you really ought to try Ritalin for your 
child. I think it is the most wonderful drug. It is the most 
amazing drug and I agree with you that learning the skills are 
so important too--time management, being organized, running--so 
that you can use it effectively.
    But what I am getting to is that I really raised my 
children with them thinking they were really the most lucky 
kids in the world and that is how I feel about myself. Because 
I do have more energy than anybody I know and over the years of 
working to stay focused, to be organized, to overcome maybe a 
natural sense of time and so forth, it has been probably the 
luckiest thing I have. It really bothers me to constantly see 
this being talked as like a mental illness and my children say 
the same thing, how much they got out of it. I would tell you 
that in our family of 6 kids the couple that are hyperactive 
are looked as the luckiest of our children. They could train 
longer in sports, they had to build up the other capabilities 
that went with it. But when you see 5 million kids in your 
statistics that had ADHD last year and you say 3 to 5 percent 
of the kids in this country have it, then we are under-
diagnosing by a lot.
    And I wonder if some of that is because of the negative 
connotations. I struggle with this because I have a right to 
disclose who I am; my children do not necessarily want their 
mother disclosing who they are. And yet, recently a talk show 
host immediately equated it to schizophrenia drugs and 
depression, and I thought--oh, boy, I am really sorry that this 
is the message going to parents who have a child they are 
considering Ritalin.

                     ``Mental Illness'' STIGMATIZES

    Dr. Hyman. Well, your comments are really right on target. 
The term mental illness, which we have inherited, is just 
completely wrong. We are talking about brain conditions. If I 
could get another word besides mental illness it would do a lot 
of people an awful lot of good. It is a holdover from ancient 
times and bad theories.

                           TREATMENT OF ADHD

    In fact, attention deficit with or without hyperactivity, 
may have been useful 300 years ago when a person was out 
hunting to survive; then, you would have been a ``healthy 
person,'' and it is only in a modern school setting that it 
becomes a disease. So, maybe it is better to think about these 
things as brain conditions and what you are really trying to do 
is help someone achieve their full and healthy potential with 
the benefits of modern medicine.
    I do not think that we disagree at all about the use of 
Ritalin. There are a lot of people out there, frankly, who have 
decided without data that these drugs have got to be bad and 
are scaring lots of parents. This occurs in general more in 
inner-cities than in suburban communities but it is a general 
problem. My feeling is that again that lots of kids who need 
it, and I think this was your point, are not getting it, but 
that some of the kids who are getting it may not need it.
    I think what we really need to do is to improve our 
practices and, of course, in this era of trying to hold down 
medical costs what is happening is exactly the opposite. 
Instead of really evaluating kids right, trying them on the 
medication, seeing if it does the right thing for them, helping 
the family understand side effects, giving them these other 
behavioral aspects, the time management, the other things they 
need, what we are getting is often slapdash prescription 
writing and that is not helping even the kids who would 
benefit.
    Mrs. Northup. Right. Let me--do I have time for one more 
question, Mr. Chairman?
    Mr. Porter. Yes.

            ENGAGING YOUNG PEOPLE IN MENTAL HEALTH TREATMENT

    Mrs. Northup. It seems to me like, a lot of parents, a lot 
of moms and dads that are my age, in their 50s, have children, 
young adults. A recurring problem with mental health for their 
children when they have children is engaging them, just exactly 
as you said, in taking their medicine and going to their 
appointments.
    Dr. Hyman. Right.
    Mrs. Northup. And one of the concerns I have about it, 
every time we talk about parity for coverage, is that the 
children or the 20-year olds or whatever, there is no amount of 
coverage that helps if that child does not feel a sense of 
being engaged in it.
    Dr. Hyman. Right.
    Mrs. Northup. And you hear one parent after another talk 
about the breakthroughs. I think of this friend of mine who 
said, one day my child said to me, ``You know, you need to get 
my prescription renewed; The child said I realized I was on the 
phone screaming at all my friends. And I went, hey, it is not 
my friends, it is me.''
    And that is when the child took seriously--I need to get my 
medicine, and I need to go see the therapist. But until then, 
the child missed appointments regularly, did not take their 
medicine, despite the fact that insurance covered it. And I 
guess I feel like there has to be some sort of engagement or 
feeling that there must be a limit. And I just wonder if you 
would address that question of parity and that sense of 
entitlement compared to the importance of being engaged in the 
therapy and the medicine.

                      TREATMENT ADHERENCE RESEARCH

    Dr. Hyman. Well, what you have struck upon, of course, is 
an issue that is true across all age spans, most difficult for 
adolescents, true for all diseases. As you know, adolescent 
diabetics also do not want to be different from other children 
and have problems with adherence.
    But this gets back to your first discussion because the 
word, mental illness, is highly stigmatizing. I mean, again, 
what we want to say is that these kids have real conditions of 
a real organ, the brain, just like any other condition and they 
deserve treatment.
    Having said that, if we can get over this barrier I think 
addressing engagement or adherence is really critical. And we 
have begun, as I said in my opening remarks, really to work 
with the behavioral science community on this and you know, 
this is not a trivial problem. We can have all of these 
wonderful fruits of molecular medicine but if the pills stay in 
the bottle no one is doing any good and also all of the common 
sense things have been tried. You know, the finger wagging, 
take your pills. I mean we know this does not work.
    I think it is really critical to begin to think about peer 
level interventions, family level interventions, school level 
interventions, really think outside the box, as to how we can 
destigmatize these disorders and get kids really engaged in 
their treatment for you are right--whether or not someone is 
insured is not going to make the difference.
    Mrs. Northup. What about the patches that deliver the 
medicine----
    Dr. Hyman. Well, those----
    Mrs. Northup [continuing]. Regularly. I am not so sure that 
some of the cases that my friend, I am not so sure that the 
child is rebelling as much as they start to get a little bit 
better and it does not become important to them.

                   COMPREHENSIVE TREATMENT APPROACHES

    Dr. Hyman. Yes. Or they want to feel like the rest of their 
peers. They do not want to be waking up every morning and 
taking a pill or reminding themselves that it is different. 
Yes, some of the drug companies are working on other ways of 
delivery, like patches, but also psychotherapy and skill 
building is important.
    And I think we can do a lot better job. You know, a kid 
arrives for cognitive behavioral therapy. You know, it is 
boring. You know, do your cognitive therapy homework. We should 
build-in modules for engaging children. I mean we have to--our 
behavioral science community I think can contribute real 
improvements in these areas.
    Mrs. Northup. Thank you.
    Thank you, Mr. Chairman.
    Mr. Porter. Thank you, Mrs. Northup.
    Mr. Jackson.
    Mr. Jackson. Thank you, Mr. Chairman.
    Thank you, Dr. Hyman, for being here today.

                          PARENTAL INVOLVEMENT

    I find this conversation to be absolutely fascinating. My 
experience is just the opposite of Mrs. Northup's. When I was 
growing up my parents wanted to put me on all kinds of drugs 
because I was a little anxious but my parents made the 
objective decision that what Jesse, Jr., fundamentally needed 
was somebody to spend more time with him. So, my mother gave up 
her career to spend a little more time with the children and 
she kind of followed me to and from school and she was very 
available whenever I would beat somebody up or bite somebody 
or----
    [Laughter.]
    Mr. Jackson. She was very available to come because she had 
this child who had all this anxiety.
    Dr. Hyman. Right, right.
    Mr. Jackson. So, I am kind of grateful today that my 
parents did not put me on any form of medication. And, you 
know, the truth of the matter is, at least from my perspective, 
that not all children who are expressing a certain level of 
anxiety necessarily need medication. I think that oftentimes we 
use medication and mental illness and mental disorders, as we 
choose to refer to them, to calm our kids down. In other words, 
to get our children to fit into our schedules on the terms that 
we want our children to relate to us, rather than being anxious 
when our children are anxious, and excited when our children 
are excited, and want to go out. We want them to calm down 
because we are tired, so, take your medication. All too often 
this is an excuse for not being a better parent.
    And if I had to speak today on this Committee on behalf of 
young people across the country who are being forced to down 
all kinds of drugs because they will not calm down, I think 
that NIH needs to spend some time developing a better parent 
drug. [Laughter.]
    And parents ought to start taking some drugs that calm them 
down and prepare them for parenthood, including taking their 
children to and from school, spending time with their children, 
making some adjustments around their careers and around their 
portfolios so they can raise the babies that they make. That is 
my own earnest opinion.

                      RESEARCH ON ``BAD BEHAVIOR''

    But suffice it to say we are not here to discuss that, even 
though it is a significant part of what you do. One Committee 
in this Congress, the Committee on the Judiciary, allows 
certain behavioral disorders to be sufficient pleas or 
justification for the criminal defendant. I am sure you are 
very well aware of many of them. And I would imagine that the 
use of these behavioral disorders for the criminal defendant 
come in various forms. Pleas for insanity, temporary insanity, 
all suggesting some mental disorder. Someone always pointing 
back to their childhood or pointing back to some significant 
event in their life that led to their present contemporary 
behavior, which the other Committee seems to refer to as 
criminal but tends to manifest itself in some significant 
behavioral or mental disorder.
    I was just wondering if, since the National Institute is 
charged with studying mental health, if whether or not the 
byproduct, for example, of being sexist, that one might 
consider the study of it a significant behavioral disorder, 
including the criminal conduct that might result: Beating one's 
wife, discrimination on the job, firing someone because they 
reject a sexual advance? I am just wondering if sexism and the 
study of it, particularly on the male brain, is significant 
enough to be categorized as a behavioral disorder?

              DEFINING THE BOUNDARIES OF MENTAL DISORDERS

    Dr. Hyman. I have philosophically tried to narrow the 
medicalization, not to overmedicalize the diversity of human 
behaviors for a number of reasons. First of all, we have really 
little evidence that any of these things like sexism or racism, 
as repugnant as they are, represent a medical condition with 
some underlying, perhaps genetic, predisposition.
    And I think, insofar as we begin to medicalize these 
things, as you imply, you begin to give people exculpatory 
stories. And, indeed, in mental health there is a gray zone. 
Things are sometimes funny. Schizophrenia, there is no doubt, 
it is never normal to be having hallucinations. But when does a 
little bit of pervasive blueness, and low energy and excessive 
guilt shade over into depressive illness? We have to handle 
that gray zone. But I think we err if we begin to take every 
negative attitude and social ill and begin to medicalize it.
    I also sometimes think about what would have happened to 
some of the opposites in other regimes in the world. Perhaps 
you recall that in the Soviet Union, people who were dissenters 
against the political system were labeled as being mentally 
ill, and there was an abuse of psychiatry. So I think it is 
very important that we do not medicalize all social problems, 
and that we never medicalize evil. We must recognize that when 
people have a real mental illness that sometimes, as in the 
case of schizophrenia or being in the throes of a manic 
episode, you really cannot tell right from wrong. And then, of 
course, we do have the insanity defense.
    But for many other people the disorders do not usurp their 
entire brain. They must remain engageable. We were talking 
about----
    Mr. Jackson. Dr. Hyman, not the medicalization of the 
concept for the purposes of exculpatory for the defendant's 
purposes, but for the purpose of the society better 
understanding the nature of the problem.

              RESEARCH ON STEREOTYPING AND DISCRIMINATION

    Dr. Hyman. So we actually do, in our basic behavioral 
science portfolio, we actually support social psychology. And 
one of the areas that is supported is the study of stereotyping 
and discrimination. And we have developed a great deal of 
knowledge about the ways in which people create stereotypes and 
the impact of those, and those--that research, tragically, I 
think has had a greater impact on Madison Avenue than it has 
had on the health professions. But the research is being done. 
I think it is very important. I would add that it is also 
applicable to mental illness because people with mental 
illnesses are also stereotyped and discriminated against.
    Mr. Jackson. I know this case because I have been trying 
to, during the course of my inquiry, trying to find out more 
numbers on the number of minority researchers at NIH. And every 
time I try and cross-examine or examine the NIH on the question 
of these researchers, somehow there is the stereotypical stuff 
about substandard research seems to be associated with, 
whenever I am asking where are minorities or where are women or 
where are Asians, somehow I just end up in a kind of mental 
disorder on the question of whether or not blacks with Ph.D.s 
and M.D.s are qualified and why they are not pursuing research 
at the advanced level at NIH.
    But I want to pursue one last question. I think my time is 
just about expired. I think it is very difficult, on the one 
hand, when we say that insanity is a sufficient defense on the 
judiciary side of the equation, but almost all of the insanity 
defenses that we have heard, particularly the very public 
cases, where the use of insanity became a factor, that there 
was some ``ism'' associated with it. O.J.'s view of women was a 
factor in O.J.'s case. The Susan Smith case in South Carolina, 
the first thing she said was an African American had done it, 
and then she claimed insanity on her own basis. The James Byrd 
situation in Texas, all of them pled some form of insanity, as 
the basis for the justification of their behavior.
    So it would appear to me then that while there is this 
broad choice that we have as human beings, there is also 
sufficient, I think, evidence worthy of study on what some of 
the ``isms'' and the implications of those who are less 
tolerant have been in our society, and its broad-ranging 
implications.
    Dr. Hyman. I agree with you. I would say one thing, so that 
I do not run on too long. What we have to remember is that our 
brain works in--and forgive me one sentence that may be 
incomprehensible even to me--works in relatively modular 
circuits. One can, on the one hand, hold a certain set of 
beliefs about black people, for example, or about gays, you 
know, in thinking about these cases, but that does not mean 
one's whole brain is taken over by this. At another level, I 
think a person has the wherewithal to know that this is not 
appropriate in our society and that whatever one's beliefs, 
that certain acts are beyond the pale. And I think what we are 
allowing is people to generalize from deeply ingrained--let's 
imagine very deeply ingrained ideas that may be racist or 
intolerant to----
    Mr. Jackson. Mr. Chairman, I know my time is expired, but 
he just raised a very interesting point, just very quickly.
    It is illegal in this society, but that does not change the 
individual brain and disorder that may be a deeply held belief 
for the individual--I am sorry.
    Dr. Hyman. No, no. I do not want to go on for too long. Let 
me just say that, remember, the brain is built not only bottom-
up by genes, but the brain is also built by our experience, and 
our laws and our social beliefs are part of what built the 
brain. In essence, you know, people in drug policies always 
separate supply side from demand side. But the laws that have 
to do with the supply side also affect the demand side because 
they create the moral environment in which we should be raising 
our children. It is involved in building their brains. That is 
a longer----
    Mr. Jackson. Thank you, Mr. Chairman.
    Mr. Porter. A very interesting course of questions. Thank 
you, Mr. Jackson.
    Ms. Lowey.

               IMPROVING TREATMENT OF CHILDHOOD DISORDERS

    Mrs. Lowey. Thank you, Mr. Chairman. And welcome, Dr. 
Hyman. I apologize that I came in in the middle of this very 
interesting and very controversial discussion. On the one hand, 
I have my colleague talking about how this child is supposed to 
be taking Ritalin and is not taking Ritalin, and how are we 
going to get the child to take Ritalin. And on the other hand, 
another colleague is saying that maybe more mothers or fathers 
should stay home and give more attention to the child, and we 
are probably all right.
    In New York, I am concerned about children being 
warehoused, put in institutions because they are not even 
examined, they do not have the mother or the father that is 
going to be able to stay home with them, even if they choose to 
stay home with them. And perhaps if that mother or father got 
some more assistance, drugs and therapy for the mother or the 
father, maybe the child would not be in such difficulty. And 
let us not even talk about that 6-year-old little boy! You 
probably did already.
    Dr. Hyman. Yes. Yes.
    Mrs. Lowey. But clearly it is very complex, and there is 
never going to be enough money to do everything we should. And 
it is very frustrating to all of us when we think of all of 
these lost people in our society, frankly, that are not getting 
help, and are being warehoused instead of getting adequate 
evaluations.
    Would you comment on how NIMH is helping address the 
significant need, this tremendous need for better understanding 
of childhood mental illnesses, better screening, better 
diagnoses, better treatment. We have this constant battle going 
all of the time, and I do not know how we can adequately 
respond to it. If you spend ``x'' number of your resources on 
the four kids in the class, how are you shortchanging the 
majority of the class? And we deal with this in just so many 
different areas. But I think we have to educate people and 
create a better understanding, and if you can comment, I would 
appreciate it.
    Dr. Hyman. Well, I think your point, actually, relating to 
Mr. Jackson's point and also to the discussion I had before, I 
do not think anybody means there is an either/or; that pills 
should never be used, pills should always be used.
    Mrs. Lowey. Right.

              CHILD MENTAL HEALTH RESEARCH INFRASTRUCTURE

    Dr. Hyman. The problem is what you are talking about, which 
is the quality of the evaluation. There are some kids, I mean, 
to take an extreme case, who are banging their heads, who are 
self-mutilating, who have uncontrollable aggressive rages. We 
do them an incredible disservice if we do not use appropriate 
pharmacologic methods.
    By the same token, as I was saying to Mrs. Northrup, there 
are kids out there who may be getting Ritalin really just for 
the convenience of teachers and parents. And the goal is to 
understand the problems of children as individuals, respond as 
best you can, and then--I think this gets to the warehousing 
issue--and then to keep evaluating them: Is what I am doing 
working? Are the side effects intolerable? Is the kid maturing 
and no longer needs this intervention? Is the kid engaged in 
treatment? These are critical questions. How do we get the 
information?
    Well, I have already mentioned that we have initiated 
large-scale clinical trials, including both psychotherapy, and 
medication and the combination in adolescent depression. We 
just completed one in attention deficit disorder. We are 
beginning to start one in toddler attention deficit disorder, a 
real public health matter. We have research. I do not want to 
sit here and give you a laundry list. But I will say one thing. 
Childhood mental health is the one area in the portfolio, and 
this stretches all the way from autism, to anxiety, to ADHD, to 
depression, where every year I would be willing to spend more 
money than I am able to spend because of the lack of an 
adequate number in this field of highly trained investigators.
    When we funded our large-scale clinical trial in adolescent 
depression, I wanted to then immediately begin one in kids 
under the age of 12, especially with the goal not only of 
finding out about the safety and efficacy of medication, but 
getting the development of psychotherapies that would be age 
appropriate. And, frankly, the infrastructure--the 
investigators--was not there. It is one of my goals to be able 
to initiate something like that within 3 years.
    We have put together expert committees, and from the tone 
of my voice, I am hopeful, but still I want outcomes, I want 
results. I do not want to just have process. And one of the 
things that we have tried to do is to bring pediatricians and 
family doctors into this because they are the front line. We 
have, I already mentioned, salary awards for anyone who wants 
to get into this from the study of adults or from general 
pediatrics. We must get the word out and build a cadre of 
effective researchers, especially for young children. The 
problems are so pressing.
    Mrs. Lowey. And once you have the research, do you feel 
that there is enough coordination? I mean, you have some 
information and you need to do more research, obviously.
    Dr. Hyman. Yes. Yes.
    Mrs. Lowey. Is there enough coordination with the public 
health centers, with the public health programs, with the 
community health centers?

                      ENHANCING PROVIDERS' SKILLS

    Dr. Hyman. There is not. There have been unfortunate 
educational and guild issues so that, while, actually, Dr. 
Robert Johnson, who is a wonderful pediatrician from the State 
of New Jersey and was on my National Advisory Council, has 
actually been advising us on this. There is an increase in 
mental health, mental illness education for pediatricians. It 
really is inadequate, given the fact that they see so much of 
it, that these illnesses are so common. And breaking down 
barriers between guilds, like psychiatry and psychology and 
pediatrics and family medicine, is never easy. We really have 
to work. I mean, even the fact that I have pediatricians on my 
National Advisory Council tells you I am trying to break down 
these guild barriers, which get in the way of the flow of 
appropriate information.
    I also would point out that I do not want to bash family 
physicians. These people are under extraordinary time 
pressures, and issues about behavior entail very long 
conversations. Mothers have no problem bringing a child with a 
cough to the pediatrician. But if a child is depressed, the 
mother is fearful she is going to be blamed and often there is 
a very--there has to be a very delicate interaction to elicit 
the proper information.
    So we have a big process ahead of us.

                COMMUNICATION BETWEEN NIMH AND EDUCATORS

    Mrs. Lowey. Do you have superintendents of schools, do you 
have teachers, do you have anyone in the education field? Steny 
Hoyer and I have been very strong advocates of comprehensive 
schools. I just feel it is not sufficient today for the mother 
to bring the kid to the pediatrician. We need to have these 
services in the schools.
    Dr. Hyman. Well, right. Schools should not just be places 
where nurses have rows of pills in front of them to give out.
    Mrs. Lowey. And one nurse for a thousand kids, right.
    Dr. Hyman. We have had, actually, very good meetings, but 
of course it is with the Federal Department of Education, and--
--
    Mrs. Lowey. You talked about your advisory committee. Do 
you have educators?
    Dr. Hyman. No, I do not, actually, on my advisory 
committee.
    Mrs. Lowey. Not a bad idea, right?
    Dr. Hyman. That is an interesting idea. But we have had--
that is a good idea. So okay. [Laughter.]
    But we have had very good interactions with education in 
the area of youth violence. There are some interesting cultural 
differences between the way we would approach things. This has 
to do with medicalization and the way they see things.
    Mrs. Lowey. I guess I heard the bell, so I will have to 
save the other questions. But, obviously, we can talk for hours 
on this because it is so critical.
    Dr. Hyman. These are fundamental issues for America's 
children.
    Mrs. Lowey. But we appreciate that you are there focusing 
on it. Thank you.
    Dr. Hyman. Thank you.
    Mr. Porter. Thank you, Ms. Lowey.
    We will take a short second round.

           RATES OF MENTAL DISORDER BY RACIAL/ETHNIC IDENTITY

    One of the things that we have heard repeatedly from your 
colleagues, the Directors of the other Institutes, is about the 
unusually high rates that minorities suffer, whether it is 
heart disease or cancer or diabetes or infectious diseases. But 
we have not heard that minorities suffer greater mental health 
problems necessarily.
    Dr. Hyman. That is correct.
    Mr. Porter. Is that because we just have not done the 
research on it or is it because there is greater mental health 
among minorities, and they do not suffer disproportionately in 
this area?
    Dr. Hyman. Yes. The research is very interesting. For the 
most serious mental disorders, such as schizophrenia, the rates 
are eerily alike among all races, they are the same in midtown 
Manhattan as in rural Kenya, which has been studied. I, 
actually, went to India for reasons about AIDS behavioral 
prevention, but I stopped at a large mental hospital in 
Southern India and interviewed patients who could speak 
English, and schizophrenia was entirely the same there. It was 
really staggering.
    For anxiety and depression, however, there is good evidence 
that grinding poverty, that being witness to violence, to 
living in a chaotic or disrupted family or a single-parent 
family, conditions to which minorities are subjected much more 
than the majority population, there is actually an impact on 
both anxiety disorders and depression. And people like Dr. 
James Jackson at the University of Michigan and Dr. Felton 
Earls at Harvard, are very much involved in helping us to 
understand the precise impact.
    It is important, however, that just because a kid has 
gotten depressed because of an experience of discrimination 
that we do not fail to treat this as a real medical disorder. 
These experiences initiate, in the vulnerable youngster, this 
brain condition, this brain disease, depression, and we have to 
then, obviously, deal with the social conditions insofar as we 
can, but not neglect the medical side.
    There is another issue with minority disparities which have 
to do with utilization and trust. And there is a tragic 
finding, from our Schizophrenia Port study, and also from prior 
work of Dr. James Jackson, that black men are much more likely 
than white men to get the diagnosis of schizophrenia and to be 
treated with high-dose antipsychotic drugs if they have ever 
had a psychotic symptom, whether or not they actually have 
schizophrenia. And this, again, gets to Mr. Jackson's question 
about stereotyping. And it is a very, very important area of 
research.
    It is interesting, the illness in our portfolio that has a 
disproportionate impact on minorities is AIDS. After all, we 
have the portfolio on behavioral prevention of HIV/AIDS. And 
although African Americans are something like 13 percent of the 
general population, they now represent 57 percent of new-
incident HIV infections. So as the demographics of the epidemic 
have moved, we have focused our prevention measures, because 
prevention measures have to be culturally sensitive, and as of 
today, $85,000,000 of the $130,000,000 in our prevention 
portfolio are focused on minorities, which is the highest 
percentage of any AIDS portfolio at NIH.

                  PUBLIC EDUCATION ABOUT CHILD HEALTH

    Mr. Porter. I am going to sneak in a second question here. 
We have been talking with CDC, SAMHSA, HRSA, and others about 
some method of getting out some, for want of a better term, 
public service interventions--and whether they are on TV or the 
Internet, we are not sure yet--that would address children's 
health, and particularly behavioral; diet, exercise, avoiding 
use of tobacco and alcohol at a young age, and drugs and the 
like. Obviously, a part of a child's health is also mental 
health. It is a very complex subject, however. Is there any way 
that this subject would lend itself to a reach-out to either 
children or their parents in a simple way that would impact 
their habits that might improve their mental health later on?
    Dr. Hyman. Yes. And as you know, we were involved with this 
American Health Foundation outreach efforts for children. I 
think that kids really would respond to simple messages like, 
you know, everybody gets sad now and then, but it is not okay 
to be sad or scared all of the time. I think kids would respond 
to messages like that.
    Mr. Porter. We are actively working on this, and we want to 
call on you for your intellect.
    Dr. Hyman. I would be delighted.
    Mr. Porter. Mr. Jackson, any further questions?
    Mr. Jackson. Mr. Chairman, yes, I would be happy to take 
this opportunity.
    I have a number of questions that I want to submit for the 
record.
    Dr. Hyman. Sure. Okay.
    Mr. Jackson. And if you could get back to me on those, I 
would be greatly appreciative.

                     MINORITY GROUPS' MENTAL HEALTH

    I want to associate myself with the Chairman's concern 
about mental illness among minorities, schizophrenia and other 
fundamental behavioral disorders. I was going to indicate to 
the Chairman that this is one subject matter that a lot of 
minorities do not want to broach, that we might be twice as 
likely to be crazy as everybody else.
    Dr. Hyman. But it is not the case.
    Mr. Jackson. Right, but it is not the case, and I am happy 
to hear that. [Laughter.]
    That there is overwhelming evidence that we have fewer 
disparities in this area. That is particularly important. And I 
am not picking on anyone because they are running for 
President, but I just want to make a point. I do not think 
anyone in this room can deny that Senator McCain's experience 
as a soldier has had a profound impact on who he is as a 
person, and I think a favorable profound impact. I think 
millions of Americans feel very strongly about the kind of 
character that his leadership represents, and I certainly feel 
that strongly about him as a colleague of his.
    But I also do not think that many Americans fully 
appreciate the depth and profundity of these discrimination 
experiences on the development of character for young African 
Americans, when they experience it from the police, or members 
of Congress, like myself, whenever I am trying to argue for 
more appropriations funds for my district, some of my 
colleagues think they are doing something for me when they have 
done something for Chicago, when most of my district is out of 
Chicago. They just assume that helping Chicago has helped Jesse 
Junior. I say, ``No, I represent 30 cities outside of the City 
of Chicago.'' But, no, you are the young African American 
inner-city Congressman from Chicago, and we have done something 
for Chicago. That is part of the stereotypical kind of problem.
    And I say that as a member of Congress, but I would 
imagine, if I were moving up the corporate ladder as a woman, 
that there are a number of ``isms'' that would put me in a 
position where I would have to be as tough as the guys and even 
tougher than the guys in order to make it up the ladder because 
those experiences, at every step of that ladder, have shaped 
the culture of who we are as a Nation, same for every Asian 
American, and Hispanic Americans and others who have been 
victims of one of the ``isms'' that I think, personally, is 
worthy of study.
    What we end up finding, based upon the Nation's history and 
the very structure of our Nation's Government, and this is a 
political statement, is that the study of some of these 
``isms'' get quite personal. I mean, the study of racism, in 
light of how many Presidents we have had in one category and 
how many thousands of people have been in Congress, and less 
than 100 of them have been African American. The study of 
racism becomes all too apparent the study of white guys. When 
we talk about the study of sexism, I mean, the population is, 
clearly, you have got to be a guy to be in the category, the 
study of men and their behavior towards women, as it has 
developed through our Nation's history and what is expected of 
men in our society. How we define manhood is a factor, I think, 
in that, and we try and pass it on to our sons.
    Well, I guess I am suggesting that many of these mental 
disorders and behavioral disorders are the sum total of our 
experiences in the society. And so I am not so sure that we can 
totally separate those experiences that might ultimately 
culminate in criminal conduct or in a certain behavior that has 
tremendous economic and legal and political consequences for 
the individuals who engage in them. So I do not know how long I 
am going to be on this committee, and something tells me that I 
am going to get run off of here real soon by the line of my 
questioning. [Laughter.]
    But I am certainly hoping that over time we are at least 
open to the idea of broader study on the questions that I am--I 
am sorry.
    Dr. Hyman. I am sorry. No, no, I am sorry.
    Mr. Jackson. No, Dr. Hyman, go ahead. My time has expired. 
Thank you, Mr. Chairman.

                 IMPACT OF LIFE EXPERIENCE ON BEHAVIOR

    Dr. Hyman. Again, I wanted to reiterate that in our basic 
behavioral science portfolio, we do study these. And, indeed, 
we intend to study these issues more as they would impact 
things that are in our clear mission, such as the risk of 
depression, anxiety disorders, post-traumatic stress disorder 
and youth violence among youth. And what you said, I would just 
add one thing, the sum total of our experiences, plus what we 
bring to the table, from our genes, our early development does 
impact who we are.
    And I would just, if you reflect for a second on the 
behavior of human beings like you and me in the former 
Yugoslavia or in Rwanda, what is it in early experience, in 
devaluation of other people, how do these ideas take hold so 
that you can dehumanize somebody else and then engage in that 
kind of violence. Nobody flew over those countries and dropped 
new DNA on the people. This really had to do with very deep-
lived experience, and it is very worthy of study.
    Mr. Jackson. If I can just sneak a little point in like the 
Chairman did. [Laughter.]
    The only problem there is it is easy to study mice and 
study raccoons and figure out their behavioral disorders. But 
when we talk about some of these ``isms'' that are fundamental 
to creating anxiety in many of our homes, and the 
dehumanization and degradation of some of our men who come home 
to their families and take it out on their wives and behave a 
certain way because job after job because they are subject to 
certain kinds of society-driven, self-study, amongst even white 
researchers at that level, particularly white male researchers, 
become something that I would imagine through the history of 
the NIH is something that is not often engaged in because it is 
not easy to just say, ``Well, that is just a general mental 
disorder,'' when the ``ism'' itself is inherent in the culture 
of the structure of the way it was set up.
    Thank you very much, Mr. Chairman.
    Mr. Porter. The Chair would note that when the gentleman 
talks about projects and programs for the City of Chicago and 
stereotyping, that occurs solely on his side of the aisle, not 
on our side. [Laughter.]
    Mr. Jackson. The Chairman has been generous. Thank you, Mr. 
Chairman. [Laughter.]
    Mr. Porter. Mr. Miller.

                        NIMH BUDGET DISTRIBUTION

    Mr. Miller. Let me talk a little bit about budgeting issues 
and some money issues. I guess that is what we are here for.
    Dr. Hyman. Oh, yes. Yes.
    Mr. Miller. What percentage of your money is extramural?
    Dr. Hyman. It is 12 percent intramural. So I was trying to 
subtract the administrative part, but it is about 85/86.
    Mr. Miller. About 85/86.
    Dr. Hyman. Yes.
    Mr. Miller. And that is a little lower or is that about 
average?
    Dr. Hyman. It is about average. Our intramural program has 
gotten smaller, percentagewise, with each year that I have been 
director, as we have been bringing in very rigorous review.

                             BUDGETARY FLUX

    Mr. Miller. Hopefully, Congress will continue on the path 
of doubling total funding for NIH over a period of time, but 
these 15-percent increases are not going to continue.
    Dr. Hyman. Yes.
    Mr. Miller. And then you reach the stage of, you know, 
there will not necessarily be, hopefully not flat funding, but 
I do not think the 15 percent will continue.
    How much of your grants, extramural, these are multi-year, 
most of your----
    Dr. Hyman. Yes; four years, on average.
    Mr. Miller. Four years, on average. So the problem we 
foresee, if you start doing 5 years off, assuming there is 
this, you know--you are preparing, and this is----
    Dr. Hyman. Yes, we are----
    Mr. Miller. All of NIH, I guess, is----
    Dr. Hyman. We are very concerned about having a commitment 
base which is so large that if one year we go from 15 percent 
to zero, there will be no ability to fund new research in that 
year.
    On the other hand, we have to spend our appropriation 
within the given year, and there are just so many things that 
we can do to manage those concerns. We hope, obviously, that at 
such a time as these healthy increases that we have been 
talking about begin to taper, that it is truly a taper and not 
a cliff.
    Mr. Miller. Right. Just kind of briefly, with what little 
time there is left, about how your research priorities and 
funding priorities have changed since you have been Chairman, 
head of NIMH.

                 REDIRECTION OF NIMH RESEARCH PROGRAMS

    Dr. Hyman. I have to say I have made a very substantial 
number of changes. NIMH came from, originally, another agency, 
ADAMHA, and the sciences of the brain really have just been 
maturing, and our science of genetics. And also, NIMH had not 
had stable permanent leadership in some time when I took over. 
And I did find it in need of enormous changes in priorities 
and, frankly, in standards.
    Although I am a psychiatrist, partly because I come from 
the mainstream biology community, I was able to call on people 
not only within the field, but throughout biological science--
molecular biologists, geneticists, cognitive neuroscientists--
for advice. And, in essence, we have changed the way we do 
business; for example, in genetics, to recognize the complexity 
of genetic risk. We have changed the way we do business in 
clinical neuroscience, bringing together basic neuroscientists 
with clinicians, instead of asking clinical investigators to be 
all things to all people. We have changed the way we do 
clinical trials to have more external generalized ability to 
real-world populations. We have changed our commitment to 
fundamental neuroscience, increasing it markedly. We have 
refocused on the need to take basic behavioral science and make 
it strong, but also have asked it to contribute to public 
health issues, again, by building teams. I have refocused 
prevention research from the romantic idea that we could 
prevent mental illness, which we don't know how to do to the 
idea of early intervention, early diagnosis.
    And I can detail these things for you. It has been a very 
exciting time. And there is, of course, a very talented 
research field that has helped in all of this reorientation. 
This is only possible, again, because of the generosity of the 
American people acting through you.
    Mr. Miller. Thank you.
    Mr. Porter. Thank you, Mr. Miller.
    Mrs. Lowey.
    Mrs. Lowey. Incidently, Mr. Chairman, I am not sure if I 
mentioned that even though Yale, and Harvard and Cambridge can 
all claim you, that you did grow up in New York, so I am 
particularly proud.
    Dr. Hyman. I did. Upper West Side.
    Mrs. Lowey. Well, I grew up in the Bronx, but it is close.
    Dr. Hyman. My mom came from the Bronx.
    Mrs. Lowey. I knew it. I knew it. I had a feeling.
    Dr. Hyman. Walton Avenue.
    Mrs. Lowey. So did I.
    Dr. Hyman. Really? Yeah. Yeah. [Laughter.]
    Mrs. Lowey. Not 975 Walton?
    Dr. Hyman. That, I do not know. Near Yankee Stadium.
    Mrs. Lowey. So did I. [Laughter.]

                          PREVENTION RESEARCH

    I just suspected good, strong roots, Mr. Chairman. We will 
have to continue that.
    Thank you. I will try to be brief because I know we have 
another hearing, and I know you did comment on your work in 
trying to reshape research priorities at the NIMH to reflect 
public health needs, and this is along your discussion.
    In several recent Mental Health Advisory Council reports, 
you have recommended improving the relevance of prevention 
research into early interventions.
    Dr. Hyman. Correct.
    Mrs. Lowey. Clinical research to actual practice, 
behavioral research to serious mental illness.
    Dr. Hyman. Correct.
    Mrs. Lowey. And I understand that changing research 
priorities at a place like the NIMH is not easy when you are 
dealing with such large institutions. But if you can discuss 
sone of the successes, some of the difficulties to change the 
Institution's direction.
    Dr. Hyman. This actually continues from Mr. Miller's 
question.
    Mrs. Lowey. Exactly.
    Dr. Hyman. Exactly. Well, scientists, although we are 
objective, of course, we also, like all humans, get into 
patterns of doing business, and often it is very hard to change 
the way people do research. And what I have invariably done, as 
I mentioned, is called on the very best people outside the 
Institute, often people who are not directly in this field. 
There have got to be some people who do not have necessarily a 
vested interest in the field, and also outstanding people who 
you want to seduce into your field because you get them 
involved in the planning process.
    And then I have taken these reports or actually they have 
been developed through our National Advisory Council, and there 
is always a healthy debate and public announcement. And then we 
have been pretty tough about changing policy; meaning, we will 
make an announcement that grant funds are available for this 
and that, that area of research, which was terrific 10 years 
ago, but is no longer relevant, we are just going to start 
phasing it out. And it has not always made me popular, but I 
think it is the only way to operate. Indeed, I think, just from 
my opening comments about this committee's and Mr. Porter's 
demand for high standards, I think it is precisely at a time 
when we are getting these healthy increases, that instead of 
allowing older ways of doing business to just continue, this is 
the time to make changes and always to point toward new 
opportunity instead of sort of getting into a rut.
    Mrs. Lowey. I think that bell counted our Walton Avenue 
discussion. [Laughter.]
    Mr. Porter. Hey, you chose it. [Laughter.]
    Mrs. Lowey. Well, we will let it be.
    Mr. Porter. If Nancy was here, she would say you probably 
went to San Francisco, too, right?
    Dr. Hyman. Yeah. That is right. [Laughter.]
    I visited.
    Mrs. Lowey. I will have to submit the next question, but I 
thank you.
    Mr. Porter. Dr. Hyman, we actually have gone way over our 
time, and that is the Chair's fault. But the discussion is 
fascinating to us, and we have been discussing with Dr. 
Kirschstein ways that we can get some of this into the minds of 
other members who are not privileged to be members of this 
subcommittee. I believe, Ruth, if we had a camera here, and I 
will not be here to do this, but if you had a camera here, 
videotaped all of the testimony of all of the Directors and 
then have somebody edit it and put it together and send it to 
the members, they might have a chance to get some of the flavor 
of the wonderful experience those of us who are members of the 
committee get from listening to the directors.
    Dr. Hyman, you do a marvelous job. You have educated us 
greatly. The discussion this morning has been just fascinating, 
and we cannot tell you how much we appreciate the outstanding 
work that you are doing there and how much we want to give you 
the resources to continue it and expand it.
    Dr. Hyman. Great. Thank you very much.
    Mr. Porter. Thank you.
    Dr. Hyman. Once again, a special thanks to you, Mr. Porter.
    Mr. Porter. Thank you, Dr. Hyman.
    The subcommittee will stand briefly in recess.
    [The following questions were submitted to be answered for 
the record:]



                                        Tuesday, February 29, 2000.

    NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

                               WITNESSES

DR. ALLEN M. SPIEGEL, DIRECTOR, NATIONAL INSTITUTE OF DIABETES AND 
    DIGESTIVE AND KIDNEY DISEASES, NIH
EARL LAURENCE, DEPUTY DIRECTOR, NATIONAL INSTITUTE OF DIABETES AND 
    DIGESTIVE AND KIDNEY DISEASES, NIH
CHARLES R. ZELLERS, FINANCIAL MANAGEMENT OFFICER, NATIONAL INSTITUTE OF 
    DIABETES AND DIGESTIVE AND KIDNEY DISEASES, NIH
DENNIS P. WILLIAMS, DEPUTY ASSISTANT SECRETARY, BUDGET, DEPARTMENT OF 
    HEALTH AND HUMAN SERVICES
DR. RUTH L. KIRSCHSTEIN, ACTING DIRECTOR, NIH
    Mr. Porter [presiding]. The subcommittee will come to 
order. We continue our hearings on the budget for the National 
Institutes of Health with the National Institute of Diabetes 
and Digestive and Kidney Diseases. We are pleased to welcome 
for the first time Dr. Allen Spiegel, the new Director. Dr. 
Spiegel, we are delighted to see you in this position. You have 
been with the Institute for 27 years, I am told, which is a 
long time, but now you are the director and we are pleased to 
have you here and look forward to your testimony.

               OPENING STATEMENT OF DR. ALLEN M. SPIEGEL

    Dr. Spiegel. Thank you very much, Mr. Porter. I would like 
to begin by introducing Mr. Earl Laurence, who is our deputy 
director, immediately to my left; Mr. Charles Zellers, who is 
our budget officer, to my far left. I believe you are familiar 
with both Dr. Ruth Kirschstein and Mr. Dennis Williams.
    Mr. Chairman and Members of the Committee, I am pleased to 
testify on behalf of the National Institute of Diabetes and 
Digestive and Kidney Diseases, particularly as NIDDK marks its 
50th anniversary this year. As you heard, I have been with the 
institute for nearly 27 of those 50 years, but just for the 
past 3 months as institute director. The challenges poised by 
the diseases within the NIDDK mission are enormous, yet we are 
poised as never before to make dramatic progress by using new 
powerful research tools, including, for example, genomics, 
bioinformatics, animal models of disease, and noninvasive 
imaging methods. All of these tools are generating new 
knowledge that will, I believe, revolutionize the treatment and 
prevention of the diseases within the NIDDK mission. Thus, I 
have a real sense of excitement and optimism in accepting the 
challenge as director of NIDDK of leading the effort to 
alleviate the burden of diabetes, endocrine and metabolic 
disorders, digestive and nutritional disorders, kidney, 
urologic and blood diseases.

                       POLYCYSTIC KIDNEY DISEASE

    One of my main goals as institute director will be to 
strengthen the connections between basic science and clinical 
research in order to accelerate progress. I will provide, in 
the interest of time, just three brief examples of how we can 
move from basic science to clinical advances. Polycystic Kidney 
Disease, or PKD, is the fourth leading cause of end-stage 
kidney failure. Basic research led to the discovery of 2 of the 
genes that cause PKD. This in turn permitted clinical studies 
that showed that cyst formation, which is the fundamental 
abnormality in PKD, like benign tumor formation, is an abnormal 
growth process.
    Just within the past month, NIDDK-supported investigators 
using a drug that blocks growth by targeting a growth factor 
receptor, were able to show that they could block cyst 
formation and enhance survival in an animal model of PKD. This 
holds out real promise for eventual treatment of the human 
disease.

                              HEPATITIS C

    Let me turn as a second example to hepatitis C which, as 
many of you know, affects an estimated 4 million Americans and 
is the most common reason for liver transplantation in the 
United States. Basic research first led to the discovery of the 
virus. This permitted methods to diagnose the disease and 
measure the virus in the blood and eventually led to clinical 
studies, which have culminated in the demonstration that anti-
viral agents in combination, interferon and Ribavirin, are able 
to clear the virus from the blood of as many as 40 percent of 
infected patients. This is not good enough, though. We are now 
launching new initiatives aimed at increasing the effectiveness 
of anti-viral drug treatment and also combatting the 
disproportionate burden this disease places on African-
Americans.

                           DIABETES RESEARCH

    Certainly, I believe one of our greatest challenges is 
diabetes. I could recite the statistics on the millions of 
Americans of all socio-economic groups that are affected and 
the devastating complications, for example, kidney failure, 
blindness, amputation and heart disease. But these numbers 
alone do not adequately depict the plight of the patients, 
young and old, suffering from diabetes. Fortunately, basic and 
clinical research offer hope to those who already have the 
disease and those who are at risk of developing it in the 
future. In type 1 diabetes, we have learned much about how the 
immune system destroys the insulin-secreting beta cells. 
Advances in genetics and immunology have led to candidate 
interventions to reeducate the immune system and allow us to 
prevent beta cell destruction. We have also learned how reduced 
insulin secretion and resistance to the action of insulin cause 
type 2 diabetes. Mutations in several genes causing rare, early 
onset forms of the disease have already been identified, and in 
each case they have been shown to impair insulin secretion.
    A subtle defect recently in one of these same genes has 
been discovered in patients with the more common form of type 2 
diabetes. In related research, a new class of diabetes drugs 
that act by increasing the sensitivity to insulin action was 
shown to work on a cellular receptor termed PPAR-gamma. Now, in 
very recent work, mutations and defects in the gene for PPAR-
gamma were identified in some patients with type 2 diabetes. 
This provides further evidence of the critical importance of 
this receptor protein in insulin action.
    Let me summarize that clinical trials have already 
convincingly demonstrated the importance of maintaining 
excellent control of blood glucose in preventing or delaying 
the onset of diabetes complications. But tight control through 
careful monitoring of blood glucose and multiple daily 
injections can be both difficult and frustrating, especially in 
children with type 1 diabetes. Thus, the NIDDK is committed to 
supporting research to improve existing insulin treatments and 
to find innovative new treatments that will represent a true 
cure for this disease.

                   PANCREATIC ISLET CELL TRANSPLANTS

    I call your attention to the figure on my left. As shown in 
this figure, normal stable levels of blood sugar can be 
achieved in monkeys lacking a pancreas who have received a 
pancreatic islet cell transplant. In contrast, the 4-year-old 
child with type 1 diabetes depicted here, despite intensive 
insulin therapy, has, as seen in the jagged line above, wildly 
abnormal fluctuations in blood sugar. Importantly, these 
excellent results in the transplanted monkeys were achieved 
with an innovative form of treatment that allows acceptance of 
the transplanted islets without chronic immuno-suppressive 
drugs. Even though it is clear that these studies are very much 
in their infancy, we have been sufficiently encouraged to open 
an entirely new branch in the NIH Clinical Center dedicated to 
exploring this and related types of treatment in both kidney 
transplants and islet transplants.
    These few examples, I believe, show only some of the 
remarkable progress we are achieving in biomedical research 
related to diseases within the NIDDK mission. Clearly, though, 
many, many challenges and opportunities remain. Minorities, for 
example, are disproportionately affected by type 2 diabetes, 
hepatitis C, and end-stage kidney failure, all diseases within 
the core mission of NIDDK. We are committed to addressing those 
significant issues in a variety of ways, but I will cite just a 
couple of examples.

                      DIABETES PREVENTION PROGRAM

    Our Diabetes Prevention Program is a large multi-centered 
trial aimed at testing a variety of interventions that could 
prevent or delay the onset of diabetes in high-risk 
individuals. The study is notable because it has enrolled 
approximately 50 percent of the subjects from minority groups 
that are disproportionately affected. We are also supporting an 
entirely new initiative aimed at the alarming incidence, 
particularly among minority groups, of type 2 diabetes in 
children. We are furthermore supporting efforts to understand 
why Native Americans and African-Americans show an increased 
susceptibility to the kidney complications of diabetes.

