[Senate Hearing 108-]
[From the U.S. Government Publishing Office]



 
  DEPARTMENTS OF LABOR, HEALTH AND HUMAN SERVICES, AND EDUCATION, AND 
          RELATED AGENCIES APPROPRIATIONS FOR FISCAL YEAR 2004

                              ----------                              


                         TUESDAY, APRIL 8, 2003

                                       U.S. Senate,
           Subcommittee of the Committee on Appropriations,
                                                    Washington, DC.
    The subcommittee met at 10 a.m., in room SD-192, Dirksen 
Senate Office Building, Hon. Arlen Specter (chairman) 
presiding.
    Present: Senators Specter, Cochran, Harkin, and Murray.

                DEPARTMENT OF HEALTH AND HUMAN SERVICES

                     National Institutes of Health

STATEMENT OF ELIAS ZERHOUNI, M.D., DIRECTOR
ACCOMPANIED BY:
        DR. DUANE ALEXANDER, DIRECTOR, NATIONAL INSTITUTE OF CHILD 
            HEALTH AND HUMAN DEVELOPMENT
        JAMES F. BATTEY, JR., M.D., PH.D., DIRECTOR, NATIONAL INSTITUTE 
            ON DEAFNESS AND OTHER COMMUNICATION DISORDERS
        WILLIAM R. BELDON, ACTING DEPUTY ASSISTANT SECRETARY FOR 
            BUDGET, DEPARTMENT OF HEALTH AND HUMAN SERVICES
        FRANCIS S. COLLINS, M.D., PH.D., DIRECTOR, NATIONAL HUMAN 
            GENOME RESEARCH INSTITUTE
        ANDREW C. VON ESCHENBACH, M.D., DIRECTOR, NATIONAL CANCER 
            INSTITUTE
        ANTHONY S. FAUCI, M.D., DIRECTOR, NATIONAL INSTITUTE OF ALLERGY 
            AND INFECTIOUS DISEASES
        DR. PATRICIA A. GRADY, DIRECTOR, NATIONAL INSTITUTE OF NURSING 
            RESEARCH
        DR. JUDITH H. GREENBERG, ACTING DIRECTOR, NATIONAL INSTITUTE OF 
            GENERAL MEDICAL SCIENCES
        GLEN R. HANSON, PH.D., D.D.S., ACTING DIRECTOR, NATIONAL 
            INSTITUTE ON DRUG ABUSE
        RICHARD J. HODES, M.D. DIRECTOR, NATIONAL INSTITUTE ON AGING
        THOMAS R. INSEL, M.D., DIRECTOR, NATIONAL INSTITUTE OF MENTAL 
            HEALTH
        STEPHEN I. KATZ, M.D., PH.D., DIRECTOR, NATIONAL INSTITUTE OF 
            ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES
        DR. GERALD T. KEUSCH, DIRECTOR, THE JOHN E. FOGARTY 
            INTERNATIONAL CENTER
        RAYNARD KINGTON, DEPUTY DIRECTOR, OFFICE OF THE DIRECTOR, 
            NATIONAL INSTITUTES OF HEALTH
        CLAUDE LENFANT, M.D., DIRECTOR, NATIONAL HEART, LUNG, AND BLOOD 
            INSTITUTE
        TING-KAI LI, M.D., NATIONAL INSTITUTE ON ALCOHOL ABUSE AND 
            ALCOHOLISM
        DONALD A.B. LINDBERG, M.D., DIRECTOR, NATIONAL LIBRARY OF 
            MEDICINE
        KENNETH OLDEN, PH.D., DIRECTOR, NATIONAL INSTITUTE OF 
            ENVIRONMENTAL HEALTH SCIENCES
        AUDREY S. PENN, M.D., ACTING DIRECTOR, NATIONAL INSTITUTE OF 
            NEUROLOGICAL DISORDERS AND STROKE
        RODERIC I. PETTIGREW, PH.D., M.D., DIRECTOR, NATIONAL INSTITUTE 
            OF BIOMEDICAL IMAGING AND BIOENGINEERING
        JOHN RUFFIN, PH.D., DIRECTOR, NATIONAL CENTER ON MINORITY 
            HEALTH AND HEALTH DISPARITIES
        DR. PAUL A. SIEVING, DIRECTOR, NATIONAL EYE INSTITUTE
        ALLEN M. SPIEGEL, M.D., DIRECTOR, NATIONAL INSTITUTE OF 
            DIABETES AND DIGESTIVE AND KIDNEY DISEASES
        STEPHEN E. STRAUS, M.D., DIRECTOR, NATIONAL CENTER FOR 
            COMPLEMENTARY AND ALTERNATIVE MEDICINE
        LAWRENCE A. TABAK, D.D.S., PH.D., NATIONAL INSTITUTE OF DENTAL 
            AND CRANIOFACIAL RESEARCH
        JUDITH L. VAITUKAITIS, M.D., DIRECTOR, NATIONAL CENTER FOR 
            RESEARCH RESOURCES
        KERRY N. WEEMS, ACTING ASSISTANT SECRETARY FOR BUDGET, 
            TECHNOLOGY AND FINANCE, DEPARTMENT OF HEALTH AND HUMAN 
            SERVICES
        JACK WHITESCARVER, PH.D., DIRECTOR, OFFICE OF AIDS RESEARCH

               OPENING STATEMENT OF SENATOR ARLEN SPECTER

    Senator Specter. Good morning, ladies and gentlemen. The 
Appropriations Subcommittee on Labor, Health and Human 
Services, and Education will proceed.
    Dr. Zerhouni, we now turn to this portion of the hearing on 
the National Institutes of Health.
    Dr. Gerberding, we thank you for your participation. If you 
would like to be a director of the NIH or one of the 
institutes, you may stay.
    If you choose to retain your current position at CDC, you 
are free to excuse yourself. Thank you very much for joining 
us.
    Dr. Gerberding. Thank you. I think I will keep to my 
present job.
    Dr. Zerhouni. We would not mind having her as a director at 
NIH.
    Dr. Gerberding. Thank you.
    Senator Specter. Dr. Zerhouni, we have already introduced 
you with your impressive background and credentials coming from 
Algiers at a young age. We thank you for the work you are doing 
at NIH. It is good to hear that you were in Mississippi with 
Senator Cochran. Thank you for coming to Pennsylvania to a very 
interesting forum we had a few months ago at the University of 
Pennsylvania. And now we look forward to your testimony.

                SUMMARY STATEMENT OF DR. ELIAS ZERHOUNI

    Dr. Zerhouni. Thank you, Senator Specter. And thank you, 
members of the committee.

                INTRODUCTION OF NEW INSTITUTE DIRECTORS

    What I would like to do first and foremost is introduce to 
you four new directors of NIH who have joined us over the past 
year. Dr. Thomas Insel is the new Director of the National 
Institute of Mental Health. Thomas can say hi. Dr. Nora Volkow 
is going to assume the directorship of the National Institute 
of Drug Abuse. Dr. Rod Pettigrew is going to be, is the new 
Director of the National Institute of Bioimaging and 
Bioengineering. And T.K. Li is the new Director of the National 
Institute of Alcoholism and Alcohol Abuse.
    To my right, I would like to introduce our new Deputy 
Director for NIH, Dr. Raynard Kington, who has replaced Dr. 
Ruth Kirschstein, who is now serving as the senior advisor to 
the directors, with us today as well and continues to help both 
Dr. Kington and I with her advice.
    Senator Specter. Let me just pause for just a moment to 
thank Dr. Ruth Kirschstein for her outstanding service at NIH 
over many years, including serving as acting director. We 
salute you and are glad to see that you are still on board.
    Dr. Zerhouni. Again, I would like to really extend our 
thanks to the full committee and to you, Mr. Chairman, and to 
you, Senator Harkin. We know that without your leadership, the 
doubling of NIH would not have occurred this year in the 
difficult economic and budgetary circumstances that we are 
facing. And we appreciate it very much.

                          RESEARCH PRIORITIES

    I would like to quickly go over what NIH is planning to do 
with the doubling of the NIH budget and what our priorities are 
going to be. First and foremost, we want to make sure that the 
resources you have given us are invested with the best people 
and are invested on the best ideas that can promote the health 
of our people.
    This is done in the context of, first of all, major 
priorities that continue to be priorities, but also evolving 
challenges. These evolving challenges are truly fundamental to 
the way biomedical research will need to be done in the future.

                            CHRONIC DISEASES

    First and foremost, we have experienced over the past 40 
years a tremendous shift in the landscape of disease in our 
country going from acute diseases that were very lethal to more 
chronic diseases. Seventy-five percent of the disease burden of 
the United States today is related to long-term chronic 
diseases. We have made great progress in cardiac diseases when 
we control acute myocardial infarction. But these patients are 
now surviving longer and have different kinds of problems.

                            AGING POPULATION

    The second challenge is that of the aging population. And 
we need to tackle that proactively.

                          HEALTH DISPARITITIES

    The third is health disparities, as I mentioned before.

                           EMERGING DISEASES

    The fourth, as you heard today, is emerging diseases. Not 
just infectious diseases, but also diseases that relate to the 
change in our environment, all conditions. For example, the 
rise in obesity and its implications on the incidence of 
diabetes in our country. Last, but not least, is the biodefense 
priorities, which we will continue to support.

                       STRATEGIC ROADMAP FOR NIH

    Now to do so and to go forward, we wanted over the past 
year to work with all the directors of NIH and all the 
constituencies to define what we would call a strategic road 
map for NIH and how we will invest the resources you have 
placed in trust with us, and what are the priorities that we 
think will make the greatest difference in terms of advancing 
research, in terms of developing the best people, promoting the 
best ideas, and essentially translating them to real benefits. 
And there are three.
    We will explore new pathways to discovery. And that is 
essentially to fully exploit the unprecedented opportunity of 
the genomic era. To us, this is the beginning, not the end, of 
an era. The genome is allowing us today to explore completely 
different ways of looking at disease than we had in the past.
    Second, because of the scaling complexity of 21st century 
research, we understand now that the problems cannot be tackled 
by individual scientists alone. We need large multi-
disciplinary teams that are going to work together to in fact 
do so.
    Third, we need to re-engineer the clinical research 
enterprise of our country. We need to more quickly translate 
our discoveries into practice. And this will be a priority of 
the NIH in the future.
    Last but not least, we are submitting to you a request for 
the fiscal year 2004 budget, which is a 2.6 percent change over 
the enacted 2003 level. When we worked--and Senator Specter and 
Senator Harkin and Senator Murray, I can tell you that we 
worked very, very hard, including myself and Dr. Gerberding and 
others to try to make sure that the impact on our programs in 
the new budget will be as limited as possible, in terms of 
critical mission areas. We did advocate internally, as you 
recommended in your statement.
    Research will not be affected at the 2.6 percent level, but 
we will be able to maintain our research to the 7 percent 
level. Excluding biodefense, we will maintain a 4.3 percent 
level. And the number of grants will go 10,509.
    At the bottom of the slide, you see why that is in 2004. 
And the reason is because many one-time expenditures that were 
related to building the infrastructure for biodefense, 
buildings and facilities that were needed in 2003 have been 
reinvested in the research portfolio in 2004. Now those are the 
main elements of the budget we are submitting. And as you said, 
Senator Specter, we are looking forward to your input in this 
process. And obviously, we will provide you with all the 
information that you may want us to provide you and answer all 
your questions in that regard.

                          PREPARED STATEMENTS

    But rest assured that we will and are committed and will be 
committed to make sure that the return on investment of the NIH 
continues to be the same it was in the past. Thank you very 
much.
    [The statements follow:]

                Prepared Statement of Dr. Elias Zerhouni

              FISCAL YEAR 2004 PRESIDENT'S BUDGET REQUEST

    Good morning, Mr. Chairman and members of the Committee. Let me 
begin by expressing my deepest appreciation for the generous and 
bipartisan support of the Congress, Secretary Thompson, President Bush, 
and the American people for the completion of the doubling of the NIH 
budget this year. I recognize and appreciate the extraordinary effort 
of this committee and, Mr. Chairman, your leadership as well as your 
efforts, Senator Harkin--without which the doubling would not have 
occurred. I thank you for it.
    I also want to assure you that NIH fully understands and embraces 
its role as the steward of our Nation's investment in medical 
discovery. We must ensure that these precious resources are used wisely 
and lead to tangible benefits that touch the lives of everyone.
    The year 2003 is truly a pivotal year for medical research. It is 
the year when we celebrate the 50th anniversary of the discovery of the 
structure of DNA and its direct consequence--the completed sequence of 
the Human Genome. We have witnessed nothing short of a revolution in 
science over the past 5 years. Some may see this year as the grand 
finale. I think of it more as the overture. As the 21st century begins 
to unfold, we are poised to make quantum leaps in our knowledge about 
how to improve people's health.
    In my testimony, I will demonstrate what health benefits have 
resulted from the Nation's longstanding investment in the NIH, along 
with some of our most recent advances. Finally, I will outline emerging 
priorities and NIH's plans for responding to the health challenges 
before us.