                    DIABETES RESEARCH WORKING GROUP

    We will also be actively pursuing the five areas of 
extraordinary opportunity--genetics, autoimmunity in the beta 
cell, cellular signalling, obesity, and clinical trials--that 
were outlined by the Congressionally-established Diabetes 
Research Working Group. In the interest of time, I will 
elaborate on this during the question-and-answer period with 
specific examples of what we are doing and what we plan to do 
in these areas.
    In my very first few weeks as NIDDK Director, I have been 
meeting with a large number of groups, both lay and scientific, 
that represent the NIDDK constituencies. I expect in the future 
to reach out to those and other groups within the NIDDK family 
to work together with them and our superb National Advisory 
Council to frame a collaborative research agenda for the 
future. I believe that working together, we can take full 
advantage of this unique moment of scientific opportunity for 
the benefit of all of the people of this country. I am pleased 
to present the President's non-AIDS budget for NIDDK for fiscal 
year 2001: $1.186 billion, an increase of $66,800,000 over the 
fiscal year 2000 appropriation.
    Mr. Chairman, if I may, before accepting questions, permit 
me to note that one of my few disappointments in becoming NIDDK 
Director was the knowledge this would be your last year as 
Chairman of this subcommittee. I would like for myself and on 
behalf of my colleagues in NIDDK, to thank you for all that you 
have done for biomedical research. I now will be pleased to 
accept questions.
    [The written statement of Dr. Spiegel follows:]



                       DIABETES RESEARCH ADVANCES

    Mr. Porter. Dr. Spiegel, thank you for your testimony and 
for your kind words about my retirement. I think it is fair to 
say that there is a great deal of excitement about your 
leadership at NIDDK, particularly among the patient advocacy 
groups. You have been at NIH for 27 years beginning as a fellow 
in 1973, and you have seen a great deal of research done on 
diabetes. Is it fair to say that while we have developed better 
means of diagnosis, better means of treatment, and better means 
of taking care of the complications of diabetes, that there 
hasn't been a lot of progress up to this point on understanding 
the disease and reaching the point where we feel we are making 
real progress on it. I get that feeling. I wonder, you said 
that you weren't going to recite the statistics, but is it not 
true that this is a disease that is getting more prevalent 
rather than less prevalent and affecting young people, 
particularly more than it used to? In other words, up to this 
point, aren't we really just barely holding our own in this 
battle and not making a lot of progress?
    Dr. Spiegel. I wonder when we will get to the tough 
questions. Let me respond in the following way, Mr. Chairman. 
First, I know that the parents of children with type 1 
diabetes, the relatives and patients themselves with type 2 
diabetes, are anxious and eager for cures and prevention. I 
absolutely empathize and wish we had these yesterday. 
Unfortunately, research in areas that are as complex and 
difficult as both type 1 and type 2 diabetes seems to be 
painfully slow. I agree with you. I have been with the 
Institute all of these years and I have observed lots of 
diabetes research taking place. And one could take the 
perspective of, ``Have we really made progress?'' I would argue 
strenuously that not only have we made very good progress but, 
as I implied in my opening statement, I believe that we are on 
an accelerating course to be able to make even more substantive 
progress given the very generous support that Congress has 
provided us.
    Let me be specific for a moment. It is absolutely true that 
we need to keep this distinction between type 1 and type 2 
diabetes in mind. Type 2 diabetes, the more prevalent form, 
according to the American Diabetes Association involves as many 
as 16 million Americans. Many don't know they even have the 
disease--it seems to be an epidemic. Obesity is a very 
important predisposing factor and that certainly seems to be an 
epidemic. No question that is growing.
    Type 2 diabetes in children, not the autoimmune destruction 
of the beta cells, but the same disease that we see in adults, 
is also increasing. We are aware of this and we are launching 
initiatives, as I mentioned, in this direction. Whether the 
other form, the autoimmune form, type 1, is increasing in the 
United States, is not so completely clear. There are some bits 
of evidence that it may be. The fact is that with as many as 
800,000 Americans, perhaps even a million involved, it is still 
too large a number by any stretch of the imagination.

                          GENETICS OF DIABETES

    Where is the evidence that we are making some headway? I 
will just mention the areas of extraordinary opportunity that 
are in the DRWG report. First, if you look at genes, several 
genes that predispose to type 1 diabetes have already been 
discovered. I know you were at the groundbreaking ceremony for 
the NIH Clinical Research Center, and perhaps you will recall 
former Senator Hatfield's comments there: ``If you tell me you 
have identified a new gene for the disease, I will be 
interested; but if you tell me you can do something about it, I 
will be excited.''
    I can relate to and understand what he is saying. It is 
important to understand that identifying these genes is a 
critical first step. By doing so in type 1 diabetes, we can 
determine who is at risk and test various preventive measures 
at various stages at the disease. We are doing exactly this and 
there are new candidate interventions. In type 2 diabetes, 
genes have already been discovered, as I indicated, and some of 
these, as in the case of this new class of drugs I mentioned, 
are already lending themselves to therapy.
    If we take autoimmunity and the beta cell, the islet 
transplant example I gave is an important example. Islet 
transplants--and this perfectly echoes what you said--have been 
around for years and have not been very successful. But now 
with newer methods of harvesting these islets, with newer 
methods of establishing immune tolerance, they may succeed.
    Obesity, a predisposing factor for type 2 diabetes, is an 
enormous problem, and yet with the discovery of leptin and 
other pathways involved in the regulation of fat we are making 
real headway.
    And finally, our major clinical trials that we are 
supporting will have public health impact, as well as pilot, 
small clinical trials to move quickly from basic science 
discoveries to an impact on the patient. I would summarize by 
saying that I share your impatience and those of the patients 
out there who are anxiously awaiting treatments and cures and 
prevention, but I really do believe that as we look back over 
just the last few years, substantive progress has been made, 
and with the appropriate resources, will continue to be made.

                    DIABETES RESEARCH WORKING GROUP

    Mr. Porter. I can squeeze in another question. What kind of 
impact on the kinds of scientific opportunities that you have 
been describing would it have if we could get to the level of 
funding suggested by the working group? In other words, is more 
money faster going to get us where we want to go faster? Is 
there that much light at the end of the tunnel or not?
    Dr. Spiegel. Let me just respond by saying that I am very 
much in accord with the scientific opportunities as outlined in 
the DRWG report. They do represent a road map for phenomenal 
progress. Working within the confines of our existing budget, 
we are attempting to address each of these areas as best we 
can. I believe that the record will show that NIDDK is 
attempting to support these areas by at least 2 percentage 
points--and it may end up being more--than the overall increase 
that the Institute received. Clearly, in several ways having 
additional resources could: (A) allow us to move faster, and 
(B) on the issue of genes and clinical trials, the power of 
such studies is always greater when you have larger numbers of 
individuals, but this is more costly.
    Finally, even though it is critical to prioritize, you 
can't take every path--but many apparently good science steps, 
different interventions for example, would be worth supporting 
if we could. Of course, how many of those different paths we 
can simultaneously support, for example in diabetes prevention 
trials, depends on the level of resources.
    Mr. Porter. We probably ought to remind ourselves that 
money alone doesn't do it necessarily. Richard Nixon declared 
war on cancer 30 or more years ago, and we poured a lot of 
money into that research. While we made progress recently, for 
a long time we didn't make much progress. We did a lot of 
research, but we didn't find what we were seeking and hoping 
that the money would get us. I think there is now great hope in 
this area, and obviously it is an area that affects so many 
Americans, including members of my own family, that I think we 
ought to pursue the good science that is available, and I 
appreciate your answering my questions.
    Ms. DeLauro.

                          GENETICS OF DIABETES

    Ms. DeLauro. Thank you, Mr. Chairman. Just to follow up 
what you have been talking about, I have two constituents here, 
Paul Rossi and Vera Updike, who represent the Juvenile Diabetes 
Foundation of New Haven, both of whom have daughters with type 
1 diabetes. You started to talk, Dr. Spiegel, about the 
identification of the gene that leads to diabetes. Let me just 
ask you about gene therapy and what is your sense of that, and 
if that is what you were leading up to talking about, do you 
think we are going to see gene therapy available. I can't ever 
ask you to guess about time to identifying the screen for 
ovarian cancer, but because of what the Chairman was talking 
about, we are trying to go a long road here. Where are we on a 
time frame?
    Dr. Spiegel. Since you raised the subject of gene therapy, 
let me address it head on. First, despite the very untoward 
recent events, the fact is I firmly believe that gene therapy 
will eventually represent an important treatment of many 
diseases. It is important not to ``overhype'' this. If you look 
at monoclonal antibodies, 20 years ago--and this comes back to 
Mr. Porter's comments--they were hyped as ``magic bullets'' and 
nothing happened. Now we have biotech companies making 
monoclonal antibodies, Herceptin, as an example for breast 
cancer, and there are numerous others including Infliximab, a 
monoclonal antibody for Crohn's disease. I believe that 
eventually gene therapy approaches will also be successful.
    But as we look into the Orkin-Motulski report, we need a 
lot of basic science to study the vectors and the way of really 
being able to deliver this in a safe way. Now, specifically to 
your question with diabetes, our institute, with the 
sponsorship of several of the other institutes at NIH, co-
sponsored in November a workshop on gene therapy in diabetes. 
In fact, there are at least 3 conceptual areas where it may be 
useful. We expect as an aftermath of that workshop to issue a 
request for proposals and applications relating to gene 
therapy. One would be specifically in terms of the 
complications. For the wounds, the amputations we hear about in 
terms of foot ulcers, there are growth factors that can help in 
wound healing and delivering them by gene therapy may be 
therapeutic. This needs to be tested.
    A second area is in prevention of beta cell destruction. We 
know that it is an imbalance of various proteins in the body 
that lead to this destruction. By using a gene therapy approach 
directed at the beta cells, we might be able to stave off or 
prevent that kind of destruction. Those are the two areas we 
are expecting to support. A third area is actual insulin 
replacement by gene therapy. A paper in Science from a biotech 
company just within this month indicated a very novel approach 
that worked in animals. Will it work in humans? It is not 
clear. But this offers promise. Again, you are absolutely 
right, we need to have a long time line. We shouldn't overhype 
this.

                         INTERSTITIAL CYSTITIS

    Ms. DeLauro. Thank you. Let me move to another area, and 
again, it is constituent-based. I have a constituent who 
suffers from a debilitating disease of the bladder known as 
interstitial cystitis or IC. She winds up battling with the 
insurance company and also dealing with a disabling chronic 
pain, a pain so bad she can no longer work outside of her home, 
and so her quality of life has clearly suffered. First, can you 
tell me how much NIDDK spent last year on basic research on 
interstitial cystitis and how much more was this than the 
previous year?
    Dr. Spiegel. This disease is one of the things that I 
really had to learn about from the ground up becoming NIDDK 
director. In my intramural role, I was not familiar with it. 
The way that I learned about it was we have a superb division 
director in this area who spearheaded our efforts. I met with 
the Interstitial Cystitis Association very early on and have 
learned how frustrating and difficult this disease can be. I 
believe that the amount of support for IC has grown 
dramatically within NIDDK over the past three years. It is 
estimated to be $11,800,000 in fiscal year 2000 and to grow 
further in fiscal year 2001. There is definitely a treatment 
trial with an agent called Elmiron under way which is supported 
by the Institute. It is too early to tell whether this will be 
successful. Most importantly, we are trying to address this not 
only on a basic level but an epidemiological level. We have 
sent out a request for proposals for a urology in America 
database. This will help to address how prevalent the disease 
really is, and what will be the diagnostic and symptomatic 
criteria. So we are committed to addressing this very, very 
important problem.
    Ms. DeLauro. What we are talking about is the 
epidemiological study that was done this spring?
    Dr. Spiegel. Exactly. We have convened various 
epidemiologists and urologists and we have close ties. Again, 
with the help of the Congress, we have a slightly expanded 
budget but still a very low Research Management and Support 
(RMS) figure. We have been able to hire a basic urologist who 
will oversee our bladder programs. Indeed, we are addressing 
this at the epidemiologic and clinical level, but also at the 
basic level, because as I stress, the basic science is key. So 
the overall condition, the painful bladder syndrome, of which 
IC is a part--it is one that we are very mindful of and are 
supporting significant research.
    Ms. DeLauro. Just to reinforce, Dr. Briggs indicated that 
there would be an epidemiological study sometime this spring. I 
also wanted to add that we have heard from so many people what 
a terrific job you are doing and we are delighted that you are 
there. Mr. Chairman, I am just going to submit a question which 
will be on Cooley's anemia. My time has expired. Thank you very 
much, Dr. Spiegel.
    Mr. Porter. Thank you, Ms. DeLauro. The subcommittee is 
currently operating under the 6-minute rule. We have, in 
addition to NIDDK, the National Library of Medicine to hear 
this afternoon.
    Mr. Bonilla.

                       TYPE 1 DIABETES PREVENTION

    Mr. Bonilla. Thank you, Mr. Chairman. Dr. Spiegel, I was 
pleased to hear about NIDDK's plans to support the promising 
areas of diabetes research as laid out in the Diabetes Research 
Working Group report. I want to ask a couple of questions 
related to this research. In your testimony, you mentioned that 
current NIDDK studies on type 1 diabetes, particularly studies 
on genetic predisposition to the disease, you talked about, and 
Ms. DeLauro talked about that as well. Could you expand on the 
status of these studies and other NIDDK studies focusing on 
prevention of juvenile diabetes in children?
    Dr. Spiegel. Absolutely. The prevention studies that we are 
currently performing include a very large trial with the 
acronym DPT1, for diabetes prevention trial for type 1, which 
looks at first degree relatives of people with type 1 diabetes, 
screens them for evidence of markers in the blood, antibodies 
against the beta cell, and then tries two forms of 
intervention. It sounds counterintuitive, but oral insulin or 
injected insulin might serve as a way of reeducating the immune 
system. For one of those arms of treatment the study has 
recruited its target goal and it is near recruiting the target 
goal for the other arm. It will still be at least a couple of 
years, if not slightly more, before we have an answer. This is 
one of the major trials we are investing in. Because of the 
accelerated pace of knowledge in this area, I met with the 
investigators in that area and others from around the world in 
a meeting recently in January. It is clear that we need to 
simultaneously launch pilot interventions, using the same 
clinical infrastructure, for other promising types of immune 
re-education. Those haven't yet been launched, but we intend to 
do that with the appropriate resources within the next fiscal 
year. This will be a kind of diabetes trial net, to allow us to 
pursue pilot interventions for things that show promise to be 
able to prevent type 1 diabetes.
    Mr. Bonilla. Is immune system re-education a fairly recent 
development?
    Dr. Spiegel. Yes and no. It is recent in terms of coming to 
the point where we consider testing it in humans. It is not 
recent in the sense that the basic science underpinning, the 
understanding of the intricacy of the immune system, is a 
years-long enterprise, but one that has been accelerating. The 
islet transplants figure I showed is yet another example of 
educating the immune system. I feel confident without putting a 
time frame on it that this will lead to a successful 
conclusion.

                        END-STAGE RENAL DISEASE

    Mr. Bonilla. A lot of us are huge advocates on this 
subcommittee for the work that you do. Chairman Porter raised 
an interesting question whether or not we are making 
significant progress relative to the amount of money we are 
investing. It was a good point that he raised, but you should 
know that we are going to give you all of the help that we 
possibly can. Many of us are committed on the subcommittee to 
doing that, to continue doing that as we have in years past.
    I have one final question here. As you know, Dr. Spiegel, 
more than 350,000 Americans have end-stage renal disease, but 
many more are at risk for the disease that could benefit from 
prevention strategies. Last year this committee expressed 
interest in exploring opportunities to develop early prevention 
technique interventions to slow the progression of kidney 
failure. On page 40 of your budget justification, you discussed 
some initial plans for NIDDK studies in this area. Could you 
elaborate on those plans, first of all, and tell us how could 
we include primary healthcare practitioners in the development 
and implementation of such early intervention strategies. Two 
parts to the question.
    Dr. Spiegel. I appreciate that question. Again, let me try 
to be brief. First the meetings that we have had with the 
American Society of Nephrology and with the National Kidney 
Foundation have led to very concrete plans to evaluate and move 
forward with the so-called National Kidney Education Program. 
The data on end-stage kidney failure in this country are 
staggering. Of course, there is a coincidence with diabetes 
there. Fully 44 percent of those cases are coming from 
diabetes. It is critical that we address it. Shockingly and 
surprisingly to me, we know very little about the progression 
before patients reach the end-stage renal failure. So it is 
this progression that we are going to need to evaluate in terms 
of the best interventions. There are certain kinds of drugs for 
blood pressure lowering, the so-called ACE inhibitors that may 
prevent kidney failure. The question of measuring protein in 
the urine as a screening method needs to be evaluated. We 
intend to convene the very best experts in all of these areas 
to determine: can we mount an effective public education 
campaign that would be a worthwhile National Kidney Education 
campaign in the same vein as the anti-hypertensive and anti-
cholesterol programs of NHLBI.
    In terms of implementing that campaign at the level of the 
primary practitioner, I think it is critical that we be able to 
demonstrate with evidence-based medicine that such screening 
measures, for example for urine protein, would be cost 
effective and relevant. This is going to require perhaps 
clinical studies, appropriate targeted studies. But I think it 
is critical that we move in that direction.
    Mr. Bonilla. Dr. Spiegel, thank you very much. I may have 
some questions for the record. Thank you for coming here today.
    Mr. Porter. Thank you, Mr. Bonilla.
    Mrs. Northup.

                   GENE THEREAPY AND ITS ALTERNATIVES

    Mrs. Northup. Thank you, Doctor. I would like to pursue the 
question on the time line and ask you about the question of 
gene therapy versus other initiatives you are talking taking. I 
do believe that the gene investigations are very important in 
terms of overall direction, and NIH is clearly the organization 
to coordinate that across the country. But I do have some 
questions, that we are looking so far down the road at those 
opportunities that we are maybe failing to fund and address 
nearer at hand approaches to treating people, preventing it, 
and possible cures. You know, I guess I feel that in terms of a 
whole new approach, it is great. It is still so unclear to me 
when we will ever really know that we will get clear enough 
information to apply it, that maybe we are overlooking 
applications today that would bring us quicker results.
    Dr. Spiegel. Let me address that in the following way. 
First of all, prevention is absolutely critical wherever we 
have the means to implement it by whatever techniques, whether 
behavioral, public health methods, or, in certain cases, 
vaccines. What about those who already have the disease though, 
where it can't be prevented? We have to come to grips with 
that. Your point about prevention is obviously critical. I want 
to correct perhaps a misimpression. Maybe I sounded impassioned 
about gene therapy. The sole justification for investigating 
genes and understanding what all of the human genome consists 
of is not to do gene therapy. There are many short-term payoffs 
both in terms of diagnosis, prevention, and, indeed, of knowing 
who is at risk. I could give you an example for sickle cell 
anemia, if I might, just as a brief way of capturing this.
    Just recently a publication on an animal model, a mouse 
model of sickle cell anemia, showed a gene therapy approach of 
raising fetal hemoglobin which was very effective in these mice 
of curing what is very similar to the human disease. That is 
great, but you are right; how long will that take in humans? It 
may take long, yet we may eventually get there. At the same 
time there are other studies using agents like hydrea and other 
types of drugs that have been shown to be effective in multi-
center trials. They are not the perfect answer, but they are a 
lower tech but effective approach to some extent. I think it 
comes back to what I was saying earlier, we need to be able to 
travel multiple paths. We need to be able to do the best we can 
do now in real time with the available evidence. But that 
doesn't mean that we should shoot for the sky. We should always 
aim high for the thing that will be most effective eventually.
    Mrs. Northup. I think you just gave a perfect example. I 
raised the question last week about sickle cell anemia and some 
of the trials that looked very promising regarding bone marrow 
transplants where you don't have to have exact matches and you 
don't have to do total ebullition, yet they are very lowly 
funded compared to the amount of money and hope we are placing 
with gene therapy. I have wondered, in sort of along the same 
lines that Mr. Porter raised, that we seem to be going so 
slowly down the road to finding real cure, real cure. It may 
eventually be that we will have to travel the whole road 
through the genetic. But in the meantime, I am concerned that 
we are not funding closer at hand possible cures.
    Dr. Spiegel. I read your questions to Dr. L'enfant and his 
responses along these lines. I am very respectful of what you 
are saying and share your views. Let me just illustrate. Dr. 
Griffin Rogers, an African-American who is the first branch 
chief in NIDDK that I named while intramural director, is a 
pioneer in the study of treatment of sickle cell anemia. He is 
currently launching specific hematopoietic stem cell transplant 
therapy studies. This is not the totipotential stem cell, these 
are blood stem cells that in a partial way without what is 
called ablative therapy may be able to address the problem of 
sickle cell anemia. Certainly we are attempting to cover all 
bets. In a way, it is hedging your bets but as I implied, that 
is important. We can't be focused solely on some distant 
future. That is not soon enough, but we can't ignore those 
possibilities.
    Mrs. Northup. I am not saying that you are ignoring them. I 
am saying that you may be underfunding them so that they are 
not moving as quickly as they could be, or we are not getting 
the test number of patients to the level that we could make 
better application of these. It is a relative question rather 
than an open or shut door on these.
    Dr. Spiegel. I really appreciate your input and this is 
something that we will have to reevaluate in light of what you 
are saying. I appreciate your comments.
    Mrs. Northup. Mr. Chairman, I think that is all. I have 
some other questions that I will submit for the record, but 
those are the main questions.
    Mr. Porter. Thank you, Ms. Northup.
    Mr. Jackson.
    Mr. Jackson. Thank you, Mr. Chairman, and thank you, Dr. 
Spiegel, for your testimony today. I must tell you that you 
began your testimony so enthusiastically I thought you were 
going to announce a cure for diabetes.
    Dr. Spiegel. I wish that I could. That is what I would most 
like to do.

                      HEALTH DISPARITIES RESEARCH

    Mr. Jackson. Let me also congratulate you in your new role 
as the director of the Institute. The President's fiscal year 
budget for NIDDK is $1,186,000,000, an increase of $66,800,000, 
and a 6 percent above fiscal year 2000 level. Included in this 
total is $34,000,000 for the following NIH areas of priority: 
New approaches to pathogenesis, $4,000,000; new preventative 
strategies against disease, $5,000,000; new avenues for the 
development of therapeutics, $2 million; genetics of medicine, 
$8,000,000; advanced instrumentation, $1,000,000; and health 
disparities, $14,000,000.
    I was reading a very interesting article that indicated 
that the President has made a commitment to the Nation to an 
ambitious goal by the year of 2010 of eliminating the 
disparities in six areas of health experienced by racial and 
ethnic minority populations while continuing to make progress 
on the overall health of the American people. It just so 
happens that one of the six areas that the President has put 
particular emphasis on is diabetes, diabetes research, but most 
importantly, eliminating--the President says--the disparities 
that presently exist between the majority population and ethnic 
minorities.
    My question for you is based upon your budget request of 
$1,186,000,000, and your 6 percent increase over the fiscal 
year 2000 level, do you believe that the President's request 
are on target toward eliminating those disparities by 2010?
    Dr. Spiegel. What I would say is that working within the 
envelope of the President's budget, working within that 
context, it is an extremely high priority to address these 
problems in terms of the disproportionate effect that type 2 
diabetes and other diseases that I have mentioned have on 
minorities. One gets into definitional problems in terms of 
singling out these areas of emphasis that you refer to. We have 
a figure, which nominally is on the order of $88 million within 
the institute that is very specifically targeted to minority 
health research. Much of what we do is in the areas of 
hepatitis C and type 2 diabetes, and some of the other diseases 
in terms of basic fundamental work, is surely relevant.
    I would just briefly respond by saying that this is an 
incredibly important priority to me. How could it not be, given 
the fact these diseases are within the core mission of NIDDK, 
but we must not overpromise. NIDDK and indeed NIH alone cannot, 
by themselves, eliminate these disparities. But I think by 
highlighting the areas where there are disproportionate effects 
on minorities, by trying to understand the scientific basis, by 
developing better treatment, by making sure that minorities are 
included as I alluded to in our important clinical trials, I 
will do my utmost to address this within the context of the 
budget.
    Mr. Jackson. I appreciate that, Dr. Spiegel. But one of my 
concerns here is the President's goal of eliminating the 
disparities by 2010 has very little to do with your own 
inclusive programs in your department, which I think are 
important. It is clear that you have the commitment to address 
some of the disparities in terms of where the resources are 
going and access to those institutions that are producing 
minority researchers. But the President here set a very 
ambitious goal of eliminating the disparities in six areas of 
health. I am just wondering if you are part of any of the 
coordination associated with the 2010 plan.

                            OBESITY RESEARCH

    Dr. Spiegel. We are part of the coordination to the extent 
that our Diabetes Division has participated in that area, the 
obesity area which is an important part of this as well, 
requiring appropriate nutrition and physical activity. We are 
actually doing some of these things. The Diabetes Prevention 
Program that I mentioned that has 50 percent minorities, which 
include Native Americans, Hispanic Americans, African-Americans 
from all over the country is testing not only drug 
interventions but healthy lifestyle modifications of diet and 
exercise. So we are committed to doing these things. We are 
coordinating in terms of nutrition in these other areas. We 
have led the trans-NIH effort in the obesity preventive 
initiative. Again, I come back to the point that we need to 
strain to do the utmost that we can within the budget context 
that we are given.

                      HEALTH DISPARITIES RESEARCH

    Mr. Jackson. Can you say with some certainty how much of 
your budget has been dedicated to help disparities in fiscal 
year 1999 and fiscal year 2000?
    Dr. Spiegel. Again, coming back to this strict definition, 
this would include a sum for training minority investigators, 
for a variety of supplements and education at all levels. We 
participate and have participated in training at every stage 
from high school through graduate and medical school. The 
figure for 1999, as I quoted earlier, is on the order of 
$88,000,000. But in my own estimation, this is really the most 
narrow, restricted definition. Many of the other things that we 
are doing are fundamental to these diseases as well. For fiscal 
year 2000, the estimated budget is $98,900,000.

               MINORITY INVESTIGATORS AND NIH PEER REVIEW

    Mr. Jackson. Let me ask you a question, Dr. Spiegel, since 
I still have a little time and the little bell hasn't gone off 
yet. The chronicle of higher education a few years ago wrote an 
article that said there was a racial imbalance at NIH. Let me 
just read a couple of paragraphs of that to you. It says--it 
begins--by Steven Byrd, ``that while scholars received 90 
percent of the research grants awarded competitively by the 
National Institutes of Health in 1991 according to a study by 
the agency. The study found in the same fiscal year, Asians had 
received about 8 percent of such grants, Hispanics 1.5 percent, 
and blacks about .4 percent. Those rates have been fairly 
consistent over the last decade,'' the report on the study 
says.
    Then it went on to say that ``many representatives of 
minority groups say that low levels of support result largely 
from flaws in the agency's peer review system. The system they 
say is made up overwhelmingly of white researchers who 
consciously or unconsciously dismiss proposals from minority 
researchers.''
    Last paragraph. ``NIH officials say that the peer reviewers 
are not told the race of grant applicants but critics of the 
agency say that the peer reviewers do not have difficulty 
discovering an applicant's racial identity. I think the people 
serving on the peer panels know the race of applicant by the 
resume, the school, and then people make assumptions.''
    I am wondering, Dr. Spiegel, since I know that you are new 
to the department, are you aware of any of this data as it 
might relate to your institute?
    Dr. Spiegel. As the Chairman said, I have actually been 
here for about 27 years in the department, so I can't evade 
responsibility. I am painfully aware of some aspects of it. Let 
me briefly respond. Within our intramural program, we have not 
a large number of minority investigators. There are four, for 
example, African-American tenured investigators, including one 
that I personally mentored in terms of becoming tenured, and 
another I alluded to who was appointed a Branch Chief. This is 
a woefully low number in comparison to the percentage of the 
population. Yet, sad to say, it is one of the highest numbers 
among the NIH Institutes.
    In terms of the general problem that you are talking about, 
which relates to extramural investigators, investigators 
applying for grants, I think that we have to address this in a 
number of ways. I would turn to Dr. Kirschstein, not to 
respond, but just to say that I know for all of her career at 
NIH and certainly now in her capacity as the Acting Director, 
she is a passionate advocate on this subject. She has launched 
a strategic planning effort that I believe will address this 
issue head on. I think under her leadership----if I can take a 
moment, to express thanks to her for her mentorship of me as I 
came in----the fact is that even with her commitment we cannot 
guarantee success. The problem needs to be addressed, and 
working with her, I believe we will do our best to address it.
    Mr. Jackson. Thank you, Dr. Spiegel. By the way, I have no 
doubt of Dr. Kirschstein's commitment. Thank you very much.
    Mr. Porter. Thank you, Mr. Jackson.
    Mr. Hoyer.
    Mr. Hoyer. Thank you, Mr. Chairman. Dr. Kirschstein, I 
would like to follow up on some of Mr. Jackson's questions. As 
you have experienced, while while you sat at the table through 
at least 3 or 4 directors, Lou Stokes and I have raised this 
issue on a repeated basis over the last 2 decades. We have had 
meetings in Congressman Stokes' office. I think we must have 
had six or seven at least over the last 12 years. This is a 
problem that is not only confronts NIH, but so many areas where 
we have great difficulty. And try as we might, the unconscious 
bias created by nonminority members participating in reviews 
and basic research, it does have an impact. We know that.
    I don't know what the answer is and I know Congressman 
Stokes was frustrated as well. I think you sincerely have 
addressed this issue. I refer to Dr. Kirschstein because it 
really is, as you pointed out, an institute-wide problem. 
Frankly, it is far beyond the Institute. My advice would be to 
you, Dr. Kirschstein, and to Dr. Spiegel, to work more closely 
with the minority members of the Congress. They have incredible 
contacts around the country. They have incredible contacts with 
young people, sons and daughters of their peers. Not Jessie's 
peers, because Jessie is so young. Jessie's peers presumably do 
not have 25- and 26-year-old young researchers ready to go. You 
heard my point. This is almost an intractable problem because 
when you look at the statistics that Lou Stokes and I started 
with back in probably 1983 or 1984 or 1985, they have changed, 
but not marketedly.

              MINORITY MEDICAL STUDENTS AND LOAN REPAYMENT

    Dr. Spiegel. If I may, I would interject one point. This 
planning effort is in the President's budget, and it is 
something that I am sure can be effective. It needs to be 
monitored and tracked. I think there is a missed opportunity 
here in terms of medical students. Since I started out my 
career--maybe this is just sort of self-serving--having been 
what I would characterize as a physician scientist, I know it 
is something that we are in danger of losing. We have something 
called the MARC program, Minority Access to Research Careers, 
which NIDDK has strongly participated in. Again, I have had 
several students in this program, both African-American and 
Hispanic, over the years. The success has been that they have 
ended up in medical school. Have they ended up in research? It 
is not clear. Not everyone necessarily should end up in 
research. But I believe that we have a desperate need for 
physician scientists, for clinical researchers. I believe loan 
repayment, which I believe is in the President's budget, could 
be an enormous incentive.
    Now, it is not just money that should be cast out there. It 
would need to be tracked and evaluated, but I think loan 
repayment is potentially a valuable approach. There are four 
historically black medical schools. Clearly, the students there 
are very bright people. Many of them should, as many of them 
do, go back to serve inner city populations. That is very 
important. But if we could recruit some of those medical 
graduates into the ranks of physician scientists, this could 
address part of the problem.
    Dr. Kirschstein. I, of course, echoed that statement for 
the last several hearings. I want to tell you what I did last 
week, Mr. Hoyer, because I anticipated, perhaps without knowing 
it, what you might say. I called Mr. Stokes, and as of this 
Friday, he is going to be a consultant to NIH in regard to how 
we increase the numbers of minority scientists we hire 
intramurally as well as work on our programs.

                            CROHN'S DISEASE

    Mr. Hoyer. I think that is spectacular. I really do. I did 
not know that. I talked to Congressman Stokes about a month ago 
before you talked to him. He is one of the most sincere, 
thoughtful human beings I have ever served with in the State 
legislature or here. He would be a wonderful addition because 
he cares greatly about this problem. He cares about it in a 
very constructive way and in a nonpolitical way. In terms of 
insuring that we have the kind of feel that we need 
intellectually, emotionally, viscerally, experience-wise, I 
think will be very helpful. That is a great step. Thank you, 
Doctor. I think, Jessie, that is a very positive step forward.
    Let me try to sneak in one question on the subjects I had 
down here. We talked about diabetes. I am not going to go 
through those. I am going to submit some questions for the 
record, which I think are sort of repetitive in some respects. 
Let me ask you about Crohn's disease. In response to one of my 
questions last year, I would like to discuss ongoing research 
into the cause of a chronic inflammatory disease that affects 
the digestive tract, also known as Crohn's disease. I 
understand there is new evidence that suggest Crohn's disease 
may be caused by infectious bacteria. Can you comment on that?
    Dr. Spiegel. Let me comment briefly. There are certain 
chronic diseases where a bacteria or other microorganism has 
been suspected for years. The most recent New England Journal 
included a report that a scientific team finally succeeded in 
culturing a bacterium for something called Whipple's disease. 
In the case of Crohn's disease, it has been long suspected, but 
there is still no cogent evidence. It needs to be looked at and 
I know that NIAID, under Dr. Anthony Fauci's leadership, is 
actually specifically addressing this problem. We want to 
cooperate with him. In terms of Crohn's disease, a type of 
inflammatory bowel disease, we are definitely pushing forward 
in terms of genetics and many other opportunities in terms of 
both prevention and treatment.
    Mr. Hoyer. Thank you, Doctor. I have other questions, but I 
will submit them.
    Mr. Porter. Mr. Wicker.
    Mr. Wicker. Thank you. I will try not to take my full 5 
minutes because I have another hearing.
    Mr. Porter. Six, actually.

                   RESEARCH FUNDING ACROSS THE NATION

    Mr. Wicker. Well, who knows. Where are you--how many 
colleges and universities are participating currently in 
diabetes research? Do you have any idea? We are farming it out 
all across the country, undoubtedly.
    Dr. Spiegel. When you say how many colleges and 
universities, we certainly have investments in research in 
diabetes throughout virtually all of the 50 states. If you are 
asking about Mississippi specifically, perhaps none.
    Mr. Wicker. Perhaps none there. You cut right to the chase 
there.
    Dr. Spiegel. I should say I haven't invoked my predecessor 
yet but I believe he was from a small town in Mississippi.
    Mr. Wicker. Indeed. I was going to suggest to follow up on 
Mr. Hoyer and Mr. Jackson that in addition to Lou Stokes, that 
maybe you hire as a consultant a former president of a very 
small university in one of those states that doesn't typically 
get the research dollars. I just want to say--and I think Mr. 
Jackson and Mr. Hoyer will agree with this--we want the best 
research done. We are not looking for substandard science just 
so we can get economic development for our constituencies. But 
it is a fact, and I would point out to you and I have mentioned 
it to Dr. Kirschstein in several hearings, that the fact that 
about half of the states receive approximately 90 percent or 
more of the research dollars. And the other half of the states, 
including my state of Mississippi, as you have already 
mentioned, are left to fend for less than 10 percent of the 
research money. I would like for you to get back to me on the 
record as to the quality of the research that you have been 
able to get from the smaller states, the F score type states, 
if you will, that traditionally have not been the beneficiaries 
of large research grants.
    And because of that, perhaps there is an institutional bias 
towards the large research universities. I would just like for 
you to look at that and comment on the record as to the quality 
of the research that you are getting, because I know that Mr. 
Jackson wants minority research. And you know that I want 
research conducted in the small states. But we want to have it 
good research. That is the first priority. But if there is a 
way to include us in this great experiment of your entire 
agency, but particularly prevention of the disease of diabetes 
or a cure for this dread disease, which I am personally 
affected by, then we would like to participate. I would like to 
have your comments on that, either today or on the record.
    Dr. Spiegel. I will not give more extended comments in the 
interest of time. But the only thing I would say is I know 
about the IDEA program which is a version of the EPSCOR program 
run by NCRR. I learned that NIDDK had not been participating. 
This is something I want to evaluate very closely because I 
think it is an opportunity. It is not a huge amount of money 
necessarily, but this is one opportunity where we could support 
research in your state. The other thing is I know that Dr. 
Gorden, in his last period as NIDDK director, did join a group 
visiting and looking into the Jackson heart study and other 
things going on in Mississippi. I have met with Dr. L'enfant. 
We are looking at a variety of areas of collaboration between 
the 2 institutes because diabetes and heart disease are very 
close. I think there may be some opportunities for NIDDK 
involvement within that context.
    [The information follows:]

   NIDDK Support for the 20 States Receiving the Least NIH Research 
                                Funding

    The list below summarizes the NIDDK support provided in 1999 for 
sixteen of the twenty states receiving the least research funding from 
the NIH. We awarded 198 projects for a total of approximately $44.1 
million. Missing from the list are Alaska, Idaho, Mississippi, and 
Montana, which did not receive any NIDDK research support in 1999. Also 
missing because of a lack of research support from the NIDDK in that 
year is Puerto Rico, whose scientists are eligible for NIH support.
    These grant proposals competed against those of scientists from all 
of the other institutions and states, and each succeeded in achieving a 
percentile ranking which placed it within our payline. The science 
supported is of equal quality to the other projects supported by NIDDK 
programs. The more fundamental problem is how few proposals are 
received from scientists in these states.

------------------------------------------------------------------------
                                           Grant Awards       Amount
------------------------------------------------------------------------
Arkansas................................              13      $2,533,146
Delaware................................               3         601,030
Hawaii..................................               1         233,462
Kansas..................................              14       4,595,871
Kentucky................................              16       3,064,324
Louisiana...............................              40       9,679,880
Maine...................................              16       3,902,312
Nebraska................................               9       1,556,542
Nevada..................................               5       2,023,642
New Hampshire...........................              19       4,308,523
New Mexico..............................               6       1,870,602
Oklahoma................................               7       1,257,468
Rhode Island............................              11       1,884,734
South Carolina..........................              18       3,398,135
South Dakota............................               3         313,286
Vermont.................................              10       1,926,588
West Virginia...........................               4         644,657
Wyoming.................................               3         355,194
                                         -------------------------------
    Total...............................             198      44,149,396
------------------------------------------------------------------------

    Dr. Kirschstein. Maybe I could add something, Mr. Wicker. 
As you know, Dr. Gorden and I did visit your fair state. We do 
have some grants at Millsaps College. We are very pleased by 
that. I hope that the next time we can go we can visit Millsaps 
in addition to the University of Mississippi. We have been 
working with the school of pharmacy at Oxford which has a 
larger grant portfolio right now than does the medical school, 
a fact that quite surprised me. We have been working with 
members of the faculty of the school of medicine who have been 
coming up to learn about opportunities and we hope we can add 
to their grant portfolio.
    Mr. Wicker. Thank you very much. I would just say, in 
conclusion, that I think you know of the tremendous support 
that you have in this subcommittee led by our chairman. We 
certainly want to be helpful and we want to look forward to the 
day when your coming before us and say we have phenomenal 
results in the prevention and treatment of this disease.
    Dr. Spiegel. I appreciate that support. Thank you.
    Mr. Porter. Thank you, Mr. Wicker.
    Mr. Cunningham.

                           STEM CELL RESEARCH

    Mr. Cunningham. Thank you, Mr. Chairman. I have a question 
and I have got a direct purpose in asking it. My own personal 
beliefs are pro-life and I don't believe in supporting taxpayer 
funding for abortions. Saying that, I support stem cell 
research and Dr. Larry Goldstein at UCSD has worked with my 
daughter in research areas. An issue has come up. Instead of 
using potent cells, I understand that you can pursue the same 
kind of research from umbilical cords or other stem cells, but 
the research, as I understand it, is different. Can you 
elaborate on why we need to do both on that? I support stem 
cell research. I would tell if you, I have had a child like I 
have met that had to take blood samples 5 times a day, and I 
have seen these parents that they don't know if their child is 
going to live--or in the future the potential damage that the 
disease could cause, I would do anything, anything, including 
stem cell research. I would try to put myself in those parents' 
and children's shoes. But I also feel that if we do this within 
the government, then many of those moral and ethical values 
that many of us hold, not saying pro-life have all ethical or 
moral values, but generally, I think that a lot of those 
concerns would be met in government involvement where they 
wouldn't otherwise. My real concern is for the funding of the 
diversification of the research itself.
    Dr. Spiegel. I would respond to that, first, by saying I 
obviously respect your personal views, and those of Mr. Dickey, 
who is not here. I have heard his views on the subject and 
those of many others. It is clearly a very important subject 
that a wide diversity of Americans could differ on. Having said 
that, it is clear that type 1 diabetics, as well as people with 
spinal cord damage, Parkinson's disease, and many other 
diseases, stand to benefit from research in this area. Let me 
just confine my comments to some technical ones. Every cell has 
all of the genes in the human genome. When we are talking about 
these stem cells of various kinds, we are talking about ones 
that are on a spectrum from those that are capable of 
activating every one of those genes: so-called toti potential 
or pluri potential stem cells to others that can activate only 
a subset of cells. Studying pluripotent stem cells can address 
new kinds of questions that studying the others can't. At the 
same time though, what you are referring to, cells from the 
umbilical cord, are hematopoietic stem cells. The ones that I 
refer to in this recent diabetes development are pancreatic 
duct cells that can then turn into insulin-secreting beta 
cells. It is clearly very important to study those that are 
further along the path of differentiation. We can learn a 
tremendous amount. Let me just leave it at that.

                              HEPATITIS C

    Mr. Cunningham. In the other questions they talk about, 
maybe we don't fund certain research. I wouldn't want the job 
of deciding precisely where the research goes. I don't think 
Members of Congress ought to do it. I don't think that the 
President ought to do it. I think it belongs in the hands of 
the professional researchers to see where the science is taking 
us, if there is any overlap.
    Another disease that is becoming at least maybe just my 
awareness more and more prevalent, Rolf Benerschke, who used to 
kick for the San Diego Chargers, has hepatitis C. He got it 
through a blood transfusion. Many of the hemophiliacs have come 
to me in the district, and not only did they pick up HIV, but 
hepatitis C. Do we have, from NIH perspective, hope in the 
areas of hepatitis? I look at Rolf Benerschke and people like 
that, and it is tearing his families apart. I haven't heard of 
any specific research in that direction.
    Dr. Spiegel. There certainly are important advances there. 
First, with regard to the issue of transfusion, due to the 
epidemiologic efforts of the CDC, NIH and others, we really do 
feel that new infections attendant to blood transfusions should 
no longer happen and they have not perhaps since 1992. But in 
terms of patients who have the disease, in terms of treatment, 
the combined agents that I referred to, interferon and 
Ribavirin, are able to actually clear the virus from as many as 
40 percent of people who are infected. We need to do better 
than that. We are launching this year a multi-million dollar 
major clinical trial called HALT C, which will look 
specifically at longer, more intensive treatment with 
interferon and other agents to see if we can improve on that.
    I mentioned African-Americans who have a disproportionate 
burden of Hepatitis C. It turns out not only is there a higher 
incidence in terms of African Americans, but there is also a 
reduced response to treatment. One initiative we are planning 
is to explicitly enroll African-Americans in the trial to look 
at the reasons why they don't respond, in order to develop 
better treatment. The other point that needs to be made though 
is prevention, and the possibility of a vaccine. This is being 
worked on intensively both in the intramural labs of NIAID and 
NIDDK as well as in other labs.
    Mr. Cunningham. I would also like to add my support of most 
of the people that I respect. On the other side of the aisle, 
Lou Stokes is one that I think is very well respected from his 
professionalism and what he could do for NIH. I know I 
personally laud that decision.
    I want to couch this next thing very carefully and I would 
like Jesse to listen. I am not being partisan, not even one 
ounce of it. But I want you to understand maybe where I am 
coming from. Quite often Republicans talk, I think, too often 
without thinking about what the results are. For example, if I 
say I am against bilingual education, there is a certain group 
of people that think I don't care about them, that they can't 
learn. If I say I am against affirmative action, there is a 
group of people that say ``well, Duke doesn't care about us.'' 
I think we have done that too much in some cases, at last until 
we come forward and say we have a better plan to affirmative 
action or bilingual education or many other areas.
    And in line with Mr. Jackson's comments, I had--I know at 
one time I heard that for example black pilots weren't as good 
as white pilots. All you have to do is look at the Tuskegee 
airmen and see what their record was given the chance. I had an 
African-American pilot who was my operations officer. He could 
hold hands with anybody. We had a spot open in the Blue Angels. 
His name was Donny. I can't remember Donny's last name, but he 
hadn't had a chance to fly the A-4, and I had him in my 
squadron, so I let him fly just so he could compete. And he 
won. But with affirmative action, and I know I have heard many 
people talk about it, I think there is a better way than 
affirmative action. I really believe that. I know it is a big 
political issue, but I am not being political here. For 
example, I went the other day to see if I could have keratotomy 
done with surgery. The doctor came out and he was African-
American. Some wonder if that doctor got in his position 
because of affirmative action, or could one have gone to a 
doctor that had more quality, but that individual was there 
because of affirmative action. I guarantee he wasn't because he 
is a very noteworthy doctor, but there is a perception out 
there in many of these cases that I think in some cases is 
taking place, especially in the higher skilled areas. I think 
the answer to concerns about affirmative action is education to 
make sure at the beginning that we don't have those disparities 
or those incorrect perceptions that exist. As we go forward in 
medical research like Mr. Jackson requests, I hope that those 
kinds of things are split apart, because I have met some very 
fantastic doctors from diverse ethnic backgrounds, not just 
African-American, but Asian as well.
    I would also hope that would extend, since my daughter 
plans on getting an M.D. Ph.D., that that goes along with women 
scientists as well, that we don't have a perception that a 
woman maybe can't perform as well as a man. I want to tell you, 
my daughter is going to kick rear end when she gets up there. I 
hope all of those opportunities--and I support the line that 
Jesse was talking about as far as the actual research in it. 
Thank you.
    Mr. Porter. Thank you, Mr. Cunningham.
    Mrs. Lowey.

                     TYPE 1 DIABETES TRIAL NETWORK

    Mrs. Lowey. Thank you, Mr. Chairman. And I want to thank 
you, Dr. Spiegel, for your presentation for all of the good 
work that you are doing, and Dr. Kirschstein, it is also a 
pleasure to see you. I want to welcome Bruce Siegel, a 
constituent, a downstate leader in JDF. Nice to see you here 
today.
    Dr. Spiegel, Mr. Bonilla asked you and you referred in your 
testimony to the pilot studies network for type 1 diabetes. How 
would that coordinate with the NIH clinical trial web site that 
was just announced? Would your network be helpful to families 
or more targeted towards researchers and physicians?
    Dr. Spiegel. They should coordinate very well. I think that 
you are about to hear from NLM, so I am sure you will hear 
about the clinical trial web site. The intention is to be 
certain that every NIH-supported trial is listed there. It will 
be accessible in a way that will provide links for primary data 
from the published literature for physicians, and information 
that is patient-friendly as well. So the trials that we are 
contemplating would certainly be represented there.