                           THE NIH TRADITION

    NIH-led progress in medical research is changing the landscape of 
disease. For example, NIH research led to a major reduction in 
mortality related to coronary heart disease and stroke. NIH contributed 
to this decline in a number of ways. First, we identified 
cardiovascular risk factors and the importance of behavior 
modification, such as smoking cessation, dietary changes, and exercise, 
to reduce risk and improve cardiovascular health. Second, we supported 
the basic science that led to the development of pharmaceuticals to 
control hypertension and high cholesterol levels. NIH-funded research 
also led to strategies as simple and inexpensive as taking aspirin to 
prevent heart disease and stroke, and life-saving procedures such as 
angioplasty and coronary artery bypass grafting. We also continue to 
evaluate best therapeutic strategies in medical practice, as in the 
recent ALLHAT trial (Antihypertensive and Lipid-Lowering Treatment to 
Prevent Heart Attack Trial) that showed that hypertension can be 
effectively managed with an initial choice of an inexpensive drug. Were 
it not for these advances and others, the expected death toll from 
coronary heart disease would have been over 1,300,000 in 2000 as 
compared to the actual death toll of 514,000.
    Progress has been equally remarkable for Hepatitis B (HBV) and 
Hepatitis C (HCV) infections. New cases of these infections are on the 
decline, in part, because of improved vaccines and the reduced risk of 
infection from blood transfusion--both outcomes of NIH-funded research. 
Because of changes in the criteria for donor recruitment and new and 
improved approaches to testing blood, the risk of infection through 
transfusion has been virtually eliminated.
    The ability to screen for HIV infection--made possible by NIH 
research serves as an important target for both prevention and 
treatment of AIDS. The mortality rate of this devastating disease is 
now one fifth of what it would have been without research on the 
fundamental biology of the HIV virus. Research on behavioral 
interventions to prevent HIV infection and improve its treatment also 
contributed to better control of the spread of this disease in our 
country.
    One more dramatic example can be found in the development of the 
Haemophilus Influenza B vaccine. The results of this NIH research have 
led to a virtual elimination of this disease in our country and, the 
disease is in the process of being eliminated worldwide. In the not too 
distant past, the complications of Hib made this disease the leading 
cause of acquired mental retardation in infants and children.

                     NEW CHALLENGES AND STRATEGIES

    Due in part to research advances; the burden of disease is now 
shifting from more acute and lethal forms of disease to chronic 
illness. Our success in conditions like myocardial infarction and 
infectious diseases is leading to better survival rates. As the result 
of such prolonged survival and the aging of the population, the 
incidence of chronic and long-term diseases, such as congestive heart 
failure, cancer, Alzheimer's disease, Parkinson's Disease, diabetes, 
and obesity, among others, is increasing.
    For example, although we have witnessed reductions in acute 
coronary heart disease, the burden of congestive heart failure has 
increased during the last 30 years of the 20th century. As another case 
in point, more people are living with cancer, as therapies transform 
this once acutely fatal disease into a more chronic and manageable 
condition.
    Furthermore, rapid changes in our environment and lifestyle lead to 
disequilibrium between our genetic make-up and our ability to adapt to 
these changes. The most dramatic recent example is the rise in the 
incidence of obesity, due in part to the greatly increased availability 
of food and reduced daily physical energy requirements.
    It is imperative that we develop more comprehensive strategies to 
address such emerging challenges. In all likelihood, these strategies 
will require a better understanding of: (1) the series of molecular 
events that lead to disease in the hope of affecting its course before 
the disease develops, so-called Molecular Prevention; (2) the 
interactions between genes, the environment, and lifestyle as they 
relate to the etiology and progression of disease; ways of delaying the 
onset of the disease and/or ways to reduce the severity of its course 
and its impact on quality of life.
    All of these strategies will need to be explored simultaneously and 
it is this systematic approach, from most basic to applied research, 
that will produce much needed results. Several important examples of 
these strategies have already proved their value.
    For example, a major cause of blindness, age-related macular 
degeneration (AMD), currently affects 1.75 million Americans. They have 
advanced degeneration in at least one eye. Over 7 million individuals 
are at substantial risk of developing AMD. Its prevalence increases 
dramatically with age; for more than 15 percent of white females over 
80 years of age have AMD. By the year 2020, the number of people with 
AMD will increase by 50 percent to 2.95 million.
    NIH is engaged in a major research program to understand the 
predisposing factors, the clinical course, and the prognostic factors 
of AMD. Researchers found that giving high levels of antioxidants and 
zinc reduce the risk of developing advanced AMD by about 25 percent. 
These nutrients also reduce the risk of advanced AMD-induced vision 
loss by about 19 percent. These findings may help people who are at 
high risk of developing advanced AMD keep their vision. Over the next 
five years, 329,000 people in the United States (66,000 per year) could 
be saved from advanced AMD. More remains to be done. We need to spread 
the word to change practices, and we need to continue work to identify 
the genes that control the risk of this devastating disease as well as 
to develop more interventions to prevent or delay the onset of 
blindness.
    In another example, many doctors today who are treating patients 
with rheumatoid arthritis remember all too well how challenging 
treatment was not so long ago. In the early 1980s, treatment was 
initiated in what was known as a therapeutic pyramid. Patients would 
first be given a course of aspirin or another non-steroidal anti-
inflammatory drug (NSAID), and would be followed to see if erosions 
occurred in the bone. If erosions did occur or if the patients did not 
respond to the NSAIDs, the next course was anti-rheumatic drugs that 
were added one-by-one as the disease progressed. Sadly, the disease-
modifying therapy was initiated only after the patient was already on 
the road to disability. The root causes of the disease were not known, 
but the discovery, originally made through cancer research, of the role 
of Tumor Necrosis Factor (TNF), a naturally occurring protein in the 
body that mediates inflammation, dramatically changed the treatment 
landscape. By specifically targeting this protein with customised 
antibodies, entirely new drugs were developed and approved for the 
treatment of rheumatoid arthritis, including etanercept and infliximab. 
These were the first biological-response modifying antibody drugs that 
behave as antagonists--meaning that they work by specifically blocking 
the action and decreasing the availability of TNF.
    These new-targeted therapies showed substantial effectiveness in 
people with rheumatoid arthritis who had not previously responded to 
other treatments. The treatments are generally well tolerated, although 
some concerns have been raised recently about the long-term effects of 
these agents. Other studies reported that infliximab and methotrexate 
used in combination not only reduced the symptoms of rheumatoid 
arthritis, but also halted the progression of joint damage when 
compared to the use of previous forms of therapy. Scientists involved 
in this study observed that in the last 2 years, aheumatoid arthritis 
research has moved further than in the previous 30 years, and that a 
wealth of new treatments is now available that have the potential to 
prevent and heal structural damage to the joints of people with this 
debilitating disease.

                    THE NEED FOR A STRATEGIC ROADMAP

    The change in the landscape of disease requires us to adopt new 
approaches and accelerate the pace of our discoveries. The need has 
never been so pressing, the opportunities have never been greater, and 
challenges have never been more daunting. The NIH must simetaneously 
learn from the past, act in the present, and plan for the future. It 
must institute the changes necessary to improve the health of the 
American people. We need to proactively define enabling initiatives--
how best to advance science as well as what science to advance. We need 
to map the terrain and over the past nine months we have been engaged 
in just such an effort.
    Soon after I arrived at NIH, I convened a series of meetings to 
develop a ``Roadmap.'' My goal was to develop a short list of the most 
compelling initiatives that the NIH should pursue that would make the 
biggest impact on biomedical research.
    This assessment was needed because powerful and unifying concepts 
of biology are emerging that hold the potential to lead to rapid 
progress. For example, in the past, cancer research was considered 
vastly different than heart or brain research. Today, with recent 
discoveries in molecular and cell biology, we know that biological 
systems obey common laws and follow similar pathways in both health and 
disease. Efforts to fully understand these complex molecular events are 
beyond the reach of any one laboratory or group of investigators. As we 
begin to decipher the tidal wave of knowledge we have amassed, the 
scope, the scale, and the complexity of 21st century science will 
require us to devise even newer ways to explore biology for the sake of 
improving health.
    Three major themes emerged from these Roadmap meetings. First, we 
must uncover new pathways to scientific discovery. For example, we must 
develop a comprehensive understanding of the building blocks of the 
body's cells and tissues and how complex biological systems operate. 
Also, structural biology will provide vital information about the 
proteins that make up the human body. Molecular libraries will give us 
new tools and targets for effective therapies. Overall, these examples, 
plus nanotechnology, computational biology and bioinformatics and 
molecular imaging will provide the foundation upon which new 
treatments, diagnostics and prevention strategies will emerge.
    The second theme that emerged from our consultations is the 
changing dynamics of the research teams of the future. Because of the 
complexity and scope of today's scientific problems, traditional 
``mentor-apprentice'' models must be replaced by integrated teams of 
specialists from numerous disciplines that were considered unrelated in 
the past. Imaging research, for example, requires cell biologists, 
computer programmers, radiologists, and physicists to work 
collaboratively on new diagnostics and treatments.
    The third theme that was voiced again and again by researchers is 
the need to re-engineer the national clinical research enterprise for 
optimal translation of our discoveries into clinical reality. The list 
of what is needed is long--it includes supporting multidisciplinary 
clinical research training career paths, introducing innovations in 
trial design, stimulating translational research, building clinical 
resources like tissue banks, developing large clinical research 
networks, and reducing regulatory hurdles. We must explore a standard 
clinical research informatics strategy, which will permit the formation 
of nation-wide ``communities'' of clinical researchers made up of 
academic researchers, qualified community physicians, and patient 
groups.
    Our vision is to make sure that our citizens benefit from a vibrant 
clinical research system--a system that will allow us to more 
efficiently translate our breakthroughs in basic research with the goal 
of improving health.
    The three thematic areas that I just described, that is, new 
pathways to discovery, multidisciplinary teams, and reengineering the 
clinical research enterprise, focus on technologies and systems that 
will enable researchers today and in the future to not only solve 
problems more quickly, but also to ask questions that we have not been 
able to ask before--questions so complex that without the aid of these 
efforts they would be impossible to address.
    Efforts to understand the building blocks of the body's cells and 
tissues and to understand how complex biological systems work can lead 
directly to new approaches to improving health or preventing disease. A 
recently discovered biological phenomenon called RNAi--or RNA 
interference--has led to the development of a new and potent research 
tool, which is being used to identify the function of specific genes in 
normal biological and disease processes.
    A recent study, co-funded by NIH, used RNAi to identify genes 
involved in the regulation of fat metabolism in the roundworm 
experimental model in an effort to better understand obesity. One at a 
time, each of the 17,000 genes of the round worm was turned off using 
this novel method. Researchers found that inhibition of 305 genes 
decreased body fat, whereas inhibition of 112 genes increased fat 
storage. With this information, researchers identified new genes 
involved in fat metabolism, genes common in many organisms, including 
humans. These genes now give researchers multiple new opportunities for 
understanding obesity and new targets for the development of therapies. 
This is just one example of how these new approaches are beginning to 
transform medical research.
    Finally and importantly, the NIH must communicate our research 
results both to the lay public and health professionals. NIH works in 
partnership with many different organizations to communicate scientific 
results and health information to the medical research community, 
health care providers, patients, the media and the general public 
across the nation. We conduct our education and outreach efforts in 
collaboration with other federal agencies, state agencies, private 
sector organizations and national health care organizations. We have 
made progress in this area. For example, the NIH Web site is now the 
most accessed of all government health and science web sites. This 
aspect of our mission will continue to be a priority for NIH.

                               BIODEFENSE

    Civilian biodefense research has become a new core priority at NIH 
and a prominent component of our budget. Over the last year and a half, 
we responded to the most urgent needs of biodefense, namely the 
development of countermeasures such as vaccines, therapeutics, and 
diagnostic tests. These will allow us to respond to and control the 
intentional or unintentional release of agents of terrorism that affect 
human health, including infectious disease and microbial toxins. We are 
also now systematically reviewing our portfolio of biodefense research 
to include radiation and chemical exposures, and mental health 
preparedness research. Biodefense research will be the topic of a 
separate hearing.
    Mr. Chairman, I am pleased to present the President's fiscal year 
2004 request for the National Institutes of Health of $27,663 million 
for the programs of NIH that fall under the purview of this Committee. 
This level will allow us to support our highest research priorities and 
continue the momentum we gained during the historic doubling of the NIH 
budget. In large part this is possible because of the very significant 
amount of one-time costs supported in fiscal year 2003 that will not be 
required in fiscal year 2004. Once these have been taken into account, 
NIH will be able to increase the amount available for research by 7.5 
percent. Even after excluding increases for the Administration's 
highest priority--homeland defense--the research components of the NIH 
budget will still increase by 4.3 percent. The request will allow us to 
support the highest number of new and competing grants in history--
10,509 new and competing grants. At this level, we will be able to 
continue to support approximately one-in-three of the research grant 
applications we receive. The final enacted fiscal year 2003 
appropriation is very close to the President's request. In the coming 
weeks, NIH will work with appropriate staff to clarify discrepancies 
between the fiscal year 2003 request and the enacted level.
    Special emphasis will be placed on areas of growing concern such as 
obesity and diabetes, the IDeA program, and the Best Pharmaceuticals 
for Children's Act. A total of $35 million is requested through the 
Director's Discretionary Fund to support our important Roadmap 
activities. As the fiscal year 2004 budget is developed, NIH will work 
with appropriate staff to clarify discrepancies.
    In sum, the plans I have outlined here today are ambitious and 
rightly so. They rise to the many scientific opportunities and 
significant health challenges that lie before us. Once again, my thanks 
to you and the American public for your continued investment in 
biomedical research to improve the health of everyone.

                    BUILDINGS AND FACILITIES PROGRAM

    The Buildings and Facilities (B&F) program supports the physical 
infrastructure required to carry out the in-house component of the 
biomedical research mission of the National Institutes of Health (NIH). 
The fiscal year 2004 Buildings and Facilities budget request supports 
efforts to sustain a robust, modern, safe and secure physical 
infrastructure for the conduct of basic and clinical research and 
research support across the spectrum of biologic systems and diseases.
    The B&F budget request is the product of a deliberate, corporate 
facilities planning process both within the NIH and the Office of the 
Secretary, Assistant Secretary for Administration and Management, HHS. 
At the NIH, the Facilities Planning Advisory Committee (FPAC) oversees 
this process and provides advice to the NIH leadership and Director. 
The FPAC is also instrumental in adjusting priorities as necessary to 
deal with unanticipated public health challenges and changes in 
national priorities. The goal of the planning process is to optimally 
meet the changing facility needs of the NIH research programs in the 
Washington, D.C., region and across the NIH field stations with a mix 
of owned and leased facilities. The fiscal year 2004 Buildings and 
Facilities (B&F) budget request supports the NIH's research 
infrastructure priorities. The request includes projects and programs 
to responsibly manage the repair and upkeep of the existing physical 
infrastructure, and to maintain our facilities at an optimal operating 
standard to meet mission as well as safety and regulatory requirements.
    The NIH appreciates the support from Congress in fiscal year 2003 
for NIH's Physical Security, Biodefense facilities, and the final phase 
of the construction of the Mark O. Hatfield Clinical Research Center.
    The fiscal year 2004 request maintains responsible funding support 
for the ongoing safety, renovation and repair, and related projects 
that are vital to proper stewardship of the entire portfolio of real 
property assets and continues the functional integration of the 
clinical research components of the existing Building 10 with the new 
Mark O. Hatfield Clinical Research Center (CRC).
    The fiscal year 2004 B&F budget request is organized among three 
broad Program Activities: Essential Safety and Regulatory Compliance, 
Repairs and Improvements, and Renovations. The fiscal year 2004 request 
provides funds for specific projects in each of the program areas. The 
projects and programs enumerated are the end result of the 
aforementioned NIH Strategic Facilities Planning process and are the 
NIH's capital facility priorities for fiscal year 2004.

                    FISCAL YEAR 2004 BUDGET SUMMARY

    The fiscal year 2004 budget request for Buildings and Facilities is 
$80 million. The B&F request includes a total of $14 million for 
Essential Safety and Regulatory Compliance programs composed of $2 
million for the phased removal of asbestos from NIH buildings; $5 
million for the continuing upgrade of fire and life safety deficiencies 
of NIH buildings; $1.5 million to systematically remove existing 
barriers to persons with disabilities from the interior of NIH 
buildings; $0.5 million to address indoor air quality concerns and 
requirements at NIH facilities; and $5 million for the continued 
support of the rehabilitation of animal research facilities. In 
addition, the fiscal year 2004 request includes $60.5 million in 
Repairs and Improvements for the continuing program of repairs, 
improvements, and maintenance that is the vital means of maintaining 
the complex research facilities infrastructure of the NIH. Finally, the 
request includes $5.5 million in Renovations for the Building 10 
Transition Program.
    My colleagues and I will be happy to respond to any questions you 
may have.
                                 ______
                                 
               Prepared Statement of Dr. Duane Alexander

    Mr. Chairman and Members of the Committee: I am pleased to present 
the fiscal year 2004 President's budget request for the National 
Institute of Child Health and Human Development (NICHD). The fiscal 
year 2004 budget includes $1,245 million, an increase of $41 million 
over the fiscal year 2003 enacted level of $1,205 million comparable 
for transfers proposed in the President's request. The NIH budget 
request includes the performance information required by the Government 
Performance and Results Act (GPRA) of 1993. Prominent in the 
performance data is NIH's second annual performance report which 
compares our fiscal year 2002 results to the goals in our fiscal year 
2002 performance plan.
    Forty years ago, the U.S. Congress charged the NICHD with a broad 
mandate. The Institute was asked to develop a research program to 
ensure that people are able to have children when they want them; that 
every child is born healthy; that women suffer no adverse consequences 
from the reproductive processes; and that children experience healthy 
physical, cognitive, behavioral, and social development, reaching 
adulthood free of disease and disability, and able to lead productive 
lives.
    We have made exceptional progress toward those goals during the 
last 40 years. Infant mortality has been cut by more than 70 percent, 
largely due to NICHD research that has lead to new ways to treat and 
prevent respiratory distress syndrome, to manage premature infants, and 
to reduce Sudden Infant Death Syndrome. Mental retardation in the 
United States has been significantly reduced because we have conquered 
and controlled some of its leading causes: Hemophilus influenza type b 
(Hib) meningitis, phenylketonuria (PKU), measles encephalitis, and 
jaundice. Infertility that deprived millions of couples from conceiving 
children can now be diagnosed and in many cases treated. Transmission 
of HIV infection from mother to baby has been reduced from 27 percent 
to less than 2 percent in the U.S. as a result of research showing the 
effectiveness of administering antiretroviral drugs to the mother 
during pregnancy and to the infant just after birth.
    We look forward to building on 40 years of scientific achievements 
and we would like to share with you recent achievements that are 
improving the health of the American people.

           PREMATURE BIRTH: NEW RESEARCH MAY REVERSE A TREND

    The number of infants who are born prematurely is increasing. While 
infant mortality rates have decreased significantly in recent years, 
the number of premature low birth weight babies born has increased by 
11 percent over the last two decades. The number of premature very low 
birth weight infants, weighing less than 1,500 grams, has increased by 
24 percent. Research supported by the NICHD has helped many premature 
infants to survive. But these infants can develop neurological, 
respiratory, or other conditions causing life-long disabilities. 
Recently, NICHD scientists discovered that weekly injections of 
progesterone, a readily available hormone, can lower premature birth by 
more than one-third among women who are at risk of premature delivery. 
In this study, like many clinical studies, some of the women received 
the progesterone and some received a placebo injection. The results 
were so dramatic that the scientists halted the study and administered 
progesterone to all women enrolled in the study.

         ORAL CONTRACEPTIVES AND BREAST CANCER: NO ASSOCIATION

    The NICHD research has also provided reassuring evidence to women 
and their physicians who may be concerned about a possible relationship 
between oral contraceptive use and breast cancer. About 80 percent of 
U.S. women born since 1945 have used oral contraceptives. Conflicting 
studies had caused concern about the possible effect of oral 
contraceptive use on breast cancer risk. The NICHD's Women's 
Contraceptive and Reproductive Experiences Study found that women 
between the ages of 35 and 64 who took oral contraceptives at some 
point in their lives were no more likely to develop breast cancer than 
other women the same age who never took oral contraceptives. Many women 
who took oral contraceptives during their reproductive years are now 
reaching the ages of greatest breast cancer risk. This study should 
resolve the long-standing concern that oral contraceptive use might be 
associated with an increased risk of breast cancer in later life.

             VASECTOMY AND PROSTATE CANCER: NO ASSOCIATION

    Another study supported by the NICHD answered an important question 
for men who have had vasectomies. About one out of six American men 
over the age of 35 has had a vasectomy. Some studies conducted in the 
United States in the early 1990s reported a moderately increased risk 
of prostate cancer among men who underwent vasectomy. Other studies 
found no such risk. Because of this conflicting evidence, many 
urologists have increased prostate cancer screening of men who had 
vasectomies and have discouraged vasectomies in men with a family 
history of prostate cancer. The NICHD study found that men who had a 
vasectomy were no more likely to develop prostate cancer than those who 
had not had a vasectomy. The study also found that men who had 
vasectomies as long as 25 years ago did not have an increased risk of 
prostate cancer. These results should reassure men who have had or who 
are considering a vasectomy.

           STROKE PATIENTS IMPROVE FUNCTION OF IMPAIRED LIMB

    The results of other NICHD-supported research provide encouraging 
news to some stroke victims. Until recently, therapy for stroke victims 
often involved teaching patients to strengthen their less impaired limb 
for several weeks after a stroke. The prevailing view among 
rehabilitation professionals was that patients' motor ability reached a 
plateau at about six months after a stroke. They believed that 
additional therapy would provide little if any additional benefit. But 
new research has shown that the use of the impaired limb can improve 
significantly a year or more after a stroke. Using ``Constraint Induced 
Therapy,'' researchers showed that constraining the good or less 
affected limb for 10 days can help restore a great deal of mobility to 
the impaired limb.

          TRAUMATIC BRAIN INJURY NETWORK FOR BETTER TREATMENTS

    Traumatic brain injury is one of the leading causes of death and 
disability in children and adults. An estimated two million head 
injuries occur in the United States each year. As a result of advances 
in emergency medicine at the accident scene and the hospital, many TBI 
victims are living longer. However, many will live with persistent 
physical, cognitive, behavioral and social deficits that compromise 
their quality of life. Research over the last two decades has 
demonstrated that not all neurologic damage occurs at the moment of 
injury, but evolves over the minutes, hours, and days after an 
accident. Research also has dramatically improved the immediate care, 
follow-on care, and rehabilitative process for TBI patients. Yet there 
are many unanswered questions about the underlying damage and the 
reasons for reduced functioning associated with TBI. In addition, to 
determine the most appropriate therapies for children and young adults 
with TBI, multiple sites are needed to evaluate various interventions 
with many patients. To address this need, the NICHD recently 
established the Traumatic Brain Injury Clinical Trials Network. The 
Network will evaluate medical, rehabilitative, and educational 
interventions to identify which ones most effectively improve the long-
term outcomes of TBI patients.

          NEW FRAGILE X CENTERS WILL DEVELOP TREATMENT OPTIONS

    Fragile X syndrome is the most common genetically-inherited form of 
mental retardation currently known. The condition occurs in every 1 out 
of 2,000 males and in 1 in 4,000 females. The syndrome is caused by a 
mutation in a specific gene (FMR1) on the X chromosome. In its fully-
mutated form, the FMR1 gene interferes with normal development. In a 
partially mutated (premutation) form, the FMR1 gene can cause fragile X 
syndrome in the children of a carrier (a person who has the premutation 
gene). Until recently, however, the premutation form was not thought to 
cause symptoms in carriers. Scientists have now identified a subgroup 
of premutation FMR1 carriers with symptoms that appear to be associated 
with the gene. Symptoms included mild cognitive and emotional problems 
and, in female carriers, premature menopause. In older male carriers, 
the premutation gene is associated with a neurological syndrome. 
Identifying a genetic basis could be a first step toward accurate 
diagnosis and, possibly, development of new treatments for these often 
overlooked symptoms. In addition, to develop improved diagnostic 
techniques and treatment options, the NICHD will begin funding three 
new Fragile X research centers in fiscal year 2003. Each center will 
call upon the combined expertise of several researchers working in 
diverse fields to investigate different aspects of the disorder. The 
new Fragile X Research Centers will study issues such as how the 
fragile X affects the developing brain and nervous system, how the 
disorder progresses throughout an individual's life span, and effective 
treatments that can improve the behavior and mental functioning of 
people with fragile X syndrome.