                         INTERSTITIAL CYSTITIS

    Mrs. Lowey. I know that we talked about stem cell research. 
I also want to follow up on my colleague, Rosa DeLauro's 
question about IC. I have several constituents, one a good 
friend, who suffer from IC. And I understand that NIDDK is 
planning an epidemiology study on IC and that there are 
meetings to develop this study in April. Are you going to be 
doing them? Attending them? How long will the study take? How 
much money would be committed? Could you explain?
    Dr. Spiegel. Yes, just very briefly. I would say that I 
have met with Vicki Ratner, who is the head of the Interstitial 
Cystitis Association. I will be meeting on March 27 with 
Deborah Slade, who is head of the National Bladder Foundation. 
We are looking for input, as I alluded to earlier, from all of 
our constituency groups. There has been some delay I am aware 
of in launching this epidemiology study but we are committed to 
it and we will do it in the best possible way and as quickly as 
possible.

                       INFLAMMATORY BOWEL DISEASE

    Mrs. Lowey. One last question before I yield a little of my 
time to my good colleague, up to a million people in America 
suffer from inflammatory bowel disease. In the committee report 
last year, we encouraged the NIDDK to support basic 
investigations that were outlined in challenges and IBD, a 
document assembled by the scientific community. Is there any 
progress being made on this? Could you discuss it with us?
    Dr. Spiegel. Yes. Very briefly, on March 10 we are going to 
be holding, as part of our digestive disease interagency 
coordinating committee, a meeting on the genetics of 
inflammatory bowel disease. This is, again, a complex genetic 
disease, but it offers some opportunity for progress. There 
have been important advances in Crohn's disease with the use of 
a monoclonal antibody that can treat a certain significant 
subset of the patients. That grew out of NIDDK-supported work 
on an animal model. It is important to be aware of that. Of our 
12, soon to be 13, digestive disease centers, several are 
committed to studies of inflammatory bowel disease. We are also 
spurring even further developments in this field in the 
intramural program as well, with NIAID.
    Mrs. Lowey. Thank you very much. I appreciate your 
important responses and the fact that you even spoke like a New 
Yorker, so I would have time to yield to my good friend, Jesse 
Jackson.

                         MINORITY INVESTIGATORS

    Mr. Jackson. Let me thank the gentlelady for yielding. I 
want to offer some clarity in the strongest possible language 
that I can possibly offer. I offer to my good friend on the 
other side of the aisle, Mr. Cunningham, and Mr. Wicker, who 
departed earlier. I want to make it very clear what the context 
is. Because of the coordination problem on these disparity 
issues which continue to get worse, and because of your 
consistent increase request in your budget, as a member of this 
body, I have some very legitimate questions about the road and 
the path that this research is taking, particularly the 
resources for this research. It just happens to coincide with 
the dearth, if you will, or the absence of a number of minority 
researchers who could be pursuing this research if, in fact, 
NIH as an institution were open to that. My colleague a few 
minutes ago said that he doesn't believe that these decisions 
should be in the hands of Congress, he doesn't believe these 
decisions should be in the hands of the President, but 
presently in the hands of professional researchers which he 
presently supports.
    There are enormous disparities in every institute across 
the NIH. That is what I am seeking to address with H.R. 2391 
which is a bipartisan bill that has Mr. Norwood on it, it has 
J.C. Watts on it, and a number of other prominent members of 
your party who recognize that what I am trying to do to address 
these questions to a single center at the NIH who would be 
responsible for that coordination across the entire institute, 
who will keep me every year from having to ask various 
institute officers and directors the same questions, because I 
will be able to drill one person, whose responsibility it will 
be to bring me the information back at every one of these 
appropriations hearings.
    But I want to be clear about one thing that I have begun to 
determine and pick up in this committee. Quite frankly, it is 
something that I am beginning to resent. Ever since I have been 
asking these questions across the center, some of my colleagues 
have offered almost a caveat to every one of their statements 
that somehow the researchers that I am talking about, those 
African-Americans with medical degrees and Ph.D.s are extremely 
qualified people, that somehow there is always this caveat. I 
know Congressman Jackson, for example, doesn't support 
substandard research. Somehow my arguments about better 
coordination about the NIH happen to be tied to affirmative 
action. I have never mentioned the words ``affirmative 
action.'' I am talking about the $18,000,000,000 that we spend 
at NIH that presently is not being coordinated across the 
minority research community, and I assume that researchers use 
fundamentally the same methods to be able to test research so 
that people can test their evidence against other research and 
be able to make determinations about that.
    But the fact that Members of Congress even refer to my 
efforts and my questions across this committee as somehow being 
supportive of or even adding to the conversation that I am 
having as substandard research, or somehow affirmative action 
related or some special program for minorities in these 
departments is precisely, Mr. Chairman, the problem that exists 
in this Congress. But beyond that, if the same culture that I 
am most worried about at NIH exists, that somehow in our effort 
to reach out to minority researchers or to find minority 
researchers or women researchers or Asian American researchers 
or Native American researchers, if there is such a culture that 
exists at NIH that suggests that their research is inferior 
based upon some of the questions that my colleagues have 
attempted to reduce my questions to, this is precisely what I 
am going at at NIH, and that is what I am trying to do with 
this bill----
    Mr. Cunningham. If the gentleman would yield, I hope you 
understand I was saying that in support of your position.
    Mr. Jackson. I appreciate that. Let me reclaim my time. 
Whenever I sit here and listen to a lot of big words that end 
in ``ology'' and ``ism'' from a lot of different directors and 
listen to all of their very sophisticated analysis of what has 
transpired over the last year before they came and asked our 
committee for 3 more billion dollars or an increase of 6 
percent, at no point in time does anyone ever question their 
research, at no point in time, not from cancer, not from 
diabetes, not from any of the institutes.
    But when I talk about minority researchers, the first thing 
someone mentions over there is substandard as if the same tests 
that are used for those researchers would fall under some 
different standard than the research that I am talking about or 
something associated with affirmative action or somehow not in 
the hands of Congress when we have responsibility and oversight 
for the money of this institute and there is documented data--
he says he has been there 27 years and still feels bad about it 
because he knows there is a dearth of researchers.
    Mr. Cunningham. If the gentleman would yield, the point 
that I mentioned wasn't a negative. It was the fact that I was 
trying to point out that given a chance that it wasn't 
affirmative action. I was speaking on the other side--oh, it 
was Donny Cochran that went with the Blue Angels. There is a 
perception out there which is not true. That is why I was 
trying to use that as an example. Not as a negative that you 
took it----
    Mr. Jackson. Reclaiming my time, I respect the gentleman. 
The gentleman knows that he and I have a great personal 
relationship, nor am I trying to suggest or use the platform 
today. Anything I have to say in private to the gentleman, the 
gentleman knows that I will handle it. But I want to be really 
clear that even having a conversation as being couched about 
the questions that I have been raising about NIH to suggest in 
any way, shape or form, there is a trailer of affirmative 
action associated with it or some special interest center that 
need to be created or associated with it or some substandard 
research that is associated with it, the fact that that is even 
associated with my line of questioning, which has absolutely 
nothing to do with substandard research, I deeply resent that. 
I want to make it clear for the record so my colleagues and 
some of the staff when they go back to their various offices, 
when they come back next week and we talk to other institutes 
do not associate those terms with the line of questioning that 
I am raising at the NIH because I want answers to my questions 
and they have nothing to do with substandard research. I thank 
the gentleman.
    Mr. Hoyer. I would like to make a comment, if I can.
    Mr. Porter. Mr. Hoyer.

                        WOMEN IN CLINICAL TRIALS

    Mr. Hoyer. One of the things that concerned this committee, 
about 10 years ago--Mrs. Lowey, would you wait one second--was 
when we found out the very low number of women in clinical 
trials, even on diseases that mostly affected women. So what 
Mr. Jackson is talking about he is correct, Duke. This is not 
affirmative action, but a recognition what we need to do in 
order to get good answers. That is what he is talking about. 
And the failure to include--I was appalled when we heard at the 
low number of women--I am sure you were, too, Dr. Kirschstein--
the low number of women in clinical trials. It was incredible. 
I don't know whether you were on the committee at that point. 
John, you remember it. And we all said, ``How can you do 
that?'' I don't think it was an effort to discriminate against 
women per se, but there was a lacking in consciousness of the 
impact of the cohorts in the research groups. So I think that 
is what Mr. Jackson is saying.
    Mrs. Lowey. In fact, as long as my colleague asked me to 
remain, if the gentleman would yield just briefly, I do 
remember that, Mr. Chairman, when including women in the 
clinical trials--and Dr. Kirschstein probably remembers--made 
them too complicated. This is what we were told, that it would 
just complicate the studies. At that time even the rats were 
all male.
    Mr. Hoyer. We won't go into that last comment, thank you 
very much.

                            TYPE 1 DIABETES

    Mr. Cunningham. This is just one of those children that has 
diabetes that I was talking about. You can see that she is an A 
student, she is a doll. She looks like she just stepped out of 
Saks Fifth Avenue.
    Mr. Hoyer. I can't from here observe that she is an A 
student, but I can certainly observe that she is a doll.
    Mr. Cunningham. Her name is Sara.
    Mr. Porter. Sara, welcome.
    Mr. Cunningham. This is her diabetes bear. She wouldn't 
give it to me.
    Mr. Porter. We are pleased to be joined by our colleague 
from Washington, not a member of our subcommittee, but the 
cochairman of the Congressional Diabetes Research Caucus and a 
man who has provided tremendous leadership and strong pressure, 
as I am sure Dr. Spiegel is aware, for increases for research 
into this dread disease. Our colleague, Congressman George 
Nethercutt. George.

                    DIABETES RESEARCH WORKING GROUP

    Mr. Nethercutt. Thank you, Mr. Chairman, and I appreciate 
your indulgence and the indulgence in the members of the 
subcommittee in allowing me to join here for a few minutes just 
to say hello to Dr. Spiegel and certainly welcome you, sir. I 
know that you have energized the institute already. Dr. 
Kirschstein, I am so happy to see you and Mr. Laurence and 
others who have been so much a part of this effort that affects 
so many in this country. And is indiscriminate in its impact on 
men, women, people of all races, religions--disproportionately, 
I might add, on the minority populations in our country. It is 
in our national best interests, it seems to me, to cure this 
disease.
    Dr. Spiegel, I welcome you, sir, and all of you here who 
are dedicated to this the same thing, in my judgment. I want to 
ask just a few questions as it relates to the actions that the 
Congress has taken and that the caucus, the Diabetes Caucus, 
has taken in the House. We have so many people who are members 
of it representing both parties, obviously, and all regions of 
the country. It is a wonderful bipartisan effort to focus on 
this disease that has such tremendous impact on our economy and 
human health.
    Dr. Spiegel, I know that you are aware of the Diabetes 
Research Working Group Report. This subcommittee and this House 
and Appropriations Committee has graciously put in the funding 
early to conduct the research and impanel the people to come up 
with the report. And it is a good report. It is comprehensive. 
I would just ask, sir, if you in your position and in your 
responsibilities would feel encouraged about the 
recommendations of the Diabetes Research Working Group Report, 
and what approach you might recommend to this committee for its 
implementation.
    Dr. Spiegel. First, I appreciate your being here and I 
appreciate your leadership in this very important issue. I 
absolutely am in accord with and view the DRWG as just the kind 
of planning process we need: with community input, public 
input, and expert scientific input. The five extraordinary 
areas of opportunity are ones that are right on the mark, and 
the specific areas of complications and other kinds of targeted 
interventions are critical. We are trying within the context of 
our existing budget to meet those recommendations as nearly as 
possible. I could get into very detailed budget specifics, but 
what I would say is fiscal year 2000 is a difficult year for us 
in that regard. We have a huge noncompeting growth of $105 
million in the research project grants mechanism. That limits 
our flexibility. Nonetheless we are aiming for at least a 2-
percentage-point increase greater than our appropriation 
increase for diabetes research using those recommendations. At 
the same time I believe that diabetes clearly is a disease that 
affects every organ system, and every NIH institute needs to be 
and is involved. I am meeting with each of the institute 
directors and meeting with Dr. Kirschstein as well. This is a 
point that I have driven home and I believe there are obvious 
areas of shared interaction with the NIAID vis-a-vis type 1 
diabetes, and with the NHLBI vis-a-vis the cardiac 
complications. I hope in that respect that we will be able to 
stimulate substantially the effort across NIH.

                  DIABETES--HEALTH AND ECONOMIC BURDEN

    Mr. Nethercutt. I appreciate that. I think those of us who 
are eminently involved with this whole subject are looking for 
a commitment on the part of NIDDK and NIH to allocate in such a 
way that we look at the dollar figures as it relates to the 
institute opportunities. And our hope is and expectation would 
be that there would be a push to try to have the dollars follow 
the disease and the impact of the disease. We think--we, I will 
speak for myself and others I think who share this view--that 
because diabetes has such a disproportionate impact on our 
health condition in this country, productivity costs are 
staggering, the Medicare costs are staggering, that is it is in 
our national best interests and NIH's best interests to 
recognize that and seek to have an application of funds that 
recognize that disproportionate impact of diabetes on our 
society. Is that something you can accept, adopt, would push 
for without pinning you down too much? We have a research 
working group recommendation on an annual basis over a period 
of time that we aren't meeting. I am wondering to what extent 
you feel that it is in our best interests to meet those 
recommendations and what you intend to do about it.
    Dr. Spiegel. I have to be perfectly candid. The 
recommendations in terms of scientific opportunities are ones 
that I totally embrace. I will do everything within the budget 
context that I am given to reach those. We are taking very 
concrete steps both in NIDDK and in terms of leadership across 
the NIH to try to increase diabetes spending. At the same time 
I would have to be candid and say that if one looks at the 
target figures--actual numbers given in what I consider a 
professional judgment budget--there isn't flexibility within 
our existing budget envelope to allow us to reach those 
figures.

                       DIABETES RESEARCH FUNDING

    Mr. Nethercutt. Would you want this committee or the 
subcommittee or the House and the Senate to reconfigure the 
figures so that it would be easier to reach the goals that you 
think we might seek?
    Dr. Spiegel. You are putting me on the spot. I want to give 
the best answer that I can to that--and I want to be mindful of 
what the DRWG report said. The chairman of that group is 
someone I met with very recently, and we had extensive 
discussions about this. The DRWG report did point out that it 
did not recommend detracting from the other very important 
diseases within the NIDDK mission. We don't want to do that. 
Given the opportunity to get additional resources, yes, we 
would be able to move faster, and we would be able to move down 
multiple paths. We would be able to put in the infrastructure 
that would enable further hypothesis-driven research. So 
certainly that would be very welcome, but on the other hand, I 
am prepared to do the best I can within the existing budget 
context.
    Mr. Nethercutt. This subcommittee and the chairman of the 
subcommittee have been extraordinary in terms of recommending 
additional funding for NIH for this effort to increase funding 
for biomedical research. It is a marvelous undertaking and it 
is very difficult in this particular subcommittee and such a 
tough one with lots of good reasons to spend money. So this 
leadership here, Mr. Hoyer, Mr. Porter and everybody else has 
been extraordinary.
    I would close because I know I am out of time. I have 
questions, if I may, Mr. Chairman, submit for the record, 
submit and seek your responses. And also offer, sir, to work 
with you and everyone at NIH and NIDDK most particularly to 
figure out ways we can hasten the cure of this disease and the 
research potential that is out there for the cure of this 
disease. Those of us who are involved in it feel absolutely 
confident that we are on the edge of a breakthrough and relief 
for the 16 million people and the next generation of Americans 
who are going to be affected by this and people around the 
world as well. So I hope we can work together and try to make 
this happen.
    Dr. Spiegel. I really look forward to working together and 
seeing you in another context.
    Mr. Porter. Thank you, Congressman Nethercutt, for being 
with us. First of all, let me say to Dr. Spiegel, you handled 
all of those questions very good. They were all real easy. Next 
time when you come we will think of some really tough ones.
    Thank you for the fine job you have begun to do there and 
have done there for many years prior to becoming Director. We 
do look forward to working with you, and I would say to my 
colleague from Washington, we are just as anxious as he is, and 
you are, to get the resources that you need to reach the goal 
of the working group and go down the multiple paths and see if 
we can't provide those kinds of research. We obviously can't do 
it in one year or maybe even two, but if we set it as our goal 
and keep working toward it we can get there, and sooner rather 
than later. So thank you for the fine job you are doing. Thank 
you for answering all of our questions.
    Dr. Spiegel. Thank you very much.
    Mr. Porter. The subcommittee will stand briefly in recess 
and then we will hear the National Library of Medicine.
    [The following questions were submitted to be answered for 
the record:]



                                          Wednesday, March 8, 2000.

 NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES

                               WITNESSES

STEPHEN I. KATZ, DIRECTOR, NIAMS
STEVEN J. HAUSMAN, DEPUTY DIRECTOR, NIAMS
MARGARET S. KERZA-KWIATECKI, ASSOCIATE DIRECTOR FOR MANAGEMENT AND 
    OPERATIONS, NIAMS
ROBYN J. STRACHAN, BUDGET OFFICER, NIAMS
RUTH L. KIRSCHSTEIN, ACTING DIRECTOR, NIH
DENNIS P. WILLIAMS, DEPUTY ASSISTANT SECRETARY, BUDGET, DHHS

                       Introduction of Witnesses

    Mrs. Northup. Good afternoon, welcome. We're going to begin 
the afternoon's hearing with the National Institutes of Health, 
National Institute of Arthritis and Musculoskeletal and Skin 
Diseases. Dr. Stephen Katz is with us today. Thank you, Dr. 
Katz, and welcome.
    Dr. Katz. Thank you very much, Mrs. Northup.
    May I introduce the people at the table? To my far left is 
our Associate Director for Management and Operations, Ms. 
Margaret Kerza-Kwiatecki; the head of our Budget Office, Ms. 
Robyn Strachan; the Deputy Director, Steve Hausman; and of 
course, you know the Acting Director of NIH, Ruth Kirschstein, 
and Mr. Dennis Williams from the Department.

                       Statement of the Director

    I'm honored to appear before this Committee today. As 
Director of the National Institute of Arthritis and 
Musculoskeletal and Skin Diseases, I'm acutely aware of the 
everyday lives of American people that are enormously improved 
by the research that our Institute supports. Children on the 
playground, women and ethnic minorities affected by so many of 
our diseases, particularly autoimmune diseases, adults in the 
workplace, elderly Americans striving to live independently--
their lives are enhanced or compromised by the health and 
functioning of their bones, joints, muscles and skin.
    I want to express my appreciation for the Fiscal Year 2000 
appropriation. It enabled us to invest in medical research with 
much greater depth and breadth than ever before. I want to 
share some examples of advances and opportunities, and also 
talk to you about our commitment to addressing health 
disparities in all areas of our mission.

                           CLINICAL RESEARCH

    The focus of my remarks today will be on clinical research. 
The ultimate goal, of course, is to improve health through the 
translation of basic research findings. Some of these research 
findings include the finding that low dose estrogen, in 
addition to calcium and vitamin D, can prevent bone loss. New 
therapies have been developed for rheumatoid arthritis. The 
bases for these new therapies were all supported by the NIH and 
the National Institute of Arthritis and Musculoskeletal and 
Skin Diseases.
    New findings tell us that normal hair growth is controlled 
by newly identified genes. These genes produce proteins that 
then form the targets for new therapeutic interventions.

                           MUSCULAR DYSTROPHY

    Research has revealed that a common antibiotic, gentamicin, 
may be useful in the treatment of Duchenne muscular dystrophy, 
a disease which is due to a genetic mutation. And with this 
antibiotic, you can overcome this mutation or so-called stop 
codon in the gene and have the gene produce a normal protein. 
This has been shown not only experimentally, in a cell culture 
situation, but also in experimental animals that have the 
disease.
    Also in gene therapy, muscular dystrophy, there's another 
disease called limb-girdle muscular dystrophy. This is a 
muscular dystrophy in which there is a mutation in a gene that 
encodes for a smaller protein; that may be an excellent target 
for new therapies. We are studying mice that have this 
particular disease, another very important advance.

                              OSTEOPOROSIS

    And another very exciting, very recent advance shows us 
that new drugs or old drugs, as well as recently identified 
hormones, can be very important in terms of the treatment for 
osteoporosis. So let me give you a couple of examples. The 
statins, for example, which are commonly used drugs to lower 
cholesterol, have been shown to have a profound effect on bone 
formation. As well, leptin, which is a hormone that's produced 
by fat cells in the body and that controls obesity, has also 
been shown very recently to control bone growth. Two very 
exciting findings that I'm sure will yield to important new 
scientific discovery.

                           CLINICAL RESEARCH

    Through our generous appropriation in Fiscal Year 1999, we 
launched a number of studies that I am sure will yield valuable 
information. I want to briefly highlight seven new studies 
we've initiated. Again, the focus is on clinical research. The 
first is a study in osteoporosis in men. We established a 
multi-center consortium to look at risk factors for 
osteoporosis in men, clearly an underserved area. We've 
initiated studies that assess combination drug therapies for 
osteoporosis; two drugs from different companies are used in 
combination. These are the types of studies that would not be 
supported by the pharmaceutical industry.
    We initiated a large, multi-center study which addresses 
surgical versus non-surgical interventions for low back pain. 
We also initiated many pilot studies in rheumatic and skin 
diseases. These are pilot studies of therapeutic interventions 
that include new treatments for leg ulcers, scleroderma, lupus 
erythematosus, and rheumatoid arthritis.
    One component of our pilot trials was the autoimmunity 
initiative. These are funds that were added in addition to the 
appropriation last year by the Congress. The NIAMS received had 
an additional $4 million for new research on autoimmunity that 
enhances and strengthens our current portfolio of research in 
this area.

                              FIBROMYALGIA

    Another area of growth in Fiscal Year 1999 was our 
commitment to 15 new grants in the area of fibromyalgia. And 
these grants will cover areas from behavioral to genetic to 
early interventions in disease. They also will identify new 
opportunities for research.
    We've also started a network, a gene searching expedition, 
in the area of the spondyloarthropathies, which is an 
inflammation of the spine, with the American Spondylitis 
Association being a true partner in this consortial 
arrangement.
    Finally, we have continued our commitment to clinical 
research training and career development. And in this area we 
went well beyond our initial commitment and funded numerous 
awards in many of our research areas.
    Through our Fiscal Year 2001 planning process, we've 
identified needs and opportunities that we will pursue. These 
are, for example, in osteoarthritis, in scleroderma, in skin 
gene therapy, in arthritis of the spine, in muscular 
dystrophies as well. And in this latter area, we have two 
meetings scheduled for May--one in the area of Duchenne 
muscular dystrophy, with the Parent Project--as well as one in 
fascioscapulohumeral dystrophy with the FSHD Society. These 
workshops are being developed along with our colleagues in the 
National Institute of Neurological Disorders and Stroke, as 
well as with the NIH Office of Rare Diseases.

                           HEALTH DISPARITIES

    In the area of health disparities, we've taken a multi-
pronged approach. With regard to research, there are a number 
of diseases that affect minorities disproportionately. We 
intend to help correct this disparity through our significant 
investment in these diseases, including lupus erythematosus, 
scleroderma, osteoarthritis, and vitiligo, which is a skin 
disease in which individuals lose pigmentation from their skin. 
It affects majority light-skinned individuals as well as dark-
skinned individuals, but psychologically, dark-skinned 
individuals are affected to a much greater extent. Keloids, 
which is an overgrowth of scar tissue, affects minorities 
disproportionately, particularly African-Americans.
    We also have a new scientific director at the Institute, 
who has initiated a new health partnership program including a 
diversity outreach program with the greater DC community. We 
hope to use this as a launching pad for a national initiative 
in this area.
    We've also expanded our information dissemination programs 
to include materials for Spanish-speaking people, as well as a 
new toll-free line in Spanish and English. We've also had 
discussions with leaders at HBCUs as well as developed new and 
enhanced programs for scientists at HBCUs as well as at 
Hispanic intensive institutions.
    Mrs. Northup, the President's budget for the National 
Institute of Arthritis and Musculoskeletal and Skin Diseases is 
$368,712,000, and I'm happy to answer any questions that you 
may have.
    Thank you.
    [The prepared statement follows:]



                                 LUPUS

    Mrs. Northup. Thank you, Dr. Katz.
    I think I'll start right where I left off last year, 
questions about lupus. You talked about the gene therapy in 
your presentation. I'd like to go back to the gene therapy, 
because I guess it's something I don't understand, both how far 
away solutions might come, who would benefit from it, in terms 
of, are there people that already have lupus, or would there be 
people that we would test that would be predisposed to it, 
where we would think maybe we could intervene before that 
happened.
    Dr. Katz. The area of lupus is not the area that we're 
particularly focusing on in terms of gene therapy. There's not 
enough known.
    Mrs. Northup. You talked about the chromosomes. I guess I 
just assumed that that was----
    Dr. Katz. Actually, you're right, I discussed it in some 
detail last year, in terms of our commitment to identifying 
susceptibility genes in lupus. Lupus is clearly not a single 
gene mutation disease. Undoubtedly, there are many regions in 
the genome that help predispose individuals to lupus 
erythematosus.
    What we're trying to do with our investment, large 
investment, actually, in many centers around the country, is 
identify those genes that increase the susceptibility of 
individuals to lupus. Once we identify those genes, that's only 
the first step. The second step is to find out the function of 
those genes. Once one finds out the function of those genes, 
one can try to interfere or somehow promote their activity.
    Mrs. Northup. And would that be done for people that 
already have developed lupus, or to protect people from 
developing lupus?
    Dr. Katz. Of course, the ultimate would be in prevention. 
But one would have to identify very strong susceptibility genes 
if one were going to try to intercede in that area. I would 
imagine that prevention would not be in the area of gene 
therapy, but would be much more in the area of conventional 
therapeutics or biologicals.
    Mrs. Northup. So then the benefit would be, once you 
developed it, you would intervene somehow. I have to admit, 
understanding what you do to intervene, I'm not sure whether 
you're talking about a pharmaceutical intervention, whether 
you're talking about some sort of transplant, whether you cause 
some mutation. Can you help me with what sort of therapy we're 
talking about?
    Dr. Katz. Yes. I would say the answer to that is yes, yes 
and yes. Because it includes all those possibilities. 
Ultimately, the goal really is to try to identify increased 
susceptibility to disease and identify the reason for the 
increased susceptibility. And ideally, we want to prevent in 
some way or somehow mask that susceptibility.
    That would occur in people who tend to be more susceptible 
to lupus erythematosus. We're trying to find out who is more 
susceptible to lupus and why. We know that it occurs in women 
to a much greater extent than men. We know that it occurs in 
the Hispanic and African-American populations to a much greater 
extent. We're trying to find out why.
    Once the disease occurs, and is identifiable, we try to 
identify who's susceptible for more severe disease, who is 
susceptible for less severe disease. It covers a broad spectrum 
of disease. Those people who are more susceptible to the kidney 
disease may get much stronger therapies early on, because that 
will obviate their getting disease later on.
    Mrs. Northup. Well, where I'm trying to go with this, I 
guess my interest is, how clearly do we know where the path is 
going to take us. It sounds like it's a wonderful path, but 
we're not sure where the path is going to take us or how fast. 
So what today are the most promising investments that you're 
making in trying to relieve the effects of lupus? 
Interventions, I know there's no cure.
    Are there any possibilities outside of the gene therapy or 
chromosome, where there are cures? If they're not cures, are 
there much better abilities to manage it? And how close are we 
to finding those? What is the level of our investment we're 
making in that?
    Since the gene, and again, I have to say, I'm not opposed 
to investing in long-term gene therapy. It just seems like 
we're becoming so fascinated with that that we're not maybe 
funding or trying to address today's need.
    Dr. Katz. Let me answer that by providing a perspective in 
terms of lupus erythematosus. You know the clinical center that 
we have on the Bethesda campus is charged with doing a lot of 
clinical studies. Well, one of the major advances in lupus 
erythematosus came about because of a very long-term investment 
in a research project that dealt with treatment of people with 
lupus nephritis. Lupus nephritis is one of the main causes of 
death of patients with lupus.
    This study began in about 1987. It ended in 1997, and the 
data are still being looked at. It has clearly changed the way 
rheumatologists and nephrologists think about treating patients 
with lupus erythematosus. The treatment is high dosage 
cyclophosphamide, which is a drug that interferes with the 
immune system, in addition to prednisone. Prednisone alone is 
helpful, but prednisone alone has many, many, many side 
effects. Cyclophosphamide has side effects not quite as severe.
    So the whole treatment of lupus was changed over those 
years, because of the investment in the intramural program at 
the NIH. People approach patients very differently nowadays.
    We continue those investments in terms of developing new 
therapies with fewer and fewer side effects. In addition, we 
know much more about the immune system. We know some, not all, 
about what causes some of the autoimmune reactions. We at least 
know how cells interact. And I will tell you that some of the 
most exciting work that's going on now in lupus erythematosus 
tries to block cells from interacting with one another, because 
we know a lot about the molecules that sit on cells.
    We have funded much of the fundamental research that now is 
being addressed by many pharmaceutical companies to try to 
block that interaction so that this cell of the immune system 
doesn't kill this cell of the skin, this cell of the central 
nervous system, this cell of the kidney, which are all affected 
in lupus erythematosus. So it's really a multi-pronged 
approach. It is not only from a more fundamental, long-term 
approach, but also for the here and now.
    Mrs. Northup. Okay. Thank you.
    Mr. Jackson.

                                 LUPUS

    Mr. Jackson. Thank you, Madam Chairwoman.
    Let me thank you, Dr. Katz, for your testimony today and 
for your work at NIAMS. The President's fiscal year request is 
$363.5 million, an increase of $19 million, and a 5.5 percent 
increase over Fiscal Year 2000. Included in this total is $9.5 
million targeted to the following NIH priorities: new 
approaches to pathogenesis, $5 million; new avenues for 
development of therapeutics, $2.5 million; genetic medicine, $1 
million; health disparities, $1 million.
    You indicated in your testimony that lupus is more 
prevalent in African-Americans, Latinos, Native Americans and 
Asians. Among African-American women, the disease afflicts 
minorities three times more frequently than white women, an 
estimated 1 in 250 African-American women between the ages of 
15 and 65 develop the disease. Unfortunately, many people, 
especially minorities, are not even aware of the disease.
    I wonder what action has NIAMS taken to augment the 
awareness of lupus in minority communities. I was also hoping 
you could comment on the number of minority researchers who are 
participating with NIH to find a cure for lupus.
    Dr. Katz. Thank you very much, Mr. Jackson.
    The effort in lupus has been long-term. We have developed 
programs, information programs, particularly targeted to black 
women. I'll be happy to send you some of that information. We 
have in small booklet form, and large booklet form, for people 
who are reading impaired, a booklet called, What Black Women 
Should Know About Lupus Erythematosus, or What Black Women 
Should Know About Lupus, I think the exact title is.
    We have also tried to work with local communities through 
our centers program to reach out to communities to increase the 
awareness of lupus erythematosus. We've also developed 
information systems for the Hispanic community now to allow 
them to make a toll-free call to the NIAMS information 
clearinghouse to become more aware of the problem.
    It is a clear problem in terms of getting the information 
out. We know from studies that we've supported that the earlier 
the diagnosis can be made, the less severe the treatment has to 
be. So it's an area that we are particularly concerned with. We 
have a very large study called the LUMINA study, which is Lupus 
in Minorities. It is run by a group in Alabama, but it 
encompasses many of the programs in the south and particularly 
addresses some of the concerns of the minority communities and 
what we can do to intervene.
    We know for example that if you even correct for 
socioeconomic status, self-efficacy--the wherewithal that one 
has in affecting one's disease--has a lot to do with how much 
one participates, how much one knows about one's disease. All 
of this is very, very important. And we're trying to address 
that.
    Mr. Jackson. Do you have any idea how many minority 
researchers are participating in your agency or your Institute 
to find a cure for lupus?
    Dr. Katz. Yes. We have awarded 4.3 percent of our grants to 
individuals who are minorities.
    Mr. Jackson. You're not aware of any of those minorities 
participating in any substandard research?
    Dr. Katz. No. Not at all. Not at all.

                      NIAMS RELATIONSHIP WITH ORMH

    Mr. Jackson. Let me ask you a question. How would you 
characterize your Institute's relationship with ORMH?
    Dr. Katz. My relationship with, my and the Institute's 
relationship with ORMH is, I would characterize, excellent. 
Since I became Director of the Institute, and I should say that 
Dr. Ruffin was the co-chair of the search committee that 
identified me as a candidate for this position, we have 
interacted very, very closely. We have co-funded many, many 
applications. We work collegially.
    I think this past year, in Fiscal Year 1999, we had $2.5 
million, close to $2.5 million of co-funding with the Office of 
Research on Minority Health. I will tell you a recent 
initiative that we've undertaken with some of the leaders at 
the HBCUs has been done in collaboration with Dr. Ruffin, and 
he and I are working on how best we can implement this.

                           HEALTH DISPARITIES

    Mr. Jackson. Let me ask one final question. You indicate in 
your opening testimony that there were a number of things that 
you have done to address some of these fundamental health 
disparities. Could you expound upon some of them and also let 
us know, let the Committee know what in the future you're also 
planning to do to help reach out to qualified minority 
researchers?
    Dr. Katz. Sure. I would say the most recent study that has 
yielded very important information is the LUMINA study that I 
just referred to. It's a study, again, based at the University 
of Alabama that addresses not only the racial differences, but 
also socioeconomic differences in terms of what brings a person 
to the doctor more readily than others. The reason for that, 
obviously, is to get patients in with chronic disease at a much 
earlier time than they would otherwise come.
    Other types of studies that we're doing are funded by our 
multi-purpose arthritis and musculoskeletal diseases centers, 
again to address socioeconomic differences, behavioral 
differences, how one motivates people to actually participate 
in the activities of the disease, of the treatment.
    Mr. Jackson. Thank you for your work, Dr. Katz. Thank you, 
Madam Chairman.
    Dr. Katz. Thank you very much.
    Mrs. Northup. Ms. Pelosi.
    Ms. Pelosi. Thank you, Madam Chair.
    Dr. Katz, welcome.
    Dr. Katz. Thank you.

                         EHLERS-DANLOS SYNDROME

    Ms. Pelosi. It's nice to see you again. Dr. Katz, I 
appreciated the discussion about lupus. Because many of us have 
constituent and personal concerns about that, so I appreciate 
the Chairperson and my colleague asking about that. It allows 
me to proceed to another issue that I think you're aware of my 
interest in. I wanted to ask you some specific questions about 
it, Ehlers-Danlos Syndrome.
    I didn't see anything mentioned in your presentation on it. 
But I was pleased when you said, children on the playground, 
women and ethnic minorities are disproportionately affected by 
many diseases that affect their daily activities. And this is 
one where women would be particularly disproportionately 
afflicted.
    Since we spoke last year about this, there has been a 
conference that was held in April by the Ehlers-Danlos National 
Foundation. They have a report on clinical and biological basis 
for Ehlers-Danlos Syndrome. I would hope that when you respond 
to it, you can be specific about this disease, as I know you 
are working very hard advancing all of the research that might 
affect it.
    One of the problems that comes forth is that knowledge of 
the clinical manifestations and natural histories of the 
different types of EDS is still evolving, whether it's the 
classical type, the vascular type, the hypermobility type, etc. 
It is thought that some of the research in some of this, and if 
I may, I'd like to give you this report, if you don't already 
have it.
    Dr. Katz. I appreciate that.
    Ms. Pelosi. Because it's a very useful resource. They are 
trying to move on their own. But of course, none of this will 
be successful unless we can have the cooperation of the 
National Institute of Arthritis and Musculoskeletal and Skin 
Diseases.
    On the clinical side, there's a need for cross-sectional 
and longitudinal studies, therapeutic trial, natural history of 
all known individuals of less common types of EDS, and it goes 
on and on. On the basic science side, Ehlers-Danlos Syndrome 
provides an outstanding opportunity to study the biomechanical 
ultrastructural and regulatory roles of collagens and 
connective tissue biology.
    In any event, this research will be beneficial not just for 
EDS sufferers, but for other diseases as well. That's what this 
summary says, which I would like to submit to you.
    So I would hope that because of the people who are 
suffering from this, the challenge that it presents, and 
hopefully the opportunity not only for EDS but for other 
diseases, that you can tell me something about the priority you 
can make this at your Institute.
    Dr. Katz. The priority is a very real one. I know of your 
concern, I know of the concern of others as well. Although I am 
sorry not to be specific, Ehlers-Danlos does fit into the group 
of diseases of heritable disorders of connective tissue. And 
that is one of our initiative areas for Fiscal Year 2001. We 
are planning a meeting, the third international meeting on 
heritable disorders of connective tissue; of course, Ehlers-
Danlos is one critical area, osteogenesis imperfecta another, 
Marfan Syndrome is yet another. We bring researchers in to try 
to identify those opportunities, similar to the meeting that 
you talked about in April, to try to identify opportunities, so 
that we at the NIH can respond, can announce to the community--
either in the form of a request for applications, which is a 
specific setaside of dollars for studies in these areas, or 
with a program announcement--that this is a high priority.
    By virtue of our having a workshop in this area--by virtue 
of our bringing in the best scientists in this area--and also 
by the way, scientists who are not so familiar with this area, 
to get them to interact to identify those scientific 
opportunities, is what our goal is for Fiscal Year 2001. That 
is a priority I have stated in my opening statement and in the 
written opening statement.
    We do need for a group of investigators to apply to the NIH 
for grants. That is critical in this area. There are some very, 
very good scientists who are working in this area. We would 
like to see more activity in this area. And that's one of the 
reasons for putting on a workshop.
    Ms. Pelosi. That's a positive side, when I can say to my 
constituents is that in this more general conference, in 
which----
    Dr. Katz. Well, Ehlers-Danlos is an integral part of it.
    Ms. Pelosi. No, I appreciate that, I'm not challenging it, 
I'm just saying that they should try to be involved with that?
    Dr. Katz. I'm sure they will be involved with it. If we are 
doing our job, they will be involved with it.
    Ms. Pelosi. Okay, but you're doing the appropriate 
outreach, so that they would be, and they're doing the 
appropriate field for it?
    Dr. Katz. I believe we are. Because of my concern in this 
area for the last couple of years, I asked Priscilla 
Ciccariello to become a member of our advisory council. She has 
been an active member of the council, not only at council 
meetings, but also at retreats, at planning retreats, where we 
include people from the public, whether it's a scientific 
planning retreat or it's a planning retreat to organize a 
strategic plan.
    Her organization is really a coalition organization, of 
which Ehlers-Danlos is a strong part.
    Ms. Pelosi. If I just may conclude, not a question, but 
just say, I appreciate that. Thank you. EDNF, the Foundation, 
is going to have a learning conference for those with EDNF and 
physicians around the country who treat them in California in 
July. So hopefully we can have some representation from the 
Institute, if that's possible.
    Dr. Katz. If we are invited, we will be there.
    Ms. Pelosi. Wonderful. That's great. Thank you very much, 
Dr. Katz.
    Thank you, Mr. Chairman.
    Mr. Wicker [assuming chair]. Thank you.
    Mrs. Lowey.

                      DUCHENNE MUSCULAR DYSTROPHY

    Mrs. Lowey. Thank you, Mr. Chairman.
    And thank you, Dr. Katz. I talked last week with Dr. 
Fischbach about families in my district whose sons are affected 
by Duchenne muscular dystrophy, which strikes children. As you 
well know, a child with DMD measures his life in months.
    The parents are understandably frustrated, anguished about 
the pace of research determining the cause and treatment for 
MD. And my staff and I have been researching ways in which we 
might encourage better progress. I know NIAMS will be part of a 
conference later this spring on MD.
    But I want to ask you to comment specifically on this 
issue. Some say that adding a specific study group on muscle 
would increase the opportunities for muscular dystrophy 
research. Do you think that would help?
    Dr. Katz. I don't think it would help, although I am not an 
expert in this area. Dr. Ellie Ehrenfeld is the head of our 
Center for Scientific Review. And as you know, she has recently 
undertaken, with tremendous collaboration and input from the 
entire scientific community, the reorganization of the study 
sections.
    We have a very large investment in muscle biology and 
muscle diseases. So the review process obviously affects us 
very, very much. We have two council members who are experts in 
this area. We've discussed the issue very openly with Dr. 
Ehrenfeld in terms of study section designations.
    The study of muscle covers a broad spectrum, from 
electrical stimulation to motors. The same people who would 
review one type of application would not really be equipped at 
times to review another type of application. The spectrum in 
terms of our investment in muscle, goes to exercise physiology 
and to clinical studies in the muscular dystrophies, whether 
they're Duchenne, Beckers, fascioscapulohumeral dystrophy, or 
limb-girdle dystrophy. All of those on that clinical spectrum 
would not be able to be reviewed by people who are 
electrophysiologists who are studying electrical stimulation of 
muscle.
    I don't think that one study section that would address 
clinical muscle diseases would really be effective, because 
there probably are not enough applications to come into that 
study section. I think what we have to be diligent about, and I 
know that Dr. Ellie Ehrenfeld is diligent about it, is to make 
sure that we have good representation on those committees to 
which the applications go. We as directors of the Institutes 
work with her to make sure that that does happen, so there is 
peer review which is really the basis of the way that we award 
grants.

                              OSTEOPOROSIS

    Mrs. Lowey. That's very helpful, and I hope we can work 
together closely on this issue.
    This morning, during the public witness hearings, I 
understand that Catherine Sharp, a 31 year old woman, shared 
her struggle with osteoporosis, and the particular difficulties 
encountered by pre-menopausal women. I want to ask you about 
the use of oral contraceptives, which Ms. Sharp referred to, 
and its impact on bone density. Can you tell us anything about 
the relationship, if any, between the use of the pill and 
osteoporosis?
    Dr. Katz. I can't tell you anything about the use of the 
pill and osteoporosis in pre-menopausal women. In post-
menopausal women, it's well known that estrogen alone, in women 
who have had a hysterectomy, or estrogen with progesterone in 
women who have a uterus, is very effective in terms of 
preventing bone loss. It's probably the best of the medications 
that can be used to prevent bone loss.
    We are now doing studies, as I said in my opening 
statement, where we're looking for combinations of drugs that 
affect osteoporosis. So two recently initiated studies, one 
this year, one last year, are looking at alendronate, which is 
otherwise known as Fosomax, in association with either low dose 
estrogen or in association with parathyroid hormone that builds 
up bone cells to see whether those combinations of therapies 
will be effective.
    This is a start into increasing our clinical studies in 
this particular area. In terms of the major advance this year, 
we know that half the usual dosage of estrogen, along with 
vitamin D and calcium, can prevent bone loss. A very important 
advance, because it enables women to make the choice a little 
bit better in terms of the potential adverse effects.
    Mrs. Lowey. You're talking about post-menopausal women.
    Dr. Katz. That's in post-menopausal women. In pre-
menopausal women, we are addressing the issue of the ability of 
patients with lupus to take estrogen to, theoretically, prevent 
bone loss.
    Mrs. Lowey. Thank you. Thank you, Mr. Chairman.

                           CLINICAL RESEARCH

    Mr. Wicker. Thank you, Ms. Lowey.
    Let me ask you, Dr. Katz, I'm sorry I had to come in late, 
and I'm sorry that so many of our members are tied up with 
other hearings. I think some of us have three hearings at the 
same time. But let me just ask you about your clinical 
research. Where is it taking place? How many locations and 
who's doing the clinical research?
    Dr. Katz. Specifically for clinical research, I would have 
to give you an answer for the record. All of our research is 
being supported at over 230 institutions around the country.
    [The information follows:]



    Mr. Wicker. And those institutions would be hospitals, 
teaching universities?
    Dr. Katz. Yes, hospitals, teaching universities, research 
institutions.
    Mr. Wicker. Research institutions?
    Dr. Katz. Right.
    Mr. Wicker. Universities?
    Dr. Katz. Universities, right, academic health centers. 
Research is also taking place in companies through the SBIR 
grants program. So the research is taking place in many, many 
areas.
    Mr. Wicker. I see. And those are clinical research grants, 
typically, is that correct?
    Dr. Katz. Well, we have in the last couple of years started 
many more clinical research programs than we were able to in 
the past. That was the emphasis of my opening statement, 
because the appropriation, the generous appropriation that came 
from this Committee last year, enabled us to go into greater 
breadth and greater depth in terms of research. And it enabled 
us to initiate many clinical research studies.
    Mr. Wicker. I see. And typically, how long would one of 
these research institutions be involved in a specific research 
program? Would it be for just one year at a time and has to be 
renewed, or is it a five year program? How does that work?
    Dr. Katz. It's anywhere from three to five years, and in 
unusual circumstances, seven years, if we think that that is 
really needed to do the study. But it's more typical for those 
studies to be five years.
    It depends on the type of study. For example, some of the 
pilot studies that we were able to initiate this year are 
taking place for three years. This is because a pilot study 
really enables a group to see whether there is a feasibility to 
a certain type of therapeutic intervention. And then hopefully 
if it is promising, it will lead to a larger study.

                          PEER REVIEW PROCESS

    Mr. Wicker. Where does your peer review process come in 
with the awarding of these contracts and these grants?
    Dr. Katz. Our peer review process comes in in two areas. In 
one area, it comes in through the Center for Scientific Review. 
In the other area, about 50 percent of our clinical studies or 
perhaps even more, are reviewed by our study sections within 
the Arthritis and Musculoskeletal and Skin Diseases Institute. 
The reason for that is because those particular study sections 
that we form will have the required depth and breadth in the 
particular area that we are interested in.
    So for example, if a project is in an area of autoimmunity, 
whether it's lupus or whether it's Wegener's granulomatosis, we 
can gather people within our study sections to provide that 
peer review. And we have a review branch that organizes that 
type of review. More of our clinical studies are reviewed by 
our NIAMS study sections than by the Center for Scientific 
Review.
    Mr. Wicker. Okay. Well, thank you very much. I'm sure 
you've been advised, as most witnesses have, that I have an 
interest in how the research dollars are awarded and how 
they're distributed and what sort of research you might get in 
some of the smaller States that traditionally haven't had an 
opportunity to participate in good research. I know Mr. Jackson 
has already asked about minority research, too.
    So I'm still, I'll say to you, Dr. Katz, and to Dr. 
Kirschstein, I'm still trying to get my arms around this 
process. I just think it's helpful for the Subcommittee to 
understand the whole peer review process and the award process. 
We just need to make sure that while we're getting the best 
science possible that we're also involving as many of our 
citizens as possible, and that we give everyone an opportunity 
to participate to the extent that it's feasible.
    Would you like to comment on that, Dr. Kirschstein?
    Dr. Kirschstein. Yes, Mr. Wicker. We've talked about this 
before. And I want to assure you, we are working on this. 
Scientists from your State will be coming up and we will be 
going back again in the spring. We will do that for all the 
States that have not participated as much as others. We're 
going to work very hard toward that.
    Mr. Wicker. Thank you very much.
    Dr. Katz. During those times when people come to the NIH, 
we put them together with people who are specialists in those 
areas.
    Mr. Wicker. Indeed.
    Dr. Katz. We try to give them really an educational program 
in terms of how it's done, what's needed in order to be 
successful.
    Mr. Wicker. Great. Well, thank you very much.
    Mr. Porter.
    Mr. Porter [assuming chair]. Let me apologize to you, Dr. 
Katz. I was called into a meeting with Chairman Young and the 
Chairman of the Senate Subcommittee, Arlen Specter, and 
couldn't be here. I apologize for that. I thank Mr. Wicker and 
Mrs. Northup for chairing in my absence.
    We have two votes coming up at a quarter of four or so, and 
because we have an entire panel to consider with the Office of 
the Director, the Office of AIDS Research, and Buildings and 
Facilities, we will need to move on. I will have to reserve my 
questions and ask that you answer them for the record.