        STRATEGIC ALLIANCES WITH MINORITY GROUPS TO REDUCE SIDS

    Less than ten years ago, the NICHD initiated a campaign urging 
parents and care takers to place infants on their backs to sleep to 
reduce the risk of Sudden Infant Death Syndrome (SIDS). Since that 
time, the SIDS rate in the U.S. has declined by more than 50 percent. 
This dramatic decline represents a significant public health 
achievement because the SIDS rates had remained tenaciously steady 
prior to the NICHD campaign. Although the SIDS rates have declined in 
all populations since the campaign began, the SIDS rate among African 
American infants remains double that of white infants. Among Alaska 
Natives and many American Indian tribes, the rates are higher still. To 
begin closing this gap, the NICHD has formed strategic alliances with 
the Alpha Kappa Alpha sorority, The National Coalition of 100 Black 
Women, and The Women in the NAACP. In collaboration with these 
organizations, the NICHD has planned and will support a series of 
``summit'' meetings in three U.S. cities with high rates of African 
American SIDS deaths. These summits will enlist the resources of faith-
based and community organizations, public health officials, and service 
organizations to help establish an infrastructure that will provide 
information, material, and support for reducing SIDS among African 
American infants. Each organization will take the lead in organizing 
one of the summit meetings and will continue to serve as the catalyst 
for SIDS risk reduction activity in that city and its surrounding 
region.
    The NICHD has also initiated a project with American Indian and 
Alaska Native groups to reduce SIDS and infant mortality in these 
populations. At NICHD-sponsored meetings in Minneapolis, MN and Rapid 
City, SD, representatives of Tribal Chairman's Health Boards and Alaska 
Native health organizations provided the NICHD with a blueprint to 
support the activities of community health workers involved in SIDS 
risk reduction education. The NICHD will develop and disseminate the 
materials for this effort during the current year.

     TESTING DRUGS TO IMPROVE HEALTH OF CHILDREN AND PREGNANT WOMEN

    In fiscal year 2004, the NICHD will continue to invest in research 
and programs that benefit the American people. One such investment is 
the fulfillment of the Best Pharmaceuticals for Children Act (BPCA). 
The immature physiology of children means that drugs approved to 
prevent or treat illness in adults may have different effects in 
younger patients, requiring children's physicians to prescribe 
different doses and make other adjustments in drug therapies. However, 
for approximately seventy-five percent of the pharmaceuticals approved 
by the Food and Drug Administration (FDA) for adults, there are 
inadequate safety and efficacy data to allow approval for pediatric 
uses, or to guide physicians in prescribing these drugs for children. 
The BPCA, signed into law in January 2002, directs the NIH to issue 
contracts to test in children off-patent prescription drugs already 
approved for adults. Working with the FDA and other experts, the NICHD 
identified a priority list of drugs to be tested through the 
Institute's Pediatric Pharmacology Research Units (PPRUs) and at other 
sites. The fiscal year 2004 budget request includes an increase of $25 
million, across all of the NIH Institutes and Centers (ICs), for these 
studies.
    Drugs prescribed to pregnant women are also a concern. Although 
nearly two-thirds of all pregnant women take at least four to five 
drugs during pregnancy and labor, the effects of these prescribed drugs 
on a pregnant woman and her fetus remain largely unstudied. In 
addition, little is known about how pregnancy-related changes in 
cardiac output, blood volume, intestinal absorption, and kidney 
function may influence drug absorption, distribution, utilization, and 
elimination. Therefore, the NICHD will establish a new network of 
Obstetric-fetal Pharmacology Research Units that will allow 
investigators to conduct key pharmacologic studies of drug disposition 
and effect during normal and abnormal pregnancies.

      EXPANSION OF NEWBORN SCREENING THROUGH MICROARRAY TECHNOLOGY

    At present, all states routinely screen all newborns for only two 
disorders: phenylketonuria (PKU) and congenital hypothyroidism. These 
are conditions for which effective treatments are available. In 
addition, most states screen for a mix of 1 to 15 other disorders, but 
some commercially available tests can screen for up to 50 conditions. A 
Secretarial-level panel and the American Academy of Pediatrics have 
recommended that an expanded and standardized approach to newborn 
screening be developed. To address this need, the NICHD proposes to 
apply the knowledge and techniques garnered from the Human Genome 
Project. Using cord blood and microarray technology, there is the 
potential to identify disease genes at birth for more than 200 single 
gene defects associated with mental retardation, nearly 100 associated 
with immunodeficiency disorders, approximately 10 causes of muscular 
dystrophy, and cystic fibrosis. Although treatments are available for 
many of these conditions, effective study of potential new treatments 
for others requires a population who has not yet developed symptons of 
the condition. Screening of newborn infants can provide this 
population. This testing could be done in one procedure so that 
economies of scale and simplicity may overcome one of the major 
obstacles to widespread acceptance of expanded newborn screening: cost.
    The NICHD will collaborate with several other ICs, research 
institutions, and industry to develop the appropriate microarray chip 
and associated technology for mass screening and pilot test the new 
screening technology. This approach would maximize the use of newborn 
screening for preventive purposes. Moreover, by developing this 
translational research, NICHD will fulfill one of the objectives of the 
NIH road map activities.
    Mr. Chairman, I will be happy to provide answers to any questions 
you have.
                                 ______
                                 
             Prepared Statement of Dr. James F. Battey, Jr.

    Mr. Chairman and Members of the Committee, I am pleased to present 
the President's budget request for the National Institute on Deafness 
and Other Communication Disorders (NIDCD). The fiscal year 2004 budget 
includes $380,377,000, which reflects an increase of $10,190,000 over 
the fiscal year 2003 enacted level of $370,187,000 comparable for 
transfers proposed in the President's request. Disorders of human 
communication exact a significant economic, social, and personal cost 
for many individuals. The NIDCD supports research and research training 
in the normal and disordered processes of hearing, balance, smell, 
taste, voice, speech, and language. Results of NIDCD's research 
investment will foster the development of more precise diagnostic 
techniques, novel intervention and prevention strategies, and more 
effective treatment methods for the millions of Americans with 
communication disorders. My testimony will highlight some examples of 
research progress in human communication sciences.
    Cochlear Implants.--If Ludwig van Beethoven were able to reverse 
his deafness and regain his hearing again as he reached the climax of 
his career as a composer, would the world have been blessed with even 
more of his music? Scientific technology has advanced significantly 
since the 18th century, and assistive hearing devices are now able to 
restore sound perception to deaf individuals. One such device, the 
cochlear implant, has provided hope to thousands of deaf individuals 
worldwide. A cochlear implant converts sound into electrical impulses, 
bypassing the damaged sensory hair cells that detect sound, stimulating 
the auditory nerve directly and restoring sound perception. According 
to the Food and Drug Administration 2002 data, approximately 59,000 
people worldwide have received cochlear implants. In the U.S., about 
13,000 adults and nearly 10,000 children have received them. With over 
30 years of NIH research investment, the cochlear implant has evolved 
from an experimental device to a commercially available treatment to 
assist those who are profoundly deaf or severely hearing impaired.
    Hereditary Deafness Gene Discovery.--Within the last seven years, 
over 70 different genes for hearing loss that is not associated with 
other inherited characteristics (nonsyndromic hereditary hearing 
impairment) have been mapped and over 25 identified. In addition, 
several genes essential for normal auditory development and/or function 
have been identified using mouse models. Recently, scientists have 
discovered a new gene of unknown function, TMC1, in which mutations 
cause deafness. NIDCD intramural scientists have identified a mutation 
in the mouse Tmc1 gene which causes similar types of dominant and 
recessive hearing loss found in large human family studies. In mice, 
mutations in the Tmc1 gene causes defects in the function of the 
specialized sensory hair cells of the inner ear. Hair cells detect and 
convert the physical stimulus of sound into electrical impulses sent to 
the brain via the auditory nerve. This research contributes to new 
models for studying specific forms of human deafness.
    Sensory Stereocilia Renewal Aid Recovery to Hearing Loss.--
Stereocilia, or hair cell bundles, are fine projections in the inner 
ear that vibrate when stimulated by sound. The movement of the 
stereocilia activates a molecular pathway that generates an electrical 
signal from the auditory nerve to the brain, which is interpreted to be 
sound. Stereocilia are located in the surface of the inner ear and are 
supported by a rigid and dense core of filaments. Until recently, this 
core was thought of as a stable structure whose sole function was to 
serve as rigid supports for changes in the mechanical property of the 
hair cells. NIDCD intramural scientists have discovered that there is a 
continuous renewal of the stereocilia core every 48 hours. This process 
occurs in the mature bundles during recovery from temporary noise-
induced hearing loss and suggests that the stereocilia core structure 
plays an unforeseen role in this recovery process. Such a renewal 
mechanism could also provide more information on the molecular basis of 
genetic, environmental, and age-related inner ear disorders that 
involve malformation or disruption of stereocilia.
    Motor Protein Facilitates the Speed of Sound.--One important 
component in the mechanical transmission of sound from the ear to the 
brain is Myosin-1C, a major motor protein involved in the movement of 
the stereocilia in the inner ear. It is hypothesized that motor 
proteins serve as the link between the stereocilia's membrane and cell 
core thereby changing the polarity of hair cells following sound 
vibration. NIDCD-supported scientists are in the process of deciphering 
how Myosin-1C works. Specifically, they used a chemical-genetic 
approach to inhibit Myocin-1C motor protein activity in mice by 
introducing a custom designed amino acid that alters the protein's 
function. The designer amino acid rendered the protein susceptible to a 
controllable inhibitor, thus allowing regulation of the protein's motor 
function. These results demonstrate the importance of Myosin-1C in 
transmitting sound to the brain, allows observation of protein function 
in a controllable native environment and permits assessment of protein 
function in a biological process.
    Antibiotic Controls the Vertigo of Meniere's Disease.--Meniere's 
disease is a distressing and often disabling disorder of inner ear 
function, characterized by spontaneous attacks of vertigo, fluctuating 
hearing loss, tinnitus and fullness in the ear. When vertigo cannot be 
controlled by diet or medication, severing of a vestibular nerve from 
the affected ear usually controls vertigo while preserving hearing. 
NIDCD-supported scientists have demonstrated that a single injection of 
the antibiotic, gentamycin, through the eardrum into the middle ear 
space, is an alternative to surgery and is effective in diminishing 
vestibular response and in controlling vertigo in individuals with 
Meniere's disease. Experimental studies suggest that gentamycin reduces 
vestibular responsiveness, and hence, vertigo, by causing a toxic 
effect on the vestibular hair cells, the sensory receptors that detect 
head motion stimuli and orientation.
    Odorant Receptors Help Mosquitoes Smell Their Prey.--The sense of 
smell (olfaction) plays an important role for blood-feeding female 
mosquitoes in finding a host. Mosquito-borne disease is a serious world 
health concern, and the mosquito is known to transmit a variety of 
deadly diseases, including malaria, West Nile virus, dengue and yellow 
fever. Host preference, especially to humans, in the female mosquito is 
a critical component of disease transmission. NIDCD-supported 
scientists are characterizing the genes that play a role in the 
function of the olfactory system of Anopheles gambiae and have 
identified odorant receptor-encoding genes selectively expressed in the 
olfactory organs of this malaria-transmitting mosquito. Blood-feeding 
and host preference selection involve only the female mosquito, so the 
scientists studied the expression of odorant receptor genes, AgOr, in 
the female mosquito's primary olfactory organ--its antennae. It was 
observed that AgOr1 is turned off in the olfactory tissue of the female 
mosquito 12 hours after a blood meal, which is consistent with 
decreased host-seeking behavior. These findings suggest that AgOr1 may 
detect an olfactory signal that is active in female mosquitoes before 
but not after a blood meal. Developing selective antagonists to AgOr1 
may help to control the transmission of malaria and other mosquito-
borne diseases, and may also represent a novel disease prevention 
approach that is based on an understanding of olfactory receptor genes. 
In addition, these findings may ultimately be useful in developing new 
repellants and attractants that are more effective, economical and 
ecologically friendly.
    Discovery of an Amino Acid Taste Receptor.--Taste is responsible 
not only for attraction and repulsion to various foods but is also 
responsible for providing important information about the chemical 
environment. The basic taste qualities are sweet, sour, salty, bitter 
and umami (the taste of monosodium glutamate or the taste associated 
with protein-rich foods). A major challenge in taste research is 
identifying the various types of taste receptors on the tongue that 
respond to different structurally diverse compounds. Recently, 
scientists have identified a taste receptor dedicated to tasting amino 
acids, the building blocks of proteins that are involved in the 
biological processes in the body. It has been known that sweet-, 
bitter- and umami-tasting substances activate G-protein-coupled 
receptors in the tongue. NIDCD-supported scientists discovered that two 
subunits in the T1R receptor family, T1R1 and T1R3, can combine to form 
an amino acid receptor, T1R1+3, that responds to most of the 20 
standard amino acids. Identification of an amino acid taste receptor 
provides a new tool to help scientists decode the molecular basis for 
detecting different taste qualities in mammals.
    Do Stutterers Have Different Brains?--To study the brain activity 
patterns in the cortical speech-language areas of the brain of 
individuals who stutter, NIDCD-supported scientists performed brain 
imaging studies on two groups of adults; those with or without 
persistent developmental stuttering (PDS). Results of the analysis 
showed that differences in the speech-language areas of the brain are 
more common in adults with PDS, although no one anatomic feature 
accounted for the group differences. The major anatomic finding was 
that the size of the right and left planum temporale (PT) of the brain 
were significantly larger in the adults with PDS. The PT is important 
for higher order processing of language information. The results about 
the PT size and other findings, such as variations of infolding 
patterns of the brain, demonstrate that atypical size or shape of the 
speech-language area may put individuals at risk for stuttering.
    Speech-Sound Disorders are Risk for Later Academic Impairments.--
Children with speech-sound disorders often have difficulties in other 
areas of language as well. These disorders are characterized by the 
inability to use speech sounds that are normal for the individual's age 
and dialect. Speech-sound disorders involve language difficulty 
affecting an individual's ability to learn and organize speech sounds 
into a system of sound patterns. Poor awareness of speech skills and a 
weakness in vocal sound classification in verbal memory may put 
children of preschool age with speech-sound disorders at risk for later 
spelling difficulties. In a recent NIDCD-supported study, the spelling 
errors of children with history of speech-sound disorders were analyzed 
to predict the association between weaknesses in spoken language skill 
in early childhood and school-age spelling abilities. The findings of 
this study support previous research indicating that children with 
early speech-sound disorders are at risk for later spelling 
difficulties. Evidence from studying these families raises the 
possibility of a common genetic cause for speech/language and written 
language disorders. Although the genetic cause for these disorders is 
not known, specific signs of the disorder suggest a male gender bias 
since brothers were also more likely to have the disorder than sisters. 
The findings of this study reveal that preschool children with speech-
sound disorders are at risk for later spelling impairments even after 
productive speech disorders have resolved.
    A Possible Gene for Childhood Language Disorders.--Children who 
fail to develop language normally (in the absence of factors such as 
neurological disorders, hearing impairments, or lack of adequate 
opportunity) have specific language impairment (SLI). SLI has a 
prevalence of approximately 7 percent in children entering school and 
is associated with later difficulties in learning to read. Research 
studies have consistently demonstrated that SLI clusters in families, 
suggesting that genetic factors may be an important cause of SLI. 
NIDCD-supported scientists are scanning the genome for the location of 
the gene suspected of causing SLI, by studying families where multiple 
members have with language/reading disorders. The study showed 
significant evidence of a link between a region of chromosome 13 and 
susceptibility to SLI. Further analysis also suggests two additional 
gene locations on chromosomes 2 and 17 that may play a role in SLI. In 
addition, mutations in the same region in chromosome 13 is implicated 
in autism, and some children with autism show language deficits that 
are very similar to SLI.
    Mr. Chairman and Members of the Committee, these are just a few 
examples of NIDCD's research advances. I would be pleased to answer any 
questions you may have.
                                 ______
                                 