                         TRIBUTE TO MR. PORTER

    Dr. Katz. I would like to personally thank you, Mr. Porter, 
for your support during my five years as Director of the 
Institute, and for your support of our medical research and 
improvement of the public health, your difference has been 
tremendous in terms of your vision, your commitment. I think on 
behalf of all my co-directors, we really are very, very 
grateful to you.
    Mr. Porter. You're very kind. As I said the other day at 
our meeting with the advocacy group, the pleasure has been all 
mine. I've learned so much, and as I said then, there isn't a 
lot, sometimes, serving in Congress, to inspire us. But NIH is 
something that does inspire all of us, and the work that you do 
is so important. We want to be just as supportive as we 
possibly can.
    Dr. Katz. Thank you very much.
    Mr. Porter. Thank you, sir.
    We'll stand briefly in recess.
    [The following questions were submitted to be answered for 
the record:]



                                      Wednesday, February 16, 2000.

                 NATIONAL CENTER FOR RESEARCH RESOURCES

                               WITNESSES

DR. JUDITH L. VAITUKAITIS, DIRECTOR, NATIONAL CENTER FOR RESEARCH 
    RESOURCES, NIH
DR. LOUISE E. RAMM, DEPUTY DIRECTOR, NATIONAL CENTER FOR RESEARCH 
    RESOURCES, NIH
DR. JOHN STRANDBERG, ASSOCIATE DIRECTOR FOR COMPARATIVE MEDICINE, 
    NATIONAL CENTER FOR RESEARCH RESOURCES, NIH
ANNE E. SUMMERS, BUDGET OFFICER, NATIONAL CENTER FOR RESEARCH 
    RESOURCES, NIH
DR. RUTH KIRSCHSTEIN, ACTING DIRECTOR, NATIONAL INSTITUTES OF HEALTH
DENNIS P. WILLIAMS, DEPUTY ASSISTANT SECRETARY, BUDGET, DEPARTMENT OF 
    HEALTH AND HUMAN SERVICES
    Mr. Porter. The subcommittee will come to order. We welcome 
Dr. Vaitukaitis, the Director of the National Center for 
Research Resources. Dr. Vaitukaitis, please proceed with your 
statement.
    Dr. Vaitukaitis. First, I would like to introduce the 
people who are with me from NCRR, Dr. Louise Ramm is to my far 
left. She is the Deputy Director. Next to her is Dr. John 
Strandberg who is the Associate Director for comparative 
medicine. To my immediate left is Anne Summers, who is director 
of our Office of Finance, and of course you know the 
individuals to my right very well.

                           OPENING STATEMENT

    Mr. Chairman and members of the committee, I am pleased to 
present the President's non-AIDS budget request for the 
National Center for Research Resources, NCRR, for fiscal year 
2001, a sum of $602.7 million, which reflects an increase of 
$33.6 million over the fiscal year 2000 appropriation. 
Including the estimated allocation for AIDS, total support 
requested for NCRR is $714.2 million, an increase of $39.1 
million over the fiscal year 2000 appropriation. Funds for the 
NCRR efforts in AIDS research are included within the Office of 
AIDS Research.
    It is a pleasure once again to have the opportunity to 
present the accomplishments of NCRR-supported investigators and 
future directions for NCRR programs. Before the recent turn of 
the millennium, doomsayers predicted the end of the world as we 
know it, and in some respects they were right. Advances in 
computer technology, bioengineering, imaging technologies, 
neuroscience and genomics will revolutionize biomedical 
research in the 21st century.
    The NCRR mission is unique among the NIH institutes and 
centers. While the other NIH components focus on particular 
diseases, organ systems, or categories of research, NCRR alone 
has a trans-NIH mandate--to develop and maintain the research 
infrastructure that enables all lines of biomedical inquiry.
    This effort transcends both clinical and basic research. 
NCRR's nationwide networks for basic and clinical research 
discern the molecular causes of disease, develop new preventive 
strategies, and assess novel therapies for diseases that affect 
majority as well as minority populations across this Nation. By 
providing scientists access to advanced technologies and 
sophisticated research facilities for collaborative clinical 
and basic research, NCRR serves as a facilitator, or catalyst, 
for biomedical discovery.
    One of NCRR's main objectives is to utilize scarce or 
expensive resources to the fullest by sharing them among many 
investigators. This strategy is efficient and cost effective. 
Each year more than 20,000 investigators, supported by more 
than $2.5 billion in competitive grant support from the other 
NIH components, use NCRR-supported research resources. To meet 
the needs of biomedical investigators for access to costly 
technologies, NCRR collaborates with the Department of Energy 
and the National Science Foundation, NSF, to provide access for 
biomedical investigators to high energy X-rays at the 
synchrotron facilities operated by those two agencies.

        BIOENGINEERING, COMPUTERS, AND ADVANCED INSTRUMENTATION

    In addition, NCRR provides access to advanced computing for 
health-related research by partnering with the NSF-supported 
San Diego Supercomputer Center, one of the two national 
partnerships for advanced computational infrastructure 
currently supported by the NSF.
    NCRR-funded resources have been critical to numerous 
projects that advance biomedical science. Many NCRR-supported 
discoveries have immediate benefits for patients; others help 
basic research move forward toward this ultimate goal. For 
example, separate groups of scientists, using NCRR-supported 
beam lines for X-ray crystallography, have determined the 
three-dimensional structure of ribosomes--our cells' protein 
factories--in unprecedented detail. These studies may expedite 
discovery of newer, more effective antibiotics.
    Animal studies conducted at an NCRR-supported primate 
center have shown that it is possible, by gene therapy, to 
reverse the brain cell destruction that is characteristic of 
Alzheimer's disease; and NCRR-supported clinical investigators 
have developed methods to assess changes in particular areas of 
the brain of depressed patients. The identification of these 
specific brain areas is fundamental to designing improved 
treatments for depression. According to the National Institute 
of Mental Health, depression affects more than 19 million 
American adults and cost society more than $30 billion in 1990.
    The ongoing technological revolution has made it abundantly 
clear that biomedical science is no longer the sole province of 
physicians, biochemists and biologists. Engineers, physicists, 
and computer scientists are essential partners for developing 
and adapting new instruments and technologies for health-
related research. For example, improved imaging systems are 
needed to investigate the pathophysiology of human disease by 
studying patients, as well as small animals and nonhuman 
primates, as disease models. NCRR proposes to support further 
technological development of high-resolution imaging tools that 
include computed tomography, magnetic resonance imaging [MRI] 
and positron emission tomography.
    Functional MRI imaging has provided investigators a 
powerful technology for studies of the human brain and has 
contributed significantly, with other complementary 
technologies, to a virtual revolution in neuroscience research. 
To further take advantage of these imaging and related 
technologies, NCRR proposes to support the establishment of 
regional MRI imaging resource centers where experts in 
developing and using functional MRI can work with 
neuroscientists to study brain disorders and also explore novel 
therapies.
    NCRR plans to functionally link those NCRR-supported 
biomedical technology research resource centers equipped with 
sophisticated imaging capabilities with general clinical 
research centers at the same host institution in order to 
accommodate patients from across this country for studies of 
neurodegenerative and other brain disorders.

                             BIOINFORMATICS

    The use of high-level computers and advanced computer 
programs are essential components of today's health-related 
research, but many biomedical scientists are not sufficiently 
familiar with bioinformatics, a key enabling technology.
    To help alleviate this urgent need, NCRR proposes to 
establish bioinformatics centers that will advance research in 
categoric areas of biomedical investigation. Those centers will 
create homes for interdisciplinary teams that will establish 
nurturing environments for exploration and research. Biomedical 
investigators are generating data in profuse quantities.
    For example, a single biomedical laboratory can generate up 
to 100 terabytes of information a year--about the same as the 
information in 1 million encyclopedias. In order to be useful, 
the data must be indexed and stored, analyzed and abstracted. 
To facilitate analysis of this data, NCRR proposes to establish 
another program that will foster development of tools to 
visualize data for analysis and to design future studies.

                              SYNCHROTRONS

    Synchrotron resources, which produce the high energy X-rays 
used to determine the 3-D structures of molecules, have an 
enormous impact on structural biology and drug design. The 
number of NIH users at NCRR-supported synchrotron beamlines 
doubled between 1995 and 1997, and requests for access to these 
facilities are increasing at an exponential rate. NCRR proposes 
to alleviate the projected substantial shortfall for access to 
beamlines by adding more staff so that the technical support is 
available around the clock. This is a short-term fix.
    New beamlines at the Advanced Photon Source at the Argonne 
National Laboratory will allow investigators to address more 
advanced structural biology grand challenges. In addition, 
several new beamlines must be built at the Advanced Light 
Source at the Lawrence Berkeley National Laboratory and 
designed for high throughput studies of less complex structures 
to meet the anticipated investigator need. This effort will 
combine new developments in beamline design, X-ray detectors, 
crystallography, robotics, and computational software.

                            GENETIC MEDICINE

    Manifestations of gene action are explored through 
phenotypic assessment of genetically altered animals. NCRR 
proposes to support regionally linked resource centers for 
these studies. In addition, NCRR must provide support for more 
technical staff to maintain the rapidly expanding biologic 
collections that include genetic stocks of zebra fish, fruit 
fly and C. elegans. Additional staffing is also needed to 
curate and standardize the genetic databases associated with 
these expanding collections. Without continuous updating and 
editing, databases quickly become useless and as a result, 
unnecessary duplication of research results.

                           Health Disparities

    NCRR proposes to help reduce health disparities in several 
diseases that disproportionately affect minority populations by 
competitively establishing several Comprehensive Centers on 
Health Disparities, CCHD. Those centers are to be hosted by 
medical schools located at universities that have an NCRR-
supported Research Center in Minority Institutions, RCMI, 
facility for clinical research. The NCRR-CCHD initiative will 
focus on diabetes, AIDS, and infant mortality, but initially 
will place increased emphasis on cancer screening and 
management of cardiovascular disease and stroke. This effort 
will be in partnership with appropriate categoric NIH 
institutes and with nearby general clinical research centers.

                           RESEARCH CAPACITY

    NCRR proposes to continue support for construction or 
renovation of biomedical research facilities to assure that 
state-of-the-art research laboratories are available to conduct 
the most sophisticated research. According to a 1998 National 
Science Foundation survey, at least 65 percent of biomedical 
research laboratories are inadequate to host sophisticated 
research.
    In addition, NCRR proposes to expand its Animal Facility 
Improvement program to meet the institutions' needs nationally 
to upgrade animal research facilities to perform genetic 
research with rodents, nonhuman primates and other animal 
models. To assist research-performing Historically Black 
Colleges and Universities and other minority-serving 
institutions in bringing their animal research facilities up to 
AAALAC standards, NCRR proposes a special initiative to address 
this problem.

                           CAREER DEVELOPMENT

    Over the past several years, fewer young physicians have 
pursued research careers. To help address that problem, NCRR 
has initiated programs to increase the number of young 
physicians in the clinical research pipeline. NCRR proposes to 
extend that effort in fiscal year 2001 to include support for a 
year-long medical student mentored clinical research training 
program. The intent of this program is to serve as a catalyst 
for young physicians to pursue careers in patient-oriented 
research. The institutional GCRC or the RCMI-funded Clinical 
Research Center will serve as a focal point for patient-
oriented research, through mentored, didactic training and 
hands-on research.
    NCRR also proposes to increase the number of Mentored, 
Patient-Oriented Research Career Development Awards to 
physicians and dentists at GCRC sites. This very successful 
effort was formerly known as the Clinical Associate Physician 
program, or CAP.
    NCRR proposes to initiate a 1-year program for veterinary 
students that will provide a mentored biomedical research 
experience at research-intensive institutions and will enhance 
the pipeline for research-oriented veterinarians. In addition, 
NCRR proposes to increase the number of Special Emphasis 
Research Career Awards to train veterinarians in health-related 
research. The NCRR programs that I described are intended to 
address the inadequate number of research-trained veterinarians 
who participate in biomedical research.
    I will be happy to respond to any questions you may have.
    [The written statement of Dr. Vaitukaitis follows:]



                          RESEARCH FACILITIES

    Mr. Porter. Thank you, Dr. Vaitukaitis. I want to kind of 
bottom-line things at the beginning and ask you, in the face of 
very strong increases for research grants at all of the 
Institutes over the last few years and with the intention, that 
that would continue so that the entire NIH enterprise would 
have doubled over 5 years, are we presently keeping up with the 
need?
    I am not talking about within NIH; I am talking about the 
extramural community as well. Are we keeping up with the 
laboratories and research facilities and equipment that is 
needed for this endeavor? Will we be able to stay ahead with 
those things as we continue to provide more research funding?
    That is the unfortunate bottom line, isn't it?
    Dr. Vaitukaitis. That is the bottom line. It is a complex 
problem because the funding that NIH, through NCRR, provides 
for upgrading laboratory facilities is only a small part of the 
total cost. In fact, on average, the Federal Government 
provides approximately 6 to 8 percent of the cost of upgrading 
facilities in general. So the onus falls on institutions for 
the most part. The institutions appreciate getting competitive 
grants for upgrading facilities from NIH because it helps them 
provide a sign of credibility to the lay community to get 
cofunding and support from donors for upgrading their 
facilities.
    One of the needs that is problematic for universities is 
paying for high-end scientific equipment. The shared 
instrumentation grant program has helped immeasurably, but that 
only provides funds for equipment up to a half million dollars. 
We do have a memorandum of understanding with the National 
Science Foundation; if a piece of equipment is to be used by 
NSF grantees, each agency contributes up to a half million 
dollars, thereby contributing to equipment that may cost more 
than a million dollars.
    It is the equipment that costs more than a million dollars 
that is problematic for universities and academic health 
centers. Academic health centers are no longer in a position to 
have a large amount of money available to help pay for high-end 
equipment, because of the impact of managed care.
    Universities are having the same problem. They don't have 
sufficiently flexible funds, although there are some programs 
that provide equipment as part of a centers program. For 
instance, through our biomedical research technology program, 
we do provide some funding. It is problematic because, for 
instance, building a new beamline at Argonne may cost $10 
million; fortunately the cost is spread over a couple of years 
because of the time that it takes to build such a facility. But 
the universities and their investigators are having a problem 
coming up with the high-end equipment, and that is an unmet 
need.
    Mr. Porter. Originally it was thought--and you can correct 
me if I'm wrong, and Dr. Kirschstein may wish to comment on 
this as well--originally the idea of indirect costs in a grant 
were to allow the academic medical center or whoever is 
receiving the grant to have the resources to rebuild or build 
new facilities as they were needed to conduct further research. 
And yet, and you alluded to this in your answer to the larger 
question, academic medical centers are under great siege 
because of the HMO revolution going on, and there seems to be 
great concern out there that they won't have the resources 
needed to build the facilities in order to absorb the grants 
and do the research that we hope will all flow from this 
increased commitment to biomedical research funding.
    I would like you to comment on that, and then I would like 
you to comment on the fact that as I read it, the President's 
budget would cut, not including the AIDS increase, about $77 
million out of your present budget. And if you include AIDS, 
its about $38 million. While the President's budget may lead to 
lower figures on grants, how are you going to make up that kind 
of money when you need it for facilities to have the research 
institutions perform their research function?
    Dr. Vaitukaitis. Let me address the indirect cost issue 
first.
    There exists no hard data to support or deny the fraction 
of indirect costs that goes to upgrading facilities. No 
systematic data has been collected that specifically identifies 
NIH indirect costs as part of that pool because it includes 
several other factors. There are two major components of 
facilities costs, including those that are paid for directly 
out of institutional funds.
    But the bigger component of the indirect cost pool probably 
is a factor of debt financing for borrowing. No data exists to 
establish what part of that cost is included within the 
indirect cost pool. Some of the accounting people at academic 
health centers and universities whom we have asked about this 
say that the indirect costs don't cover more than 10 percent of 
the cost; but that is based on impression and not fact. I 
strongly feel, and I know others feel this way, that a 
systematic study needs to be undertaken so that we know exactly 
where we stand and how to address this ever-increasing problem, 
because research is becoming more complex.
    Dr. Kirschstein. Mr. Chairman, in fact, we plan such a 
study. Dr. Varmus asked and I have also asked a subunit of the 
Advisory Committee to the Director to add several members to 
that group, persons who are knowledgeable about construction 
from our academic centers--both those that have medical schools 
and those that do not--and they will be meeting sometime in the 
spring to come up with an entire analysis and perhaps a new 
thought, some new recommendations as to what to do about this 
situation.
    I have asked Dr. Vaitukaitis to chair this committee, with 
these people, and we hope we will have some answers.
    It is not an easy problem. The indirect costs clearly were 
intended for this. They have not been able to handle it very 
well. We have had funds for the construction, and the shared 
instrumentation funds. Facilities are getting more and more 
sophisticated, and we really need to work on this.
    Mr. Porter. Now the question about the President's budget. 
How are you going to do this with $80 million less next year 
than you got last year?
    Dr. Vaitukaitis. It will be creative on our collective 
part.
    Mr. Porter. I might be misreading this, my staff tells me.
    I am looking at the appropriation for fiscal year 2000, 
$680 million, and the request for fiscal year 2001 at $602 
million.
    Dr. Kirschstein. That is non-AIDS. The total is $714.2 
million.
    Mr. Porter. I am looking at parallel lines, but that is not 
the way that you compare it. So there is some increase in the 
President's budget, some $34 million. I apologize and withdraw 
the question.
    Mr. Bonilla.
    Mr. Bonilla. Thank you, Mr. Chairman.

                          SOUTHWEST FOUNDATION

    Dr. Vaitukaitis, it is good to see you again, and I thank 
you for all of your work. I understand that the NCRR is 
planning to increase funding for the Regional Primate Research 
Center at the Southwest Foundation for Biomedical Research in 
San Antonio. We have had one on one conversations about this 
obviously over the last couple of years, and I appreciate the 
support that you have given it. They are doing good work and 
there is a true commitment from the community to make this a 
premier center. I hope if we are able to increase your budget, 
you will be able to increase their funding as well.
    Dr. Vaitukaitis. They would be pleased.
    Mr. Bonilla. We will give it every shot we possibly can. My 
question does not involve the Primate Research Center today. I 
want to go directly to a question about diabetes research.

                           DIABETES RESEARCH

    Last year Congress asked NCRR to follow the diabetes 
research working group's recommendation to increase NCRR 
support of diabetes research. I understand that NCRR is 
accepting applications to establish centers to isolate islet 
cells for transplantation in diabetes patients.
    Can you expand on your goals for diabetes research at NCRR?
    Dr. Vaitukaitis. We are still negotiating this, but it is 
our intent to put together a request for applications for 
fiscal year 2001 to establish three to four centers that would 
have standardized protocols for isolating human pancreatic 
islet cells for both basic research and for transplantation 
into Type I diabetics.
    Mr. Bonilla. But you expect this to happen?
    Dr. Vaitukaitis. I am an optimist. We had a meeting 
yesterday with the NIH representatives to the Diabetes Working 
Group to discuss this, and this is our highest priority.
    Mr. Bonilla. If you run into unforeseen barriers, let me 
know because we would like to help you work through those.
    Dr. Vaitukaitis. Thank you very much.
    Mr. Bonilla. Thank you, Mr. Chairman.
    Mr. Porter. Thank you, Mr. Bonilla.
    Mr. Dickey.
    Mr. Dickey. Dr. Vaitukaitis, how are you?
    Dr. Vaitukaitis. Just fine.

                    INSTITUTIONAL DEVELOPMENT AWARDS

    Mr. Dickey. Yesterday, I mentioned to Dr. Kirschstein my 
concern that Arkansas was not getting its share of NIH research 
grants.
    Dr. Vaitukaitis. Yes, I heard that statement.
    Mr. Dickey. Well, that is all that I want, favoritism. In 
what ways can we increase the research capabilities in rural 
Arkansas?
    Dr. Vaitukaitis. The institutions in your State are 
eligible for the IDeA program that we have designed 
specifically to enhance the competitiveness and train young 
investigators in IDeA-eligible States. The reason that the 23 
IDeA-eligible States and Puerto Rico get so little NIH funding 
is that they account for only 8.5 percent of all of the NIH 
applications. That was based on data analyzed in 1998, and that 
indicates too few investigators who are trained in biomedical 
research. We designed a program intended to address that 
problem, which requires that a multidisciplinary center be led 
by an established investigator, who already is funded and who 
can serve as a mentor for more junior faculty. This, in turn, 
will enhance the quality of faculty at the universities and 
enhance recruitment of students who will be trained in these 
areas. We think that this has a reasonable chance to work.
    The other wrinkle is something novel. We invited program 
staff from the other institutes to work with NCRR and with the 
applicants from the various states where it relates to the 
mission of their institute. For instance, we have NCI program 
staff who will work with those applicants who are putting 
together cancer-related applications. All of the major NIH 
institutes are participating.
    We are hoping with this kind of approach and follow-up 
after awards are made that we will be able to help transition 
the centers to be supported, not through the IDeA program, but 
by the categoric institute to which the center relates. That 
would be a sign of success for us.
    Just for your information, last year we awarded a General 
Clinical Research Center to the University of Arkansas for 
Medical Sciences.
    Mr. Dickey. I knew that. That is fantastic. Last year, was 
it?
    Dr. Vaitukaitis. Yes.
    Mr. Dickey. Tell me again what that does.
    Dr. Vaitukaitis. It is a General Clinical Research Center. 
It provides infrastructure for doing clinical research and the 
institution at the University of Arkansas competed very well.
    Mr. Porter. We are going to look into this. I am not sure 
that----
    Mr. Dickey. Are you saying that we don't have enough 
applicants?
    Dr. Vaitukaitis. The bottom line is that there are not 
enough trained investigators who do health-related research. In 
some cases it is because there are no medical schools in the 
State, but that is not true of yours.
    Mr. Dickey. That is correct.
    Dr. Vaitukaitis. It should be easier to work with faculty 
at the medical school to help address this problem in Arkansas.
    Dr. Kirschstein. Indeed, Mr. Dickey, it seems to me that 
this notice of a General Clinical Research Center could be very 
important, because physicians who are in rural parts of 
Arkansas, but who want to do research related to health in 
those rural areas, could spend time coming to Little Rock to 
work with the physicians in the General Clinical Research 
Center; and we probably could work up some sort of a program in 
that regard.
    I would suggest that Dr. Vaitukaitis work with many of us 
and, in addition, with some of the activities of the former 
Agency for Health Care Policy Research, now the Agency for 
Health Care Research and Quality; that could be a combined 
effort, too. So we will look into that and work with you.
    Dr. Vaitukaitis. Actually, we host a lot of research from 
that agency.
    Mr. Dickey. Dr. Vaitukaitis, you mentioned 24, and I had 
26.
    Dr. Vaitukaitis. It is 23 States and Puerto Rico.
    Mr. Dickey. That is 24. I thought 7 percent was spread over 
26 states.
    Dr. Vaitukaitis. You are quoting the number that is in Mr. 
Istook's bill. Currently there are 23 States and Puerto Rico 
that are eligible for funding through the IDeA program.
    Mr. Dickey. Thank you very much for your consideration, Mr. 
Chairman.
    Mr. Porter. Thank you, Mr. Dickey.

                     CHIMPANZEE MANAGEMENT PROGRAM

    Dr. Vaitukaitis, I want to raise a question about 
chimpanzees. This is a very small part of your overall 
responsibility, and yet I sit here and worry about things like 
a headline saying NIH neglects aged chimps. It is not a good 
headline. We see some problems with the Coulston Foundation and 
the way that they are maintaining about 600 chimpanzees that 
are no longer used in research and tend to be something that is 
over there and we don't have to worry about it, but we do. I 
wonder if you can give us your take on how well the Coulston 
Foundation is doing the job that they are entrusted with? What 
are the costs and what are the problems and isn't there a 
better way that we can do this?
    Dr. Vaitukaitis. The Coulston Foundation is a private 
foundation. NCRR currently supports a colony of about 110 
chimpanzees at the Coulston Foundation as one of the five sites 
that we have supported for several years. In addition to that, 
many of the animals at the Coulston Foundation have been used 
by investigators for HIV-AIDS related research, and for 
hepatitis B and hepatitis C vaccine development and other 
activities, as well as studies trying to develop childhood 
vaccines for RSV, respiratory syncytial virus. We have been 
very concerned about the animal well-being at the Coulston 
Foundation, and Dr. Wendy Baldwin, the Deputy Director of 
Extramural Research at NIH, has been working closely with the 
USDA and with my staff to assure that the animals are being 
well maintained. The animals have been systematically examined 
by veterinarians that are responsible to us, and they have 
advised us that the animals are well taken care of.
    We have worked with the USDA on this issue. We do not own 
any animals at the Coulston Foundation. One of the agreements 
with the USDA is that Coulston has agreed to divest himself of 
several hundred chimpanzees. We would be willing to assume 
ownership of those chimpanzees if they were offered, but we 
cannot make a request to the Coulston Foundation because of 
technicalities legislatively.
    Dr. Kirschstein. We are deeply concerned at NIH and are 
giving it one of the highest priorities to try to solve this 
problem. Dr. Baldwin and the staff that is seated here with Dr. 
Vaitukaitis are working very hard, and we hope we will have a 
reasonable solution. We know that it is important to make sure 
that these chimpanzees, many of whom are young and will live to 
be 50 years of age are appropriately cared for, regardless of 
expense.
    Mr. Porter. There is legislation that has been introduced 
in Congress to provide a permanent chimpanzee sanctuary. Does 
NIH support that?
    Dr. Vaitukaitis. We have developed a Chimpanzee Management 
Plan in keeping with the study that the National Academy of 
Sciences carried out a couple of years ago. We have the 
elements of that administratively in place so that we would be 
able to have chimpanzees in reserve for research purposes, for 
development of vaccines should they be needed.
    We are between the proverbial rock and a hard place. If we 
were to place the animals in a sanctuary, as outlined in that 
bill, we essentially would not have access to them for 
biomedical research except for some noninvasive kinds of 
activities. If a virus that is unknown to us currently became 
problematic and a chimpanzee was an ideal model to develop the 
vaccine, we would have no real place to turn to.
    Mr. Porter. What if we could work out that problem?
    Dr. Vaitukaitis. We could handle that currently within the 
Chimpanzee Management Program, and if we could adapt any 
program that was like that, we could work within that 
framework.
    Mr. Porter. I think we need to sit down and work this 
through and see if we can't find a better way to address this.
    Dr. Kirschstein. Dr. Baldwin has met with Congressman 
Greenwood several times, and we are trying to work out these 
issues. It is one of our highest priorities.
    Mr. Porter. Thank you very much.
    Dr. Vaitukaitis. We are concerned about the animals.
    Mr. Porter. I know you are. I don't want to let this thing 
drift. There seem to be some problems.
    Dr. Kirschstein. I agree.

                       CLINICAL RESEARCH TRAINING

    Mr. Porter. We are aware of the decline of physician 
scientists going into clinical research and the need to do 
something to stop this decline. Support for the General 
Clinical Research Centers is one step in this process. What is 
NIH doing to enhance the centers and encourage more medical 
students to pursue a career in clinical research, and what are 
your plans for the future?
    Dr. Vaitukaitis. In speaking with representative physician 
investigators across the GCRC sites, one recommendation was to 
initiate a program to support medical students at those sites 
to have hands-on clinical research opportunities and to work 
with established investigators. We are putting this kind of 
program in place hoping to maintain the interest of medical 
students in patient-oriented clinical research so they will 
pursue a career.
    Another component has been included in other bills that are 
still pending: a loan repayment program for clinical 
investigators. This has been supported at various levels at 
NIH; the burden of debt is seen as one of the barriers to 
attracting and maintaining well-trained, patient-oriented 
physician investigators in clinical research.
    Separate from that, you are well aware of the several 
programs that NIH started about a year and a half ago. These 
new career developments mechanisms, the K-23 and the K-24, are 
programs to support physician investigators who have completed 
fellowship training, for the most part, as well as to support 
faculty members half-time, who can then serve as mentors for 
junior investigators, including medical students to try to 
enhance research opportunities.
    We are also trying to provide ancillary support through the 
GCRCs to facilitate research, for instance, to provide more 
research nurses that go out of the physical unit to work with 
investigators to facilitate their research needs, to provide 
data managers and computerization of data that would help the 
investigator. They are more pressed for time than ever, but by 
the same token, the research tools that are available for 
clinical research are unprecedented.
    There is a tension with investigators being pressed for 
time and junior investigators being pressed because they have a 
large debt. There are a significant number interested in 
careers in clinical research when they graduate from medical 
school, but we are not taking advantage of that. We are hoping 
that we are starting to address that issue.
    Mr. Porter. I want to try to remember something from 
yesterday and that was, New Jersey is the first State to--
correct me if I'm wrong--to require repayment of the cost of 
clinical trials?
    Dr. Kirschstein. Yes. That is correct.
    Mr. Porter. Would that help with this problem where there 
is a flow of funds, if other States were to adopt or the 
Federal Government were to adopt a standard?
    Dr. Kirschstein. It would help clinical research trials if 
there really was that type of support. Then I suspect that 
physicians in training, medical students, would see something 
that would give them the stability to want to enter research 
careers.
    Mr. Porter. Because they would know the funding would be 
there, which has been threatened by this revolution in health 
care delivery?
    Dr. Kirschstein. That is correct.

                              SYNCHROTRONS

    Mr. Porter. Dr. Vaitukaitis, can you tell me whether a 
synchrotron is very similar to a particle accelerator?
    Dr. Vaitukaitis. It is a form of a particle accelerator, 
except that you are accelerating a lot more electrons in a 
physical facility that could be as long as a mile--in a circle, 
that is.
    Mr. Porter. Could Fermi Lab's particle accelerator be used 
for this same purpose?
    Dr. Vaitukaitis. I am not a physicist----
    Mr. Porter. Neither am I.
    Dr. Vaitukaitis [continuing]. So I would have to check. I 
think it is a different kind of device. Usually they are used 
for bombarding in a straight line, whereas synchrotrons have 
magnets that bend the electrons and photons around the field 
and then use the X-rays that they can bend off with special 
adjusting devices to bombard a crystal to calculate the 
structure of the protein.
    Mr. Porter. How many synchrotrons do we have available now?
    Dr. Vaitukaitis. The Department of Energy has synchrotrons 
at the Advanced Light Source, at Lawrence Berkeley, at 
Stanford's Synchrotron Radiation Resource, at Argonne National 
Laboratory and at Brookhaven. And then the National Science 
Foundation supports one at Ithaca, New York.
    Mr. Porter. Does NIH pay for users to use each of those 
facilities?
    Dr. Vaitukaitis. We don't pay for users, per se. We pay for 
building the beamlines, and we provide staffing for the 
beamlines because research is becoming very complex for 
investigators. They have to use a lot of different kinds of 
technologies, and they don't have time to learn 
crystallography, although they have to understand the 
principles. So they are requiring more support time at the 
beamline sites that we support. We are also providing access 
around the clock to increase the throughput at each beamline.
    Mr. Porter. And the use of these facilities has increased 
greatly in recent times.
    Dr. Vaitukaitis. Yes. With the several genomes being 
sequenced, there are many with unknown function and very small 
crystals for study of macromolecules expressed by these genes. 
They are using synchrotron radiation, because one can use very 
small quantities of crystallized material to get the three-
dimensional structure for many if not most proteins.
    Mr. Porter. So we can expect that the use of these devices 
will increase even more?
    Dr. Vaitukaitis. Substantially, absolutely.
    Mr. Porter. And will we have enough time to meet the need?
    Dr. Vaitukaitis. Our current professional judgment is that 
we won't.
    Mr. Porter. Did you say $10 million?
    Dr. Vaitukaitis. $8 to $10 million for a single beamline, 
but that is at Argonne. At the Advanced Light Source it costs 
about a quarter of that for building--one could argue why not 
build them all at ALS? The capabilities at Argonne are 
considerably greater for dealing with more complex substances, 
and we don't have that capacity at ALS. By addressing the needs 
at both resources, one can do it more cost effectively.
    Mr. Porter. I went out and saw the facility at Argonne and 
they didn't call it a synchrotron when I was there.
    Dr. Vaitukaitis. Advanced Photon Source.
    Mr. Porter. That is what they called it.
    Dr. Kirschstein. The National Center for Research Resources 
and the National Institute of General Medical Sciences are both 
deeply concerned about this and have been keeping up with a 
study of what would be needed and are trying to help in this 
regard. You will recall that Dr. Varmus used his 1 percent 
transfer money to provide funds for upgrading the synchrotron 
facilities to third generation light sources.

                           SCIENCE EDUCATION

    Mr. Porter. What role does NCRR have in encouraging science 
education? Do you do a lot in that area?
    Dr. Vaitukaitis. With this committee's help and your help, 
we now have an expanded program, which I think is going to be 
dynamite. The report language encouraged us to include science 
museums and technology centers within the cohort of resources 
that we support for science education.
    With that in mind, I attended the meeting of the 
Association of Science Museums and Technology Centers last year 
in Florida and met with the leadership of the science centers 
and technology centers. I was so impressed with how creative 
and imaginative these individuals are. I think it is going to 
be a very creative approach collectively to addressing the main 
issue, which is enhancing the public's knowledge of what NIH is 
doing in its research and how that research impacts on our 
educational lives and our choice of lifestyles. It will also be 
designed to pique the interest of youngsters in science so they 
can make appropriate lifestyle changes, but also select 
appropriate courses in school and perhaps choose science as a 
major in college, and then go on to graduate school.
    The main focus is for public education. We held a technical 
assistance workshop for these individuals about 6 weeks ago on 
the morning after a snowstorm shut down the airports in 
Washington. These people drove from New York, Philadelphia, and 
they arrived at the meeting and the local people stayed home. 
We had over a hundred attendees at this meeting, and Dr. 
McNairy and his staff put together a summary of the meeting up 
on our Web site, so those who could not make the meeting 
because of the problems with weather have access to the 
information and the advice that was provided at the meeting. We 
are very enthusiastic about this and we think that this may 
have a major impact in helping inform the public.
    Mr. Porter. Anecdotally, if you look across the research 
spectrum, don't you find a lot of the scientists to be foreign-
born, and perhaps foreign trained? Haven't we made up a lot of 
our deficiency in science interest or education in our country 
with people coming in from other societies to enrich ours and 
provide this additional intellectual power?
    Dr. Vaitukaitis. I think that is a fair observation.
    Mr. Porter. It seems to me as a matter of policy, we should 
not assume that this is going to happen forever. We hope it is, 
but we better be doing something to get our young people into 
science and interested in science at a young age and looking 
forward to careers in science, or we are going to find 
ourselves in a bind at some point. I think we have been very 
fortunate. That is one of the great attractions of freedom, 
scientists believe in truth, and obviously have to have freedom 
in order to do their work and the United States has gotten the 
benefit of that. I wonder why we can't do more with our own 
young people.
    Are you seeing a change in interest among young people that 
you didn't see five or 10 years ago, or are we still seeing 
that everyone wants to be a stockbroker?
    Dr. Vaitukaitis. We have not been exposed to a large enough 
cohort.
    Dr. Kirschstein. I think there is still concern. I would 
like to see this change. Many of us go out and talk at schools 
and bring young people to NIH for the summer, but I don't think 
that we are doing enough.
    Mr. Porter. I wonder when you sit here on the Committee and 
just listen to the Directors of the Institutes, you get a 
feeling, I think, if you are not science trained, of the 
overwhelming complexities that are there today, and I wonder if 
a lot of young people say, oh, my goodness, this is too 
difficult for me to think about undertaking when really if you 
get the training and break it down, they could easily be a part 
of it.
    Dr. Kirschstein. You are absolutely right, but part of the 
issue is how they are taught. If you make any field, reading, 
mathematics, geography and science interesting, and if the 
teachers are absorbed in the subject, the young people will get 
stimulated. But that does not always happen. We have a program 
in the intramural part of NIH where we bring local teachers to 
the campus for the summer, so they can get hands-on experience 
with our intramural scientists that undoubtedly makes them 
better teachers when they go back to teach science.
    Mr. Porter. I think we ought to put a lot more resources 
into this area. I think the initiative is a good start, but we 
have to do more.
    Dr. Kirschstein. This has been a sort of pull-and-push area 
for NIH. The major mission of both the Department of 
Agriculture and the National Science Foundation is science 
education. So we have, to some extent, used those 
organizations. The Office of Research on Minority Health has a 
memorandum of understanding with the National Science 
Foundation about providing money to that organization for 
science education for young, particularly minority, students. 
So we have tended to do pilot programs like those Dr. 
Vaitukaitis has described, and some others, but also to try to 
help the major agencies that have the responsibility.
    Mr. Porter. What we need to do is bring some of our great 
marketers in here to reach kids with the right messages and the 
right inspiration to get them locked into that as a possibility 
for their career path.
    Dr. Kirschstein. Exactly.
    Mr. Porter. Dr. Vaitukaitis, you are doing a wonderful job. 
I very much appreciate your testimony this morning. We want to 
provide you the resources you need to meet all of the 
challenges out there, and there are many, and we are going to 
do the best to provide those resources. Thank you for appearing 
today.
    Dr. Vaitukaitis. Thank you, and I would like to thank you 
on behalf of my staff and the grantees in the community for all 
of your enthusiasm for biomedical research in general.
    Mr. Porter. Thank you for saying that. It is easy to be 
enthusiastic when I hear all of the wonderful things that are 
happening.
    The subcommittee will be in recess until 2:00 p.m.
    [The following questions were submitted to be answered for 
the record:]



                                          Wednesday, March 1, 2000.

         NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

                               WITNESSES

ANTHONY S. FAUCI, M.D., DIRECTOR, NIAID ACCOMPANIED BY JOHN La 
    MONTAGNE, M.D., DEPUTY DIRECTOR
THOMAS WILLIAMS, M.B.A., FINANCIAL MANAGEMENT OFFICER
MILTON HERNANDEZ, M.D., DIRECTOR, OFFICE OF SPECIAL POPULATIONS AND 
    RESEARCH TRAINING
RUTH KIRSCHSTEIN, M.D., ACTING DIRECTOR, NIH
DENNIS P. WILLIAMS, DEPUTY ASSISTANT SECRETARY, BUDGET, DHHS
    Mr. Porter. The subcommittee will come to order. We 
continue our hearings on the budget for the National Institutes 
of Health, with the National Institute of Allergy and 
Infectious Diseases. We are pleased to welcome Dr. Anthony S. 
Fauci, the Director. Wonderful to see you, as always. I know 
you have got an interesting presentation for us, and let me say 
that we appreciate the outstanding work that you do at NIAID. 
We think you do an absolutely marvelous job.
    Dr. Fauci. Thank you.
    Mr. Porter. Good to see you again.
    Dr. Fauci. Thank you.
    Mr. Porter. Why don't you proceed with your statement.
    Dr. Fauci. Thank you very much, Mr. Chairman. Before I do 
proceed, let me introduce my colleagues at the table. On my far 
left is Dr. Milton Hernandez, who is the Director of the Office 
of Special Populations and Research Training; Dr. John La 
Montagne, who is the Deputy Director of the Institute; and Mr. 
Thomas Williams, who is the Director of the Office of Financial 
Management; and you know Dr. Ruth Kirschstein and Mr. Dennis 
Williams.
    Before I get started and give my formal oral presentation, 
Mr. Chairman, I just want to take the opportunity, as many of 
my colleagues have, to tell you how much I have appreciated and 
continue to appreciate all of the extraordinary things that you 
have done for the biomedical research community and for the 
health of our Nation. You have earned our universal respect and 
affection, and we will miss you very much. Thank you for 
everything.

                             GLOBAL HEALTH

    My written statement is submitted for the record. I would 
like to just spend a few moments reviewing for you some of the 
past accomplishments and future directions of NIAID.
    [The information follows:]



    Dr. Fauci. You recall from last year that I emphasized, as 
I did the year before, the question of global health and how 
that fits in not only with NIAID, but with the NIH in general. 
But we are particularly attuned to the concept of global health 
from a number of standpoints. There are many reasons to be 
intimately involved in the global health endeavor. The 
humanitarian objectives, in and of themselves, are enough 
reason. But also there is relevance to domestic health 
problems, as well as globalization of health problems, not the 
least important of which we discussed at this committee many 
times, including malaria, tuberculosis, and AIDS, particularly 
its impact in the United States, as well as what we are paying 
more attention to. For example, the economic development and 
political stability of nations that we deal with in a very 
close manner who are impacted in a very negative way by 
problems in their nation, such as sub-Saharan Africa.
    [The information follows:]



                          INFECTIOUS DISEASES

    Dr. Fauci. Given that this is the NIAID, we are interested, 
obviously, infectious diseases to point out that infectious 
disease is the leading cause of death worldwide in young people 
less than 45 years old. And if I showed you a chart of less 
than 5 years old, it would be even a greater disproportion of 
deaths due to infectious diseases. These are due to standard 
diseases that we see all of the time, as well as to the 
emerging and re-emerging infections, one of which we have been 
discussing with this committee now for the last 18 years, and 
that is HIV/AIDS.
    [The information follows:]



                                  AIDS

    Dr. Fauci. This little inset is the chart I showed you last 
year, you might recall, where the deaths due to AIDS were 
rising until 1995. And then with the advent of the combination 
therapies that have placed a major impact positively on HIV-
infected individuals, there was a dramatic decrease in deaths 
due to HIV.
    I also mentioned at that time that there are problems that 
we were starting to see with the currently available anti-HIV 
drugs. Now, one further year into that, we are starting to see 
that, despite these extraordinary positive effects, there are 
limitations in the current anti-HIV drugs: quality of life 
issues; toxicities; persistence of viral reservoirs and 
persistence of the replication of the virus; appreciating now, 
to our dismay, that we will probably not be able to eradicate 
the virus from these individuals, we have to think of creative 
ways to control the virus, and I hope we get a chance to 
discuss that during the question period; the emergence of 
resistance; and cost access.
    [The information follows:]



                               NEVIRAPINE

    Dr. Fauci. There was one thing that happened this year, and 
I will not use the word ``breakthrough,'' Ms. Pelosi, but 
something really very important happened this year that I want 
to point out to you that I am sure you have heard of, and that 
is a collaborative study that was done with NIAID, the Fogarty 
International Center, and our Ugandan colleagues, which studied 
the transmission of HIV from infected mother to a baby, 
comparing a regimen of a drug called Nevirapine in a single 
dose to the mother at the onset of labor and a single dose to 
the baby within 72 hours of birth and compared that with the 
much more expensive AZT regimen. As a matter of fact, the 
Nevirapine did 50 percent better than the AZT. The important 
part about the study is that the total cost of the whole study 
was $4, which now makes this economically feasible in countries 
that just brushed off the possibility of ever treating anybody 
for HIV under any circumstances. And this is something I 
believe we need to pursue.
    [The information follows:]



                           EMERGING DISEASES

    Dr. Fauci. Now, one of the other things I spoke to you last 
year about was emerging and re-emerging diseases. I know you 
see a lot of charts, but I showed a chart that had about 20 to 
35 new emerging infectious diseases that had occurred over the 
past 5 to 10 years.
    Just to underscore the point I was making last year, these 
are just what happened since I testified before this committee 
last March. You are aware of it. We have the West Nile fever 
problem in New York and surrounding States; we have dengue now 
in Texas and in Florida; and we have the ever-present threat of 
influenza, which I hope we also will get a chance to talk to 
you about in a little bit more detail later because this is 
something that I think will dwarf some of the other emerging 
disease threats, but because of the word ``influenza,'' the 
flu, we tend to think it is not something very important when 
compared to some of the more esoteric infections.
    [The information follows:]



                       PATHOGEN GENOME SEQUENCING

    Dr. Fauci. One of the approaches we are having towards 
these infectious diseases is bringing infectious disease into 
the age of genome. You have heard a lot about the Human Genome 
Project. We have a project now that is sequencing many of the 
major human pathogens. And the reason this is important, just 
as when you get the human genome, you could do so many things 
with it, when you get the genetic sequence of these microbes, 
you can then have a much greater ability to develop 
diagnostics, drugs and vaccines.
    A couple of examples is the sequencing of the second 
chromosome of the Plasmodium falciparum, the sequencing of the 
Haemophilus influenzae b, the sequencing of syphilis 
microorganisms, tuberculosis, et cetera.
    [The information follows:]



                               IMMUNOLOGY

    Dr. Fauci. Let me switch very briefly to the question of 
immunology, the other major discipline that we cover. This is 
the cover of the journal Cell from January of this year making 
the point that I would like to underscore; namely, as we enter 
the 21st Century, immunology is coming of age and beginning to 
translate what I have been talking to you about over so many 
years of basic research findings into something that really is 
a practical benefit for human health.
    [The information follows:]



                        IMMUNE TOLERANCE NETWORK

    Dr. Fauci. And, again, just to make the connection between 
last year and this year, this slide I showed you last year 
explaining the mechanisms of what we call immunological 
tolerance; how you can stop the body from reacting against 
something that you do not want it to react against, like a 
transplanted tissue, like its own tissue in autoimmunity or to 
have a better insight into vaccine development. You can do that 
by interfering with certain of the signals that the cells show 
to each other.
    This is fine in its conceptual standpoint. What we have 
done since last year is implement now our clinical research on 
immunological tolerance into a network. In other words, we have 
40 research institutions with the largest contract that was 
ever let by NIAID, $144,000,000 over 7 years involving 
transplantation, autoimmunity, and most recently, asthma and 
allergy, which I hope will really bring asthma and allergy into 
the 21st Century as a sophisticated science.
    [The information follows:]



                           HEALTH DISPARITIES

    Dr. Fauci. One of the things that has been brought up 
several times during this hearing, particularly when we were 
all here for Dr. Kirschstein's hearing, is the question of 
health disparities. NIAID, because of the nature of what we do 
and the diseases that we study, is particularly sensitive to 
that from three standpoints:
    Many of the diseases that we are involved with--sexually 
transmitted diseases, HIV/AIDS, tuberculosis, malaria--from a 
scientific standpoint, are involved in the question of 
disparity; also, our attention to training minority scientists, 
which I hope we get a chance to get into; as well as the 
question of enrollment of minorities into our clinical trials 
process.
    [The information follows:]



                          NIAID STRATEGIC PLAN

    Dr. Fauci. And, finally, let me close by putting forth the 
question that is asked of us here at the hearings, and a lot of 
other places: Can we well spend the money that has been so 
generously given to us over the past several years and 
hopefully into the future?
    We, as other institutes, have developed a strategic plan, 
the cornerstones of which are listed here: Global health and 
emerging infections, HIV/AIDS, vaccines and immune-mediated 
diseases. And we have a process that goes from the grassroots 
of the constituencies, our individual scientists, as well as 
input from a number of ad hoc groups that has put into the 
planning process something that I think will be a very good 
road map for spending the money very well that hopefully you 
will give to us.
    Thank you very much. I would be happy to answer any 
questions.
    [The written statement of Dr. Fauci follows:]



               WORLDWIDE DEATHS FROM INFECTIOUS DISEASES

    Mr. Porter. As always, Dr. Fauci, that is a fascinating 
presentation.
    Dr. Fauci. Thank you.
    Mr. Porter. Can you give us an idea of worldwide deaths or 
death rates from HIV/AIDS, tuberculosis, malaria and influenza, 
give us an idea of the impact. And maybe I am leaving out 
something major, but----
    Dr. Fauci. No, actually, if you look at the totality of the 
AIDS epidemic, for example, there 50 million people infected, 
33/34 million of which are still alive, which means about 16 
million have already died, 2.6 million of which have died just 
last year. So AIDS is accelerating with regard to deaths.
    However, we often forget or at least put on the back burner 
the diseases that I alluded to in my presentation regarding 
global health. Tuberculosis kills up to 3 million people a 
year; malaria kills 2.7 million people, most of which are 
babies under 1 year of age in sub-Saharan Africa.
    Influenza is an ever-present threat. It depends on the 
individual year. In the United States, the baseline that you 
see of epidemic threshold in the winter months is generally 
about 20,000 deaths per year. When you have a bad year, like we 
had in 1957 or 1968, it can go up to 35,000-45,000 or more. 
When you have a catastrophic year, like 1918, it goes up to 20 
million worldwide and 750,000 or more in the United States. So 
these are real threats. The numbers are really astounding.
    The thing that we are concerned about, why I, for the past 
couple of years, have been emphasizing global health is that 
although AIDS is always on our radar screen, we really need to 
pay very special attention to diseases like tuberculosis and 
malaria because the number of deaths from those really actually 
outstrip HIV/AIDS.