              Prepared Statement of Dr. Francis S. Collins

    Mr. Chairman and Members of the Committee: Due in great part to the 
visionary leadership and commitment of Congress, this month the 
International Human Genome Project (HGP), led by the National Human 
Genome Research Institute (NHGRI) of the National Institutes of Health 
(NIH), will have accomplished all of its original goals, ahead of 
schedule and under budget. This historic achievement, in the month of 
the 50th anniversary of Watson and Crick's seminal publication of the 
structure of DNA, opens the genomic era of medicine. April will also 
witness the publication of a bold vision for the future of genomics 
research, developed by the NHGRI. This vision, the outcome of almost 
two years of intense discussions with hundreds of scientists and 
members of the public, has three major areas of focus: Genomics to 
Biology, Genomics to Health, and Genomics to Society.
    Genomics to Biology.--The human genome sequence provides 
foundational information that allows development of a comprehensive 
catalog of all of the genome's components, determination of the 
function of all human genes, and deciphering of how genes and proteins 
work together in pathways and networks.
    Genomics to Health.--Completion of the human genome sequence offers 
a unique opportunity to understand the role of genetic factors in 
health and disease, and to apply that understanding rapidly to 
prevention, diagnosis, and treatment. This opportunity will be realized 
through such genomics-based approaches as identification of genes and 
pathways and determining how they interact with environmental factors 
in health and disease, more precise prediction of disease 
susceptibility and drug response, early detection of illness, and 
development of entirely new therapeutic approaches.
    Genomics to Society.--Just as the HGP has spawned new areas of 
research in basic biology and in health, it has created new 
opportunities in exploring societal issues. These include analysis of 
the impact of genomics on concepts of race, ethnicity, kinship, 
individual and group identity, health, disease, and ``normality'' for 
traits and behaviors, and defining policy options regarding the use of 
genomic information in both medical and non-medical settings.

                         NEW NHGRI INITIATIVES

    The NHGRI has already begun several new initiatives, and is 
planning others, to meet the challenge of this new vision for the 
future of genomics. Below are examples of these cutting edge programs.

The Creation of a Human Haplotype Map
    Multiple genetic and environmental factors influence many common 
diseases, such as diabetes, cancer, stroke, psychiatric disorders, 
heart disease, and arthritis; however, relatively little is known about 
the genetic basis of common diseases. The NHGRI has begun to create a 
``haplotype map'' of the human genome to enable scientists to find the 
genes that affect common diseases more quickly and efficiently. The 
power of this map stems from the fact that each DNA variation is not 
inherited independently; rather, sets of variations are inherited in 
blocks. The specific pattern of particular genetic variations in a 
block is called a haplotype. This new initiative, an international 
public/private partnership led and managed by NHGRI, will develop a 
catalog of haplotype blocks, the ``HapMap.'' The HapMap will provide a 
new tool to identify genetic variations associated with disease risk or 
response to environmental factors, drugs, or vaccines. Ultimately, this 
powerful tool will lead to more complete understanding of, and improved 
treatments for, many common diseases.

The ENCODE Project: ENCyclopedia Of DNA Elements
    To utilize fully the information that the human genome sequence 
contains, a comprehensive encyclopedia of all of its functional genetic 
elements is needed. The identity and precise location of all 
transcribed sequences, including both protein-coding and non-protein 
coding genes, with their structure, transcription start sites, 
polyadenylation sites, and alternative splicing variants must be 
determined. The identity of other functional elements encoded in the 
DNA sequence, including promoters, enhancers, and other transcriptional 
regulatory sequences, and determinants of chromosome structure and 
function, such as origins of replication and hot spots for 
recombination, also is needed. The NHGRI has developed a public 
research consortium to carry out a pilot project, focusing on a 
carefully chosen set of regions of the human genome, to compare 
existing and new methods for identifying functional genetic elements. 
This ENCyclopedia Of DNA Elements (ENCODE) consortium, which welcomes 
all academic, government, and private sector scientists interested in 
facilitating the comprehensive interpretation of the human genome, will 
greatly enhance use of the human genome sequence to understand the 
genetic basis of human health and to stimulate the development of new 
therapies to prevent and treat disease.

Chemical Genomics
    One novel way that the NHGRI plans to pursue translating genomics 
to human health is the development and deployment to the biomedical 
research community of libraries of small organic compounds. This is a 
fundamentally new approach for research in the public sector, and will 
accelerate understanding of the function of the human genome and the 
development of new treatments. The NHGRI proposes to use the types of 
organic molecules in most marketed pharmaceuticals, ``drug-like,'' or 
``small'' molecules, as a core of this resource. In collaboration with 
other NIH institutes, the NHGRI is planning for a resource that 
includes: (a) large libraries of chemical compounds of appropriate 
structural diversity and properties; (b) assay development capacity; 
(c) robotic assay capacity, also termed high throughput screening 
(HTS); (d) medicinal chemistry capacity to transform ``hits'' 
identified by HTS into workable chemical probes; and (e) distribution 
capacity to disseminate the reagents to the biomedical research 
community efficiently.

Genome Technology Development
    The NHGRI continues to invest in technology development that 
furthers the uses of genomics. Technical advances have caused the cost 
of sequencing to decline dramatically, from $10 to less than $0.09 per 
base pair, but this cost must decline even further for all to benefit 
from genomic advances. The NHGRI, along with many partners, will 
actively pursue the development of new technologies to sequence any 
individual's genome for $1,000 or less. Other areas of technology 
development are also ripe for expansion and the NHGRI plans to pursue 
them vigorously.

Studying the Genetic Basis of Health
    Analytic methods to find genetic variants that contribute to 
disease can also help find genes and genetic variants that contribute 
to health. The NHGRI plans to support development of new tools and 
analytical methods to discover the genetic components of resistance to 
diseases, disorders, toxins, and drug reactions. By finding genetic 
variants that convey reduced susceptibility, researchers will better 
understand disease processes and how to slow, or even prevent, them. 
Promising approaches for identifying disease-resistant gene variants 
include studying people at high risk for a disease who do not develop 
it, relatives of people with disease who do not themselves have the 
disease, or individuals who reach extreme old age without serious 
illness.

                 RECENT SCIENTIFIC ADVANCES IN GENOMICS

Progress in Sequencing Model Organisms
    From the Human Genome Project's outset, the NHGRI and its partners 
have included, among their research goals, mapping and sequencing the 
genomes of several non-human organisms, since they would be of great 
value in understanding the biological data encoded in the human DNA 
sequence and, thus, in combating human disease. Genomic sequences for a 
number of important organisms, beyond those initially identified by the 
HGP, have been determined. Primary among these is the laboratory mouse. 
In December 2002, an analysis of an advanced draft of the mouse genome 
was published and provided a key tool for interpreting the human 
sequence. The first assembly of the rat genome sequence was announced 
in the same month by the Rat Genome Sequencing Project. A peer review 
process now selects new genomes to sequence. To champion an organism, 
scientists write a ``white paper'' that presents arguments for 
prioritizing their proposed target for sequencing. After two rounds of 
white papers, this process determined the highest priority as: chicken, 
chimpanzee, cow, dog, a set of fifteen fungi, honeybee, sea urchin, and 
two protozoans. Sequencing of the chicken, chimpanzee, and honeybee has 
already begun.

       ETHICAL, LEGAL AND SOCIAL IMPLICATIONS OF GENETIC RESEARCH

    The NHGRI devotes five percent of its annual budget to research 
involving the ethical, legal and social implications (ELSI) of genetics 
and genomics. Below are examples of this program's important work.

Genetic Discrimination
    Most Americans are optimistic about the use of genetic information 
to improve health, but many are also concerned that insurers and 
employers will misuse genetic information. These concerns deter 
participation in important biomedical research and the clinical use of 
genetic information. The NHGRI has supported research efforts to 
elucidate this issue. Such research has helped inform legislative 
activity; over 40 states have passed genetic nondiscrimination bills.

Reducing Health Disparities
    The NHGRI recognizes the critical importance of ensuring that the 
potential of genomic research benefits all racial and ethnic groups. 
The NHGRI has taken steps to engage and empower minority communities in 
genomic research. The rewards of genomic research will be realized only 
with active participation of all racial and ethnic groups. An important 
area of genomic research is investigating how DNA sequence variation 
affects differing susceptibility to disease among various populations. 
The significant societal ramifications of this research also need 
attention. Genomic research affects all populations; thus, all groups 
need to set the research agenda and examine the broader issues it 
raises. The NHGRI has intensified its efforts to address health 
disparities by developing a strategic plan that identifies goals in 
areas such as research projects, information sharing, development of 
partnerships, and increasing diversity of the research workforce.

Effects of Gene Patents and Licenses on Genetic Testing and Research
    The NHGRI continues to be concerned about the issues of gene 
patenting and licensing. To gain a better understanding of these 
issues, it has funded case studies and surveys to describe and analyze 
the effects of patents that award proprietary claims to the use of DNA 
sequences. The NHGRI held a roundtable discussion in December 2002 with 
outside experts in gene patenting to explore the ramifications on 
healthcare delivery and research of patenting and licensing genetic 
sequence data and single nucleotide polymorphisms. The NHGRI will 
utilize the insights provided at this roundtable to define further 
research to inform the policy process.

                               CONCLUSION

    This year marks a very exciting transition in the field of 
genomics, with the full sequencing of the human genome marking the 
successful achievement of all of the HGP's original goals, and thus the 
advent of the genomics era. When Congress decided to fund the HGP it 
did so with the justifiable belief that this work would lead to 
improved health for all. The ability to accelerate the realization of 
this vision now lies before us. At the same time, we must be sure that 
all our citizens have access to these technological advances and that 
this information is not misused. It is our sincere belief that the 
newly created discipline of genomics will make a profound difference on 
the health and well being of the people of this world. We are 
profoundly grateful for the support the Congress has given to this 
program.
    Mr. Chairman, I am pleased to present the President's budget 
request for the National Human Genome Research Institute. The fiscal 
year 2004 budget includes $478,072,000, an increase of $13,467,000 over 
the fiscal year 2003 enacted level of $464,605,000 comparable for 
transfers proposed in the President's request.

                                 ______
                                 
           Prepared Statement of Dr. Andrew C. von Eschenbach

    The early part of the 21st century promises to be a period of 
unprecedented progress in conquering our most debilitating diseases 
especially cancer. The nation's unwavering support of the biomedical 
research enterprise, in particular, the unified effort by this 
committee, all of Congress, and the President to double the NIH budget 
over the past five years, has positioned us to attack this devastating 
disease more effectively. Cancer affects nearly every family in 
America. In 2003, 1.4 million of our citizens will face a diagnosis of 
cancer--and over 560,000 of our citizens will die from their disease 
this year. Every day, 1,500 Americans lose their own battle with 
cancer. These are daunting statistics, and the aging of the baby boomer 
population and shifting demographics of America during the next 15-20 
years represent enormous healthcare and economic challenges that we 
must begin to prepare for now.
    But, there is reason for optimism! Our nation's investment in basic 
research has fueled the engine of discovery, thereby enabling 
unparalleled advances in illuminating the genetic changes and molecular 
mechanisms that ultimately produce cancer. The sequencing of the human 
genome and associated progress in new areas such as functional 
genomics, animal models of cancer, and proteomics, provide us with a 
clearer picture of the disturbances that cause cancer to develop and 
ravage the human body. For the first time, we have within our grasp the 
ability to design target-specific interventions to preempt this 
process. We must enrich these extraordinary advances in basic science 
with equally extraordinary efforts to develop new agents and 
technologies to actualize these interventions at key steps in cancer 
progression. We now understand that cancer is a process--a process with 
multiple opportunities to develop new, more effective interventions to 
prevent, detect and treat cancer.
    To capitalize on this knowledge, we must significantly accelerate 
the pace of progress across the entire research continuum. The pathway 
begins with discovery of knowledge that underpins the development of 
new molecules and tools and ends with the delivery of diagnostics and 
therapeutics to patients. Discovery, development and delivery are 
interlinked, and it is crucial that we take the steps needed to ensure 
that all phases of the research enterprise are functioning optimally.
    I believe that we stand at an ``inflection point'' in our nation's 
effort to conquer cancer. The research enterprise has delivered 
remarkable scientific achievements in biomedical research over the past 
decades, and we now are positioned to experience a rapid increase in 
the trajectory of this research. This affords us an unprecedented 
opportunity to harness strategically these achievements to confront the 
challenges of cancer today and tomorrow.
    We now envision a time when the suffering and the death that are 
caused by cancer will be eliminated; and we believe that it is 
realistic to set ourselves a challenge goal to achieve this vision by 
the year 2015. I have presented the cancer research community with this 
challenge and am confident that they will achieve the goal. I want to 
be clear what we mean by ``reduce suffering and death from cancer,'' 
and to explain why I believe that this vision is achievable.
    We are not saying that all cancer will be cured or eliminated. What 
we are saying is that in this 12-year time-frame, many cancers will be 
cured, but many more will be transformed into chronic, manageable 
diseases that patients can live with--not die from. There is precedent 
for this paradigm shift. In a single generation, we made enormous 
strides in reducing deaths from coronary artery disease and converting 
this disorder into a condition that people live with and manage. 
Likewise, using our knowledge of the AIDS virus, molecular biology, and 
skills in developing target-based therapy, we have developed treatments 
for AIDS patients that both save lives and preserve quality of life. I 
think we can do the same for cancer.
    This vision presents new challenges for the NCI and for everyone 
working to conquer this devastating disease. We will meet those 
challenges by further strengthening basic research, especially in 
advancing our understandings about the mechanisms of cancer 
progression. In parallel, we will intensify our focus on developing the 
clinical research and delivery systems needed to provide the promise of 
everything that science can provide to everyone in need.
    I discovery, we will establish a national effort to ``map'' the 
critical events of the complex of integrated cancer disease pathways at 
the cellular level. This ``systems biology approach'' will allow us to 
dissect strategically the complex and redundant reactions and 
interactions within cells, and will enhance our technical capabilities 
to identify molecular targets and create new therapies. We will also 
focus on the exploration of new technologies, in reas such as molecular 
imaging, proteomics and genomics, and nanotechnology. These new 
technologies offer the promise of developing new platforms to monitor 
cells, identifying intricate molecular changes, and delivering 
therapeutics to specific targets within the cell. The application of 
these advanced technologies is no longer a dream. Advances in positron 
emission tomography, coupled with new molecular imaging agents, now 
make functional monitoring possible, permitting clinicians to 
``visualize'' the biologic progress of cancer. Scientists and engineers 
are working to achieve this goal through NCI's unique programs that 
foster the development of innovative technologies for cancer diagnosis 
and treatment.
    The NCI will also place new emphasis on the development process--
the translation of basic research advances into new products that are 
ultimately delivered to cancer patients. This is especially true in the 
area of cancer therapeutics. It currently takes 15-20 years for a 
promising new molecule to reach patients. That is just unacceptable in 
the 21st century. Genomics and proteomics are providing us with 
hundreds, potentially thousands, of new therapeutic targets for cancer; 
but the enterprise is not optimized to develop and deliver these ``new 
paradigm'' drugs. This is a systems problem and it can be solved. In 
collaboration with he NIH, the Food and Drug Administration (FDA) and 
other partners, we will work to ``re-engineer'' the clinical trials 
infrastructure for the evaluation of new cancer interventions. 
Underpinning all of these initiatives will be the deployment of a 
bioinformatics infrastructure that will allow us to use artificial 
intelligence to convert massive amounts of data into new knowledge that 
will inform discovery, development, and delivery to benefit patients.
    The NCI will undertake programs to optimize the process of 
developing new drugs trough an emphasis on validating new cancer 
targets. We will also work more closely with the FDA to facilitate the 
science necessary to create a seamless system of drug discovery, 
development, and delivery. To achieve these goals, the NCI will create 
novel partnerships with all of the sectors involved in developing and 
delivering these new drugs. In all that we do, we will encourage the 
removal of barriers that separate us by creating a new environment that 
encourages and rewards multi-disciplinary research.
    The emerging field of proteomics provides us with unimagined 
opportunities to apply these new targeted therapies and preventive 
strategies by detecting cancer early enough to stop, slow, or possibly 
reverse disease progression. Novel disease biomarkers are finally 
providing us with new screening tools to detect early-stage cancer in 
populations and individuals; and the NCI will utilize its enormous 
strength in molecular epidemiology to provide rational strategies for 
cancer prevention and disruption of progression within populations.
    All of these tactics will be directed to reducing suffering and 
death from cancer. That does not mean that we will lessen our emphasis 
on curing cancer--quite the opposite--but that will no longer be our 
only defining goal. We will also embrace the vision of changing the 
course of cancer by reducing its morbidity and mortality through the 
application of technologies and knowledge that were only a dream just a 
few short years ago. Those dreams can become reality.
    Finally, I believe we stand at a pivotal crossroads--a defining 
moment in the history of this nation's effort to prevent and cure 
cancer. We now embark on a new course that will enable patients to live 
with cancer as a chronic, non-debilitating disease that doesn't 
threaten their vitality, careers, and families. An ever increasing body 
of scientific knowledge and an array of advanced technologies provide 
us with the opportunity to detect cancer early and preempt the 
progression of the disease. We will be able to remove the fear of 
cancer for many more people, but more importantly for those who must 
live with their disease, life will take on new meaning. We have within 
our grasp the power to eliminate the suffering and death from cancer--
and we will succeed.

                            BUDGET STATEMENT

    The fiscal year 2004 budget includes $4,770 million, an increase of 
$183 million over the fiscal year 2003 enacted level of $4,587 million 
comparable for transfers proposed in the President's request.
                                 ______
                                 
               Prepared Statement of Dr. Anthony S. Fauci

    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's budget request for the National Institute of Allergy 
and Infectious Diseases (NIAID) of the National Institutes of Health 
(NIH). The fiscal year 2004 budget includes $4,335,255,000, an increase 
of $631,126,000 over the fiscal year 2003 enacted level of 
$3,704,129,000 comparable for transfers proposed in the President's 
request. The NIAID budget request includes the performance information 
required by the Government Performance and Results Act (GPRA) of 1993. 
Prominent in the performance data is NIAID's third annual performance 
report, which compares our fiscal year 2002 results to the goals in our 
fiscal year 2002 performance plan.

                           NIAID: AN OVERVIEW

    Since 1948, NIAID has conducted and supported basic research into 
the etiology and pathogenesis of allergic, immunologic, and infectious 
diseases, as well as targeted research to develop new and improved 
interventions to prevent, diagnose, and treat these illnesses. Over the 
past half century, and in the past decade in particular, progress in 
the core disciplines of the Institute--immunology, microbiology, and 
infectious diseases--has been extraordinary. The rapid growth in 
scientific knowledge and the availability of new research tools has 
facilitated the development of numerous vaccines, therapies and other 
interventions that have saved or improved the lives of millions of 
individuals. For example, NIAID-supported scientists helped develop 
many of our most useful vaccines, including new or improved vaccines 
that protect against invasive Haemophilus influenzae type b (Hib) 
disease, pneumonia and meningitis caused by pneumococcal bacteria, 
pertussis, influenza, measles, mumps, rubella, chickenpox, and 
hepatitis A and B. These and other vaccines helped reduce infectious 
disease mortality in the Unites States more than 14-fold in the 20th 
century.
    The scientific advances realized during 55 years of NAID research 
have been applied to long-standing global health problems such as 
asthma, autoimmune diseases, diarrheal diseases, malaria, and 
tuberculosis, as well as to diseases and pathogens that have recently 
emerged or re-emerged. Examples of the latter include the acquired 
immunodeficiency syndrome (AIDS), highly virulent influenza viruses, 
West Nile virus, drug-resistant microbes, severe acute respiratory 
syndrome (SARS), and a new kind of emerging disease--one spread 
deliberately by bioterrorists. As has been the case with AIDS and other 
emerging health crises, the NIAID response to the threat of 
bioterrorism has been swift and comprehensive, resulting already in 
important progress both in basic science and in the development of 
biodefense countermeasures.