                               INFLUENZA

    Mr. Porter. If you look at all of these diseases and the 
emerging diseases, what worries you most?
    Dr. Fauci. Well, I sort of alluded to that on my emerging 
disease slide. What I am concerned about a lot, I mean, I am 
concerned about all diseases, be they esoteric or common 
diseases, that have the capability of re-emerging in a form 
that we cannot control, one of the examples of which is 
antibiotic-resistant microbes, which is of great concern.
    The thing that I think potentially can be the most 
catastrophic is another influenza epidemic the likes of which 
we saw in 1918 because of the nature of the spread of this 
virus, respiratory borne, in an era of travel, where you can 
have someone get influenza in China and then fly in 13.5 to 14 
hours to the United States and all of a sudden you see it in 
the United States.
    The problem with influenza is that we know historically, 
and we have decades of experience of this, is that there are 
drifts of antigenicity or those components of the virus that 
the body recognizes, and then there are shifts. We have drifts 
from year to year. So that if I get infected with the flu and I 
get a subclinical infection this year, next year, get my 
vaccination, I get a little boost, then I probably will avoid 
flu disease or if I get infected, it will be subclinical. But 
when you have a complete shift of the antigenicity, and there 
are what we call naive people in the population, and the 
majority of the population is naive, they do not have that kind 
of immune protection, and what you see is a normal season that 
is just the people who are missing work for several days to a 
week to a catastrophic situation. That can happen. I do not 
want to do scare tactics, but that can happen.
    Mr. Porter. And the vaccine would not be of any help 
because there has been this shift.
    Dr. Fauci. In general, we are pretty good at predicting the 
drifts. But when you have an abrupt shift; for example, we 
really dodged that silver bullet a few years ago with the bird 
flu in Hong Kong that I spoke to this committee about, the H5 
N1. Luckily, it did not mutate enough to be able to get 
transmitted from person to person. It got transmitted from pig 
to person. Had there been enough mutation in that, there would 
have been complete naivete in the population against that 
particular strain. So we would have been in serious trouble if 
that had happened.
    Mr. Porter. Do we adjust the vaccine year by year?
    Dr. Fauci. Yes.
    Mr. Porter. It is not the same vaccine that you got a year 
ago.
    Dr. Fauci. Yes. There is a committee, a coordinated group 
of people--CDC, FDA, NIH, et cetera, World Health 
Organization--that gets inklings and samples from what was 
there the year before to be able to predict, given the level of 
immunity in the population, as well as the antigenicity, which 
is the reason why next year there is going to be a slight shift 
in the flu components, the three components that we had this 
year. There is going to be a slight shift in the year 2000.

                        IMMUNE TOLERANCE NETWORK

    Mr. Porter. You mentioned a $144,000,000 contract with 40 
institutions over 7 years. Did you mean contract?
    Dr. Fauci. Yes.
    Mr. Porter. Is this a contract?
    Dr. Fauci. It is a contract, yes.
    Mr. Porter. Give us some more background on this because 
this is very unusual in size, at least.
    Dr. Fauci. Yes. It is unusual in size, but what we have 
done is that we have gotten truly the cream of the crop of 
immunology and the cream of the crop of transplantation and 
autoimmunity, and now we are enlisting our colleagues in the 
asthma and allergy field.
    And what we have done is made a long-term investment in 
translational research from the fundamental basic observation 
that you can interfere with the immune system's ability to 
recognize an antigen without necessarily coming in with a 
sledgehammer and suppressing everything. You know, one of the 
real problems with both transplantation and autoimmunity is 
that in order to suppress the aberrant immune response, you 
have to suppress the entire immune response, which leaves 
people at great risk for opportunistic complicating infections. 
With tolerance, you can selectively block only the response to 
the particular antigen.
    So what we have done is that now that we have this 
knowledge, we have set up this network of centers that are 
going to entertain proposals to put these into clinical trials. 
We actually just had the first meeting of the group that is 
going to look at the proposals that came in, and I had the 
opportunity to address them and talk to them a little bit about 
some of the things that we are talking to you about here now.

                               NEVIRAPINE

    Mr. Porter. You mentioned a new drug that is being used for 
preventing the transmission of HIV/AIDS from mother to child.
    Dr. Fauci. Right.
    Mr. Porter. And you said that it was Nevir----
    Dr. Fauci. Nevirapine.
    Mr. Porter. Four dollars per dose.
    Dr. Fauci. Four dollars for both doses. Four dollars for 
the mother's and the baby's dose.
    Mr. Porter. That sounds to me like a really very 
inexpensive drug, but to many African countries that I 
understand spend $1 or $2 per person on health care--all health 
care--a year, it is probably still very expensive.
    Dr. Fauci. Yes.
    Mr. Porter. How do we propose to get the resources to get 
countries to even use this drug?
    Dr. Fauci. There are foundations, and I believe there are 
Government organizations, also. See, what you are talking about 
is there have been estimates, that if you really wanted to 
treat everyone in Africa the way we treat people here in the 
United States, notwithstanding the infrastructure problems you 
are going to get in trying to even deliver the drugs, but just 
the drugs themselves, it would cost in the tens of billions of 
dollars. When you are talking about $4 per save here, you are 
not talking about billions of dollars, you are talking about 
millions of dollars, and I think that is doable.
    There are foundations that we are working with right now 
that are willing and able to go ahead and do that. What we have 
got to do now is build up the trust of our African colleagues 
that this is something that will ultimately be to the benefit 
of their country, because there are concerns about the 
development of resistant microorganisms or the inequity of 
giving it just to infected mothers. Should you then have to 
treat the mother? But we will do that in a very ethical way in 
getting the ethicists from those countries, as well as our own 
people, to sort of work together to come up with a plan.
    Mr. Porter. Is there any money in the President's budget to 
UNAID or any direct aid proposal that the United States would 
give additional money for this purpose?
    Dr. Fauci. Certainly not in our budget.
    Mr. Porter. No, I know it is not in yours.
    Dr. Kirschstein. Mr. Chairman, I think there was some 
proposed at a speech that the Vice President made at the United 
Nations.
    Mr. Porter. Yes, I think it was Vice President Gore that 
did make that proposal. I have not seen the numbers.
    Dr. Kirschstein. I have not either.
    Dr. Fauci. Right.
    Mr. Porter. Thank you very much.
    Ms. Pelosi?
    Ms. Pelosi. Thank you very much, Mr. Chairman.
    Welcome, Dr. Fauci, and to all of your colleagues, Dr. 
Kirchstein, welcome to you as always. Thank you for your 
excellent presentation.
    A couple of things, and I know the time is short and there 
is so much to ask. I was very impressed by what your study in 
Uganda produced and I am always interested in communication and 
collaboration, domestically and internationally. What is 
important about Uganda is that the leadership of Uganda, the 
President and the First Lady took responsibility, freed 
themselves of the denial that many countries experience, 
including our own, in the early stages of HIV/AIDS. This is an 
example where we can learn from Africa, as well as transmit our 
expertise to them.
    So congratulations on that. And hopefully, in our foreign 
operations budget, the Chairman sits on that committee as well, 
as does Mr. Obey, Mr. Jackson, and Mrs. Lowey, we can make sure 
that we have some funds specifically for Nevirapine.
    The Vice President mentioned at the UN that he was going to 
ask for an increased number for U.S. International AIDS. We 
have been fighting that fight for many years. Hopefully, this 
additional visibility and your success will make our job 
easier. Congratulations on that.
    Later this morning, I am going to join with Senator John 
Kerry in introducing legislation for tax credits on the 
research and sale of vaccines for AIDS, malaria and 
tuberculosis. We introduced this bill last year, Senator Kerry 
and I just for research and development, and then when the 
President mentioned in his State of the Union that he wanted to 
include a credit for the sale of the vaccine, we expanded it. 
That is what we are introducing today. So, hopefully, we will 
be able to assist with tax credits, in addition to 
appropriations.
    Again, I always ask in our other committee, ``What 
collaboration do you have with our domestic agencies?'' and I 
am asking you, here, what collaboration do you have with our 
international agencies? You have made the point.
    Dr. Fauci. Yes.

                                 ASTHMA

    Ms. Pelosi. So getting back to communication, on the 
subject of asthma, we have seen in our other hearings, et 
cetera, that children going to schools that are not clean, 
where there are roaches and all that comes with them, it 
increases the incidence of asthma attacks, if not increases 
asthma. Do you have any collaboration or communication with the 
Education Department? For example, the School Modernization 
bill that the President is proposing to build new schools and 
to upgrade the condition of many schools would have an impact, 
especially on children in poor areas. It certainly is true in 
the African-American community in our city.
    Dr. Fauci. Yes. The study you are referring to actually was 
done by an inner-city asthma study group that the NIAID and 
NIEHS did.
    Ms. Pelosi. It was yours.
    Dr. Fauci. And we found that relationship between cockroach 
antigens and asthma and pollutants and cleaning up the 
environment. I am pleased to say that an important part of that 
study has been outreach and education, not only of the 
physicians in their treating, but also of the patients 
themselves and their surroundings, including schools. So we do 
have that kind of outreach and collaboration.
    When we set the program up, we even had some criticism that 
it was not all basic science, and we should just be worrying 
about the scientific components. But we insisted that we would 
have an important outreach and educational and behavioral 
modification component of those inner-city asthma programs. And 
they have been very, very successful.
    Ms. Pelosi. Well, I appreciate that. And I think that your 
study is a good argument for the President's School 
Modernization bill as well. You talk about other environments 
in which children spend time, but school is one very important 
place, and we have a responsibility for that directly.

                                  AIDS

    Moving on to AIDS. Research on HIV and AIDS has led to 
scientific advances that go well beyond the AIDS epidemic. You 
have testified to that many times. Can you tell the committee 
how the research being done by your Agency on HIV/AIDS is 
advancing the field of immunology and helping NIH develop 
treatments for other diseases?
    Dr. Fauci. Yes. There are some very good examples of that. 
The opportunities, the way some of the original immunologists 
used to say decades ago, are an experiment of nature, really, 
which is what AIDS is. It happens to be a microbe that 
specifically and directly infects the immune system and a 
particular type of cell of the immune system.
    The insight we have had into what we call the regulation of 
the immune system has really been astounding and has caused us 
and allowed us to learn about things, like the tolerance that I 
mentioned to you, and our tolerance networks, and suppression 
of immune responses and hyperactivity that one sees in 
autoimmunity.
    Specifically, if I can give you some hard facts about what 
has happened, in the arena of drug design, the whole concept of 
targeted drug design is now spilling over into other areas, and 
we are seeing targeted drug design for other diseases. And even 
some drugs that were originally made for HIV/AIDS are now 
having a great impact on other infections. Lamivudine, which is 
one of the better drugs for AIDS, is now the state-of-the-art 
treatment of hepatitis B, as is a drug that did not do very 
well with HIV/AIDS, Adefovir is now used for hepatitis B. We 
also have interferon alpha and ribavirin for hepatitis C. All 
of these things had their beginnings when we were looking at 
the earlier treatments of HIV. So there are conceptual 
connections like understanding the immune system, as well as 
specific drugs that actually got developed.
    Ms. Pelosi. I appreciate that. Thank you, Dr. Fauci.
    Ever since I have been in Congress, and certainly on this 
committee, I have known how blessed we have been to have you 
where you are, especially one whose district is so affected by 
the AIDS/HIV epidemic. Over 15,000 people in my district have 
died. But you have been relentless in your work to find the 
details of how HIV works and to develop effective drugs, and I 
want to congratulate and commend you for that breakthrough.
    How are we doing on time? I should not have asked.
    Thank you, Mr. Chairman. We will have another round, I 
hope.
    Mr. Porter. We are operating under the 7-minute rule. Maybe 
we should give you a warning.
    Mrs. Lowey.

                      HPV AND TOPICAL MICROBICIDES

    Mrs. Lowey. Thank you, Mr. Chairman. I want to join my 
colleagues in admiration for you too. Things are going 
extraordinarily well, and we are so proud of the work you do, 
and we thank you.
    I want to particularly ask you about sexually transmitted 
diseases, and we did talk about HIV quite a bit. And we know 
that there are 15,000 a day new HIV infections around the 
world. These numbers are extraordinary. And I am particularly 
interested in a lot of the information that, at least for me, 
is rather new concerning HPV. Obviously, the information to 
date is that some strains of HPV lead to cervical cancer. We 
have discussed these issues with Jeff Koplan at CDC, Rick 
Klausner at the NCI, and I want to ask you to address the issue 
of microbicides or any other information you have, research 
that has been conducted, specifically focused on HPV. It is 
extraordinary to me that there is so much ignorance out there 
regarding HPV and that there is no prevention, there is no 
drug, there is no cure. And we know that it is a smaller 
number, a smaller percent that leads to cervical cancer, but I 
am really very focused on what we are doing about it and the 
progress that is currently being made.
    Dr. Fauci. There are a lot of things we could say. Let me 
just take two components of it. One is the question that you 
brought up about what we are actually doing scientifically. As 
you probably know, when you discussed with Rick Klausner, that 
the NCI and NIAID have a major collaboration in HPV. The 
collaboration is from both an epidemiological, as well as from 
a fundamental basic science standpoint.
    Our science now in microbes is very heavily centered, and 
it will be with HPV, in both the sequencing of the microbes and 
the determination of important antigenic determinants in 
diagnostics, therapeutics and vaccines. Clearly, the answer to 
the HPV problem is going to be vaccination so that women can be 
vaccinated, particularly women who are at high risk of getting 
transmission from a partner. We have been very successful in 
the sequencing of a number of microbes such as chlamydia 
trachomatis, which is a very important sexually transmitted 
disease.
    The other side of the coin is what you alluded to earlier; 
namely, the topical microbicides, where we have really, I 
believe, are starting to make some progress. I had the 
opportunity to meet just a few weeks ago in early February with 
Polly Harrison, who is the Director of the Alliance for 
Microbicide Development, and we discussed our game plan for the 
development of microbicides, the testing of new concepts, what 
we have, where we are going. And, in fact, we put in an extra 
$6,500,000 into that effort for Fiscal Year 2001. So we are 
accelerating our effort.
    I believe not only for microbes like HPV and others, but 
also for HIV, that the idea or the concept of being able to 
empower women to take into their own hands their ability of 
inhibiting or blocking sexually transmitted diseases that their 
sexual partner may not be amenable to, because of a variety of 
sociological and other reasons, is a very important priority 
for us.

                          HPV VACCINE RESEARCH

    Mrs. Lowey. Could you discuss any research that is ongoing 
with a vaccine. Because as you well know, many women are not 
even aware they have HPV, a smaller percent of the strains lead 
to cervical cancer. I think a vaccine is really critical.
    Dr. Fauci. Well, we are obviously working on it. I mean, we 
do not really have a vaccine right now, but we are working on a 
vaccine. We are also working on more sensitive diagnostics at 
the molecular level, the same way we did with chlamydia 
trachomatis, where you can actually diagnose something without 
necessarily culturing the microbe by doing molecular probing 
with what we call PCR, polymerase chain reaction. So there is 
both a diagnostic and a vaccine component to the work. 
Hopefully, in future hearings, I will be able to report more 
success in that.
    Mrs. Lowey. So when you are talking about diagnostics, you 
are talking about once the infection is there.
    Dr. Fauci. Right, finding out if it is there, and then 
seeing if one can develop a specific treatment for it.
    Mrs. Lowey. To neutralize it and to actually cure it.
    Dr. Fauci. Exactly. Right.
    Mrs. Lowey. Not continue to treat it.
    Dr. Fauci. Right. Microbes that ultimately lead to cancer 
generally need to be around for a significant period of time. 
So if you can get someone early in the diagnosis and have an 
effective treatment, you may be able to avoid the problem that 
one has with the development of cancers, in the same way that 
hopefully the adequate treatment of some of the hepafitic now 
will decrease the incidence of hepatic cancer associated with 
them.
    Mrs. Lowey. I thank you very much. I am particularly 
interested in this area, and I look forward to being kept up-
to-date on it, and I thank you.
    Dr. Fauci. You are welcome.

                                 ASTHMA

    Mrs. Lowey. My colleague, Congresswoman Pelosi, referred to 
asthma, and we are all aware of what a tremendous health 
problem this is, specifically in inner cities. Can you update 
the subcommittee on your research regarding asthma.
    Dr. Fauci. Yes. We are particularly pleased with what I 
alluded to just a little bit earlier about the inner-city 
asthma study that we are doing in collaboration with the 
National Institute of Environmental Health Sciences, where we 
looked at up to 1,000 children and made the important 
observation of the connection, the causal connection, between 
environmental antigens, such as cockroach antigens, and the 
triggering of asthmatic attacks. Inherent in that also is the 
educational component, whereby we educate both the physicians 
and the patients, or prospective patients, in how to self-
manage asthma.
    One of the real tragedies, particularly in inner-city areas 
among minorities, which is very likely one of the reasons, one 
of the important reasons, why the deaths due to asthma are much 
higher in minorities than they are in nonminorities, and that 
is the environment in which they are in and the fact that they 
do not get what I consider to be adequate instruction in self-
management. Asthma is a disease that you can manage yourself, 
with the help of physician. But if we do not take the time to 
go into the community and tell people how to self-manage, then 
they have a problem. This is something we are working on, and I 
think The results are going to show some considerable 
improvement.
    On a more fundamental science basis, just this past few 
months, we have now integrated our asthma and allergy program 
into the immunological tolerance network. Of the $144,000,000 
contract that I told you about, there were several components: 
kidney and islet cell transplantation, autoimmunity, and now we 
are going in with asthma and allergy.
    So I am optimistic that this is going to elevate the 
science of asthma and allergy really, as I say, into the 21st 
Century, to not just make it something that you hit the person 
with a lot of different drugs, which are good and work, but you 
can actually turn off the mechanism that triggers the asthma 
attack. That is really where we are going now in the 21st 
Century to turn the mechanisms off and get away from this 
carpet-bombing type of approach that we have with therapy, 
which, as difficult as it is, it works in many people, but it 
has a significant degree of toxicity. So I am actually very 
excited about what is going to be happening in asthma over the 
next few years. We just initiated this program, literally 
within the past 6 months.
    Mrs. Lowey. Thank you, Dr. Fauci.
    Thank you, Mr. Chairman.
    Mr. Porter. Thank you, Mrs. Lowey.
    Mr. Jackson?

                           HEALTH DISPARITIES

    Mr. Jackson. Thank you very much, Mr. Chairman, and thank 
you, Dr. Fauci, for your testimony, but also for your 
outstanding work at the Institute. And I want to associate 
myself with all of my colleagues who congratulated you for the 
work that you have done.
    Mr. Chairman, Dr. Fauci's work is so outstanding that I 
understand that he has been appointed to co-chair an effort to 
strategically improve NIH's response to health disparities. I 
am wondering, Dr. Fauci, if you could tell the committee what 
exactly this effort and work will do and what you hope to 
accomplish. And I am also interested in your role in 
interacting with Dr. Ruffin's office.
    Dr. Fauci. I would be happy to do that, Mr. Jackson.
    The panel that I co-chair with Dr. Yvonne Maddox, under the 
broad leadership of Dr. Kirschstein, is a panel that is going 
to take a fresh, new look at the health disparity situation at 
the NIH. And what our task is, and we are really on a fast 
track, we have had our first meeting, we have had our 
instructions sent out to the ICD Directors, and there are a 
couple of components that Dr. Kirschstein alluded to in her 
testimony at the overview.
    First of all, this is going to be a committee of Institute 
Directors. It is not going to be a committee of people who 
report to the people, who report to the people, who report to 
the Institute Directors because we want the Institute Directors 
there, understanding and hearing what is going on.
    We have charged them, at our first meeting, to develop, 
according to a framework that has some commonality to it, so it 
is not disparate and everybody does their own thing, to have a 
strategic plan for the individual institutes. Then we are going 
to develop an overall NIH strategic plan, and that is really 
the bottom-line task of what this panel is. And we want very 
much for it not to be just the sum of the strategic plans of 
the individual institutes, but something that is far greater 
than the sum of the parts and have a philosophy, a road map, of 
where we are going.
    The fast track is looking to get it done by the end of the 
spring, so that when we get into our next budget cycle, we can 
actually translate this health disparity situation into 
something that will be in our budget-building process for the 
next fiscal year.

                        NIAID MINORITY PROGRAMS

    Mr. Jackson. Let me thank you for that answer, Dr. Fauci. I 
think all of my colleagues acknowledge that at the Institute 
for Allergy and Infectious Diseases, there is probably no one 
better in the country to do and who continues to do what you 
do.
    One of the reasons that I filed my bill, H.R. 2391, was so 
that you could continue to do what you do well, and the 
responsibility for coordinating across the entire NIH these 
issues of disparities would not fall upon you, it would fall 
upon someone else who would cover for this committee and tell 
us and share with us what that overall strategic plan is and 
how each of the institutes are indeed addressing that. So I do 
want to thank you for the added burden that we have placed on 
you and that the director has placed on you to try and follow 
up on some of this.
    In your written testimony, you say that NIAID has a 
longstanding commitment to increasing the cadre of minority 
investigators in biomedical research. I am wondering can you 
elaborate on this statement.
    Dr. Fauci. Actually, could I post it up for you?
    Mr. Jackson. Sure, you can, sir.
    [The information follows:]



    Dr. Fauci. As I mentioned, there are three ways that we try 
and do this. We have basic research, we have people accruing at 
the clinical trials, and we have programs. There are a number 
of programs, some of which are shared with other institutes, or 
other institutes actually take the lead. You are familiar with 
many of them, but let me just point out a couple. I do not 
think we have time to go through all of them. The research 
supplements for underrepresented minorities you know about. We 
have at NIAID a ``Bridging the Career Gap'' symposium, where we 
bring in minority investigators and essentially try to get them 
into the mainstream of grantsmanship, about how you can get in 
and compete with people who have more experience, who have been 
more successful.
    The Minority Scientist Enhancement Awards, the Introduction 
to Biomedical Research Program, I'm particularly proud of this. 
We have done this now for 21 years. Each year we bring in 50/
60/75 minority students to the NIH for an intensive 3- to 4-
day, getting to know us, and we are getting to know them, and 
we use----
    Mr. Jackson. Dr. Fauci, let me ask you just one question, 
if I can. Are you aware of any of these programs promoting or 
supporting substandard research?
    Dr. Fauci. No.
    Mr. Jackson. None of them.
    Dr. Fauci. No.
    Mr. Jackson. Has it been your experience that your minority 
investigators promote substandard research?
    Dr. Fauci. No.
    Mr. Jackson. And that has not been acceptable standard.
    Dr. Fauci. No.
    Mr. Jackson. Okay. But these programs do reach out and 
broaden the pool of minority researchers.
    Dr. Fauci. This one, I would like you to see sometime. 
These kids are extraordinary. The track record of these 
youngsters, who have gotten their M.D.s, their Ph.D.s and their 
M.D.Ph.Ds, who come back to the NIH and work in our labs, this 
is a showcase program, this Introduction to Biomedical Research 
Program, and we are happy to compete with anybody, wherever 
they come from.
    Mr. Jackson. Is this the kind of coordination that you 
would like to see across the entire NIH, in terms of----
    Dr. Fauci. A lot of it is going on, but I think that making 
it even more coordinated would be better.
    Mr. Jackson. Thank you, Dr. Fauci.
    Thank you, Mr. Chairman.
    Mr. Porter. Thank you, Mr. Jackson.
    Mr. Wicker.

                                HIV/AIDS

    Mr. Wicker. Thank you, Mr. Chairman. And, Dr. Fauci, it is 
good to have you with us today. The testimony is fascinating, 
and it always strikes me how interrelated the various 
Institutes are at NIH and how you have to work together because 
the diseases that affect us and that affect people worldwide 
cross so many disciplines.
    Let me start by asking about HIV/AIDS. You say, in your 
written testimony, HIV infections have reached an unacceptable 
plateau of 40,000 per year in the United States. How long have 
we been at that plateau?
    Dr. Fauci. About 8 or 9 years.
    Mr. Wicker. How is the rate of HIV/AIDS infection, then, in 
Africa, as compared to that?
    Dr. Fauci. Let me mention, if I might, Mr. Wicker, just 
backtrack on your question because that is a misleading number, 
40,000. Although the 40,000 has plateaued for 8 or 9 years, 
there is a shift in the demography within that, where it is now 
disproportionately going towards African-Americans and 
Hispanics and disproportionately going towards women. So 
although it has plateaued, we really need to pay attention to 
making sure that we shift the direction of our education, our 
behavior modification, as well as our getting these people into 
the appropriate clinical trials, which is one of the things 
that I alluded to about as one of the three-pronged components 
of our health disparity initiative.
    But getting back to Africa, sub-Saharan Africa right now, 
as we have said here for a couple of years, is really a 
disaster. There are 33 million people living with HIV infection 
in the world today; two-thirds of which are living in sub-
Saharan Africa. The number of new infections per day is about 
16,000, about 75 to 90 percent of which are in sub-Saharan 
Africa. Just last year there were over 4 million infections, 
about 5 million infections with HIV. So it is on this type of a 
curve in sub-Saharan Africa.
    What is even as frightening as that is that we are starting 
to see the same thing now a couple of years behind in India, 
and Asia and South Asian countries. So developing countries 
have not even begun to peak yet.
    Mr. Wicker. If that trend continues in Asia and sub-Saharan 
Africa, play the scenario out for us a decade from now.
    Dr. Fauci. A decade from now, if there is absolutely no 
leveling off and decreasing in that, we are going to have 
nations that are going to fall. I believe so. And when I spoke 
last year here I made the comment, and I was a little hesitant 
because it is getting out of my field--I know you were talking 
about foreign ops and things like that that we do not do--but 
this is something that should almost be a foreign policy 
initiative I think, and we have heard inklings of that now. We 
have heard inklings of that from the Congress, we have heard 
inklings of that from the administration.
    We are going to have allies that we depend upon, not only 
economically, but politically and militarily, who are going to 
actually fall. When you have an army in which 45 percent of the 
officer corps is infected with HIV, that is just completely 
unacceptable. So the implications completely transcend a very 
important component, which is the humanitarian. It goes into 
the economic, the political stability. So there is really going 
to be truly a disaster on several fronts.
    [The information follows:]



                               NEVIRAPINE

    Mr. Wicker. And that brings me then, and I hope someone 
will put up that slide about Nevirapine in Uganda while I ask 
this question. I have been curious for a while, and I hope you 
will help the subcommittee understand the process for the type 
of research that has gotten us to the point where we are now 
with the Nevirapine drug that costs $4 for the two doses and 
can potentially save 400,000 lives worldwide, I understand.
    So how long have we been working on that? How many 
consortiums have been involved?
    Dr. Fauci. Well, let me give you an example. It is years. 
The drug itself got developed as part of a drug development 
program that we have been involved in, in collaboration with 
our industrial counterparts, our pharmaceutical colleagues and 
collaborators. So it started off as a basic science approach: 
Here is a target of the virus. We know that if you block this 
component of the virus, we can block transmission.
    Mr. Wicker. And when was that that it got started?
    Dr. Fauci. That was at least 6 or 7 years ago. Then you 
wind up showing that that drug works in a combination in what 
we call highly active anti-retroviral therapy, forgetting 
transmission from mother-to-child, for people who are already 
infected. We know that it works.
    But we find out something about it, and this is the real 
fun and excitement of it, that unlike other drugs, it has a 
particularly long half-life; in other words, if you give it to 
me today, it hangs around for a day or two or three, as opposed 
to giving me a drug that you have to take three or four or five 
times a day.
    So then you get the idea, if you want to do an experiment 
and you want to do it in a way where you just want to hit that 
virus at that one point as it is getting transmitted from the 
mother during labor to the baby and then give it to the baby 
during that first couple of days when the baby is breast-
feeding and may still have some virus from the mother. So you 
give a dose to the mother, a dose to the baby, and it is purely 
done on the basis of what we call the pharmacokinetics of the 
drug. We know how the drug acts. Now, that is the science of 
it.
    The infrastructure is something that we built up again 
several years ago.
    Mr. Wicker. Well, where are these experiments taking place? 
Any number of places across the United States? Are they taking 
place in Africa?
    Dr. Fauci. This is a totally African collaboration. This 
was done in Uganda, in collaboration with the NIAID, the 
Fogarty International Center, and the Ugandan Ministry of 
Health, and it was done in our network of vaccine prevention 
therapeutic trial network.
    We have, in the United States and worldwide, in sub-Saharan 
Africa, in Uganda, in Mali, in Tanzania, in South Africa, these 
networks where we train people, we bring investigators there, 
we support their infrastructure so that when you are ready for 
a trial like this or a vaccine trial, you are there.
    Mr. Wicker. Let me just follow up. You say a trial and a 
potential. How far along and how sure are you that this is the 
way to go? Have you determined that this is going to work or is 
it just----
    Dr. Fauci. If I had my way and I had the control of 
everything, I would get some money from some foundations, and I 
would go there, and with a minimal infrastructure, I would 
start treating HIV-infected mothers. In fact, there is even an 
argument----
    Mr. Wicker. And then what is to stop you from having your 
way? Does some agency have to further approve this and 
clinically try it some more?
    Dr. Fauci. In fairness to the other agencies, who are as 
excited as I am about it, there are difficulties in getting the 
host nations to buy into something like this because they get 
involved in a lot of political and in-country type things that 
really get in the way of what the real issue is.
    Mr. Wicker. What kind of things, if I may----
    Dr. Fauci. Well, for example--I hope I do not get into 
trouble, but what the heck. [Laughter.]
    Mr. Wicker. You will not be the first one this week. 
[Laughter.]
    Dr. Fauci. But I am, hopefully, going to do it for a good 
reason here.
    The idea that if you give a single drug to a woman and a 
single dose to a baby that you might then develop resistance to 
the antiviral drugs is a real consideration, if you are going 
to go in and treat people, everybody in the country with the 
antiviral drug. So, in other words, they are saying, ``Well, if 
I give a single dose to the mother, then that mother might 
develop resistance to antiviral drugs.'' So that in the 
hypothesis that we are someday going to treat that mother with 
an $18,000-a-year regimen, which is completely ridiculous 
because we will never treat them with that, that is given as a 
reason to not treat the mother to prevent infecting the baby, 
which I, quite frankly, with all due respect, find to be a very 
spurious argument.
    Mr. Porter. Who makes that argument?
    Dr. Fauci. The Ministers of Health of the developing 
countries.
    Mr. Porter. Why? I mean, obviously it is a spurious 
argument. What is their interest here?
    Dr. Fauci. It is very complicated, Mr. Chairman. It really 
is. There are a lot of political things that go on between 
Ministers of Health and Ministers, Prime Ministers, that I 
just, I am not experienced enough to be able to decipher that 
out, but it does not happen.
    Mr. Hoyer. Experienced enough not to comment on it. 
[Laughter.]
    Mr. Porter. Thank you, Mr. Wicker.
    Mr. Hoyer?

                        IMMUNE TOLERANCE NETWORK

    Mr. Hoyer. I think your phrase about humanity's shared 
vulnerability to disease is a wonderful phrase and the AIDS 
epidemic, like so many others, point out how shared this 
vulnerability is. We tend to think we are relatively secure in 
the United States. We thought that from a defense standpoint 
and we now think about it from a health standpoint, but you 
pointed out that 13.5 hours from some place in Asia somebody 
can be in the West Coast or for that matter the East Coast.
    But let me ask you some questions about the budget. I know 
that is sort of unique in this Committee. A $144,000,000 for 
one contract----
    Dr. Fauci. Right.
    Mr. Hoyer [continuing]. Which is about what, 16 percent of 
last year's budget of $881,000,000.
    Dr. Fauci. Right.
    Mr. Hoyer. Now, that $144,000,000, is that a----
    Dr. Fauci. Seven years.
    Mr. Hoyer. Seven years. So, we are talking about two--
$20,000,000 this year.
    Dr. Fauci. Right. For 40 sites. So, about a half a million 
a site.
    Mr. Hoyer. And that is what I was going to ask. Forty 
sites?
    Dr. Fauci. Forty sites, right.
    Mr. Hoyer. Okay. Now, how does that make it one contract? 
Is it one----
    Dr. Fauci. Yes.
    Mr. Hoyer [continuing]. Recipient?
    Dr. Fauci. What we have, when we do these clinical trial 
networks, our experience, Mr. Hoyer, over the years has been 
you get the very best person as sort of the head of the 
executive committee for all of the sites. Because if you just 
go out and say, do your own individual thing, any individual 
site may not be able to get enough patients to ask and answer a 
question that you need a coordinated effort among 40 sites.
    So, you cannot do them individually. You have got to have 
one group, one center, one person who is the primary, what we 
call, principal investigator. And that person is a fellow named 
Jeffrey Blustein from the University of Chicago, really one of 
the best immunologists in the country and he is the head of 
that executive committee, but the members of the executive 
committee are representatives from all of those sites. So, when 
you let a contract, you give the contract to the PI and then 
the money is disbursed among the different groups, depending on 
their size, depending upon their application, depending upon 
their capability of conducting whatever particular type of 
research you are interested in.
    We do the same thing with the AIDS Clinical Trial Group. It 
is a single cooperative agreement, a single grant, as it were, 
but there is an executive committee that runs that.
    Mr. Hoyer. How does that affect, the question I have asked 
from time-to-time, the payline? That is to say is this 
perceived as one grant?
    Dr. Fauci. No. It does not have any impact whatever on the 
payline because it is a contract.
    Mr. Hoyer. Okay. So, it is not----
    Dr. Fauci. It does not enter into the payline at all.

                             NIAID PAYLINE

    Mr. Hoyer. Then let me ask you, what is the payline now at 
your agency?
    Dr. Fauci. Ours is----
    Mr. Hoyer. What will it be based upon the 2001 budget?
    Dr. Fauci. Same as last year, 20th percentile which would 
give us a projected success rate of about 31, 30.5 percent 
success rate, which is about the same as it was last year.

                            UNFUNDED SCIENCE

    Mr. Hoyer. All right. Given that percentage of grantees 
awards, how much good science in terms of a percentage, Doctor, 
do you believe that we are unable to fund?
    Dr. Fauci. You can never give an exact number but I have 
thought about this a lot over the years as we have gone better 
and worse and I think when you get to about 45 percent, 44, 45 
percent, you are still doing very, very good science. So, if I 
could fund 40 to 45 percent of the grantees that come in as 
opposed to 31 percent I would be doing top-notch science, top-
notch science.
    Mr. Hoyer. Am I correct in interpreting those numbers to 
say then that we are leaving approximately one-half of the good 
science unfunded?
    Dr. Fauci. Right. If you take 15 percent of the 30, it 
would be about one-half.

                                 ASTHMA

    Mr. Hoyer. Let me go to a specific question. A lot of 
questions have been asked about asthma. Obviously, asthma is a 
growing concern. Although I heard some sort of conflicting--I 
think Dr. L'Enfant said in point of fact it is how you count 
that really may have some impact on what the incidence of 
asthma is.
    Dr. Fauci. Right.
    Mr. Hoyer. But cigarette smoking, tobacco smoking, have we 
made a nexus between cigarette smoking and asthma?
    Dr. Fauci. Oh, there is no question about that. I mean not 
only cigarette smoking----
    Mr. Hoyer. Or any other tobacco products.
    Dr. Fauci [continuing]. But a lot of these nondescript 
environmental pollutants. In fact, that was one of the things 
that came out of our inner-city asthma study, the most 
publicized of which because it was such a concrete example, was 
the cockroach allergen exposure. But in addition to that, there 
are a number of pollutants in the inner-city areas that make it 
even more problematic for the youngsters who are getting an 
ever-increasing amount of attacks from asthma. So, there is no 
question environmental and cigarette smoke, either directly 
your own smoking, or secondary smoke is clearly an 
environmental pollutant, without question.
    Mr. Hoyer. You mention in the context of one of your 
answers to asthma was the management was a great problem and 
those who managed it better, who had more knowledge, were very 
substantially less at risk of death as a result of that.
    Dr. Fauci. Correct. And hospitalization. Because our metric 
was not only death, it was hospitalization and the 
hospitalizations were decreased by about 30 or 40 percent.
    Mr. Hoyer. In that context, all of us, many of us saw the 
movie, ``As Good As It Gets'' which was about an asthmatic 
child who did not get proper----
    Dr. Fauci. Right.
    Mr. Hoyer. And, of course, we used it, talking about 
managed care reform et cetera, et cetera, but it occurs to me 
as you said that, that there probably is no third party 
reimbursement for education and training of how to manage that 
except presumably through a doctor or health professional who 
will take the time to do that, in effect, on the side.
    Dr. Fauci. Yes.
    Mr. Hoyer. Is that correct?
    Dr. Fauci. That is correct. That is correct.
    Mr. Hoyer. Have we talked to CDC and others about that 
question? I mean this is the whole question of healthy 
lifestyles and how you keep healthy. But it seems to me this 
may be, particularly when--I am sorry Mr. Jackson has left the 
room--because what your point was that there are a lot of 
families who do not have the ability to manage well and the 
child suffers great damage as a result of it.
    Dr. Fauci. Right.
    Mr. Hoyer. Have you thought about how we could perhaps get 
at that?
    Dr. Fauci. Yes, I have, but it is, again, one of those 
things unfortunately, Mr. Hoyer, that is out of our purview. 
But the only thing that I think I can do and I try to do is to 
keep hammering away at that and advertising it, publishing it 
in the proper journals, when we go to conferences to make that 
point. To me management of a youngster with asthma with 
standard drugs properly to me is as important as developing a 
new wonder drug. So, if they are going to pay for the new 
wonder drug, you would think maybe we should think about the 
possibility of fostering the self-management.
    Mr. Hoyer. Mr. Chairman, frankly, I think that was an 
excellent statement and, Mr. Chairman, I think that is a very 
pointed critical statement and it responds to the concerns some 
have about well, we have got an existing illness, we know how 
to treat it and we are spending money on finding out about new 
illnesses. Obviously, we have to do both. The good news is our 
country is wealthy enough to do both.
    But, Mr. Chairman, we, I think, ought to address that issue 
and, in particular, when you have our expert saying if you 
manage this well you are going to prevent deaths, 
hospitalization, incredible loss of time at schools, 
absenteeism through proper management. We ought to pursue that 
and I will do that with you, Mr. Chairman.
    Thank you.
    Dr. Fauci. Thank you.
    Mr. Porter. We will have a second round at 3 minutes and 
try to get in four questions. There is some research that 
suggests HIV prevalence in one area versus another is not due 
to behavior only. Is this good research and, if so, what are 
the implications?
    Dr. Fauci. I am not sure when you say--I would have to say 
and, as a scientist, I flinch away from criticizing statements 
or research that I have not examined, but I know a lot about 
HIV and it is due to behavior. Now, the only thing that I think 
you might be referring to is the transmission from mother to a 
baby. I mean the baby has no behavior that the baby can avoid 
to not get infected. And that is what we often hear when people 
who are making a statement against the behavioristic approach, 
namely, what are you talking about behavior? There are a lot of 
situations. Someone who gets transfused in a country that does 
not screen their blood, that is not a behavior problem. A baby 
who gets infected, that is not a behavior problem.
    Mr. Porter. Those are the only two instances.
    Dr. Fauci. Right, exactly.
    Mr. Porter. Doctor Klausner has told us about 
collaborations on cancer research on a multi-nation basis where 
we all ought to say the next world war ought to be the war on 
disease and if we can get enemies together at the table working 
on the same problem maybe that will head off future conflict. 
Do you do the same kinds of things in your Institute?
    Dr. Fauci. Absolutely. In fact, the international nature of 
the diseases that we study are extraordinarily amenable to that 
philosophy, which as I showed on my first slide, I mean that is 
our early theme, global health and----
    Mr. Porter. But I am talking about getting two nations that 
might be at each other's throats, otherwise, working together.
    Dr. Fauci. Well, we have in the Middle East the Anasheim 
University collaboration between Israel and Egypt that has been 
on parasitic diseases. I believe it is schistosomiasis, John, 
is it?
    Dr. La Montagne. Tick-borne diseases.
    Mr. Porter. Yes.
    Dr. Fauci. We have that. In fact, we have had that now for 
I would say at least 15 years.

                HUMAN CHOREATIC AND AUTOTROPHIC HORMONE

    Mr. Porter. I think the more we can do in this area of 
finding ways to work peacefully toward the same goals is very, 
very helpful.
    Researchers have found that a human hormone found in 
pregnant women's urine contains a protein which destroyed the 
HIV virus in preliminary experiments. Is this something that 
NIAID is researching?
    Dr. Fauci. Again, I am not sure what they are referring to. 
In the urine that destroys----
    Mr. Porter. It contains a protein which destroyed the HIV 
virus in preliminary experiments. You have not heard that one?
    Dr. Fauci. Well, can I poll the audience? [Laughter.]
    Yes. Okay. I think I know what you are talking about. See 
that? Thank you, the audience. There is a hormone called human 
choreatic and autotrophic hormone, HCG, and there is a lot of 
work done by a former NIH'er, Bob Gallo, who is now up at the 
Institute for Human Virology at the University of Maryland, who 
has demonstrated that actually not the hormone, itself, but 
something that co-purifies with the hormone, is capable of 
blocking HIV and also having an anti-Kaposi's sarcoma effect. 
So, it is real research and it is good research.
    I have seen it, if that is what you are referring to.
    Mr. Porter. And this is not funded by NIAID?
    Dr. Fauci. Oh, yes.
    Mr. Porter. It is funded?
    Dr. Fauci. Oh, yes, we fund Gallo very heavily.
    Mr. Porter. And, so, you are saying that this ought to be 
pursued?
    Dr. Fauci. Yes, yes.
    Mr. Porter. Thank you.
    Mrs. Lowey.

                              LYME DISEASE

    Mrs. Lowey. Thank you.
    The question that I wanted to pursue comes from 
constituents, who have been victims of Lyme disease. I just 
asked my staff to give to me more information on a particular 
constituent recently who came to me regarding the success of a 
longer treatment for Lyme disease as compared to the usual 
shorter course of antibiotic treatment.
    Dr. Fauci. Right.
    Mrs. Lowey. Now, she was all upset because I guess this is 
controversial, the longer treatment is controversial. It worked 
with her and it has not been accepted by the scientific 
establishment. I would not give you the name, it probably would 
not be appropriate even if I remembered it now, but perhaps you 
could comment on it.
    Dr. Fauci. Yes. There is a study that we are sponsoring 
right now to address just this question. One of the problems 
with Lyme disease is that there are two components of Lyme 
disease. One is very well characterized, relatively easily 
treatable, and successfully treated. That is acute Lyme 
disease. If someone gets bitten by a tick you identify the 
original and early manifestations which are skin 
manifestations, you treat someone, the success rate is very 
high.
    There is another form of Lyme disease that is more 
controversial but I believe, nonetheless, real. There are 
probably more people who are diagnosed as chronic Lyme disease 
who actually do have chronic Lyme disease which actually clouds 
the picture but it is a situation that is felt to be due to the 
fact that the microbes, after they initially infect you, get 
into your joints, into your meninges and the brain, and cause a 
variety of neurological and arthritic problems. The difficulty 
in proving that is that the organism is in such a form when it 
gets to that point or it is being relatively well-contained by 
the immune system or maybe even the immune system is doing 
damage, that it is unclear what we call the pathogenesis of 
chronic Lyme disease is. Is it micro-driven or is it an 
aberrant immune response to the microbe?
    With that as a background, investigators have decided to do 
a clinical trial to determine if you treat someone not for the 
usual 10-days-to-2-weeks, the way you would do for acute Lyme 
disease, but treat them for 6 months, would you get that very 
last microbe out of there that would turn the disease off? And 
some people have empirically tried that and it has worked, and 
other people have empirically tried it and it has not worked.
    Now, the problem with that statement is that there are 
people in that group who do not really have chronic Lyme 
disease. So, they may go on a chronic therapy for 6 months and 
at the end of the 6 months feel better because they had 
something else that spontaneously got better or there may be 
people in there who truly do have chronic Lyme disease. So, in 
order to answer that very perplexing question, we have a 
clinical trial going that will hopefully do that.
    Mrs. Lowey. I heard the bell go off but perhaps just a 
quick one. Are the longer treatments covered by most insurance 
plans or is that part of the controversy?
    Dr. Fauci. I do not think so. I do not think it is an 
accepted therapy so it probably would not be covered by 
standard third party payers.
    Mrs. Lowey. So, we will have to wait for the completion of 
this trial?
    Dr. Fauci. Right. Once something is established in the 
literature as being an effective therapy then what usually 
happens is that the companies come in and then put it on their 
list of payable expenses.
    Mrs. Lowey. Was that bell real so I should wait or ask the 
next question.
    Mr. Porter. That was real.
    Mrs. Lowey. Thank you, Doctor.
    Mr. Porter. Thank you, Mrs. Lowey.
    Mr. Jackson?