                       NIAID BIODEFENSE RESEARCH

    The anthrax attacks in the fall of 2001, which occurred soon after 
the horror of the September 11 terrorist assaults on the World Trade 
Center and the Pentagon, starkly exposed the vulnerability of the 
United States and the rest of the world to bioterrorism. Since the fall 
of 2001, NIAID has rapidly accelerated basic and clinical research 
devoted to the prevention, diagnosis, and treatment of diseases caused 
by potential agents of bioterrorism. Indeed, biodefense research 
spending now accounts for approximately one-third of the NIAID research 
portfolio. Our efforts have focused both on ``Category A'' agents 
considered to be the worst bioterror threats (smallpox, anthrax, 
botulinum toxin, plague, tularemia, and hemorrhagic fever viruses such 
as Ebola), as well as on a longer list of Category B and C priority 
pathogens agents that also pose significant threats to human health. 
The NIAID biodefense program is guided by the NIAID Strategic Plan for 
Biodefense Research, as well as by detailed research agendas for 
Category A agents and Category B and C priority pathogens. Each of 
these documents was prepared in consultation with blue-ribbon panels of 
experts, and delineates immediate, intermediate, and long-range NIAID 
plans for biodefense research and countermeasures development. Using 
the roadmap outlined in these agendas, NIAID has developed a total of 
46 biodefense initiatives to stimulate research in fiscal years 2002 
and 2003: 30 are new initiatives and 16 are significant expansions. 
During this same time period, NIAID has seen a 30 percent increase in 
the number of grant applications; the vast majority of these are in 
response to our biodefense initiatives.
    The NIAID biodefense research program is anchored in the 
traditional NIH processes of basic biomedical research; concurrently, 
we are aggressively pursuing the goal of translating the findings of 
basic research into definable and quantifiable endpoints such as 
diagnostics, therapeutics, and vaccines. NIAID historically has sought 
to translate basic research findings into ``real-world'' interventions, 
as with the vaccines noted above. Until now, however, the path to 
product development has not been central to our research strategy. The 
attacks of September 11, 2001, and the subsequent anthrax incidents 
have compelled us to modify somewhat the way we do business, with an 
increased focus on translational research and product development. This 
applied research is based on the strongest possible foundation of 
fundamental knowledge of pathogenic microbes and the host immune 
response.
    As we pursue innovative biodefense countermeasures, we have 
strengthened our interactions with the private sector, including 
biotechnology companies and pharmaceutical manufacturers. Many 
biodefense products do not provide sufficient incentives for industry 
to develop them on their own, because a profitable market for these 
products cannot be guaranteed. Therefore, NIAID has developed public-
private partnerships with industry to overcome such obstacles so that 
new and improved interventions against bioterror threats can quickly be 
developed.
    A number of significant advances in understanding, treating, and 
preventing potential agents of bioterror already have been realized. 
For example, NIAID-supported scientists have identified antivirals that 
may play a role in treating smallpox or the complications of smallpox 
vaccination, as well as new antibiotics and antitoxins against other 
major bioterror threats. Investigators have demonstrated that existing 
stores of smallpox vaccine can be diluted five-fold and still retain 
their potency, greatly increasing the Nation's available stock of 
smallpox vaccine. These studies of diluted smallpox vaccine helped 
fulfill an immediate goal delineated in our strategic plan for 
biodefense. In the intermediate-term, new and improved vaccines against 
smallpox, anthrax, and other potential bioterror agents are being 
developed and evaluated at NIAID intramural facilities, as well as by 
our grantees and contractors in academia and industry. One of these is 
a smallpox vaccine based on a strain of the vaccinia virus that 
replicates less robustly than the traditional smallpox vaccine virus, 
and is known to be less reactogenic than the current smallpox vaccine. 
In the long-term, we will develop even safer vaccines against smallpox 
virus and other pathogens.
    Advances in biodefense, as well in other areas of infectious 
diseases research, are being facilitated by the detailed information 
about pathogens that now can be rapidly gleaned by determining their 
genomic sequence. The field of pathogen genomics has made remarkable 
progress: sequencing of the genomes of more than 100 pathogens is 
complete or nearing completion. Among them are approximately 30 
different Category A, B and C agents, including multiple strains of the 
anthrax bacterium. This genomic information is being used to inform the 
development of new antimicrobials, vaccines, and diagnostics.
    Progress in biodefense research depends on the availability of 
research resources, such as animal models, standardized reagents, and 
appropriate laboratory facilities, as well as on human capital, that 
is, well-trained investigators. Among many initiatives to improve the 
biodefense research infrastructure, NIAID will establish in fiscal year 
2003 a nationwide network of Regional Centers of Excellence for 
Biodefense and Emerging Infectious Disease Research, and design, build, 
and renovate a system of Regional and National Biocontainment 
Laboratories. These facilities will include a small number of Biosafety 
Level-4 (BSL-4) laboratories, which have the containment safeguards 
necessary to study highly pathogenic organisms. The new Centers and 
laboratories will serve as national resources for biodefense research 
and product development, as well as for the study of other emerging 
diseases such as influenza and West Nile virus.
    The many new NIAID initiatives in biodefense research will provide 
benefits far beyond protection from deliberate acts of bioterrorism. 
After all, the general philosophy and strategy of biodefense is 
essentially the same as that for defense against naturally emerging and 
re-emerging infectious diseases that threaten global public health. 
With the careful NIAID planning process, new biodefense resources will 
unquestionably have enormous benefits in our struggle against other 
diseases, endemic and emerging, that far transcend the specter of 
bioterrorism.

               ACQUIRED IMMUNODEFICIENCY SYNDROME (AIDS)

    Another major focus of the Institute, accounting for approximately 
one-third of NIAID spending, is research devoted to finding 
interventions to slow the pandemic of the human immunodeficiency virus 
(HIV), the cause of AIDS. HIV/AIDS is the defining health crisis of our 
generation, having claimed well over 20 million lives since the 
beginning of the pandemic. Another 42 million people worldwide are 
living with the virus. Most of the world's HIV-infected people live in 
resource-poor countries, where HIV frequently is superimposed on other 
significant health challenges, including endemic diseases such as 
malaria and tuberculosis, and malnutrition. By 2010, more than 45 
million new infections will occur, for a cumulative total of 105 
million infections, according to estimates of the Joint United Nations 
Programme on HIV/AIDS.
    Despite these grim numbers, significant progress has been made 
against the HIV/AIDS, much of it due to the research and prevention 
efforts of NIAID and other NIH Institutes, the Centers for Diseases 
Control and Prevention, and other agencies of the Department of Health 
and Human Services. In this country, prevention efforts have reduced 
the annual number of new HIV infections in the United States from 
approximately 150,000 per year to about 40,000 annually. In recent 
years, we have seen the positive impact of advances in HIV therapeutics 
for many living with HIV/AIDS in the United States and other western 
countries, and more recently the promise these medicines offer for 
those in the developing world. All but one of the 19 antiretroviral 
drugs licensed in the United States target one of two viral targets: 
the HIV protease enzyme or the HIV reverse transcriptase enzyme. Over 
the past few years, NIAID-supported scientists and their collaborators 
have identified new targets for HIV therapy and novel drugs that block 
other stages of the virus replication cycle. Among them are agents that 
block viral genes from entering the host cell nucleus, and drugs that 
keep the virus from attaching to or entering the cell in the first 
place. In the latter category, a drug known as Fuzeon or T-20 that 
blocks the fusion of HIV to the host cell membrane was recently 
approved and holds great promise for the many HIV-infected patients who 
harbor HIV that is resistant to current therapies.
    To help turn the tide of the global HIV/AIDS pandemic, NIAID has 
established research collaborations with international colleagues to 
develop comprehensive approaches to the HIV pandemic in poor countries, 
encompassing prevention activities, antiretroviral therapy when 
feasible, and care of the HIV-infected person. These collaborations 
have yielded extraordinary results, notably in developing methods to 
reduce mother-to-child transmission of HIV. However, a rate-limiting 
factor in HIV/AIDS research efforts in developing countries has been a 
lack of funds for the purchase of antiretroviral drugs and for 
improving existing healthcare infrastructure. In January 2003, the 
Institute's international AIDS program received a substantial boost 
with the announcement of the President's Emergency Plan for AIDS 
Relief. This plan commits $15 billion over 5 years ($10 billion of 
which is new money), starting with $2 billion in fiscal year 2004, for 
HIV/AIDS prevention, treatment, and care in 14 of the hardest-hit 
countries in sub-Saharan Africa and the Caribbean. This lifesaving 
effort will not only reduce the suffering caused by HIV/AIDS in 
countries that account for 50 percent of the world's HIV infections, 
but will provide a framework that will facilitate NIAID research 
efforts to develop new and improved tools of treatment and prevention.
    Many approaches to HIV prevention are being developed or refined, 
but the ``holy grail'' of HIV prevention remains the development of a 
safe and effective HIV vaccine. Numerous vaccine candidates have shown 
promise in monkey models of HIV infection, and the most promising ones 
are rapidly being moved into human trials on the NIH campus and in the 
domestic and international sites of the NIAID HIV Vaccine Trials 
Network.

                             OTHER VACCINES

    In addition to developing HIV and biodefense vaccines, NIAID 
continues to make significant progress in the quest for new and 
improved vaccines for other diseases of global health importance. The 
NIH has three broad goals in vaccine research: identifying new vaccine 
candidates to prevent diseases for which no vaccines currently exist; 
improving the safety and efficacy of existing vaccines; and designing 
novel vaccine approaches, such as new vectors and adjuvants, substances 
that improve vaccine performance.
    More than 100 vaccines currently are being developed by NIAID-
funded researchers, including promising candidates against emerging 
diseases such as Ebola virus, West Nile virus, dengue, and dangerous 
strains of influenza virus. Of particular note are novel tuberculosis 
vaccines, which soon will enter clinical trials. These trials will mark 
the first time in more than 60 years that new approaches to TB 
vaccination have been assessed in humans. These vaccines are a tangible 
``payoff'' of research funded by NIAID and others that led to the 
availability of the complete genomic sequence of the tuberculosis 
bacterium. The quest for a malaria vaccine received a significant boost 
in 2002 when researchers funded by NIAID and others published the 
genomic sequences of the malaria parasite Plasmodium falciparum, and 
one of its main mosquito vectors, Anopheles gambiae. Together, these 
projects are probably the most significant pathogen genome sequencing 
effort to date. With the availability of the human genome sequence, 
scientists now have detailed genomic information for each of the 
organisms involved in human malaria: the human host, the mosquito 
vector and the malaria parasite itself. This groundbreaking malaria 
research promises to provide new targets for vaccine development and 
other interventions against a disease that claims the lives of more 
than a million people each year, most of them children in sub-Saharan 
Africa.

                        IMMUNE-MEDIATED DISEASES

    Immune-mediated diseases such as autoimmune diseases, allergic 
diseases, and asthma are important health challenges here and abroad. 
Autoimmune diseases, for instance, afflict 5 to 8 percent of the U.S. 
population; asthma and allergic diseases combined represent the sixth 
leading cause of chronic illness and disability in the United States. 
The past two decades of fundamental research in immunology have 
resulted in a wealth of new information and extraordinary growth in our 
conceptual understanding of the immune system and the pathogenesis of 
immune-mediated diseases. Researchers now know a great deal about the 
effector molecules that contribute to many immunological conditions, 
knowledge that has led to the design and discovery of drugs to block 
those molecules. For instance, we now have powerful treatments that 
selectively target several of the immune system molecules that cause 
inflammation, a hallmark of many autoimmune diseases. Blockers of an 
immune system molecule called tumor necrosis factor-alpha are now 
routinely used in patients with rheumatoid arthritis and other 
immunologic conditions.
    A relatively new avenue of research suggests that it may be 
possible to interrupt deleterious immune responses, without dampening 
protective ones, and provide patients with long-term clinical benefit. 
The ability to induce ``immune tolerance'' by selectively blocking 
deleterious immune response holds great promise for treatment of many 
immune- mediated conditions, including type 1 diabetes, rheumatoid 
arthritis and multiple sclerosis, as well as asthma and allergic 
diseases. For example, researchers have shown in a small trial 
conducted by the NIAID-sponsored Immune Tolerance Network (ITN) that 
antibodies to the CD3 molecule on T-cells, given for two weeks soon 
after patients were diagnosed with type 1 diabetes, appeared to halt 
the destruction of the patients' insulin- producing cells for at least 
a year, preserving their ability to produce some of their own insulin. 
Further follow-up is underway to determine the long-term benefits of 
this experimental therapy; a larger trial is currently recruiting 
patients.
    Induction of immune tolerance is also one our highest priorities in 
organ transplantation research. The ability to selectively block the 
immune response to a transplanted organ would diminish or eradicate the 
risk of rejection, as well as the risks and morbidities associated with 
current methods of immunosuppression. A trial currently underway in the 
ITN is using a unique approach involving simultaneous bone marrow and 
kidney transplantation in patients with multiple myeloma. Although only 
a very small number of patients have undergone the procedure, early 
results are encouraging, as they have tolerated their transplanted 
kidneys without immunosuppressive medications for up to 3 years.
    Another important NIAID research focus is the development of new 
interventions to reduce the burden of asthma. NIAID has long been at 
the forefront of discoveries leading to the characterization of asthma 
and allergic diseases and is now vigorously pursing the translation of 
basic knowledge into more effective treatment and prevention 
strategies. The NIAID-sponsored Inner-City Asthma Study, completed in 
2002, evaluated the effects of a home-based environmental intervention 
on asthma symptoms and health care utilization in inner-city children 
with moderate to severe asthma. The intervention led to an additional 
three weeks of symptom-free days and a 14 percent reduction in 
unscheduled emergency room or clinic visits in the first year of the 
intervention; these effects largely persisted for a year following the 
intervention phase. The improvement in symptoms was correlated with a 
reduction in levels of key allergens in the home. Building on these 
results, the NIAID in 2002 launched the Inner-City Asthma Consortium, 
to conduct clinical trials of novel immune-based agents to treat or 
prevent asthma.