                          MICROBICIDE RESEARCH

    Mr. Jackson. Thank you, Mr. Chairman.
    Doctor Fauci, I have three questions and I am going to read 
them all so that in light of the time constraint maybe you can 
answer them at your leisure.
    Dr. Fauci, from a variety of statements that you have made, 
I know you strongly support microbicide research and 
development and I appreciate the work that NIAID is doing in 
this area. Microbicides will be an important complement to the 
HIV vaccines currently under development since they are likely 
to be available sooner. I am wondering also because it is clear 
that they will also be easier and cheaper to distribute and it 
will be effective against a range of sexually transmitted 
diseases in addition to HIV.
    A central problem for microbicide development is a lack of 
adequate Federal investment. And I understand that you have 
personally recently committed to increasing NIAID investment in 
this area. I am wondering what NIAID spent on microbicides in 
fiscal year 2000 and what you plan to spend in fiscal year 
2001? And given that your fiscal year 2001 figure is based on 
the President's budget, if this Committee is able to increase 
NIH's budget above what the President has recommended can we 
expect to see additional resources devoted to microbicides R&D 
during fiscal year 2001?
    And I have also heard the concern that an additional 
problem is that NIAID does not have staff scientists who are 
solely dedicated to microbicide R&D. I understand that you have 
two individuals who work on this issue in addition to managing 
other responsibilities. Can you dedicate more focused staff and 
resources on this issue?
    Thank you.
    Dr. Fauci. Okay. I will try to give you some quick answers. 
The amount that we spent in fiscal year 2000 was about 
$20,000,000. The amount we are spending with the President's 
budget is about $22,000,000. And if we do get more money I have 
already promised Polly Harrison, who is from the Alliance for 
Microbicidal Research, that we will give an extra amount of 
money probably to the tune of about of $6.5 million or more 
depending upon the budget. So, we are committed to increasing 
it.
    A designated staff for a portfolio of that size, I think is 
somewhat problematic. We will pay attention to it, Mr. Jackson, 
I promise you that. If we get some activity going and the money 
gets to be a greater amount and we have greater programs we 
will put more people on that, I promise you.
    Mr. Jackson. Thank you, Dr. Fauci.
    Thank you, Mr. Chairman.
    Mr. Porter. You see, even the newest member of our 
Subcommittee has learned how to get around the 3-minute rule 
and ask all his questions. [Laughter.]
    He knows I will not cut off the answers, you see. 
[Laughter.]
    Well, Dr. Fauci, thank you for your testimony today. I say 
often I have the greatest job in the world. I am not sure that 
you do not have the greatest job in the world. But one of the 
great rewards of my position has been the opportunity for all 
these years to listen to you and your colleagues at NIH and to 
learn and try to understand the great progress that is being 
made in the war on disease. If every member of Congress could 
be here this morning and listen to your testimony and 
understand what is going on and the great intellect that is 
brought to bear on problems afflicting humankind, I do not 
think there would be any doubt about achieving greater funding 
and funding all of the science that is truly good science that 
is available to be funded and you have indicated that we are 
funding maybe half of it in your institute.
    So, I thank you for all of these years of inspiration and 
understanding and learning that I have gained from listening in 
the short time that we have had to do that. I just know that 
the work that is being done in NIH by you and your colleagues 
is always going to have the support of the American people and 
of Congress, if only they can learn more about it. We talked 
with Ruth about this yesterday how we can get that information 
out to more members of Congress. You are just doing an awesome 
job.
    Dr. Fauci. Thank you.
    Mr. Porter. Thank you so much.
    Dr. Fauci. Thank you very much, Mr. Chairman.
    Mr. Porter. We stand briefly in recess.
    [The following questions were submitted to be answered for 
the record:]



                                          Wednesday, March 1, 2000.

                         NATIONAL EYE INSTITUTE

                               WITNESSES

DR. CARL KUPFER, DIRECTOR,
DR. JACK A. McLAUGHLIN, DEPUTY DIRECTOR
JUDITH DUFF, EXECUTIVE OFFICER
CAROL LIPSON FIVOZINSKY, BUDGET OFFICER
DR. RUTH L. KIRSCHSTEIN, ACTING DIRECTOR, NIH
DENNIS P. WILLIAMS, DEPUTY ASSISTANT SECRETARY, BUDGET, DHHS
    Mr. Porter. The subcommittee will come to order. We 
continue our hearings with the appropriation for the National 
Eye Institute, and we are very pleased to welcome the dean of 
the Institute directors, Dr. Carl Kupfer.
    Dr. Kupfer, it is always wonderful to see you, and we just 
cannot tell you how much we appreciate the job that you are 
doing there at the Eye Institute, and obviously, we want to be 
as supportive as we possibly can.
    Why do you not proceed with your statement after you 
introduce the people that are with you, and then we will have 
some questions.

                       Introduction of Witnesses

    Dr. Kupfer. Fine. Thanks, Mr. Chairman.
    To my far left is Ms. Judith Duff, Executive Officer, and 
to my immediate left is Ms. Carol Lipson Fivozinsky, who is our 
Budget Officer. To my right is Dr. Jack McLaughlin, the Deputy 
Director, and of course, Dr. Kirschstein and Mr. Williams.

                           Opening Statement

    Mr. Chairman, I would like to start with the fact that the 
National Eye Institute was created in 1968, and I came to be 
its first director in January of 1970. It seems to me it would 
be appropriate to give you a 30-year report, but not take a 
long time to do that.
    I think it is worth just looking at some of the 
accomplishments. In the opening statement that I have prepared, 
we list 12, but I would like to call attention to three or 
four. And what I really think we want to stress is what have we 
done to change the practice of ophthalmology to benefit the 
American public.
    I think our first major contribution has been to decrease 
blindness from diabetic eye disease from 50 percent, when I 
came here in 1970, to less than 5 percent today.
    A second contribution that we really are very proud of 
deals with the inflammation of the optic nerve that occurs 
primarily in young women, and very often leads to multiple 
sclerosis. A recent clinical trial has shown that with 
appropriate treatment, we can not only increase the speed with 
which the vision recovers, but perhaps equally important, 
reduce the recurrence rate, so that patients do not have this 
loss of vision once again.
    A third area is the work done on premature infants with, 
retinopathy of prematurity. We all recognize that although this 
only affects maybe 2,000 infants a year, a blind infant, will 
be blind for 50, 60, 70, 80 years. So it is very, very 
important to have a major impact. We first examined the effect 
of freezing the retina, where the abnormal blood vessels were 
growing, and now we are using the laser and can reduce, by 
almost 50 percent, the rates at which these children will 
eventually lose vision.
    I think these are just some of the success stories, and 
there are many more, that are listed in the opening statement. 
I want to stress that the major results that I find most 
fulfilling are those that result from our clinical research 
activity.
    Now, what are the challenges in the future? Well, the nice 
thing about being successful is that it generates more 
questions and it generates more research opportunity. So what 
are we looking at now? Well, the first area really plays very 
well into what Dr. Collins has just been talking about. Once we 
find the gene, the work has really just begun, because we must 
find out what protein that gene produces, where the protein is 
in the cell, what the normal function of the protein is, and 
what happens when the gene is mutated and produces either an 
abnormal protein or no protein at all. This is the area that 
all the institutes, including ours, are moving ahead very, very 
rapidly at the present time. As the genome project begins to 
fill in the gaps, our job now is to find out what is the normal 
situation and what happens when there is a mutation. So 
functional genomics is going to be a very major thrust of the 
Eye Institute.
    The second area that is very exciting is anti-angiogenesis 
activities of certain drugs on certain naturally occurring 
proteins. The Eye Institute is very well situated for this, 
because the problems that we have with new vessel information 
are in the area of diabetes and the area of macular 
degeneration. We can look into the eye and see these new 
vessels growing, so if we are going to develop agents that stop 
this abnormal growth, we can see it very, very easily by just 
looking into the eye. And just recently some very exciting 
results have come from some agents which stop the new vessel 
development in animal models of diabetes, and I think we are 
going to see, in the next 5 or 10 or 15 years, a major thrust 
in not only preventing blood vessels in diabetic eye disease 
and macular degeneration, but in other areas. It is a very 
important area for cancer research, because of the need for 
cancer to be nourished with blood vessels. If we could turn 
those blood vessels off, that will have a major impact, and of 
course, it is very important in heart disease also.
    A third area is to look at the reason why various racial 
groups respond differently to diseases. African-Americans have 
about a 5- to 6-fold increase in glaucoma and rates to 
blindness are equally high. Hispanics have a very high 
prevalence of complications of diabetes. Asians have a very, 
very high prevalence of high myopia. Now, usually when you 
think of myopia, oh, yes, you put on a pair of glasses and 
everything is all right. But if you have high-myopia, this 
predisposes to retinal detachment and to holes in the macula, 
in which there is a significant loss of visual function and 
sometimes blindness.
    So these are three areas where we are moving very, very 
rapidly forward.
    I want to mention very briefly the National Eye Health 
Education Program. Last year you were interested in the point 
that we were making on having an exhibit in shopping malls, and 
we had our first in Birmingham, Alabama just a couple of months 
ago. It was a great success. You had raised the question 
whether people who go to a shopping mall are more interested in 
shopping and do not want to stop and look at educational 
things. We are told by the owners of shopping malls that the 
shopping mall has now become Main Street, USA, and people go 
there, not only to shop, but to congregate, to attend art 
shows, music festivals, all sorts of activities. And the owners 
of these malls are very anxious to have health fairs and health 
projects introduced. So we are looking forward to this being a 
very effective way of bringing information about diabetes, 
about glaucoma, and now more recently, low vision and what can 
be done about it, to the American people.
    We are very much involved in translational research. We 
like to take things from the laboratory and apply them to the 
clinic, and this is moving ahead very, very rapidly in the 
areas of autoimmune disease and in inflammatory disease.
    And finally, bio-engineering is an area that is suitable 
very much to the visual system, because we are dealing 
basically with an optical instrument, the eye, and the bio-
engineer has many, many techniques to enhance the image that we 
can see. The whole area of adaptive optics is moving very, very 
rapidly.
    The budget request we have for fiscal 2001, the non-AIDS 
budget is $462,776,000, and the budget with the AIDS is 
$473,952,000. I will be happy to answer any questions.
    [The written statement of Dr. Kupfer follows:]



                 COMPUTER CHIP FOR RETINITIS PIGMENTOSA

    Mr. Porter. Has there been a development in respect to 
retinitis pigmentosa that involves the implantation of a 
computer chip? Can you describe that to us?
    Dr. Kupfer. Yes, sir. There has been great interest in 
trying to introduce visual stimuli that are translated into 
electrical impulses that would stimulate the remaining cells in 
the retinas of patients with retinitis pigmentosa.
    Although the cells that capture the light have usually 
disappeared in retinitis pigmentosa, the cells that directly 
connect the eye with the brain still appear to be present and 
normal. So the idea is that if you can stimulate these cells 
with images, then an individual might be able to see general 
shadows, general shapes, nothing that is going to enable the 
individual to read, but perhaps be helpful in ambulating, 
getting about.
    The latest development has used a small video camera 
mounted on a pair of glasses, and the video camera translates 
the light that comes in to a series of electrical impulses 
which then goes through a small implant that either can be 
positioned on the retina, or what has been done up to now, 
several fine wires from the implant actually sit on the retina 
for short periods of times. And when that video camera is 
exposed to a letter or an object, the individual can ``see'' 
certain areas of darkness and light. And I think this is really 
the first step to--if you will--provide proof of principle, 
that, yes, you can stimulate a retina of a patient with 
retinitis pigmentosa, yes, there can be some visual result, and 
yes, this is a feasible approach.
    The approach up to now has always been to try to stimulate 
the brain directly, what is called the visual cortex. That is 
fraught with many, many complications, so I think the fact that 
the area has moved into a situation where the retina is 
stimulated directly is a major step forward. We have just 
funded a very major program which will involve four or five 
centers throughout the United States to work on this project in 
the animal, and perfect it. And the interesting thing about 
this is that it is not only a multi-center study at about $2 
million a year, but it is going to have matching funds from a 
private donor organization to enhance the effectiveness of this 
project. So we are moving very rapidly. This is a good example 
of bio-engineering application.
    Mr. Porter. Just to clarify something, when you said 
``high-myopia,'' that would be severe myopia; is that correct?
    Dr. Kupfer. Yes, sir.
    Mr. Porter. Very, very poor far vision.
    Dr. Kupfer. That is correct.

                           FUNDING INCREASES

    Mr. Porter. Is it possible for you to tell us what projects 
you have been able to pursue by reason of having larger 
increases than the Administration has suggested for the past 
two years, that you would not have been able to pursue if you 
had not had that money? This is sort of another way of seeing 
whether the money is well spent.
    Dr. Kupfer. Right. Well, I think the first thing I would 
like to mention is that we have been doing program planning 
since 1972, and we are in our sixth iteration. Our plan is 1999 
to the year 2003, so we are basically in the second year. We 
lay out, every 5 years, where the research opportunities are, 
and where the needs are and try to match those two up. So that 
what we now are able to fund has sort of been identified by the 
vision research community itself, and looked at by a number of 
organizations representing scientists, representing lay people 
who are advocates of various diseases.
    The area of trying to determine what genes do normally and 
what happens when they are mutated is an area that we are 
moving into, and could not have moved into without increased 
funding, because the technology is important, very expensive, 
and the computer requirements are very intensive. As Dr. 
Collins pointed out, the need to marshall large numbers of 
people to collaborate on these types of projects is great. We 
have got to supply resources in terms of reading those chips. 
As Dr. Collins said, you can run the chip in the afternoon, but 
the analysis may take months. So this is a very expensive, 
intensive type activity, and we are really able to move into 
this area because of the resources that are being made 
available.
    The whole area of angiogenesis is going to take tremendous 
effort and resources to develop a whole host of new drugs and 
new therapies to prevent the development of these abnormal 
vessels. This is a very important determinant of preventing 
diabetic eye disease, not to treat it, but to prevent it, and 
to prevent macular degeneration, the wet type, which is what 
usually causes the blindness.
    The area of bio-engineering is going to require major 
expansion. I mentioned the adaptive optics. This is a new 
technology introduced from astronomy, interestingly enough, 
because the astronomers have trouble when there is a lot of 
turbulence in the atmosphere. The light from the stars become 
distorted, so the light, which consists of many, many 
wavelengths, does not reach the telescope at the same time. 
There is distortion. What has been developed is a telescope 
mirror and lens system which actually can change its curvature 
in response to the aberration in the light coming in. In other 
words, you want the light to come in as a straight plane, but 
if it is distorted, the mirror and the lens will distort in the 
opposite direction to correct for that. This has now been 
picked up by bio-engineers, who are incorporating it into 
instruments to view the back of the eye.
    And just to give you an idea of the technology, the photo 
receptors, the little elements that capture the light, are 
about 3 microns across in diameter. A red cell is about 8 
microns, so you could probably fit about 3 of these in a red 
cell. You know how small the red cell is. And we can now 
visualize these photo receptors individually with great 
clarity. So this gives you an idea of the potential of 
harnessing bio-engineers to biological problems, and I think 
this whole area is going to open up. Without additional funds, 
we would not have been able to move in this direction.

                        ADDITIONAL OPPORTUNITIES

    Mr. Porter. Dr. Fauci this morning was able to say--and I 
am not sure this is a fair question--he was able to say that he 
felt that in his area we were funding perhaps 50 percent of the 
good science that was available. Are you able to quantify that 
in any way, or even give us a feeling about the availability of 
good science and the chance with increasing funding of doing 
better?
    Dr. Kupfer. We have five programs. We have a program in 
corneal disease, in cataract, in glaucoma, in retina, and in 
the central nervous system. The last two, retina and central 
nervous system, account for about 70 percent of all our 
funding. We, at every single Council meeting, with Council 
members, agonize over the fact that there are insufficient 
funds to fund the best science that is there.
    Vision research tends to attract people outside vision 
research when there are new research opportunities, and 
bioengineering is a good example. It is just suited to the 
study of the visual system. So we are seeing people coming in, 
excellent researchers, who want to begin on problems in the 
visual system and we do not have sufficient funds, despite the 
fact that almost all our funds extramurally, as you well know, 
go to the individual investigator-initiated research grants. We 
do not fund large center grants. We do not fund large program 
projects. We have a very small contract program. We put our 
money into the individual researcher. And even despite that, we 
are falling short of being able to fund the very best 
researchers.
    I think we could easily move our funding rate up to 50 
percent and still fund the very, very best research that is 
being done in any field.
    Mr. Porter. Dr. Kupfer, members of Congress need to know 
this. Obviously when you increase any institution or program as 
rapidly as we have, questions are immediately raised: Is the 
money being well spent? How can it possibly be well spent? 
Somehow the Directors need to send a message to members that, 
in fact, it is and there is even more out there that is going 
unfunded that is good science and they need to know that.
    I do not know how we can do that, Ruth. I am looking at Dr. 
Kirschstein here as I talk to you. We really need to get the 
message into their minds.
    Dr. Kirschstein. We are working on some plans.
    Mr. Porter. Good.
    Dr. Kirschstein. One of the things we want to do is involve 
the director of the Center for Scientific Review, who gets an 
overall picture of the kinds of grant applications that are 
received and who can elucidate quite well what she thinks is 
left over by the peer review groups, and we are going to work 
on that.

                        MYOPIA AND NIGHT LIGHTS

    Mr. Porter. Left unfunded, yes.
    There was an article in USA Today back in May that talked 
about in an NEI-funded study that found the rate of myopia or 
nearsightedness was higher among children who had slept with a 
light on. Is this so and what are the implications?
    Dr. Kupfer. I would like to answer that at two levels. 
First of all, the research was actually stimulated by some very 
interesting observations in animals, especially chickens. If 
the light is kept on 24 hours a day, seven days a week, the eye 
of the chicken will slowly become larger and larger and the 
chicken will become myopic. That is a fact. Everyone agrees to 
that.
    Now what these investigators did at the University of 
Pennsylvania, very cleverly, was to look at a group of children 
who they had been examining, some who were myopic, some who 
were not, and they asked the parents whether the child slept 
with a light on in the room when they went to sleep, whether 
the light stayed on for an hour or two, or whether it stayed on 
all night long.
    And based upon that, they concluded that there appeared to 
be more children with myopia in which the parents had kept the 
light on all through the night.
    This is very, very interesting, but when you do an 
experiment like this where the design of the experiment was not 
to ask the question is light causing the development of myopia, 
you can sometimes be led astray.
    For instance, it may be that parents who would tend to have 
more myopia amongst themselves and for whatever reason may be 
from a different group would tend to keep the light on and, of 
course, their children will tend to have a higher amount of 
myopia, unrelated to the light being on but due to the fact 
that the parents have myopia. There are many other confounding 
variables.
    Now, there will soon be publications by two other 
investigators using the same technique with the same flaws who 
will not be able to confirm this. But what we want to see is a 
controlled clinical trial done where we can really get the 
answer in the appropriate way, and I think we will slowly move 
in this direction.

       LIGHT-ACTIVATED DRUG FOR AGE-RELATED MACULAR DEGENERATION

    Mr. Porter. At this time last year there was a light-
activated drug being tested that might slow down vision loss 
due to age-related macular degeneration. Is it anticipated that 
this drug could be available within a year? Can you tell us the 
status of this? And is there currently available anything to 
slow the process of vision loss, either a drug or behavioral 
treatment, for patients with AMD?
    Dr. Kupfer. Yes, Mr. Porter. This is a dye that is actually 
injected into the blood vessels and if there are abnormal 
vessels, such as there are in macular degeneration, one can 
then use a laser that will activate the drug which is in these 
abnormal vessels. The drug will release poisons that will cause 
the wall of the vessels to trap platelets and a clot will form 
and the blood supply will be turned off to that cluster of 
vessels. And this works; there is absolutely no doubt about it.
    The problem is that the clot eventually will reopen and 
another treatment must be required in two or three months. 
However, it still is very effective in about 15 to 20 percent 
of patients with this wet type of macular degeneration. The 
FDA, just last month, issued a letter of intent saying that 
they were going to consider approving this and I think it will 
be approved within the next month or two.
    So this again is another approach to the treatment of 
macular degeneration. It is not perfect but for those who would 
be eligible for this and who are willing to undergo treatment 
every three or four months, it can maintain good vision.

                               CATARACTS

    Mr. Porter. If you look at cataract surgery, it is a major 
component of the cost of Medicare Part B and presumably as we 
live longer, it is likely to grow as time goes on. Is there any 
new treatment on the horizon that might bring that cost down or 
make it simpler than it is today?
    Dr. Kupfer. Well actually, the reimbursement for Medicare 
for cataract surgery has come down considerably as----
    Mr. Porter. I know. I am talking about on the technical 
side.
    Dr. Kupfer. We have a very high priority of trying to find 
out how to slow down the development of cataracts. We would 
settle for slowing it down because we know if we could slow it 
down just by 10 years, we would reduce the number of cataract 
operations by 50 percent, so that would be a major impact.
    We have a number of very good researchers, but I cannot say 
at this time that we have had any major breakthrough that is 
going to be helpful. Now, this may happen tomorrow or next week 
or next month.

                       VISION CORRECTION SURGERY

    Mr. Porter. We talked last time you were here about radical 
keratectomy. Am I pronouncing it correctly?
    Dr. Kupfer. Radial keratotomy.
    Mr. Porter. Radial keratotomy. We talked about how safe it 
was and you assured us it was a fairly safe procedure.
    My question, and I may be seeking free medical advice here, 
but my question is, if a person, an older person, has this 
procedure to correct myopia, what effect does this have upon 
the problem of reading and the hardening of lenses?
    Dr. Kupfer. Well, Mr. Porter, there are a number of 
operations now. Radial keratotomy, which I think you are 
referring to, is the first operation that was developed. That 
has now been----
    Mr. Porter. That is not what I am referring to. I am 
referring to the LASIK surgery.
    Dr. Kupfer. LASIK; that is correct. And the LASIK operation 
is being done; I think it is very rapidly approaching a million 
operations a year. It is considered both safe and effective by 
the FDA that has reviewed the data, but you put your finger on 
a very important point. That is that those of us who reach the 
age of 45 notice that we need reading glasses, except if you 
are very nearsighted. Then all you have to do is take your 
regular glasses off and you read perfectly well.
    Well, if you are nearsighted and you have an operation done 
like LASIK and then your eye is corrected for distance, you are 
now going to have to use reading glasses.
    So it is very important to realize that you cannot throw 
your glasses away. You are just exchanging glasses that you 
must wear for distance for glasses you must wear for reading.
    Mr. Porter. So it has no effect upon that problem.
    Dr. Kupfer. That is correct.

                             COLLABORATIONS

    Mr. Porter. Interesting.
    I was interested as you gave your opening statement how 
much effect the health of the eye has in respect to other 
health problems and you described some of them. What kind of 
collaborations do you have, for example, with NINDS and the 
National Institute of Mental Health on brain function and 
neurology and the eye? Are there any projects that are going on 
now?
    Dr. Kupfer. Well, this is a very interesting question 
because I have had discussions with Dr. Fishbach, the director 
of NINDS. There is a tremendous amount of overlap in what our 
interests are and they are complementary. They are not 
duplicative.
    Let me give you an example. We are very much interested in 
damage to the optic nerve. We can take the cells that make up 
the optic nerve--the cell body is in the retina and the ending 
is in the brain--and we can grow these cells in tissue culture. 
These are the only cells of the central nervous system today 
that can be grown in media that is free of all other enzymes or 
hormones or any growth factors. We can study what keeps these 
cells alive, what is needed. For instance, they will not stay 
alive unless they are stimulated electrically and there are 
certain enzymes that must be present. We learned this.
    Those cells are the equivalent of the cells in the spinal 
cord. So what we learn about the optic nerve is directly 
translatable to the spinal cord and vice versa. Some of the 
most interesting experiments about regeneration have been done 
in the spinal cord and those experiments are translatable to 
the optic nerve.
    So in that sense we are working in parallel with very good 
cross-talk, if you will.
    I was having a discussion with Dr. Fischbach about the fact 
that one of the things we know in Parkinson's disease is that 
if in an experimental animal like a monkey that is alert and 
awake--and this is a technique that is used in a number of 
laboratories; it was begun in our intramural laboratory by 
people who were trained to do this--you can selectively and 
reversibly inhibit that part of the brain that makes dopamine, 
the substantia nigra. You can just inhibit it for two or three 
hours, and the monkey will show certain eye movements which are 
characteristic of Parkinson's disease. And, of course, as the 
inhibition wears off, the normal movements will return.
    Now, this seems to be a very interesting model to develop 
further and see whether we can monitor eye movements in 
Parkinson's because it is very, very difficult to make the 
diagnosis in early Parkinson's, and this may be a very 
effective way. So discussions are being held with Dr. Fishbach 
along these lines.
    I would say that I know we all talk about trans-NIH 
activities. I think all the things that each institute does are 
trans-NIH. Back in the mid-1980s we had an investigator who was 
looking at the gene-causing retinoblastoma, which is a tumor of 
the eye. They isolated the gene, the RB gene, which was the 
first gene to be shown to prevent cancer as long as it was 
present but allowed cancer to develop if it was absent. That 
had a major impact on the whole area of cancer biology.
    Equally, the cancer community has come across treatments 
for graft rejection which we are now using to treat uveitis in 
the eye. So there is a tremendous amount of trans-NIH activity 
going on all the time. I think it is only going to increase 
because our problems are becoming more complex.

                          CONGENITAL NYSTAGMUS

    Mr. Porter. I am going to try to pronounce this correctly. 
Congenital nystagmus is a condition where the eyes oscillate 
continuously and uncontrollably, which begins at birth or early 
infancy. I understand NEI is conducting a phase one clinical 
trial in humans on a surgical procedure that has been shown to 
decrease nystagmus and improve visual function. Are infants 
included in this clinical trial and is there a difference in 
brain behavior as patients with this condition mature?
    Dr. Kupfer. The condition of congenital nystagmus is a 
problem because with the eyes continually moving, the visual 
acuity for distance is usually not very much better than 20/
200, which means you can barely see the top letter on the 
chart.
    We have begun a phase one/phase two study of an operation 
which has been shown to be effective in a group of dogs that 
are born with congenital nystagmus. It reduces the nystagmus 
and from a behavioral point of view, appears to enable them to 
see better.
    We have begun the study, to do the operation, first in 
adults to be absolutely certain that it is safe to do. As soon 
as the Data and Safety Monitoring Committee is convinced of 
that, and they are the people who are watching the results of 
this study, we will then probably move to children over the age 
of six.
    Now, it is important to move to children because if we are 
really going to effect the reduction of this congenital 
nystagmus, the earlier we do it, the more flexible the brain 
will be in being able to respond to any surgical intervention.
    So eventually we will move to children, but I think at 
first we will say age six and over and then gradually lower the 
age if we find it to be successful.
    Mr. Porter. Dr. Kupfer, thank you for your testimony.
    I was thinking as Dr. Kupfer was answering the questions 
and before in his opening statement, Dr. Kirschstein, that if 
we videotaped these sessions and got Members into a theater 
situation and showed them the testimony, they would be as 
excited about the developments in biomedical research as the 
Members of this subcommittee are and I think we would not have 
any problem getting the increase in funding.
    Dr. Kirschstein. You get the Members; we will do the 
videos.
    Mr. Porter. Getting the Members is a little more difficult 
than doing the videos. But it is absolutely fascinating to see 
all the wonderful developments over which you are presiding and 
to understand the depth of the connections in human health that 
involve the eye, which is rather amazing, I think.
    And, as I said before, I have benefited greatly all these 
years. I had not realized that you had been--I knew you were 
here before I was here. I have been here 20 years now but you 
were here 10 years before I was here. That is a wonderful, 
wonderful----
    Dr. Kirschstein. He preceded me by four.
    Mr. Porter. By four.
    Dr. Kupfer. Mr. Porter, I want to add my voice to thanking 
you for the energy and the understanding that you have had of 
what we are doing at the National Institutes of Health and your 
fantastic support.
    Mr. Porter. Well, Dr. Kupfer, I was going to thank you 
because I have benefited more than anyone. I really stand in 
awe of the work that you do at the Eye Institute, at all the 
Institutes. It is just amazing, the progress that has been and 
is being made. If only Members of Congress knew about it 
better, again we would have no problems.
    So thank you so much for the outstanding work that you do.
    We stand in recess until 10 a.m. tomorrow.
    [The following questions were submitted to be answered for 
the record:]



                                          Wednesday, March 8, 2000.

                         OFFICE OF THE DIRECTOR

                               WITNESSES

RUTH L. KIRSCHSTEIN, ACTING DIRECTOR, NIH
YVONNE T. MADDOX, ACTING DEPUTY DIRECTOR, NATIONAL INSTITUTES OF HEALTH
NEAL NATHANSON, DIRECTOR, OFFICE OF AIDS RESEARCH
JOHN RUFFIN, ASSOCIATE DIRECTOR FOR RESEARCH ON MINORITY HEALTH
VIVIAN W. PINN, ASSOCIATE DIRECTOR FOR RESEARCH ON WOMEN'S HEALTH
DENNIS P. WILLIAMS, DEPUTY ASSISTANT SECRETARY, BUDGET, DHHS

                            Opening Remarks

    Mr. Porter. The Subcommittee will come to order.
    We're pleased to have Dr. Ruth Kirschstein, the Acting 
Director of NIH, to head a panel that I'm going to allow her to 
introduce. This is our last hearing on NIH budgeting.
    I would inform members of the audience that I have also 
asked Dr. Kirschstein to bring with her Dr. Francis Collins, 
who will be back about 4 o'clock to address some questions that 
we have about gene research that has been discussed recently in 
the press. So Dr. Collins will be able to talk to us about that 
as well.
    Dr. Kirschstein, we're going to have votes shortly, so 
we're going to try to get as far as we can along.

                       INTRODUCTION OF WITNESSES

    Dr. Kirschstein. Thank you, Mr. Chairman.
    And we're going to have a panel at this last session. I 
want to introduce the members at the table. We will start with 
Dr. Neal Nathanson, who is to my far left and will be 
presenting the Office of AIDS Research. Then when we have time, 
Dr. Yvonne Maddox, whom I personally chose as my Acting Deputy 
Director, will present the Office of the Director. And I will 
then present the request for buildings and facilities.
    Dr. Vivian Pinn, the Director of the Office of Research on 
Women's Health and Dr. John Ruffin, the Director of the Office 
of Research on Minority Health, are also here because I think 
there will be members of the Committee who wish to speak to 
them specifically. And I have my colleagues from the Office of 
the Director behind me to help us with the questions.
    We'll start with Dr. Nathanson.

             BUDGET REQUEST FOR THE OFFICE OF AIDS RESEARCH

    Dr. Nathanson. Thank you.
    Mr. Porter, members of the Committee, I am pleased to 
present the President's request for the Office of AIDS Research 
for fiscal year 2001. And before I begin, I also want to join 
the many other directors of NIH institutes and centers in 
thanking you and the whole Committee for your stalwart support, 
not only of the whole of NIH, but also for the AIDS research 
program.
    I am going to speak from these boards, so if you don't 
mind, I'll stand up and speak from there.
    This year, I would like to focus on two major issues in my 
presentation to the Committee. I'll try to speak loudly so you 
can all hear me. One is the global situation and particularly 
in the developing world, the impact of the AIDS pandemic. The 
other is the AIDS epidemic in the United States and its impact 
on minority communities and the health disparities, which this 
reflects. I will start off by reviewing briefly some facts that 
you're all generally familiar with, namely the AIDS epidemic, 
which in fact drives our research programs. Then I will turn to 
some of the research programs themselves.
    [The information follows:]



                             AIDS EPIDEMIC

    Dr. Nathanson. This first board shows, for sub-Saharan 
Africa, which is the epicenter of the global epidemic, exactly 
how severe the epidemic has become. There are now over 20 
million individuals living with HIV or AIDS [Figure 1]. And of 
course, there are 10 to 15 million in this area who have 
already died of AIDS.
    This pandemic is so severe that in one of the recent 
reports from Senator Durbin, who recently returned from Africa, 
he referred to one of the countries as ``a nation turned 
hospice,'' which says it all. For the first time in January, 
the U.N. Security Council recognized a disease, namely the AIDS 
epidemic, as a security risk. So clearly, this is the biblical 
plague of our times.
    [The information follows:]



    Dr. Nathanson. Now, turning to the United States, we have a 
somewhat different situation. Compared to 4 million new 
infections a year in Africa, we're talking about 40,000 in the 
U.S. [Figure 2]. But there are two problems here. The first to 
which Dr. Fauci made reference last week, is the fact that the 
number of new infections per year, which is the most important 
index of our public health success, has remained constant for 
almost 10 years. This should really be considered a public 
health failure. To get this disease under control, we should be 
reducing the number of new infections each year.
    Another reflection is that we have approximately 800,000 
individuals living with HIV or AIDS in the United States, all 
of whom under present circumstances will eventually die of this 
disease, because at present we do not have any cures.
    [The information follows:]



    Dr. Nathanson. The other problem that we face in the United 
States is shown on the next board [Figure 3], namely, the fact 
that the AIDS epidemic in fact is not static. I'm sorry that 
Mr. Jackson can't see this board, although you are aware of all 
the facts. The AIDS epidemic is moving more and more into our 
minority communities. Over two-thirds of those affected with 
AIDS each year are from the minority communities. In addition, 
of course, women are much more affected now, representing about 
25 percent of the new cases of AIDS.
    [The information follows:]



    Dr. Nathanson. When you look at the incidence of new 
infections, the discrepancies, the health disparities, are even 
more extreme [Figure 4]. On the left, African-American men and 
women, in the middle, Hispanic men and women, and on the right, 
the white population. Certainly, this is a very dramatic 
demonstration of a health disparity that has, in fact, been a 
major theme in developing our research programs.
    [The information follows:]



                         AIDS RESEARCH PROGRAMS

    Dr. Nathanson. Now, I want to turn to the research programs 
themselves. I would like to focus first on our therapeutics 
program [Figure 5]. I will have to be quite brief here, then of 
course I'll be glad to answer questions. In therapy, we are 
continuing to invest a large amount of money in the development 
of new targets and new drugs. This program is the one that gave 
rise to the drugs we presently have.
    But turning to the clinical application, we have run into 
two major problems, to which Dr. Fauci also alluded. The first 
is that although we have a very effective group of drugs called 
highly active anti-retroviral therapy, these have failed to 
cure infections and eliminate the virus. That has meant that 
individuals who are under therapy must continue indefinitely.
    This has led to the discovery that there are many side 
effects and other problems, such as drug resistance, and 
there's also a problem of adherence or compliance. It's very 
difficult for people to take these drugs, a very complicated 
and expensive regimen, for many, many years. That's led to a 
whole paradigm shift, or an additional set of clinical trials 
that focus on issues like when to start therapy, what drugs to 
use.
    But the third point down here which I want to emphasize is 
one that impacts particularly on minority communities, namely 
that the application of optimal therapy is not equal throughout 
the United States. In one survey, approximately 25 percent of 
people were estimated to be getting less than optimal 
treatment. So we are also supporting research efforts that are 
focused on trying to reduce this health disparity, including an 
outreach to minorities and training of minority investigators.
    [The information follows:]



    Dr. Nathanson. Turning now to prevention, of course, that's 
the ultimate approach to an infectious diseases, and this 
summarizes a great deal of work in many, many programs [Figure 
6]. The essence of prevention is starting with an infected 
individual, to prevent transmission to an uninfected 
individual. Our programs, and I don't have time to go into all 
of them specifically, partly attack the various ways in which 
we can reduce the possibility or the probability or the 
likelihood that an infected individual will transmit to an 
uninfected individual. Then we have a set of approaches that 
are designed to protect the uninfected individual, again using 
a variety of approaches.
    [The information follows:]



    Dr. Nathanson. Of course the ultimate prevention technique 
is a vaccine. My last board focuses on vaccines [Figure 7]. Our 
progress there is incremental. It is substantial but slow. This 
just epitomizes one piece of the research program, namely an 
animal model, where we can quickly test vaccine candidates. 
What this shows is the amount of virus in the blood of a monkey 
infected with a simian AIDS virus that will in fact develop a 
counterpart of human AIDS. And by contrast, the effect of a 
vaccine which reduces progression to AIDS and also reduces the 
amount of virus, although it doesn't give absolute protection.
    [The information follows:]



    Dr. Nathanson. Now, I would like to summarize by returning 
to the global picture and pointing out that our program really 
focuses primarily in two major areas [Figure 8]. First of all, 
the developing world, particularly sub-Saharan Africa, where 
approximately 95 percent of all AIDS cases and infections take 
place. There our focus is on prevention including perinatal 
prevention that Dr. Fauci described, but moving on to 
prevention of heterosexual transmission and of course, 
increasingly, vaccine trials.
    In the United States, where 800,000 to 900,000 people are 
living with HIV and AIDS, our focus is on trying to go where 
the epidemic is to deal with health disparities and also to add 
to a prevention agenda a major investment in improved therapies 
and new therapies. But also with considerable attention to 
making sure that these are delivered where the epidemic is, 
which is increasingly in our minority communities.
    We thank you again for your support, and of course, I'd be 
pleased to answer your questions.
    [The prepared statement follows:]



             BUDGET REQUEST FOR THE OFFICE OF THE DIRECTOR

    Dr. Kirschstein. We're going to ask Dr. Maddox now to 
present the Office of the Director's budget.
    Dr. Maddox. I'm pleased to present the President's fiscal 
year 2001 budget request for the Office of the Director of the 
National Institutes of Health. This is the first time that I've 
had an opportunity to come before this Committee to provide 
testimony, and I welcome the opportunity to do so.
    Mr. Porter, I too would like to join my colleagues in 
thanking you for all your efforts under the auspices of this 
Committee. We really appreciate all that you've done on behalf 
of the American people and I thank you on behalf of the 
National Institutes of Health.
    As you know, the Office of the Director provides leadership 
and coordination related to the research activities of the 
entire agency, both the intramural and the extramural programs. 
Thus, the OD is the entity that's responsible for the 
management of the essential centralized services, programs and 
functions. In addition, the OD is responsible for a number of 
special research programs and offices established within its 
purview.
    The President's fiscal year 2001 budget request for the OD 
is $262.5 million, an increase of $25.2 million over the fiscal 
year 2000 appropriations, not including AIDS, of which Dr. 
Nathanson has already addressed.
    I should mention that the specific budgets for each of the 
offices that come under the purview of the OD are contained 
within this budget request. The specific dollar figures are 
each within the entity and also these can be found in the 
justification document, as well as a description of each 
individual office. I've also added some specifics of the 
offices in my written statement.
    Thus, I would like to take the few minutes left to me to 
highlight some of the accomplishments of the offices that come 
under the Office of the Director of the National Institutes of 
Health. I have sat and listened attentively at these hearings 
and have heard members of this Committee speak about the 
importance of engaging youngsters early in life in the science 
arena. And particularly, we've heard that there is a role for 
NIH in this. And also, that there's a role for NIH in making 
the public more aware of what NIH is and what NIH does.

                      OFFICE OF SCIENCE EDUCATION

    I'm pleased to present to you some of the activities that 
come within the purview of the Office of the Director, and 
specifically, some of the activities that have been coordinated 
through the Office of Science Education. I'm pleased to have 
Dr. Bruce Fuchs here with me today, who is helping in the 
display, but, also, he is the director of that office. You have 
at your place settings some of the specific brochures that have 
come out of this office.
    [The information referred to follows:]



    Dr. Maddox. I'm using this simple poster [Figure 1] to 
illuminate and to speak to you about some of the special 
programs that we have put in place over the last year. In the 
area of science education, we're very much interested in 
developing curriculum that will assist teachers as well as 
parents in educating children early on. Here, we're speaking to 
a curriculum supplement series that we developed that serves 
the kindergarten as well as through 12th grade programs. These 
supplements were developed with the Office of Science 
Education, but not in isolation. The Office of Science 
Education works with the Office of Research on Women's Health, 
the Office of Research on Minority Health, the ICs and 
specifically works with the scientists in the community as well 
as the teachers to develop these series.
    The series that you have in front of you is a series that 
we have developed for grades 9 through 12. But on the left 
here, you'll see a new series that we are developing for 
youngsters in grades first and second. This series will be 
available to the teachers and the community beginning in late 
fall.
    We also believe in and agree with everything that this 
Committee has said to us as it relates to our role in educating 
the adult public. And specifically, we're talking about the lay 
as well as the professional public. The Office of Science 
Education has also worked with scientists and experts in the 
community to develop a mini-med school. This is a program in 
which we actually design curricula as well as lecture series 
that we present on the NIH campus. We're now working with 
universities and colleges around the country to assist them in 
developing their own mini-med schools.
    Another attraction that the Office of Science Education has 
been very active in producing has been something that we call 
our science in the cinema series. And this series has allowed 
us to bring more than 15,000 participants to the NIH campus to 
visualize films that have a medical or research theme. We bring 
in expert scientists who actually introduce the films and are 
available for discussions of the films later.

                         LOAN REPAYMENT PROGRAM

    The reason I bring up this whole business of cultivating 
medical researchers is because it's important not only to plant 
the seeds of medical research, but also to support the plants. 
This other mechanism that I'm bringing to your attention is our 
loan repayment program. The loan repayment program is a program 
that is right now, for the most part, a program that's 
conducted through the intramural program at NIH.
    This program allows us to provide loan repayment to 
clinical researchers, undergraduate scholarships for 
disadvantaged students. We also have a loan repayment program 
for individuals who come to the NIH who want to work in AIDS 
research, and we have a general research loan repayment program 
for individuals who want to do clinical as well as basic 
research.
    For the fiscal year 2001 budget request, you will also see 
$1.4 million requested to bring a loan repayment program to the 
extramural program. This would be specifically to develop a 
clinical research loan repayment program for the extramural 
scientists.
    Mr. Porter. Dr. Maddox, I'm sorry to interrupt you, but 
we're going to have to go vote, and take a short recess. Then 
we'll be right back. Time is running out.
    The Subcommittee will stand in recess for the votes.
    [Recess.]
    Mr. Porter. Now, then, please proceed.

              ACADEMIC RESEARCH ENHANCEMENT AWARD PROGRAM

    Dr. Maddox. I'd like to finish this segment on cultivating 
medical researchers by spending some time talking to you about 
the AREA research program, or the Academic Research Enhancement 
Award Program. This program is designed to support research at 
institutions that are less research intensive. So here we're 
talking about the smaller universities that don't have an awful 
lot of NIH funding. For fiscal year 1999, the OD provided 
support for 164 of these awards to various programs around the 
country for an amount of about $16.5 million. We're requesting 
as part of the President's budget request $17.3 million to 
advance and enhance this program.
    We do feel that smaller institutions and colleges need to 
be involved in our research endeavor, and specifically as it 
relates to cultivating researchers. Because many of the 
researchers do go to the smaller institutions.
    [The information follows:]



                           HEALTH DISPARITIES

    Dr. Maddox. Each of the institute directors who has come 
before you at this hearing, as well as Dr. Kirschstein, when 
she began her opening remarks, spoke to you about how NIH plans 
to address the issue of health disparity. I bring this chart 
[Figure 2] to your attention, there are copies of it at your 
places. I will say that the NIH certainly is committed to 
addressing and eliminating health disparities.
    But we plan to do more than just develop a strategic plan. 
You've heard many of the institute directors speak about the 
trans-NIH working group made up of IC directors and how this 
group will be working to devise their own individual strategic 
plans as well as to come up with an NIH plan that will then be 
overseen by Dr. Ruffin and his office, as well as Dr. 
Kirschstein. It is important to have a research agenda as part 
of our plan.
    We believe that NIH, being a premier research enterprise, 
needs to do more than just establish a research initiative. We 
need a program of action. In looking at this poster, you can 
see that we are planning to put together a real effort here to 
recruit and train more minorities to go into research 
investigations. We also plan to do more in the community 
outreach phases and to enhance public awareness of the NIH 
programs that are directed toward research in minority 
communities.
    We're going to work hard to include more minorities in the 
rank and file, as well as to include more minorities in peer 
review groups as well as in conferences. And when we talk about 
enhancing the public awareness, we believe that this is a time 
for us to be more proactive, and we have a health fair that's 
coming up in June, on the 2nd and 3rd. We will be focusing 
specifically on health disparities at this fair.
    We also believe that we could be doing more in building 
bridges and partnerships between the various institutions, both 
the Hispanic serving institutions as well as the historically 
black colleges and universities and the tribal colleges, and we 
will be stepping up our activities in those arenas.
    Last, but not least, we believe that we need to do more in 
defining health disparities and then being able to code, to 
track, to analyze and to evaluate the progress and results that 
we have. This would be important for us in budget 
considerations, but also in informing the public about what NIH 
is doing in this area.
    We believe that this is an important time for the agency. 
We think we've learned a lot over this last year in particular, 
as it relates to issues surrounding health disparities. And we 
think the time has certainly come for us to be addressing this 
and aggressively approaching solutions.
    Thank you, Mr. Chairman.
    [The prepared statement follows:]



    Mr. Porter. Thank you, Dr. Maddox.
    [The following questions were submitted to be answered for 
the record:]



                                          Wednesday, March 8, 2000.

                        BUILDINGS AND FACILITIES

                               WITNESSES

RUTH L. KIRSCHSTEIN, ACTING DIRECTOR, NIH
YVONNE MADDOX, ACTING 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
SUSAN QUANTIUS, ASSOCIATE DIRECTOR FOR BUDGET, NATIONAL INSTITUTES OF 
    HEALTH
DENNIS P. WILLIAMS, DEPUTY ASSISTANT SECRETARY, BUDGET, DHHS

              BUDGET REQUEST FOR BUILDINGS AND FACILITIES

    Dr. Kirschstein. Mr. Porter, I'm now going to speak to the 
Buildings and Facilities Request. Our scientists have to have a 
safe and efficient set of operating facilities, facilities 
which continually evolve to meet the changing demands of the 
new facets of science and technology. So our B&F program 
involves a multi-year planning process, of requirements not 
only for new facilities, but for facilities improvements and 
for essential maintenance. And I want to describe these to you 
by four examples.
    First, we are, through the generosity of this Committee, 
halfway through the construction of the new Clinical Research 
Center. We're carefully planning the occupancy, for 2003, of 
this wonderful, new modern hospital and clinical research 
facility. We're excited by the great opportunities that 
clinical research can provide to us through our modern 
surgical, imaging and day care facilities.
    But its activities must be and will be, through further 
careful planning, fully integrated into the research programs 
of the rest of the NIH intramural activities.
    Second, as you heard the other day from Dr. Fischbach, we 
will be creating a national neurosciences research center on 
the NIH campus. This is needed because the area of neuroscience 
is rapidly expanding through collaborations, to name but a few, 
among basic neurobiologists, neurophysiologists, behavioral 
scientists and neurochemists, along with clinical researchers 
in neurology, neurosurgery, brain imaging and the sciences 
related to addiction, aging, communications disorders and 
ophthalmology. And there are many other areas as well.
    We are asking to be able to have this new facility where 
interactions can occur naturally and easily and where there 
will be modern equipment, imaging facilities and laboratory 
space that can be shared. We're requesting $47.3 million for 
fiscal year 2001 and an advanced appropriation of $26 million 
for fiscal year 2002 for the first phase of this neuroscience 
center. It is going to provide us with opportunities for major 
advances in many diseases: autism, mental illness, alcoholism, 
drug abuse, Alzheimer's and Parkinson's disease, and 
depression.
    Third, our current central facility to house animals is a 
one story complex which has long been outmoded and totally 
inadequate to sustain the new technologies and needs of modern 
American animal research. Animal models are becoming more and 
more important to elucidate all aspects of human disease and to 
develop new diagnostics and therapeutics. The fiscal year 2001 
request is for funds to develop schematics and the design of a 
central vivarium which will have a state of art modern animal 
holding and quarantine facility.
    Finally, fourth, in order to assure that our scientists and 
staff throughout the NIH facilities, but particularly on the 
NIH central campus, can perform their important duties and be 
creative and productive, we must provide them with safe, 
healthy, comfortable and efficient facilities. This is assured 
through the general repair and improvements programs for 
physical facilities and utilities and by the renovations as 
needed.
    The request for the buildings and facilities program is 
$148.9 million.
    With that, the presentations are completed, and my 
colleagues and I will be pleased to answer questions.
    [The prepared statement follows:]




    Mr. Porter. Thank you, Dr. Kirschstein.
    Dr. Collins has returned just this moment. Before I call on 
him, I just want to say, Dr. Maddox, that was your first 
presentation before this Subcommittee, if I am correct, is that 
right?
    Dr. Maddox. Yes.
    Mr. Porter. Very, very impressive job. You did a wonderful 
job. I'm very impressed with how you handled that. Thank you.
    Dr. Maddox. Thank you, Mr. Chairman.

                      SEQUENCE OF THE HUMAN GENOME

    Mr. Porter. Dr. Collins, why don't you join your colleagues 
at the table. Dr. Collins, what I'd like you to do is to give 
us your perspective on the dispute that apparently exists or 
the discussions at least that have been underway for some time 
with Celera and what you see might be happening in the future 
with respect to those discussions.
    Dr. Collins. Thank you, Mr. Porter. I really appreciate the 
opportunity to appear as part of the OD presentation today and 
clarify some of those issues, because I think they are quite 
important.
    First of all, let me say that I was personally stunned by 
the decision of the Wellcome Trust to release this confidential 
letter this past Sunday. I think that was a regrettable 
decision on their part. I'm also disturbed and distressed by 
the level of rhetoric that's appeared in the press over the 
last two or three days about negotiations with a private 
company called Celera. Those negotiations were between a group 
of four of us representing the international sequencing 
consortium and representatives of Celera Genomics Corporation. 
We had hoped that these discussions would lead to a 
collaborative outcome that would have satisfied Celera's 
business needs but also benefitted the public.
    Unfortunately, that was not the outcome. As a little bit of 
background, informal conversations between the sequencing 
consortium and Celera began back in October, 1999, leading over 
the course of several months--with much time being devoted to 
this by our busy genome center directors and by myself and by 
Harold Varmus, acting as an advisor, not as NIH director, but 
as a senior scientist--to a meeting that was held on December 
29th with top executives of Celera to talk about a possible 
model, where their data set, which they are producing with 
their own funds, and the public DNA sequence information, might 
be merged in a way that would be beneficial to all.
    The model that we put forward, which we thought might well 
be acceptable to them based on informal discussions, was that 
the merging process would begin this summer, would extend over 
the course of about three months time, and then would result in 
a joint publication by both groups and release of the data into 
the public domain for all to use.
    I'm sure you know, Mr. Porter, because you've been a strong 
supporter of this, that the need for access to the data has 
been a cardinal principle of the Human Genome Project since its 
outset. So we were very concerned to know if there would be any 
limitations on access to this information.
    Unfortunately at that meeting on December 29th, it became 
clear that for business reasons Celera was not in a position to 
have the access be as broad as our negotiating team felt it 
should be. To be specific, Celera expected that this merged 
database, which included roughly half publicly produced data 
and half data that they had produced, would not be permissibly 
used in any other commercial database other than their own. 
Furthermore, they specified that it could not be used for the 
generation of important research tools like DNA chips, because 
that was also part of their business plan.
    This came as somewhat of a surprise, particularly the part 
about using this collaborative effort for things other than 
databases, and the public consortium representatives felt 
rather strongly that agreeing to these conditions would be a 
betrayal of our responsibility to make this data available for 
any scientist who has a good idea.
    It seemed we were quite far apart at that juncture. Over 
the course of two months, efforts were made to try to see if 
there was grounds for continuing the negotiations. But there 
was no real encouragement coming back from Mr. White, the CEO 
of the parent company of Celera, that such negotiations were 
going to be fruitful.
    So in an effort to define the position that we felt put us 
in a circumstance where we could not really go forward, a 
letter was constructed from the four of us who had served as 
negotiators, those being myself, Dr. Varmus, Robert Waterston 
of the St. Louis sequencing center, and Martin Bobrow, a member 
of the Wellcome Trust Board of Governors. That letter was sent 
to the Celera team, basically outlining the points that we felt 
we could not agree to and giving the reasons why. Virtually all 
of those points surrounded the process of public access.
    These are very important issues, and one of my concerns is 
that the unfortunate rhetoric that's going on right now in the 
press has clouded over the really important principles. This is 
not just any old product, this is the sequence of the human 
genome. This is our shared inheritance. This is the bedrock 
information on which much of the future of medical research 
resides.
    To have that data restrained in any way, particularly to 
have it restrained in a way that prevents many of the most 
creative tools of the future from being developed by other 
companies or academic institutions with good ideas, is an 
outcome which we just could not agree to. That is the reason 
that these collaborations did not succeed.
    Now, I am happy to report that yesterday we did receive a 
letter from Dr. Craig Venter indicating that there might still 
be some grounds for re-entering those conversations. As Dr. 
Varmus is in India, I have not yet had a chance to discuss this 
letter with him and the other two negotiators. When that 
opportunity arises, which will be soon, we will see whether 
there are some possible grounds for re-entering those 
conversations and if so, we will be happy to do so--but only 
under the circumstance where we feel we've lived up to our 
obligation for public access to this critical information for 
all.
    Mr. Porter. Thank you, Dr. Collins. Looking at this 
situation, one would say, I think, isn't there an inherent 
conflict here? You want to get the data into the hands of 
scientists and the public, without charge, immediately, and 
their interest is to get it into their hands only on their 
terms and with costs involved. It seems to me, at the very 
outset, what's there to negotiate about, except that I realized 
there must have been some kind of an agreement regarding the 
fruit fly genome where you did collaborate and where you did 
combine data.
    Can you kind of put that into perspective for us and tell 
us why you thought there was a possibility of getting an 
agreement in this instance?
    Dr. Collins. That's a very appropriate question. With the 
fruit fly, the sense, at the time of entering into that 
collaboration a little more than a year ago, was that the value 
of the sequence information itself as a commercial product was 
much more limited. Hence, Celera was willing to agree to a 
collaborative effort where our grantee, Gerry Rubin at the 
University of California-Berkeley, would work with Celera using 
two different but complementary scientific strategies to 
assemble this sequence. Dr. Rubin had been working on this 
sequence for three years and had already finished 25 percent of 
the work, but this collaboration could make it go faster.
    In that instance, perhaps because of the perceived lesser 
value of the sequence itself as a product, Celera was willing 
to enter into the collaboration with no strings attached as to 
how that sequence would be used. In fact, this collaboration 
specifically implied and insisted that the sequence would be 
placed in Genbank, which is a database that everybody has 
immediate access to with no strings attached.
    We would have loved to work out a collaboration like that 
for the human sequence. Those terms would have been entirely 
acceptable and most welcome. But what has happened is, over the 
course of time, I think the business needs of what is clearly a 
commercial concern have become more prominent. What might have 
been at the outset of the founding of this company an intention 
to make the sequence itself available and to try to make money 
by providing annotations of it, has gradually merged into a 
different view--that the sequence itself also needs to be part 
of their property.
    That is reflected not only by this changed view in terms of 
access to the data, but also by patent filing, which initially 
had been projected by Celera as something that would be done 
very sparingly, and in fact has been done on quite a large 
scale. Understandably, in a business perspective, this may make 
good sense. But having a monopoly on the human genome sequence, 
while it might be a good business plan, is clearly not in the 
best interests of science or the general public.

                        FRUIT FLY COLLABORATION

    Mr. Porter. Dr. Collins, is it fair to say that in 
reference to the fruit fly sequencing, what basically was done 
here is that you purchased the data that Celera had developed, 
sequences that they had developed from them? They must have 
been paid something for all of this sequencing that was done, 
is that correct?
    Dr. Collins. No, actually, it was done as a collaboration 
where they provided the funding for the sequencing they were 
doing out of their own private sources.
    Mr. Porter. They did? What did they get out of this?
    Dr. Collins. They got a wonderful opportunity to work with 
an experienced investigator who had already started down this 
path and who was a fruit fly expert. They had the opportunity 
to work with him on a daily basis, scientifically to see how to 
merge these two very different sorts of data, which is 
effectively a pilot project for what they wanted to do for the 
human sequence.
    Mr. Porter. But they got no compensation for this?
    Dr. Collins. They did not get compensation directly for the 
sequence they produced.
    Now, I will tell you, they do have an intention of 
providing a version of the fruit fly sequence with a lot of 
other added value information attached to it and putting that 
on a database that you have to pay to see. We have no trouble 
with that.
    Mr. Porter. But you have it already out in the public.
    Dr. Collins. The sequence itself, the As, Cs, Gs and Ts, is 
publicly accessible. Their commercial product in that instance 
is not the sequence, it's other things attached to it.

                      SEQUENCE OF THE HUMAN GENOME

    Mr. Porter. My final question, if I may. When you went to 
these discussions with the four representatives and Celera, 
were you authorized to enter into an agreement with Celera at 
that point, or would you have had to bring that agreement back 
to NIH?
    Dr. Collins. Oh, absolutely we would have had to bring it 
back.
    Mr. Porter. You weren't prepared to contract at that time, 
it was just a discussion, is that correct?
    Dr. Collins. Right. We were there as the chosen 
representatives of the 16 genome centers around the world that 
are doing the majority of the work. The sequencing consortium 
had basically felt that these four people could represent their 
views. But we were there as negotiators without decision making 
authority. If we had arrived at some sort of a model for 
collaboration, we would then have brought it back to those 16 
centers and to the funding agencies, which would be the NIH 
most prominently, but also the Department of Energy and the 
Wellcome Trust in the United Kingdom.
    Mr. Porter. Given where you are today, do you see any 
possibility of this discussion leading to an actual 
collaboration on the human genome?
    Dr. Collins. It's possible that some other more limited 
model might be developed where we could agree to cooperate and 
coordinate with the various aspects of the work. I think this 
very close collaboration--where there would be a fairly open 
exchange of data and co-publication of the results--seems, as 
you have very articulately pointed out, to collide with the two 
very different missions of the enterprise, and not, to my view, 
to be all that viable.
    I would be happy to find out otherwise, and we will 
continue to explore that.
    Mr. Porter. Well, if I may say so, it seems to me that what 
the American public is entitled to is to have this data put 
into the public stream of information, and for scientists to 
have it readily available to them, which is exactly what you're 
doing. Any means of disrupting that ready availability, it 
seems to me, is counterproductive to the public investment.
    Dr. Collins. I appreciate your saying so, Mr. Porter. I 
want to reassure you that the public sequencing effort is in 
very good shape. We are within a few months of having 90 
percent of this sequence in working draft form and in the 
public domain where anybody can use it with no strings 
attached. We'll move on from that to close up all the gaps and 
have the final coverage of all the human chromosomes by 2003 or 
hopefully sooner.
    Mr. Porter. Thank you, Dr. Collins.
    Mr. Jackson.

         OFFICE OF RESEARCH ON MINORITY HEALTH ADVISORY COUNCIL

    Mr. Jackson. Thank you, Mr. Chairman.
    Dr. Kirschstein, during last year's hearings, we began a 
very extensive dialogue regarding NIH and its Office of 
Research on Minority Health. This dialogue was prompted in many 
ways by the IOM report that outlined many shortcomings within 
the NIH organization as it relates to addressing minority 
health and training issues.
    The main outcome of this discussion was my proposal to 
elevate the Office of Research on Minority Health to center 
status. On issues of importance to NIH, such as the NIH 
graduate school, among other issues, I am aware of the value 
that the agency places on the advice of advisory councils. It's 
my understanding, and I remember reading this, that the 
advisory council to then-Director of NIH Harold Varmus, Nobel 
laureate, NIH director, that the advisory council did not agree 
with the director's planned development of an NIH graduate 
school, and the agency has at least for the time being 
abandoned the idea of pursuing the development of a graduate 
school.
    First, I have several questions for you regarding the 
Congressionally-mandated ORMH advisory committee. What are the 
qualifications for becoming a member of the Congressionally-
mandated advisory committee on research on minority health?
    Dr. Kirschstein. I think in some ways Dr. Ruffin could be 
better able to answer the question, but I will start. I think 
the requirements are that they be scientists, and perhaps, I 
don't know, do you have any lay people on your advisory 
committee?
    Dr. Ruffin. Most of the individuals on the committee are 
scientists.
    Dr. Kirschstein. The reason I raise the issue of lay people 
is that there is a requirement for advisory councils to have 
one-third of the members be lay members.
    Mr. Jackson. Who makes the appointments, Dr. Kirschstein?
    Dr. Kirschstein. The advisory councils are appointed by the 
Secretary.
    Mr. Jackson. They are appointed by the Secretary.
    Dr. Kirschstein. But in the case of Dr. Ruffin's advisory 
committee, there was not, I didn't think, but I didn't remember 
quite, that's why I asked him, a requirement that there be lay 
people. So the individuals are scientists who work in various 
areas of science, most of whom either have worked in 
specifically minority educational institutions that do 
research, or majority educational institutions where they have 
had interests in minority activities and many of them have run 
training programs for minority scientists.

       CENTER PROPOSAL FOR OFFICE OF RESEARCH ON MINORITY HEALTH

    Mr. Jackson. What if any advice has the committee provided 
to the NIH Director regarding the status of ORMH?
    Dr. Kirschstein. The Committee has met several times. In 
its first set of meetings, as I recal--and I attended all those 
meetings although I may not have stayed for the entire meeting, 
when I was Deputy Director--they were learning a great deal 
about the activities of the ORMH. The Committee then began to 
advise Dr. Ruffin specifically on what might be important 
programs.
    In regard to your question as to whether that committee was 
specifically asked to review your center proposal, it did 
eventually do so, but it took some time. It did it at its last 
meeting and maybe the meeting before. And actually sent several 
letters to NIH about it.
    Mr. Jackson. Yes, I am aware of the advisory committee on 
research on minority health and all the members of the advisory 
committee signed a resolution in support of elevating the 
Office of Research on Minority Health to the level of center 
status. I'd like to submit this for the record, also, to 
provide Chairman Porter with a copy, as well as other members 
of the Committee.
    I was just wondering, it appears that when the advisory 
council indicated to Dr. Varmus that they disagreed with his 
idea of creating an NIH graduate school, it appeared that the 
Director of NIH followed the advisory committee's advice. But 
when the advisory committee for the Office of Research on 
Minority Health offered its advice that therefore, we 
unanimously support H.R. 2391 to elevate ORMH to center status 
as one step in increasing the focus on investment in reducing 
the continuing disparities in minority health status and 
minority research training, I'm wondering what was NIH's 
response to the advice it received from the Congressionally-
mandated advisory committee on research on minority health 
regarding the status of ORMH?
    Dr. Kirschstein. Mr. Jackson, I cannot tell you 
specifically what the response was. What I can tell you, and 
I'm not using this as an excuse, is that when legislation is 
introduced, it is the position and must be the position of all 
the agencies under the Department of Health and Human Services, 
to ask what the Department's position and the Administration's 
position is in regard to specifically supporting such 
legislation.
    Mr. Jackson. I can understand that. But certainly, I would 
imagine that those advisory committee members, Ph.D.s, M.D.s, 
all the scientists that you have suggested have obviously 
acknowledged that the Office of Research on Minority Health is 
worthy of such elevation, they go on to say that organization 
elevation alone will not be enough. That's pretty 
authoritative.
    Authority to grant priorities, to direct grant priorities 
to disparities in minority health with the appropriate 
increased funding resources to support it is clearly needed for 
the proposed center to succeed. They conclude, we expect that 
this additional funding should supplement and not supplant 
existing institute-specific activities.
    The reason I'm raising this concern, Dr. Kirschstein, while 
I've simply tried to codify some of the concerns that they 
feel, the advisory committee, are problematic and existing at 
NIH already, it didn't require Congressional legislation for 
then Dr. Harold Varmus to consider elevating or creating a 
graduate school at the agency. And obviously, if he was going 
to create such a graduate school at some point in time it would 
have required Congressional legislation to fund such a graduate 
school.
    So there was certainly some activity occurring under Dr. 
Varmus' leadership that would have created a graduate school 
that would have ultimately led to legislation. And I simply 
have legislation that might be on, I actually think it's on the 
back side of activity that's already taking place over there on 
these questions. But that notwithstanding.
    I do have a couple more questions, Mr. Chairman. I have a 
report from the U.S. Commission on Civil Rights dated September 
1999. This report is entitled Health Care Challenge, 
Acknowledging Disparity, Confronting Discrimination and 
Ensuring Quality. At a minimum, I recommend that each member of 
the Subcommittee read the level of transmittal and summary.
    I have yet to complete all my review, but what stands out 
most to me are not only the laudatory comments about the Office 
of Research on Minority Health, but also the recommendations to 
elevate the office to center status. In fact, the report 
references my proposed legislation.
    There are eight findings and recommendations related 
specifically to ORMH. I'm wondering, Dr. Kirschstein, one, are 
you familiar with this document?
    Dr. Kirschstein. Yes, indeed. I participated in discussions 
with the Civil Rights Commission, as did Dr. Ruffin and many 
other members of my staff. I was deeply involved, and I think 
if you'll read that report carefully, they will talk about the 
various activities which I was involved in which they found 
laudatory.
    Mr. Jackson. I'm really interested in this. We have 
scientists on the one hand who are saying, elevate the Office 
of Research on Minority Health to center status, we have a 
former director of NIH that doesn't need the support of an 
advisory council in order to create a graduate school, but 
followed the advisory council's advice to not create a graduate 
school. But when I asked about elevating the Office of ORMH to 
center status, you indicated in your previous answer that 
somehow, we're waiting, that it requires some approval or 
something from the Secretary or the President. Help me 
understand that.
    Dr. Kirschstein. What I'm explaining to you is what was the 
situation. That when specific legislation has been introduced 
into Congress, as you have done, it is the Department's 
position that its agencies are not to support or provide lack 
of support to such legislation until such a time as the 
Department has a position. Mr. Jackson, if I may.
    Mr. Jackson. Yes, ma'am.
    Dr. Kirschstein. The issue, I think, of what's gone on this 
past year is something that happened and I would like to say we 
should move on. And I hope we will. We are already in the 
process of developing a center within the Office of the 
Director, because that's the only authority we have by which we 
can do that now. We cannot unilaterally establish an 
independent center as are the Institutes and other centers 
without some sort of authority.
    I agree with you----
    Mr. Jackson. But let me say, Dr. Kirschstein, that, Mr. 
Chairman, I have enormous respect for the outstanding work that 
Dr. Kirschstein has done, and I could not possibly begin the 
process of even coming close to challenging her commitment to 
this. And I also want to congratulate Dr. Ruffin and all of you 
who have been through a very lengthy hearing process with me on 
some questions that I've been raising.
    Mr. Chairman, I have examined and queried across the NIH 
and I must tell you that there is definitely the spirit and 
commitment to address some of the fundamental concerns that 
exist at the NIH. What I am suggesting now is that at the level 
of the Secretary and at the level of the President, we are 
still at loggerheads on the appropriate policy to pursue. And 
while I cannot hold these institute directors responsible, that 
our legislation is raising some very important questions at the 
level that should be answered at the level of the Secretary and 
answered at the level of the President.
    So I want to thank you, Dr. Kirschstein, and all of the 
centers and directors at NIH who have put up with me through 
this period, and I want to thank all of you once again for the 
outstanding work that you continue to do. I suspect next year 
when we sit down again hopefully we will have made significant 
progress on what Dr. Maddox has presented for us today.
    Thank you, Dr. Kirschstein, and thank you, Mr. Chairman.
    Dr. Kirschstein. I want to thank you, Mr. Jackson. I think 
you've clarified our thinking a good deal. What we want to do 
now, before the inception of the 2001 budget, is to work to 
establish a center so it will be a jump start for what we do 
when we start fiscal year 2001 and, of course, when we present 
the fiscal year 2002 budget, which will have the plans and the 
fiscal aspects based on the strategic plan.
    Thank you very much.
    Mr. Jackson. Thank you, Dr. Kirschstein. Thank you, Mr. 
Chairman.

                          AIDS CLINICAL TRIALS

    Mr. Porter. Thank you, Mr. Jackson.
    Dr. Nathanson, in your presentation you talked about an 
AIDS vaccine trial that's going on with animal models. Is there 
not one also going on with humans?
    Dr. Nathanson. The clinical trials in humans, Mr. Porter, 
are phase I, which is safety, phase II, immunogenicity, and 
then phase III, are efficacy. There are and have been many 
phase I and a number of phase II trials being conducted. There 
is currently a phase III trial that is mainly supported by 
VaxGen, a private company.
    But in addition to that, we are heading into a decision 
whether or not to start another phase III trial, and with a 
recent meeting about 10 days ago, meeting, but I know the 
essence of it, where a plan for a phase III trial, another 
phase III trial of a fairly promising product, was discussed in 
some detail. That will come to a decision, and if it's a 
positive decision, probably move forward to begin in another 
year or so.
    Just for your information, that's what's called a prime and 
boost regimen, where you start with a recombinant virus that 
contains some of the genes of HIV incorporated in an attenuated 
pox virus, similar to vaccinia that was used for vaccination 
but attenuated from that. Then there's a protein boost, that 
boosts the antibody response.
    And that's looking fairly promising, although there's some 
discussion in the scientific community as to how promising it 
is. But my guess is that will probably move forward to a phase 
III trial. So that will be a second phase III trial.
    But meanwhile, many other things are being tried for 
immunogenicity in phase I and phase II trials.

                              AIDS VACCINE

    Mr. Porter. When Dr. Fauci was here, and I'm asking you to 
confirm it or correct me, my understanding was that the 
knowledge that we have of the HIV virus is such that because it 
mutates or changes, that you can't develop a vaccine like a 
polio vaccine to eradicate the disease. All you can develop, 
and likely will be able to develop, is a vaccine like the flu 
vaccine where you have to change the vaccine each year or so in 
order to try to anticipate the mutation of the virus. Is that 
correct or not?
    Dr. Nathanson. Well, this is my personal opinion, I don't 
know exactly what Dr. Fauci's view would be, that it is true, 
this is a virus that does change and mutates quite rapidly. But 
in fact, the problems in developing the vaccine are in a sense 
more profound than that. I will only mention one aspect just to 
give you an idea.
    With polio or many of our other viruses, people who are 
naturally infected develop what we call neutralizing 
antibodies. That means antibody in the blood serum that will 
inactivate the virus. And then it's relatively easy to 
replicate that with either a live attenuated or an inactivated 
version of the virus. In fact, Dr. Kirschstein and I both 
worked many years ago on the polio vaccine in that respect.
    And with the AIDS virus, people who are naturally infected 
develop antibodies. But those antibodies do not inactivate the 
virus, they don't neutralize the virus. And it's been very 
difficult to make a candidate vaccine which produced that 
neutralization even against the virus that you started out 
with, so you didn't have to worry about antigenic variation.
    So we have problems even before you get to the issue of 
antigenic variation. This virus has been a peculiarly difficult 
one to develop a vaccine for, for basic biological reasons. 
That's only one of them, actually.

                               U.N. AIDS

    Mr. Porter. I know this is not a fair question, but you 
might have some information that we don't have. You raised the 
question of the terrible situation in Africa and other places 
in the world. The President proposed earlier this year or maybe 
late last year a very significant contribution by the United 
States to UNAIDS, I believe it was $1.3 billion.
    Do you know the status of that whole situation?
    Dr. Nathanson. I don't, actually. One of the things we did 
look into as a follow-up to the discussion you had with Dr. 
Fauci was the deployment of Nevirapine for perinatal 
transmission. Actually, we've talked to Brooks Jackson, who is 
the professor at Johns Hopkins who did the Nevirapine trial in 
conjunction with his colleagues in Uganda. He had just returned 
from Uganda, so I can give you a little more information. 
Because that would be an example of an immediate application.
    Uganda is not a country which is generically opposed to the 
use of Nevirapine. The main issue is that they simply don't 
have the resources to apply it widely. They are probably going 
to do some pilot projects, particularly in Kampala, the 
capital, where the main medical school is located and where 
most of the research takes place.
    But they have calculated that to apply this regimen to the 
whole country would cost about $10 million. They don't have 
those resources. And less than 10 percent, it turns out, would 
be for the price of the drug itself. They would start with a 
population in which there are about a million pregnancies every 
year. Of these, approximately 160,000, about 16 percent, are 
women who are HIV-infected. Of those 160,000 births in infected 
women, about 40,000 would be infected babies. Nevirapine 
potentially could reduce that 40,000 by half to about 20,000. 
This just gives you a sense of the numbers.
    But in order to do this, they would have to do voluntary 
counseling and testing on an individual basis for all the 
million women and then go on to test them individually. Those 
who are tested would have to be counseled again about 
Nevirapine. So there's a lot of ancillary expenses which turn 
out to be about 10 times as much as the drug itself. The truth 
is that they don't have the money to do this. But also, they 
probably lack the infrastructure to do this. Because their 
medical infrastructure is rather minimal at present.
    But that is a potential application. We also did query the 
folks at CDC who are much more involved with this deployment. 
Because this is not research, it's sort of deployment. They 
knew of no immediate plan to use any of the money that the 
President has talked about for this purpose. We certainly would 
think, if I can say so, that this would be an appropriate use 
of some of those funds. Because that's the most immediate 
intervention that we're aware of in countries that really don't 
have the infrastructure to support therapy.
    I just wanted to expand on that because I knew you were 
very interested in the Uganda situation, from your questions to 
Dr. Fauci.
    Mr. Porter. That would be a bilateral intervention, 
presumably.
    Dr. Nathanson. Oh, yes.
    Mr. Porter. Not through UNAIDS, is that correct?
    Dr. Nathanson. Well, it could be done by either the leading 
public health people and medical researchers in Uganda, some of 
whom I know quite well, would be very pleased to interact with 
any agency that came forward to support that.
    Mr. Porter. I understand. What I'm asking really is, would 
you be confident if we worked with the UN agency and worked 
through them?
    Dr. Nathanson. Oh, yes. We're on very close terms with 
Peter Piot, who heads UNAIDS. Frankly, they are underfunded but 
they have some very competent, very dedicated people at UNAIDS. 
I think they would be very capable of playing a major role in 
all this. Yes.

                                 BECON

    Mr. Porter. Thank you, Dr. Nathanson.
    Dr. Maddox, Dr. Baldwin is doing a great job with BECON, 
the bioengineering consortium. There was language in the report 
accompanying the bill last year talking about creating an 
office first, with the thought that a thorough review would be 
made discussing the potential of creating an institute of 
bioimaging and bioengineering. Can you give us the status of 
all that and what the latest thoughts are?
    Dr. Maddox. Yes, Mr. Porter, we have begun to really look 
at the Office of Biomedical Engineering and Bioimaging very 
carefully. Dr. Baldwin, who is here with us today, has assured 
us that she has now begun to look at establishing a position 
description to hire someone to actually run the office. As you 
may recall, we had $200,000 put in the fiscal year 2000 budget 
to sort of get the idea off the ground and started. And in 
terms of fiscal year 2001, we are also expecting to put 
additional funds in there, pending the outcome of the budget 
process.
    But we are underway to getting the office established. We 
are looking now to put some personnel in place. Dr. Baldwin has 
someone working in her office now to sort of get this off the 
ground and running before the time we can actually hire 
someone.
    Also, I should add that the BECON effort, which is an 
effort that's been ongoing, would be one of the aspects that 
this office would take under its consideration and would be 
coordinating. I'm wondering if Dr. Baldwin had anything she 
wanted to add.
    Dr. Baldwin. The establishment package is moving forward. I 
hope to have the search underway shortly. The community, as you 
know, AIMBE has been very supportive and very helpful in this. 
And what we'd like to do is make sure we can build on the 
accomplishments of BECON which we've really tried to construct 
in a way that is an additional help to the Institutes, as 
opposed to being competitive with the Institutes.
    I think that is essential for an office like this. For the 
office to really make the most of what we can do in 
bioengineering, it needs to work with the Institutes and 
Centers. Certainly the bioengineers have been very happy with 
the outcome of the BECON initiative so far, and the growth in 
support for bioengineering. So we're cautiously optimistic.
    Mr. Porter. Where does the $200,000 come from? From the 
Office of the Director?
    Dr. Kirschstein. Office of the Director.
    Mr. Porter. Is $200,000 enough?
    Dr. Baldwin. It's enough for this year because we won't 
have the office up and running until the end of FY 2000. Even a 
new Director, hired this year, probably wouldn't come on board 
until the end of the fiscal year. So the $200,000 is fine for a 
startup level. That was never intended as the ongoing level for 
that office.
    But the office was not intended to be a granting office. It 
was to provide an institutional home for the activities of 
BECON, and the bioengineering research would stay in the 
Institutes.
    Mr. Porter. Thank you, Dr. Baldwin.
    Dr. Maddox. Mr. Porter, our estimate in the President's 
budget for 2001 would be that we would need about $1 million 
for that office in 2001.

                   REFORM OF THE PEER REVIEW PROCESS

    Mr. Porter. All right. I think that Dr. Katz began talking 
about this when I came in the room, but I'd like, Dr. Maddox, 
if you would tell us about the reform of the peer review 
process. Where are we in all that?
    Dr. Maddox. Through the period of time that Dr. Ellie 
Ehrenfeld has been on board as the Director of the Center for 
Scientific Review, indeed, peer review has undergone a lot of 
changes. As you might recall, when Dr. Ellie Ehrenfeld came on 
board, the Center for Scientific Review at that time was called 
the Division of Research Grants. But with the arrival of Dr. 
Ehrenfeld, she not only looked to giving the office more 
visibility and sort of raising the stature of the office, as 
well as the employees associated with it, but also she began 
looking at the structure of the study sections.
    At this point in time, we have completed the rearranging 
and the restructuring of the neurosciences study sections. 
We've completed the reorganization and restructuring of the 
AIDS study section. And at this point in time, you may have 
heard of Dr. Ellie Ehrenfeld's report, the first draft of this 
report that we've termed the Boundaries report, which again is 
looking at a more formal reorganization and perhaps assessment 
of all of the study sections, not just the ones in the 
neurosciences or the AIDS arena.
    In particular, there's been a lot of interest in the 
community at reorganizing and restructuring study sections 
based on diseases and disease entities, as opposed to 
scientific areas. So the first phase, the first report of the 
Boundaries committee is out, and I believe that the second 
phase is underway.

                      SCIENCE EDUCATION ACTIVITIES

    Mr. Porter. Thank you. You talked about science education 
activities funded through the Office of Science Education. How 
do those differ from the activities funded through the science 
education partnership award program within NCRR?
    Dr. Maddox. Actually, Mr. Porter, all of the ICs really 
contribute significantly to the activities of the Office of 
Science Education that come out of the Office of the Director. 
You may recall in looking at our budget figures that the budget 
for the Office of Science Education is very slim, it's slightly 
over $3 million. So, much of the activities that we have 
undertaken within the Office of Science Education is through 
collaborative efforts.
    In fact, the supplement program that I spoke of earlier is 
a program in which three Institutes get involved in the 
supplement series. And it's through their funding and 
collaboration with Dr. Fuchs and his staff that we're able to 
move these programs along. The budget of the Office of Science 
Education would not allow us to conduct these types of studies.
    As we talk about the program that comes out of the NCRR, 
again, that program is supported in collaboration with the 
Center, as well as with the Office of Science Education. So the 
minimal amount of funds that come out of the Office of the 
Director are mainly for staffing and for some small support for 
resources. But the bulk of the funds that come to these 
programs, and to developing these programs, are in 
collaboration with the Institutes and Centers.
    Dr. Kirschstein. Mr. Porter, in addition, both the Office 
of Research on Women's Health and the Office of Research on 
Minority Health contribute to those programs.

                         CHILD CARE FACILITIES

    Mr. Porter. Dr. Kirschstein, since you did the buildings 
and facilities yourself, I have one question. My understanding 
is that there is a joint child care facility being constructed 
in the research triangle park with NIEHS and EPA. I wonder, in 
the original design, was this child care facility included in 
the original design of the EPA facility? What's the total cost 
of it, and how much is EPA contributing to it?
    Dr. Kirschstein. I'm going to ask Mr. Ficca to answer that 
question.
    Mr. Ficca. This child care facility will replace the child 
care facility supported through a lease. The collaboration with 
EPA was to share the cost. The money that's in our budget is 
only the NIH portion. I am not sure that I can give you the 
exact figure that EPA is contributing to that. But I would be 
happy to provide that for the record.
    [The information follows:]

    The Research Triangle Park child care faciltiy was included 
in the original design of the EPA facility. At the time of the 
design, the capacity of the child care facility was only 
projected for 100 children in 9,900 GSF (6875 (NSF) of space at 
a cost of $2 million (EPA's contribution to the facility). 
Since then, the projected need for child care has increased to 
180 children. The NIH Buildings and Facilities request for 
funds of $1.6 million raises the total funds required to $3.6 
million and the building space to approximately 18,000 GSF.

    Mr. Porter. Another question, while you're there. There's a 
request for $500,000 for a child care facility on the Bethesda 
campus. How would this facility compare in size to the one in 
North Carolina?
    Mr. Ficca. The proposed child care facility on the Bethesda 
campus, what is called the northwest temporary facility, will 
replace an existing temporary facility on campus. It will house 
approximately 100 to 120 children. The one shared by the EPA 
and the National Institute of Environmental Health Sciences is 
about the same size. I can provide the approximate size of the 
Bethesda facility for the record as well.
    Mr. Porter. I would appreciate your doing that. Thank you 
very much.
    [The information follows:]

    The initial request of $500,000 is only for the design of 
the new child care facility on the NIH Bethesda campus. This 
facility is planned to be approximately 20,000 GSF.

    Mr. Porter. I want to thank all of you. In fact, Ruth----
    Dr. Kirschstein. Mr. Chairman, may I make a final 
statement?
    Mr. Porter. Certainly.
    Dr. Kirschstein. On behalf of all of us, in closing these 
sessions, Mr. Porter, my colleagues and I, in particular, want 
to thank you for your support and efforts on behalf of 
biomedical research, which have been of so much importance to 
improving the health of the American people, and in fact, the 
people of the world. We wish to present you with a framed 
photograph that was taken several weeks ago, and we want to 
rise and salute you.
    [Applause.]
    Mr. Porter. Ruth, that is really special. I had no idea you 
were going to do this.
    I've said it many times before, but let me say again that 
the work that is done by all of you, all the people at NIH, the 
whole community, is of such great importance to all of 
humankind. We think of it as the American people, but it's 
really the whole world. We just feel that our role is to give 
you all the support we possibly can to further the wonderful 
scientific opportunities that are now available to help to 
conquer disease.
    For me, during all the 21 years I've been on this 
Committee, I have found such fascination and inspiration with 
what has been done at NIH, the research that has gone forward 
and the progress that has been made, that to me, I think if 
every member of Congress were able to hear what I've heard, 
they wouldn't have one moment's hesitation in saying that this 
is the best spent money anywhere in Government, that it 
furthers the interest of human beings everywhere, and that it 
ought to be increased as rapidly as we can possibly increase 
it, so that the discoveries that are waiting to be made can be 
brought on-line faster.
    So everything that you do is, I think, done so well, so 
thoughtfully, there's so much intellect that goes into every 
aspect of NIH. I have just felt that the NIH story needs to be 
known by more people. I know you're working on it. [Laughter.]
    It is so fascinating and so compelling, and so inspiring. 
In a time when the news is often so negative, we need the 
inspiration that NIH provides us.
    This picture will have the most honored position in 
whatever office I have next year. I can't tell you how much I 
appreciate the association, the friendship and the sharing of 
values that I think all of us have, both on this side of the 
table in this Subcommittee and on that side in terms of the 
interests of our country and all human beings.
    So thank you for this, it's so special to me. I really 
appreciate it. Thank you so much.
    The Subcommittee will stand in recess until 10:00 a.m. 
tomorrow.
    [The following questions were submitted to be answered for 
the record:]



                                           Thursday, March 2, 2000.

       NATIONAL CENTER FOR COMPLEMENTARY AND ALTERNATIVE MEDICINE

                               WITNESSES

STEPHEN E. STRAUS, M.D., DIRECTOR
RICHARD NAHIN, PH.D., DIRECTOR, OFFICE OF EXTRAMURAL PROGRAMS
PATRICK WILLIAMS, ACTING EXECUTIVE OFFICER
CHRISTINE HOLLINGSWORTH, FINANCIAL MANAGEMENT OFFICER
RUTH KIRSCHSTEIN, M.D., ACTING DIRECTOR, NIH
DENNIS P. WILLIAMS, DEPUTY ASSISTANT SECRETARY, BUDGET, DHHS

                            Opening Remarks

    Mr. Porter. The subcommittee will come to order. We 
continue our hearings with the National Center for 
Complementary and Alternative Medicine. We are pleased to 
welcome, for the very first time, Dr. Stephen Straus, the new 
Director.
    Dr. Straus, I apologize to you that the first Institute 
went so long this morning. We will allow extra time. We are 
very anxious to hear what you have to tell us.
    Dr. Straus. Thank you, Mr. Chairman.
    Allow me, first, to introduce, on my far left, Dr. Richard 
Nahin, the Director of our Extramural Program; to my immediate 
left, Ms. Christine Hollingsworth, our new chief budget 
officer; and, of course, Dr. Kirschstein, who has been a great 
adviser, and who has been very accessible in helping me grow 
into this position.
    Thank you. It is an honor to appear before the subcommittee 
for the first time. Let me say, as Dr. Hyman did, that my 
pleasure is tempered by the fact that this will be my one 
opportunity to appear before you in your period of truly 
inspiring leadership of the subcommittee.
    Mr. Chairman, and members of the subcommittee, the very 
establishment of the National Center for Complementary and 
Alternative Medicine, a little over a year ago, is testimony to 
the extraordinary, growing interest of the American people in 
the opportunities that complementary and alternative medicine 
appear to hold for them. By many estimates, over 40 percent of 
Americans today are using one or more such modalities with the 
belief and expectation that it will sustain and improve their 
health. It is unfortunate that they do so, however, without the 
guidance of a true evidence base that the American public needs 
and deserves to help in their selection of these modalities. It 
is the challenge to provide

that evidence base that energizes both me and my new colleagues 
in the Center to help apply the well-established tools of 
excellent and rigorous research.
    [The information follows:]




                             STRATEGIC PLAN

    Dr. Straus. We have begun our efforts by developing a 
strategic plan. I have outlined for you on the display board to 
my left the cardinal priorities that guide our approach to 
succeeding in this area. First and foremost, as with all NIH 
Institutes and Centers, is our investment in research. In this 
context, this is research of the highest standard. It is not 
the generation of additional anecdotes, but true solid 
evidence.
    Because ours is a new scientific venture, addressing a very 
ancient and venerable series of practices, we need to invest in 
training of investigators to seduce them, as Dr. Hyman said, 
into joining our field and sharing with us the excitement and 
opportunity that it represents.
    We need to articulate to the American public, in a very 
clear way, the results of our research findings; to reach out 
to our many stakeholders and constituents and explain to them 
what works and what does not work, what is safe and what is not 
safe. The end result of our research should provide the kind of 
evidence that will allow the seamless integration of those safe 
and effective practices into the daily practice of medicine in 
the United States today. Finally, in our strategic plan, we are 
cognizant of the responsibility that we bear to steward the 
resources you have placed in our hands.
    It is this strategic plan that guides the diverse research 
portfolio that we are in the process of developing. That 
portfolio extends, on the one end, from novel and unbiased 
investigations of modalities that the public has great interest 
in, but for which there is, in fact, very little or no 
scientific support, such as magnet therapy and energy healing. 
On the other end of the spectrum, we extend to the largest and 
most definitive randomized trials ever conducted of 
complementary and alternative medical modalities. I will 
illustrate one such study for you to show how our philosophy 
bears on this approach.

                               DEPRESSION

    Dr. Hyman introduced the area of depression very well, and 
the ability to address depression with powerful synthetic 
drugs. This is an opportunity that we, in NCCAM, can address as 
well, because ancient herbs, such as St. John's wort, are 
widely used with the expectation that it sustains mental 
balance and improves mild to moderate depression. We are 
mounting a definitive study in collaboration with Dr. Hyman and 
his colleagues, and with the Office of Dietary Supplements, 
just as we mount all of our large studies in collaboration with 
the other Institutes, Centers and health agencies, we are 
mounting a definitive study.
    [The information follows:]



    Dr. Straus. I show you two pieces of data here that provide 
the important backdrop for this study. Data from the British 
Medical Journal, from this past November, show the results of a 
randomized trial in which patients with depression were treated 
with St. John's wort, or with an old mainline tricyclic anti-
depressant, Imipramine, or with a placebo. As Dr. Hyman 
indicated, this was a typical brief 6-week anti-depressant 
study. Here, we are showing the improvement in depression with 
St. John's wort as comparable to that with Imipramine, and, in 
both cases, superior to that of placebo. Thus, St John's wort 
is a natural product which appears to be active. The study we 
are mounting, together with NIMH, is substantially larger and 
is a 6-month study. We can address efficacy and safety in ways 
that represent a new standard for the field.
    [The information follows:]
    If we expect these agents to be active, they should, as 
well, have potential risks; we need to address these as well. 
They are illustrated here with data from my colleagues at the 
NIH, published in the Lancet on February 12th, where volunteers 
were given the highly active and important HIV protease-
inhibiting drug, Indinavir.
    [The information follows:]



    Dr. Straus. It sustained a high blood level, shown in 
green, and that level exceeds the threshold, the dotted line, 
that one needs to successfully inhibit the growth of the virus. 
It does so routinely in people, and that is why it is a great 
drug. When St. John's wort, in standard dosage, was added to 
the Indinavir treatment, it so sped up the body's metabolism of 
Indinavir that it reduced the blood levels tenfold, to a level 
that is no longer therapeutic for HIV.

                        NEW RESEARCH PRIORITIES

    We have to appreciate the opportunity and the challenge, 
and that is what guides our research portfolio. In addition to 
studies like that of St. John's wort other large clinical 
trials, our new priorities for the year 2001 are listed in this 
next display panel.
    [The information follows:]



    Dr. Straus. First, we are expanding rapidly our investment 
in investigator-initiated research, the jewel in the crown of 
the NIH research portfolio. We will increase by approximately 
threefold the number of such investigations we fund from 1999 
to 2001. Because so much of complementary and alternative 
medicine has arisen in the context of many indigenous peoples 
and cultures over the millennia, we have a special privilege 
and opportunity in NCCAM to conduct our research, and at the 
same time address issues of health disparities. We will speak 
more about that issue.
    As I indicated, one of our goals is to have successful data 
lead to successful integration, and we will be performing 
studies of the barriers that prevent physicians from taking on 
new ideas and integrating them into their practice, as well as 
the tools that facilitate that process.
    We will be mounting, in 2001, a new large definitive trial, 
like the St. John's wort study, of an ancient herb known as 
milk thistle or Silybum marianum, which is long believed to 
treat cirrhosis and chronic hepatitis. We and NIDDK held a 
workshop this past fall which coalesced the preliminary data, 
saying that the time is right for such a study.
    Finally, we are now building our own intramural research 
program, guided on a large clinical research emphasis. We 
believe that the unique and rich environment of the NIH 
Clinical Center and the new, Clinical Research Center, that you 
are permitting us to build provides an opportunity to us to do 
unparalleled research, and for us to bring to NIH itself the 
concept of integration of successful CAM therapies.
    It is my belief that this approach will make NCCAM the 
international leader in applying rigorous scientific tools. We 
have a bully pulpit to occupy, to spread to the American public 
the word that science can help provide them definitive answers.
    The tools of science will permit medicine in its virtual 
and longstanding dynamic process to evolve, to change, and to 
integrate the best practices, while the data will be so clear 
that an informed American public will embrace the best of them. 
They will reject those practices that are marketed to them 
today, which are neither safe nor effective.
    Thank you. I am happy to take your questions.
    [The written statement of Dr. Straus follows:]



                      SETTING RESEARCH PRIORITIES

    Mr. Porter. Thank you, Dr. Straus.
    Your mission is different from almost all of the 
Institutes, because they are working to develop a base of 
knowledge that leads to new discovery. While that may be a part 
of your portfolio, the main part is that there are already, on 
the market, many different alternative therapies We do not know 
whether they are safe or efficacious; we do not know that they 
may have drug interactions, that may be dangerous, or that they 
make other drugs less efficacious.
    I guess that the end product of what you do will be to 
integrate certain nontraditional therapies that are found to be 
safe and efficacious into the traditional therapies, and to 
expand the base of what is available and effective for people 
to address health problems.
    The first question I have is how do you determine where to 
start? Because there are so many different things out that are 
on the market already. What gives you a look at what you ought 
to be doing? Do you try to balance those that may have positive 
therapeutic and safe advantages against those that you worry 
that the public is buying that are either unsafe or 
nonefficacious?
    When you find something that is unsafe or nonefficacious, 
how do you change behavior in the marketplace? How do you get 
that information across to people so that they will not waste 
their money or endanger their health?
    Dr. Straus. Thank you, Mr. Chairman. Those are excellent 
questions.
    Our prioritization, of course, is complex. There are at 
least 1,500 different herbs, not to mention other biologicals, 
chemicals, natural products, energy-healing systems, massage 
therapies and body work, and spirituality. It is a huge buffet 
to choose among.
    Our prioritization is based upon a number of 
considerations. First and foremost is which of these modalities 
are used the most by Americans today? Which have the potential 
to address the most important public health problems? So our 
modalities are towards diabetes, mental health, cancer, and 
heart disease. Our priorities, in terms of the disease areas, 
are the same as those of the other Institutes, because we know 
the public health message is important.
    We invest the largest amount of our energy and funds in 
those areas that seem, at this time, to be the most promising, 
like the preliminary data from the St. John's wort study, 
because the American public deserves definitive answers sooner. 
At the same time, we invest lesser amounts in exploratory 
studies to create a pipeline that will explore things that are 
more novel, for which there are little preliminary data. This 
entire analysis is not done by sitting in our Offices in 
Bethesda, but through the context of a constant dialogue with 
the American public, with patients, with their advocates, with 
members of industry, advocacy groups around specific diseases, 
and our advisory councils.
    I had the pleasure of addressing our Council for the first 
time on January 24th; I shared with them our prioritization, 
and their feedback was a very important, and instructive 
process for me.
    The results of this investigation, as you correctly said, 
Mr. Chairman, will have two potential outcomes. It will either 
show that something is effective or it is not. Frankly, if 
everything we do proves ineffective, no one will believe our 
message. In all honesty, one of our strategies for starting 
with things for which there is good evidence today, is to 
provide successes which will build trust with the American 
people, their advocates and our many constituents.
    If we give clear messages in an unbiased and scientific way 
that this works, but this does not, they are inclined to 
believe both of them. Because these products are in the 
marketplace, there may still be individuals who will have the 
freedom to choose what they wish. However the message from 
science can be a strong and effective one. Let us witness, for 
example, the change in demands for Laetrile 15 to 20 years ago, 
when many individuals were clamoring for it. Very good studies 
suggested, in fact, that it was not effective. There are still, 
today, people who seek and use Laetrile, but the number is much 
smaller. I think our message can have an impact on the public 
use.
    Mr. Porter. Thank you, Dr. Straus.
    Ms. Lowey.

                           DIET AND EXERCISE

    Mrs. Lowey. Thank you, Mr. Chairman, and welcome Dr. 
Straus. We wish you great success, as another New Yorker, even 
though you grew up in Brooklyn. I will not take too much time 
for that. [Laughter.]
    This is an Institute that has interested me for a long 
time, and I look forward to working with you because I think it 
is so very important for the public, for all of the reasons 
that our distinguished Chairman mentioned.
    In several of these hearings, we have been talking about 
diet, exercise, the confusing messages that have come out: 
drink a glass of red wine, do not eat the pasta, better to have 
fats and bacon, et cetera. I think most people do agree that we 
should exercise a few times a week and that Snickers and candy 
are not good for you.
    But the messages really are very confusing. And I wonder to 
what extent this Institute will be focusing on diet and the 
connections between that and good health. I would be interested 
in your comments.
    Dr. Straus. Thank you.
    First of all, Mrs. Lowey, let me say it is a pleasure to 
testify before you, and I look forward to establishing a 
relationship with your office. In sharing our experiences, my 
mother was born in the Bronx. [Laughter.]
    The issue of diet and exercise is a very important one to 
public health today. Fortunately, Americans are changing their 
practices, and it is for that reason that the mortality from 
cardiac disease has decreased as much as it has. Our young 
people are getting the message better than before, but it is 
still not adequate.
    The importance of diet and exercise are agreed upon by 
public health authorities and physicians. While we in NCCAM 
speak to the very same message, diet, merely for the sake of 
weight loss is not a high imperative for our research portfolio 
because that is so well-integrated into studies by NIDDK and 
others Institutes.
    Mrs. Lowey. Which diet?
    Dr. Straus. Ah.
    Mrs. Lowey. You see, it is the contradictory messages.
    Dr. Straus. Thank you.
    Mrs. Lowey. And I refer to the panel and the discussion at 
the Department of Agriculture, when you had Dr. Atkins on one 
side, Barry Sears on the other, Dean Ornish, I do not know, 
someplace in the middle. I guess he would be on the other side.
    Dr. Straus. There was an interesting debate among them. In 
the context of normal diets, low cholesterol, and low fat, I 
think we can agree with the limitation of calories. You are 
correct. There are extreme diets, and fad diets, and diets that 
incorporate the use of additional botanical products and 
supplements to help speed weight loss. Those are areas that we 
can address and invest in, and we do so.
    One of the issues related to diet, in fact, that bears on 
the Chairman's question as well has to do with the use of 
herbal and metabolic products along with diet, such as ephedra 
to speed weight loss.
    Mrs. Lowey. What is that in picolinate [ph.]? Something 
like that.
    Dr. Straus. I am sorry?
    Mrs. Lowey. Picolinate or that is in almost all of these--
--
    Dr. Straus. No, that is chromium.
    Mrs. Lowey. Chromium.
    Dr. Straus. Yes.
    Mrs. Lowey. But there is a second word, ``chromium''----
    Dr. Straus. Picolinate.
    Mrs. Lowey. Right.
    Dr. Straus. Yes. Thank you.
    Ephedra, a botanical that speeds metabolism, it is a drug 
like amphetamine, actually, and its chemical composition is 
used for diet. That is something we are interested in studying. 
In fact, I met recently with Mr. Levitt from the FDA. His group 
is charged with looking at all of the incidents of serious 
toxicity from long-term ephedra use in otherwise healthy young 
individuals. Chromium is important in its use in diet, both 
because it is said to ``burn fat,'' as well because of claims 
that it balances the body's use of sugar and sugar metabolism. 
We are developing a program, together with Dr. Alan Spiegel and 
his colleagues in NIDDK, to mount some studies of chromium for 
its effect on diabetes and diet.
    There are many dietary areas that do fall within the 
context of critical public health issues to which we can 
address our resources.
    Mrs. Lowey. How high a priority is it? Because we hear, and 
we discuss this probably because so many of our personal 
experiences bear on it, we have discussed this with many 
Institutes because obesity is the cause or one of the factors 
in so much illness. How high a priority is it at the Center?
    I have known several people who have been taking chromium 
picolinate. Where is it in terms of priorities?
    Dr. Straus. The Center is one year old and we are just 
mounting our portfolio, but it is already on our list of the 
top ten new priorities for new investment, depending upon our 
budgetary options for 2001. This is a priority that I have 
discussed with NIDDK.
    Mrs. Lowey. Well, I thank you, and I hear the buzzer. I 
look forward to working with you because, as our distinguished 
Chairman has said, these are, substances that millions of 
people are using. The health food stores are selling them, and 
I think it is an absolute priority and an urgency for the 
Institute to really do more research.
    Dr. Straus. Thank you. I agree with you. It is the public 
health opportunity that exists to address complementary and 
alternative medicine that really convinced me to take this 
position. I think this is a truly important issue for the 
American public. Because a substance is natural does not mean 
that it is ineffective or effective, and it certainly does not 
mean that it is safe. We need to address both of those at the 
same time.
    Thank you, Mrs. Lowey.
    Mrs. Lowey. Thank you.
    And thank you, Mr. Chairman.
    Mr. Porter. Thank you, Ms. Lowey.
    Mr. Jackson?

                         ESTABLISHMENT OF NCCAM

    Mr. Jackson. Thank you, Mr. Chairman, and thank you, Dr. 
Straus. I want to welcome you and thank you for taking the time 
to talk about NCCAM's budget.
    Dr. Straus, when was the Office of Alternative Medicine 
elevated to the National Center for Complementary and 
Alternative Medicine?
    Dr. Straus. The language, I believe, was in 1998, and it's 
established by the Secretary February 1999.
    [Clerk's note.--The Language was part of the FY 1999 
Omnibus Appropriation and its establishment was approved by the 
Secretary in February 1999.]
    Mr. Jackson. How many people were using alternative 
medicine at the time OAM was elevated to a Center?
    Dr. Straus. The estimate that year was upwards of 40 
percent of Americans.
    Mr. Jackson. That is very interesting because many of the 
disparities that I have been talking about over the course of 
the line of my questioning during these hearings actually 
predate the elevation of your department to a center, but I see 
that this approach to alternative medicine has at least been 
elevated to the level of a center as a priority. I am wondering 
what was the need to elevate the OAM?
    Dr. Straus. I was not in the OAM at that time and cannot 
speak to all the issues. I am sure that Dr. Kirschstein could 
give you that history better than I. As I reflect on it, I know 
that it was in response to the true public health significance 
of the opportunities and challenges brought by complementary 
and alternative medical practices today.
    Mr. Jackson. Public health significance?
    Dr. Straus. Yes.

                              ROLE OF FDA

    Mr. Jackson. One of the reasons I have been trying to 
elevate the Office of Research in Minority Health to the level 
of center is because I have always, at least from my 
perspective, assumed that addressing some of these disparities 
are of significance as well.
    I assume that before alternative medicines can be used that 
they are researched and approved by the FDA?
    Dr. Straus. No.
    Mr. Jackson. They are not?
    Dr. Straus. These are modalities that are in the market 
place and available today. You could walk into the supermarket 
and pull off the shelf and purchase any of the hundreds of 
different supplements and botanical products.

                           DRUG INTERACTIONS

    Mr. Jackson. I would imagine then that part of the 
responsibility and mandate of your center is to make sure that 
the coordination of various types of alternative medicines do 
not create complicated problems for individuals who might be 
taking, let us say, ginko biloba on the one hand, but drinking 
Earl Gray tea on the other hand, that that such combination 
might be troubling for someone?
    Dr. Straus. Exactly right. If we are to presume that the 
chemical and biological modalities, as opposed to magnets and 
other things, are truly active then they can be active only 
because they can affect the body's inherent physiology. This 
would mean that you are drawing upon its effects for beneficial 
purposes; there may be expected or unexpected and, in some 
cases, serious untoward effects as well. As I illustrated in my 
prior comments, our studies of St. John's Wort provide just one 
such example. We are funding investigations through botanical 
centers, together with the Office of Dietary Supplements, to 
address the pharmacology of these substances, and drug 
interactions.
    As I pointed out in the display panel, there was a 10-fold 
reduction in blood level of an important HIV drug, simply by 
adding St. John's Wort into the drug cocktail, at a level which 
is now at risk of being ineffective in promoting treatment 
effectiveness.
    Your question is a very important one for our research 
agenda.

                        DEMOGRAPHICS OF CAM USE

    Mr. Jackson. I have just maybe two more questions if I can 
squeeze them in before the bell goes off.
    You said an estimated 40 percent of Americans were using 
alternative medicines. I wonder if there is any data to suggest 
that let us say 45 million Americans who do not have any form 
of health care are using alternative medicines because they 
cannot afford prescription drugs, or the vast majority of those 
Americans who have no form of health coverage, whatsoever, that 
they are using alternative medicines as a way around a system 
that they fundamentally cannot afford?
    Dr. Straus. That is an important question. Although there 
are surveys reported, I believe that we can do better in 
surveying the American people, and I have been meeting with 
staff from the Centers for Disease Control to talk about how we 
can do a better analysis of the demographics of CAM use across 
the country regionally, in terms of ethnic and racial groups, 
by gender, and by socioeconomic and educational status.
    The existing data suggest that there is a greater use in 
wealthier Americans, because these treatments are not 
reimbursable and they are paid for out-of-pocket. Americans 
spent over $27 billion out-of-pocket in 1996 to 1997 for these 
therapies.
    But individuals who do not have the same disposable income 
do turn to complementary and alternative therapies, because in 
many instances they have grown up with them. Our studies have 
the capacity to address health disparities in a unique way 
through our center. African Americans in the rural South, 
Hispanic Americans in the Southwest, Native Americans in the 
Southwest, the Inuits and the Hawaiians, as well as immigrants 
from other countries, brought with them or sustain from their 
own cultures the belief in their own approaches to health care. 
In some instances, these practices do replace mainstream, 
conventional therapeutics.

              TOTAL HEALTH CARE COSTS ASSOCIATED WITH CAM

    Mr. Porter. Thank you, Mr. Jackson.
    Dr. Straus, let us talk about dollars. Are there estimates 
as to the total health care costs including all forms, all 
therapies and then is there an estimate of those that are under 
your purview? In other words, what proportion of the total 
health care costs would you be looking at?
    Dr. Straus. Mr. Chairman, I do not know the answer to that 
question because a lot of that data has not been accumulated. I 
do know the estimates of out-of-pocket expenditures, as I have 
indicated, and I also know that health maintenance 
organizations and insurers are increasingly reimbursing the 
costs of cam treatments, particularly for acupuncture and 
chiropractic care. Over 70 percent of HMOs are offering some of 
these practices, not necessarily because they are proven. 
Although there are proven benefits of acupuncture for chronic 
pain, for example, some are offered because the market is 
demanding it.
    Mr. Porter. I guess that there is no way to really draw the 
line between what is traditional because acupuncture, for 
example in my judgment, has crossed the line into traditional 
now.
    Dr. Straus. Yes. That is absolutely correct.
    Mr. Porter. It is accepted.
    Dr. Straus. Acupuncturists are licensed in many states and 
it is practiced in all 50 States. Many individuals are turning 
to acupuncture for relief of chronic pain when they cannot 
obtain relief elsewhere.

                          FUNDING GOOD SCIENCE

    Mr. Porter. If we look at the office that preceded you and 
we looked at their budget, and then we looked at where we are 
today and where we are likely to go, in fiscal year 1998 there 
was about $20,000,000 put in this account and none of that 
could be used directly by the office to fund research. It had 
to go through an institute----
    Dr. Straus. That is correct.
    Mr. Porter [continuing]. And get them to approve it. We 
raised it to $50,000,000--I am using round figures--in fiscal 
year 1999; $68,000,000 in this fiscal year and while the 
President is indicating $72,000,000, we hope to go considerably 
higher than that. And, so, your office, now-center, is going to 
have perhaps a 400 percent increase in four years or 100 
percent average increase per year.
    Now, there is not a research community out there that has 
been doing this kind of research, at least on these particular 
therapies or modalities. Are you able to spend that kind of 
increase wisely? In other words, has science lined up to do 
this kind of research in the last year or two in a way where 
you know you are funding good research, using the money wisely?
    Dr. Straus. That is a very important question. And let me 
say that I am convinced that we are funding good science, that 
we are getting increasing numbers of applications and they are 
increasingly excellent. In fact, our ability to fund 
applications, percentage-wise, will fall over the coming year 
or two because of the rate of new applications.
    Part of the reason for the growth in applications and their 
quality has to do with the fact that there is, a latent need 
that had not been addressed previously to study these various 
modalities. Many of these modalities have been, can be, and are 
now being studied by some of the country's best investigators.
    So, for example, the St. John's wort study is a multi-
center trial that is being conducted by some of the best mental 
health scientists, psychiatric experts and investigators of 
antidepression, of antidepressant drugs. Our Ginko Biloba trial 
is being conducted together with the National Institute on 
Aging by the best individuals who understand the process of 
dementia in aging Americans. So, a lot of our early research 
advances require nothing more than seducing good, smart people 
to turn their focus where there is a great new opportunity and, 
of course, money speaks.
    These investigators recognize the potential of cam. Not 
only is the scientific community embracing what we are doing, 
the patient advocate community seems to be thrilled as well 
with what is happening. My colleagues in the other NIH 
institutes and centers have come to the plate, as well. I have 
personally met with all the institute and center directors as 
well as representatives of all the other health agencies in a 
trans-agency committee that I chair and they are eager to 
collaborate. For example, this afternoon I am addressing a 
planning committee for the FY 2002 portfolio for the Aging 
Institute. I will be addressing the advisory council of the 
Arthritis Institute.
    We are joining together and funding good research. While 
your generous funding has allowed a rapid growth in NCCAM's 
budget, at the same time the total spending over the past three 
years by the other institutes has not diminished; it has 
increased by an additional 181 percent. So, we could address 
the increase. Now, if you gave us a billion dollars tomorrow we 
could not address wisely. We have to do this in a tiered, 
thoughtful way.
    Mr. Porter. Yes, sir. Well, that is exactly what I wanted 
to know. Mrs. Lowey, any further questions?
    Mrs. Lowey. I do not think so, Mr. Chairman.
    Mr. Porter. Mr. Jackson
    Mr. Jackson. Thank you, Mr. Chairman.
    I just have a brief statement. Dr. Straus has really 
motivated me today.
    Mr. Porter. Good.
    Mr. Jackson. Because of the rapid growth of his field of 
expertise and the rapid growth of funding across NIH and 
certainly the considerations that this Committee are going to 
make with respect to his budget but particularly his ability to 
offer grants in areas that further explore and study this has 
just motivated me for a number of reasons, Mr. Chairman, and I 
want to congratulate Dr. Straus for what I am sure will be an 
extremely beneficial effort on behalf of all the American 
people in the Office of Alternative Medicine, now, elevated to 
National Center for Complementary and Alternative Medicine. I 
hope to elevate at some point in time if we see the wisdom in 
this, the same type of coordination across centers for minority 
health and minority research so that whomever that director 
might be one day they might be able to come and say that I got 
a very busy schedule this afternoon because I have to go to the 
Cancer Institute and I have to go to the Diabetes Institute and 
I am coordinating across the entire Center these efforts and we 
are going to be issuing some grants to study this in this area.
    And I want to make just one other brief argument. And that 
is the cultural argument that you made that some of these roots 
in alternative medicines come from Native American culture, 
they come from Africa, they come from a lot of rural cultures 
that have had to rely upon not the sophistication that NIH has 
offered but what is available to them as alternatives to pain 
and disease and illness. It would just seem so logical to me 
that these alternative medicines which have deep roots in these 
various cultures, that much of the research since these have 
been very long-standing traditions in many of these cultures 
that the experts in this area would, at some point in time, 
begin to reflect those cultures for which have been using these 
various remedies for a number of years.
    And, so, I thank you, Dr. Straus and thank you, Mr. 
Chairman, for the time.
    Dr. Straus. Thank you, Mr. Jackson.
    Mr. Porter. Thank you, Mr. Jackson.
    Dr. Straus, what you are doing is to us very, very 
important. The buying habits of people in a free society ought 
to direct us to have our energies applied to making sure that 
their money is wisely spent and they are safe from materials or 
therapies that could be dangerous to them. And I think the 
amount, the field that you have to cover is absolutely huge. We 
are anxious to give you the resources you need to do as much of 
that as quickly as possible but with good science.
    I will watch, perhaps a little bit outside the institution, 
but watch with great interest as your mission grows and is 
fulfilled and see the kinds of good scientific work that can be 
brought to bear on understanding what does work and what does 
not.
    I think it is very, very important. We am glad you are 
there. We wish you well.
    Dr. Straus. Thank you, Mr. Chairman, and I look forward to 
continuing to learn your perspective for coming years.
    Mr. Porter. Thank you, Dr. Straus.
    The Subcommittee will stand in recess until 2 p.m.
    [The following questions were submitted to be answered for 
the record:]





                           W I T N E S S E S

                              ----------                              
                                                                   Page
Baldus, A.C......................................................   299
Barros, C.F......................................................   415
Christoferson, D.P...............................................    61
Duff, Judith.....................................................  1073
Fauci, A.S.......................................................   921
Ficca, S.A.......................................................  1389
Fischbach, G.D...................................................   299
Fitzsimmons, W.T.................................................   511
Fivozinsky, C.L..................................................  1073
Grady, Dr. P.A...................................................     1
Hausman, S.J.....................................................   761
Hernandez, Milton................................................   921
Hodes, Dr. R.J...................................................   415
Hollingsworth, Christine.........................................  1435
Hyman, S.E.......................................................   511
Itteilag, Anthony................................................  1389
Johnson, Laurie..................................................   177
Katz, S.I........................................................   761
Kerza-Kwiatecki, M.S.............................................   761
Kirby, K.E.......................................................   299
Kirschstein, Dr. R.L.............................................    1,
     61, 177, 299, 415, 511, 617, 761, 845, 921, 1073, 1137, 1389, 1435
Kupfer, Dr. Carl.................................................  1073
Laurence, Earl...................................................   617
Lenfant, Dr. Claude..............................................    61
Leveck, Dr. Mary.................................................     1
Little, F.V......................................................   177
Maddox, Yvonne...............................................1137, 1389
McLaughlin, Dr. J.A..............................................  1073
Nahin, Richard...................................................  1435
Nakamura, R.K....................................................   511
Nathanson, Neal..................................................  1137
Olden, Kenneth...................................................   177
Penn, A.S........................................................   299
Pine, J.R........................................................   511
Pinn, V.W........................................................  1137
Quantius, Susan..................................................  1389
Ramm, Dr. L.E....................................................   845
Rivera, Heriberto................................................     1
Rosano, W.V......................................................     1
Ross, K.S........................................................   415
Roth, Dr. Carl...................................................    61
Ruffin, John.....................................................  1137
Speigel, Dr. A.M.................................................   617
Strachan, R.J....................................................   761
Strandberg, Dr. John.............................................   845
Straus, S.E......................................................  1435
Summers, A.E.....................................................   845
Tibbs, John......................................................    61
Vaitukaitis, Dr. J.L.............................................   845
Weiblinger, G.M..................................................   511
Wetle, Dr. Terrie................................................   415
Williams, D.P....................................................    1,
          61, 177, 415, 511, 617, 761, 845, 921, 1073, 1137, 1389, 1435
Williams, Patrick................................................  1435
Williams, Thomas.................................................   921
Wilson, S.H......................................................   177
Zellers, C.R.....................................................   617


                               I N D E X

                              ----------                              

                 National Institute of Nursing Research

                                                                   Page
Administrative Supplements.......................................    22
Area Program.....................................................    24
Average Size of Grants...........................................    22
Chronic Illness Research.........................................     2
Conclusion.......................................................     3
Competing Renewal Grants.........................................    22
Competing and Noncompeting Grants................................    20
Education Level of RNs...........................................    14
End-of-Life Research............................................. 2, 19
Geographic Distribution of Grants................................    24
Health Disparities Research......................................     2
Health Care of the Future........................................    15
Intramural Laboratory for Health Promotion.......................    28
Intramural Wound Healing Laboratory..............................    26
Introduction of Witnesses........................................     1
Justification of the FY 2001 Budget Request......................    30
Mechanism Table of NINR Funding..................................    26
Medical Imaging..................................................    18
Medical Errors...................................................    18
Needs of Family Caregivers.......................................    29
NIH Development of Technology....................................    18
Opening Statement of the Director................................     1
Pain Research....................................................    13
Prevention of Illness............................................    16
Regional Differences in Health Care..............................    20
Research Centers.................................................    23
Self-Management of Chronic Illness...............................    16
Telehealth Technology............................................    17
Telehealth Projects..............................................    27
Training and Career Development..................................     3
Transitional Care for Heart Failure Patients.....................    28

               National Heart, Lung, and Blood Institute

Addressing Health Disparities....................................    77
Asthma.............................................67, 84, 97, 109, 119
Behavioral Programs..............................................   118
Black Lung.......................................................   115
Budget Mechanism Table...........................................   103
Clinical Research Networks......................................75, 115
Congenital Heart Defects.........................................   110
Congenital Heart Research........................................   104
Congestive Heart Failure.........................................    65
Cord Blood Transplantation Study.................................    95
Coronary Artery Disease..........................................    92
Diabetes.........................................................91, 97
Dietary Sodium and Blood Pressure................................    98
Disease Areas....................................................    99
Dr. Atkins Diet..................................................   118
Focus on the Individual Patient..................................    75
Funding for Disease Areas........................................    94
Gene Therapy.....................................................    87
Government Performance and Results Act...........................    77
Heart Failure....................................................    81
Jackson Heart Study..............................................    86
Justification of Budget Estimates................................   121
Kidney Disease...................................................    91
Magnetic Resonance Imaging.......................................69, 74
Minority Data Collection.........................................    85
Minority Medical School Research................................86, 108
Minority Training Programs.......................................   104
National Emphysema Treatment Trial...............................    94
Neurofibromatosis................................................    77
Opening Remarks..................................................    61
Opening Statement................................................    72
Patient Information Access.......................................    83
President's Request..............................................    77
Primary Pulmonary Hypertension...................................   111
Programs for Genomic Analysis....................................    73
Programs of Excellence in Gene Therapy..........................74, 105
Public Access to Defibrillators..................................    89
Research Opportunities...........................................    82
Retinoic Acid Clinical Trial.....................................    98
Sleep Apnea......................................................   106
Sleep Disorders..................................................   116
Spiral Computed Tomography.......................................   109
Trans-Agency Conference on Cardiovascular Disease................   113
Using MRI to Diagnose Heart Attack...............................    74
Women's Health Initiative........................................95, 98

          National Institute of Environmental Health Sciences

Agricultural Health Study........................................   229
ARCH.............................................................   227
Biomarkers.......................................................   226
Biomedical Research Laboratories and Clinical Facilities.........   222
Breast Cancer..................................................212, 241
Budget Mechanism.................................................   221
cDNA Micoarray Technology........................................   204
Children's Health................................................   233
Children's Health Research Agenda..............................205, 240
Children's Research Database.....................................   228
Collaborations with NCI..........................................   209
Community Concerns...............................................   248
Cooperative Initiative with CDC and EPA..........................   227
Cre-lox System...................................................   226
Education of Physicians..........................................   216
Electric and Magnetic Fields.....................................   220
Eliminating Uncertainties........................................   184
Environmental Health Decision Making.............................   177
Environmental Health Problems....................................   246
Environmental Justice..........................................220, 247
Finding Minority Biomedical Researchers..........................   210
Health Disparities...................................215, 224, 245, 249
Health Disparities and Environment...............................   237
Herbal Medicines.................................................   214
Huntger's Point Shipyard.........................................   239
Individual Susceptibility......................................180, 208
Interdisciplinary Conference on Fibroids.........................   230
Introduction of Witnesses........................................   177
Justification of FY 2001 Budget Estimate.........................   250
Low Levels of Exposure...........................................   206
Minority Researchers and or Minority Serving Institutions........   249
Mixtures.........................................................   213
National Allergen Survey.........................................   223
National Toxicology Program......................................   219
National Toxicology Report on Carcinogens........................   234
Oceans and Human Health..........................................   217
Opening Statement................................................   188
Outreach Efforts.................................................   211
Parkinson's Disease..............................................   215
Pediatric Asthma.................................................   243
Pesticides.......................................................   224
Red Tide in Florida..............................................   232
Superfund........................................................   219
Time Frame for New Technology....................................   207
Town Meetings....................................................   220
Transgenic Animals.............................................204, 223
Women's Health Research..........................................   229
Workshop on Risks................................................   236

        National Institute of Neurological Disorders and Stroke

Alzheimer's Research.............................................   318
Amyotrophic Lateral Sclerosis (ALS)........................... 324, 346
Animal Models of Disease.........................................   337
Areas of Research Promise........................................   351
Batten Disease...................................................   329
Brain:
    A Healthy Brain for Life.....................................   307
    Brain Cell Replacement.......................................   317
    Brain Development............................................   347
    Healthy Brain Project........................................   335
    Working Together to Fight Brain Disease......................   309
Diabetes Neuropathy..............................................   341
Dissemination of Information.....................................   323
Dopamine.........................................................   341
Drug Design......................................................   328
Duchenne's Muscular Dystrophy....................................   323
Dystonia.........................................................   333
Epilepsy................................................. 330, 336, 344
FSH Dystrophy....................................................   352
Fiscal Year 2001 Budget Request..................................   305
Funding for Specific Diseases....................................   327
Halting the Process of Neurodegeneration.........................   308
Health Disparities:
    Health Disparities........................................ 303, 320
    Reducing Health Disparities..................................   309
    Rural Health Disparities.....................................   348
Infrastructure Supplement Program................................   301
Justification of the FY 2001 Budget Estimates....................   356
Lou Gehrig's Disease.............................................   337
Multiple Sclerosis:
    From Discovery to Practice...................................   316
    Multiple Sclerosis...........................................   302
National Neuroscience Research Center............................   303
Neurodegenerative Disorders......................................   335
Parkinson's
    Parkinson's Centers..........................................   328
    Parkinson's Disease..........................................   303
    Parkinson's Research.........................................   301
Reflex Sympathetic Dystrophy.....................................   354
Pediatric Neuroimaging...........................................   327
Plans for FY 2001................................................   302
Poor Dietary Habits..............................................   326
Repairing the Injured Nervous System.............................   308
Replacement of Lab Equipment.....................................   317
Research Funding Policy..........................................   349
Specialized Centers..............................................   330
Spinal Cord Injury...............................................   339
State Strengths..................................................   348
Statement of the Director........................................   306
Stem Cell Research...............................................   333
Strategic Planning...............................................   300
Stroke:
    Dietary Factors and Stroke...................................   322
    Genetics and Stroke..........................................   343
    Stroke.......................................................   347
    Stroke in Minorities.........................................   319
    Stroke Research..............................................   321
    t-PA and Stroke Research.....................................   341
Use of Funding Increase..........................................   300
Use of FY 2000 Increase..........................................   306
Witnesses........................................................   305

                      National Institute on Aging

Aging Population.................................................   455
Alzheimer's Disease Research......... 415, 428, 436, 448, 452, 457, 458
Anatomy of Memory (Chart #1).....................................   417
Becoming Physically Fit Reduces Mortality in Elderly Persons 
  (Chart #4).....................................................   423
Behavioral and Social Research...................................   475
Biology of Aging......................................... 420, 430, 474
Cancer Research..................................................   452
Collaboration With Other NIH Institutes..........................   441
Complementary and Alternative Medicine...........................   439
Declining Disability Rates.......................................   441
Elder Abuse......................................................   453
Exercise.........................................................   456
Interdisciplinary Aging Research.................................   455
Justification of the FY 2001 Budget Estimates....................   459
Lifestyle and Health.............................................   437
Longevity Genes Across Species (Chart #3)........................   421
Medication Problems..............................................   449
Mild Cognitive Impairment..................................... 437, 440
Neuroscience of Aging............................................   464
NIA Budget--FY 1998 to FY 2001...................................   450
Nutrition........................................................   444
Opening Statement............................................. 415, 427
Production of Amyloid Plaques (Chart #2).........................   419
Reducing Disease and Disability.......................... 422, 431, 469
Reducing Health Disparities................................... 424, 433
Resource Directory for Older People..............................   452
Significant Items in the House and Senate Appropriations 
  Committee Reports..............................................   492
Stem Cell Research...............................................   448
Strategic Plan...................................................   453
Success Rates....................................................   445

                  National Institute of Mental Health

Accessing the Newest Advanced Treatments.........................   569
Antidepressant Effects on SAM-e..................................   562
Applying Behavioral Science to Public Health.....................   517
Areas of New Investment..........................................   521
Atrophy of the Hippocampus in Depression (Figure 1)..............   514
Attention Deficit Disorder Study.................................   513
Behavioral Aspects of Gambling...................................   552
Budgetary Flux...................................................   548
Centers for Translational Science................................   522
Communication Between NIMH and Educators.........................   543
Comprehensive Treatment Approach.................................   538
Defining the Boundaries of Mental Disorders......................   539
Disseminate Best Practice Information............................   534
Engaging Young People in Mental Health Treatment.................   537
Enhancing Providers' Skills......................................   543
Growing Awareness of Mental Disorders............................   511
Healthy Brain Project............................................   556
Heightened Public Awareness of Mental Illness....................   521
Homeless Mentally Ill People.....................................   557
Identifying Vulnerability Genes for Mental Disorders.............   523
Impact of Life Experience on Behavior............................   547
Improving Treatment of Childhood Disorders.......................   541
Justification of the FY 2001 Budget Estimates....................   573
Medication for ADHD..............................................   552
Mental Illness:
    Childhood....................................................   560
    Incarceration................................................   570
    Stigmatizes..................................................   536
Minority Researchers.............................................   564
Minority Investigators and Institutions..........................   571
Minority Groups' Mental Health...................................   545
Multi-Modal Treatment Assessment of ADHD.........................   524
New Approach to Clinical Trials..................................   512
New Brain Cell Growth (Figure 2).................................   516
New Brain Imaging Technologies...................................   535
New Clinical Effectiveness Trials................................   523
NIMH Budget Distribution.........................................   548
NIMH Budget Mechanism Table Including AIDS.......................   554
Parental Involvement.............................................   538
Public Education About Child Health..............................   545
Rates of Mental Disorder by Racial/Ethnic Identity...............   544
Redirection of NIMH Research Programs............................   548
Research:
    Basic Research of Mental Disorders...........................   515
    Child Mental Health Research Infrastructure..................   542
    HIV Prevention Research Centers..............................   566
    NIMH Support of Research on Selected Disorders...............   553
    Prevention Research..........................................   549
    Protection of Research Participants..........................   557
    Research Collaborations With India...........................   558
    Research Grant Success Rates.................................   530
    Research on ``Bad Behavior''.................................   539
    Research on Health Disparities...............................   524
    Research on Stereotyping and Discrimination..................   540
    Translation of Research Advances Into Treatment..............   568
    Treatment Adherence Research.................................   537
    Treatment Research on Autism.................................   523
    Use of Research Budget Increase..............................   531
Ritalin and Hyperactivity........................................   535
Stress and Mental Health.........................................   527
Suicide:
    Adolescent Suicide Rates (Figure 3)..........................   519
    Risk Factors for Youth Suicide...............................   531
    Suicide and Young People.....................................   569
    Trends in Youth Suicide......................................   528
    Youth Suicide................................................   520
Transcranial Magnetic Stimulation................................   534
Treatment of ADHA............................................. 536, 562
Use of Psychoactive Medications in Children......................   532
Violence:
    Research on Youth Violence...................................   524
    Societal Role Models for Youth Violence......................   529
    Violence by Young People.....................................   561
    Youth Violence...............................................   526
Viral Role in Schizophrenia......................................   556

    National Institute of Diabetes and Digestive and Kidney Diseases

Acute Liver Failure and Brain Function...........................   663
Autoimmune Diseases..............................................   679
Budget Mechanism Table...........................................   665
Clinical Guidelines on Overweight and Obesity in Children........   663
Clinical Trial Networks..........................................   678
Cooley's Anemia..................................................   686
Crohn's Disease..................................................   645
Database for Urologic Diseases...................................   672
Designer Antibodies..............................................   667
Diabetes:
    Diabetes--Health and Economic and Burden.....................   655
    Diabetes Prevention Program..................................   619
    Diabetes Prevention Trial....................................   662
    Diabetes Research............................................   618
    Diabetes Research Advances...................................   634
    Diabetes Research Funding....................................   656
    Diabetes Research Working Group............ 620, 635, 654, 687, 689
Diabetic Foot Ulcers.............................................   664
Disease Funding..................................................   660
End-Stage Renal Disease..........................................   639
Funding History of Diabetes-Related Research.....................   660
Future of Medical Research.......................................   683
Gene Therapy and Its Alternatives................................   640
Genetics of Diabetes.......................................... 635, 636
Health Disparities Research................................... 641, 643
Hepatits C.................................................... 618, 649
H. Pylori Education Campaign.....................................   659
High Risk Research...............................................   672
Inflammatory Bowel Disease.......................................   651
Insulin..........................................................   669
Interstitial Cystitis.................................... 637, 651, 681
Intramural Transplant Program....................................   670
Introduction of Witnesses........................................   617
Justification of the FY 2001 Budget Request......................   690
Kidney Disease in Minority Population............................   674
Kidney Disease Prevention Effort.................................   674
Kidney Genome Program............................................   675
Kidney Genome Anatomy Program (KGAP).............................   684
Medical Therapy of Prostate Symptoms Clinical Trial..............   668
Minority Investigators...........................................   651
Minority Investigators and NIH Peer Review.......................   643
Minority Medical Students and Loan Repayment.....................   644
National Analgesic Nephropathy Study.............................   658
National Diabetes Education Program..............................   661
National Kidney Disease Education Project........................   683
MIDDK Funding....................................................   687
NIDDK Implementation of DRWG Recommendations.....................   688
NIDDK Support for 20 States......................................   647
New Urology Research.............................................   669
Obesity Research.................................................   642
Opening Statement................................................   617
Pancreatic Islet Cell Transplants................................   619
Polycystic Kidney Disease........................................   618
Research Funding Across the Nation...............................   646
Research Management Support......................................   667
Stem Cell Research...............................................   648
Study of Health Outcomes of Weight-Loss Clinical Trial...........   664
Transplant Biology...............................................   679
Treating Hepatitis C.............................................   671
Type 1 Diabetes:
    Type 1 Diabetes............................................654, 677
    Type 1 Diabetes Prevention...................................   638
    Type 1 Diabetes Trial Network................................   650
Urology Research Plans...........................................   668
Vaccine Against H. Pylori........................................   659
Vaccine Against Urinary Tract Infection..........................   658
Women in Clinical Trials.........................................   653

 National Institute of Arthritis and Musculoskeletal and Skin Diseases

Alternative Medicine.............................................   793
Autoimmunity.....................................................   766
Biographical Sketch..............................................   770
Cardiovascular Lupus.............................................   787
Clinical Research.........................................762, 765, 779
Conclusion.......................................................   769
Duchenne Muscular Dystrophy......................................   777
Ehlers-Danlos Syndrome...........................................   775
Fibromyalgia...................................................763, 767
Funding for Disease Areas........................................   787
Gene Therapy.....................................................   792
Health Disparities........................................763, 769, 775
Intramural Research Program......................................   795
Intramural Research Training.....................................   791
Introduction of Witnesses........................................   761
Justification of FY 2001 Budget Estimates........................   796
Location of NIAMS Funded Clinical Research.......................   780
Lupus..........................................................772, 774
Muscle Diseases..................................................   767
Muscular Dystrophy...............................................   762
NIAMS Budget Mechanism...........................................   788
NIAMS Relationship with ORMH.....................................   775
Osteoarthritis............................................767, 790, 794
Osteogenesis Imperfecta..........................................   789
Osteoporosis....................................762, 768, 778, 790, 793
Peer Review Process..............................................   784
Skin Diseases....................................................   768
Sports Injuries..................................................   789
Statement of the Director........................................   761
Stem Cell Research...............................................   791
Systemic Lupus Erythematosus.....................................   768
Tribute to Mr. Porter............................................   785

                 National Center for Research Resources

Animal Research Facilities at HBCUs..............................   880
Bioengineering, Computers and Advanced Instrumentation........ 846, 853
Bioinformatics................................................ 847, 873
Budget Mechanism Table...........................................   870
Career Development....................................... 848, 856, 875
Chimpanzee Management Program....................................   863
Clinical Research................................................   878
Clinical Research Training.......................................   864
Computers in Biomedical Research.................................   877
Diabetes Research................................................   861
Director's Biographical Sketch...................................   858
Extramural Construction....................................... 871, 879
Extramural Facilities......................................... 871, 880
Funding for Selected Programs....................................   869
Genetic Medicine.............................................. 848, 855
Health Disparities.............................................848, 855
Institutional Development Awards.............................. 861, 872
Justification of FY 2001 Budget Estimates........................   882
NCRR Impact......................................................   874
Noncompeting Research Grants.....................................   872
Opening Statement of Dr. Judith L. Vaitukaitis, M.D..............   845
Primate Research Centers.........................................   869
Research Capacity........................................ 848, 856, 875
Research Centers in Minority Institutions........................   880
Research Facilities..............................................   859
Research Intensive Schools.......................................   876
Science Education................................................   867
Southwest Foundation.............................................   861
Supercomputers...................................................   871
Synchrotrons.................................................. 847, 865

         National Institute of Allergy and Infections Diseases

AIDS:
    AIDS...................................................... 926, 967
    AIDS Therapies...............................................  1010
    Centers for AIDS Research....................................  1014
    HIV/AIDS................................................. 973, 1007
    HIV Prevention Efficacy Trials...............................  1013
    HIV, Tuberculosis, and Malaria Vaccine Research..............  1011
Antibacterial and Antifungal Study Groups........................   990
Asthma................................................... 966, 969, 979
Autoimmune:
    Autoimmune Diseases....................................... 985, 999
    Immune Mediated Diseases and Autoimmune Diseases.............   998
    Immune Tolerance Network........................ 936, 964, 977, 990
    Immunology...................................................   934
Availability of Primates.........................................   995
Bioterrorism.....................................................   992
Consortia Involved in Nevirapine.................................   996
Emerging Diseases................................................   930
Genome:
    Pathogen Genome Sequencing...................................   932
    Sequencing Genome Pathogens..................................   988
Global Health....................................................   921
Health Disparities............................................ 938, 970
Hepatitis C Research.............................................   986
HPV:
    HPV and Topical Microbicides.................................   968
    HPV Vaccine Research.........................................   969
Human Choreatic and Autotrophic Hormone..........................   981
Infectious Diseases:
    Infectious Diseases..........................................   924
    Status of Approaches and Vaccines for Infectious Diseases....  1005
    Worldwide Deaths from Infectious Diseases....................   963
Infectious Etiology of Chronic Diseases..........................   994
Influenza.................................................... 963, 1006
Introduction of Witnesses........................................   921
Justification of FY 2001 Budget Estimates........................  1020
Lyme Disease:
    Accuracy of Current Lyme Disease Tests.......................  1004
    Guidance for Diagnosis and Treatment of Lyme Disease.........  1004
    Lyme Disease.............................................. 982, 987
    Lyme Disease Diagnostic Tests................................  1005
    Tests for Lyme Disease.......................................  1003
Malaria..........................................................  1006
Microbicide Research..............................983, 1015, 1018, 1019
Nevirapine...........................................928, 965, 976, 996
NIAID Funding for Autoimmune Diseases............................   999
NIAID Genomics Resource Center...................................   989
NIAID Minority Programs..........................................   971
NIAID Payline....................................................   978
NIAID Strategic Plan.............................................   940
Opening Statement..............................................921, 943
Participation of Veterans in NIAID Research......................  1016
RMS FTEs.......................................................988, 990
Ryan White Care Program..........................................  1010
Tuberculosis.....................................................  1009
Unfunded Science.................................................   979
Vaccines:
    HIV, Tuberculosis, and Malaria Vaccine Research..............  1011
    Vaccine Safety...............................................   997
Various Spending Levels..........................................   985

                         National Eye Institute

Additional Opportunities.........................................  1086
Budget Mechanism Table...........................................  1092
Cataracts....................................................1088, 1094
Collaborations...................................................  1089
Computer Chip for Retinitis Pigmentosa...........................  1084
Congenital Nystagmus.............................................  1090
Core Grants for Vision Research..................................  1093
Funding Increases................................................  1084
Introduction of Witnesses........................................  1073
Justification of the FY 2001 Budget Estimates....................  1098
Laser Surgery/Lasik Eye Surgery..................................  1096
Lens Research....................................................  1096
Light-Activated Drug for Age-Related Macular Degeneration........  1087
Myopia and Night Lights..........................................  1086
NEI Funding......................................................  1097
Opening Statement of Dr. Carl Kupfer.............................  1073
Pink Eye.........................................................  1094
Summary of Eye Disease Funding...................................  1092
Uveitis..........................................................  1094
Vision Correction Surgery........................................  1088

                        Office of AIDS Research
                                  and
                         Office of the Director

Academic Research Enhancement Award Program......................  1165
Actual Outlays by Institute......................................  1192
AIDS and Gene Therapy............................................  1178
AIDS Epidemic....................................................  1140
AIDS Research Programs...........................................  1148
Benefits of AIDS Research:
    For Developing Nations.......................................  1186
    To Other Diseases............................................  1181
Budget Request:
    Office of AIDS Research......................................  1138
    Office of the Director.......................................  1162
Competing/Non-Competing Grant Awards.............................  1190
Consensus Conference.............................................  1200
Dietary Supplements..............................................  1201
Discretionary Fund...............................................  1176
Domestic Health Disparities......................................  1197
Figures:
    AIDS Incidence by Race and Sex, USA..........................  1143
    AIDS Therapy.................................................  1147
    AIDS Vaccine.................................................  1151
    Addressing Health Disparities................................  1166
    Annual HIV Infection Rate per 100 Persons....................  1145
    Estimated Number of Persons Living with HIV/AIDS.............  1153
    HIV/AIDS Prevention..........................................  1149
    HIV Incidence and HIV/AIDS Prevalence, Sub-Saharan Africa....  1139
    Incidence and Prevalence of HIB/AIDS, USA....................  1141
    Special Programs.............................................  1163
Funding From Foundation..........................................  1200
Health Disparities...............................................  1167
HIV Prevention Research..........................................  1187
Introduction of Witnesses........................................  1137
Investment in AIDS Research......................................  1179
Justification of Budget Estimates:
    Office of AIDS Research......................................  1205
    Office of the Director.......................................  1244
Loan Repayment Program...........................................  1164
Minority Health Initiative...................................1197, 1198
National Nutrition Summit........................................  1201
OD Office Funding Levels.........................................  1190
Office of AIDS Research..........................................  1176
Office of Science Education......................................  1162
Opening Remarks..................................................  1137
Opening Statement:
    Office of AIDS Research......................................  1155
    Office of the Director.......................................  1168
Outlays:
    FY 1996......................................................  1193
    FY 1997......................................................  1194
    FY 1998......................................................  1195
    FY 1999......................................................  1196
Peer-Reviewed Grants.............................................  1197
Prevention of Mother-To-Child Transmission.......................  1177
Priorities in Behavioral and Social Sciences.....................  1200
Pubmed Central...................................................  1203
Research Development at Institutions.............................  1202
Study of Security at Bethesda Campus.............................  1202
Tobacco Litigation...............................................  1203
Unobligated Carryover Balance....................................  1191
Viral Reservoirs.................................................  1178
Women's Health Initiative........................................  1199

                        Buildings and Facilities

AIDS Clinical Trials.............................................  1402
AIDS Vaccine.....................................................  1403
BECON............................................................  1405
Brain Research Centers...........................................  1412
Carribean Primate Research Center................................  1411
Central Vivarium.................................................  1413
Child Care Facilities............................................  1407
Curriculum Vitae.................................................  1394
Essential Safety and Health Improvements.........................  1409
Fruit Fly Collaboration..........................................  1397
Justification of the FY 2001 Budget..............................  1415
Office of Research on Minority Health Advisory Council...........  1399
Oral Remarks.....................................................  1389
Opening Statement................................................  1391
Phoenix, Arizona Laboratory Funding..............................  1412
Power Plant and Boiler System....................................  1414
Reform of the Peer Review Process................................  1406
Safety and Health Improvements...................................  1413
Science Education Activities.....................................  1406
Sequence of the Human Genome.................................1395, 1398
U.N. AIDS........................................................  1403

       National Center for Complementary and Alternative Medicine

Acupuncture for Treatment During Pregnancy.......................  1472
Budget Mechanisms--FY 1999, 2000, 2001...........................  1466
CAM Therapies for HIV/AIDS.......................................  1475
CAPCAM...........................................................  1469
Clinical Trials..................................................  1465
Combined Health Information Database.............................  1468
Coordination with Other Federal Agencies.........................  1475
Demographics of CAM Use..........................................  1458
Depression.......................................................  1438
Diet and Exercise................................................  1455
Drug Interactions............................................1458, 1473
Establishment of NCCAM...........................................  1457
Funding Good Science.............................................  1459
Health Care Costs Associated with CAM, Total.....................  1459
International and Traditional Medicine...........................  1476
International Research Program...................................  1472
Justification of FY 2001 Budget Estimates........................  1480
NCCAM:
    Mandated Activities..........................................  1463
    Research Centers.............................................  1463
    Web Site.....................................................  1466
Opening Remarks..................................................  1435
Opening Statement................................................  1445
Patient/Practitioner Communication and Integration of Alternate 
  Medical Therapies..............................................  1470
Research on Dietary Supplements..................................  1478
Research Priorities:
    New......................................................1442, 1443
    Setting......................................................  1454
Role of FDA......................................................  1458
SAM-e............................................................  1474
Strategic Areas..................................................  1437
Strategic Plan...................................................  1438
Temporomandibular Disorders......................................  1465
Training of CAM Researchers......................................  1469
Vedic Medicine...................................................  1466
White House Commission...........................................  1467
Workshop on Medicinal Herbs......................................  1473

                                
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