                               CONCLUSION

    The role of NIAID in fighting infectious and immunologic diseases 
has never been more important, particularly in the post 9-11 world. 
Working with our many collaborators in the public and private sectors, 
we hope to further reduce the burden of diseases endemic in the United 
States and abroad, to enhance our preparedness against bioterrorism, 
and to continue to prepare for new threats to public health that will 
inevitably emerge in the future.

                                 ______
                                 
              Prepared Statement of Dr. Patricia A. Grady

    Mr. Chairman and Members of the Committee: The fiscal year 2004 
budget includes $134,579 million, an increase of $4,060 million over 
the fiscal year 2003 enacted level of $130,584 million comparable for 
transfers proposed in the President's request.
    Nursing research and nursing practice are converging to address the 
challenges of maintaining and improving health and healthcare in our 
country. During this time of heightened uncertainty in many aspects of 
our lives, nursing research, which informs the practice of the nation's 
largest number of healthcare professionals--2.7 million nurses--is 
critical to developing and testing interventions that improve health. 
Increasingly there is a need for health promotion research, which is a 
special strength of nursing research. This need is reflected in a 
recent Department of Health and Human Services (DHHS) Fact Sheet that 
attributes 40 percent of premature deaths to unhealthy behaviors, such 
as smoking and poor eating habits. Conversely, of the 30-year average 
gain in life expectancy in the last century, the DHHS report states 
that 25 of those years came from advances in public health, principally 
from health promotion. Consistent with the NIH Research Roadmap for the 
future, nursing research also focuses on multidisciplinary and clinical 
research. The goal is to help healthcare professionals work smarter by 
capitalizing on new technologies and research-tested methodologies that 
extend the reach and quality of their practice in promoting health, 
managing illness, and improving care. Now let me discuss some findings.

    REDUCING POSTMENOPAUSAL WOMEN'S RISKS FOR CARDIOVASCULAR DISEASE

    Heart disease is the leading cause of death in women in the United 
States. Even though the death rate has decreased in recent years, the 
benefit is less for women than men. More needs to be known about the 
effects of preventive strategies, such as exercise and diet, in 
reducing risks of the disease. We know lowering total and low density 
lipoprotein cholesterol (LDL-C) and raising high-density lipoprotein 
cholesterol (HDL-C) reduces risk of cardiovascular disease in women. 
Nurse researchers did a study that asked the question of why HDL-C, the 
``good cholesterol,'' drops when post-menopausal, obese women adhere to 
a low-fat diet. On a low-fat diet, weight loss occurs and the 
deleterious LDL-C decreases, but the weight loss is accompanied by a 
reduction of the good HDL-C. Findings of the study indicate that the 
causal factor for the HDL-C reduction was not the type or amount of fat 
the women consumed, but rather that they substituted simple sugars, 
such as syrups and refined sugar, for fat in their diets. What the 
women should have done was substitute complex sugars, such as high 
fiber vegetables and starches. The current American Heart Association 
guidelines recommend consuming 55 percent of energy from carbohydrates, 
without specifying complex or simple. This study points out the need to 
write more specific dietary guidelines that differentiate between types 
of carbohydrates, in addition to types of fat. This study is especially 
timely in an age where low-fat and fat-free foods often depend on 
simple sugars to improve taste.

   REDUCING RISK FACTORS FOR OBESITY AND HYPERTENSION IN ADOLESCENTS

    Obesity continues to be a major health problem in the United 
States. The Centers for Disease Control and Prevention states that 
about 15 percent of children and adolescents are overweight, a 4 
percent increase since the last survey in 1994. The U.S. prevalence of 
obesity increased by 61 percent in the 9 years prior to 2001. Habits 
formed in childhood become the lifestyles that drive this upswing. 
Researchers testing an intervention in children and adolescents have 
been able to decrease risk factors for hypertension and obesity. As 
part of the Cardiovascular Health in Children and Youth study, 
researchers tested rural, mostly African-American middle school 
students in an eight-week physical activities program combining 
exercise and health education. Subjects were divided into four groups--
exercise, education, or both, and controls. Those in the two exercise 
groups had a lower increase in body fat, and the blood pressure of the 
three intervention groups decreased compared to controls. These results 
demonstrate the effectiveness of regular aerobic exercise and health 
education programs for school-aged children to help reduce their risks 
for cardiovascular disease later in life.

           COPING WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE

    People with Chronic Obstructive Pulmonary Disease (COPD), which 
causes discomfort at best and severe, life-altering changes at worst, 
report that there is little available to help improve their breathing. 
Shortness of breath often results in inability to work, limited social 
activities, and even difficulty in dressing themselves. As the nation's 
fourth leading cause of death, COPD affects over 22 million people. In 
confronting this issue, nurse investigators tested a ``self 
management'' inspiratory muscle training technique to assist patients 
in improving their own breathing and respiratory muscle strength. For 
30 minutes, 5 days a week, over a 16-week period, patients used a 
mouthpiece attached to a tube with openings that gradually decreased in 
size to make inhalation more challenging. Following training, these 
subjects' breathing, respiratory muscle strength, and endurance were 
considerably improved compared to a control group, and they could once 
again perform daily activities. The study also showed that subjects 
were able to self-manage by performing inspiratory muscle training at 
home without direct professional assistance.

                 IMPROVING CARE AT THE END-OF-LIFE CARE

    Another important healthcare issue involves end-of-life and 
palliative care. As the lead Institute at NIH for coordinating this 
research, NINR supports research to improve the way the healthcare 
system addresses end-of-life issues. A recent study commissioned by 
Last Acts contributed more evidence of the need for change, concluding 
that the United States does only a mediocre job of caring for seriously 
ill and dying patients. The study also indicated that although many 
would prefer to die at home or in a hospice, most die in the hospital, 
where high tech efforts to prolong life and where patients' diminished 
control over decisions are common.
    Nurse researchers studied the outcomes for patients enrolled in the 
Program for All-inclusive Care for the Elderly (PACE), a managed care 
program for people 55 and older. Results showed that unlike the general 
population, where 44 percent die in the hospital and 20 percent die at 
home, the numbers are almost reversed in PACE, with 45 percent dying at 
home and 21 percent in the hospital. Another outcome was improved 
consistency and predictability of care. End-of-life care is often 
fragmented, and in the case of advance directives, written instructions 
may not be honored in the hospital, since staff may not have immediate 
access to patient records from other care facilities. The PACE program, 
however, offers consistent care, thus increasing the likelihood that 
advance directives will be followed. PACE also helps older people 
develop advance directives.

                      NEW AND EXPANDED INITIATIVES

    For fiscal year 2004, NINR plans include launching a new pediatric 
end-of-life initiative, stimulated by the Institute of Medicine's 
report: When Children Die: Improving Palliative and End-of-Life Care 
for Children and Their Families. This report concluded that pediatric 
end-of-life issues have received insufficient research attention. We 
will also support the development of ethnically and culturally 
sensitive interventions for those near the end of life and approaches 
to improve communications between care providers, patients and 
families.
    Research on strategies for self-management of chronic illness will 
be expanded to include reducing symptoms related to high blood 
pressure, diabetes, dementia and developmental disabilities. These 
strategies will incorporate age, gender, and ethnic and cultural 
factors.
    Minority men will be targeted for interventions that promote 
healthy lifestyles, since they have a shorter life span and a higher 
mortality rate than Caucasian men and all subgroups of women. NINR will 
stimulate research on factors that influence decision-making for 
healthy choices, such as nonsmoking, exercise, and proper nutrition. 
Other issues to be addressed include: How can these men improve 
management of stress? How do their families and their communities 
influence their health-related behaviors? Because young minority men 
are often underserved, studies in this area could create an important 
strategy for effective public health interventions to follow.
    We continue to have a strong interest in the significant health 
disparities for minority women. NINR will expand research that targets 
prevention of low birthweight babies, since according to Healthy People 
2010, of the Department of Health and Human Services, the incidence 
rate for low birthweight African-American women is twice that of 
Caucasian women. Puerto Rican women are also especially likely to have 
low birthweight infants. Issues include improving early identification 
and management of complications during pregnancy, such as infection, 
hypertension, and diabetes.

               TRAINING NURSE RESEARCHERS FOR THE FUTURE

    NINR is addressing the future of nursing science--how to ensure 
that sufficient, high-quality research continues to grow and play a 
fundamental role in health care. In the early 90's, and again in 2000, 
the National Academy of Science's National Research Council stated that 
the number of nurse researchers must increase. Over the next four to 
six years, our Nation is facing a critical nursing faculty shortage. 
Nurse researchers form the backbone of university faculty in schools of 
nursing. In rising to this workforce challenge, NINR emphasizes early 
entry into research careers, including fast-track baccalaureate-to-
doctoral programs, to increase the number of nurse investigators. Other 
opportunities are made available through the NINR Centers programs and 
NINR/NIH research training mechanisms and career development awards.
    Our centers provide an environment and infrastructure to promote 
early entry into and sustained participation in research programs. NINR 
funds nine Core Centers, each of which offers research and research 
training opportunities to those in their geographic areas. We also fund 
nine Developmental Centers that enhance emerging research programs. Our 
recently-launched Nursing Partnership Centers to Reduce Health 
Disparities funded 17 Centers which pair research-intensive nursing 
schools with minority-serving schools of nursing. These Partnerships 
are expected to expand research on health disparities and increase the 
number of minority nurse investigators.
    NINR is focusing on ways to integrate genetic science into nursing 
research, education, and practice. Strategies include facilitating 
lifestyle changes for those at risk, genetic counseling, and selecting 
optimal therapeutic interventions based on genotype. The fourth NINR 
Summer Genetics Institute will be offered this year. This is an 
intensive, eight-week genetics training program held on the NIH campus. 
Its goal is to produce graduates who develop successful research 
careers and help integrate genetic information into research and 
educational programs across the country.
    Mr. Chairman, this concludes my remarks. I would be pleased to 
answer any questions you and other members of the Committee may have.
                                 ______
                                 
             Prepared Statement of Dr. Judith H. Greenberg

    Mr. Chairman and Members of the Committee, good morning. I am 
pleased to present the President's budget request for the National 
Institute of General Medical Sciences (NIGMS). The fiscal year 2004 
budget includes $1,923 million, an increase of $76 million over the 
fiscal year 2003 enacted level of $1,847 million comparable for 
transfers proposed in the President's request.
    The NIH budget request includes the performance information 
required by the Government Performance and Results Act of 1993. 
Prominent in this data is NIH's fourth annual performance report, which 
compared our fiscal year 2002 results to our fiscal year 2002 
performance plan goals.

                       AN IMPRESSIVE TRACK RECORD

    Since its creation more than 40 years ago, the National Institute 
of General Medical Sciences has built an impressive track record as a 
strategic investor in the future of basic biomedical research. Though 
not a household name, NIGMS is highly respected in the scientific 
community as an Institute that nurtures the nation's brightest minds in 
biomedicine. Through its forward-thinking funding programs, NIGMS 
supports thousands of scientists nationwide whose fundamental research 
is laying the foundation for promising new advances in disease 
diagnosis, treatment, and prevention.
    Perhaps the most notable indicator of that track record is the 
number of NIGMS-supported scientists who have won Nobel Prizes-a 
remarkable 53 to date. In 2002, both the Nobel Prize in Physiology or 
Medicine and the Nobel Prize in Chemistry went to long-time NIGMS 
grantees, Dr. H. Robert Horvitz of the Massachusetts Institute of 
Technology and Dr. John B. Fenn of Virginia Commonwealth University, 
respectively. Dr. Horvitz's discovery of key genes controlling cell 
death shed new light on illnesses such as AIDS, Parkinson's disease, 
stroke, and cancer. And Dr. Fenn's refinement of a technique called 
mass spectrometry has made it possible to analyze large molecules in 
biological samples, an advance now widely used for blood testing.
    Our Institute's leadership in supporting biomedical science was 
also recognized in 2002 with the prestigious Albert Lasker Award for 
Basic Medical Research. NIGMS grantees Dr. James E. Rothman of the 
Memorial Sloan-Kettering Cancer Center and Dr. Randy W. Schekman of the 
University of California, Berkeley, were honored for discovering the 
universal molecular machinery that drives ``cellular trafficking.'' 
Their work helped explain vital processes such as how insulin is 
released in pancreatic cells, how organs develop inside embryos, and 
how viruses infect their hosts.
    Yet another acknowledgment of NIGMS' contributions to biomedical 
research came late last year when the journal Science declared the 
discovery of how small RNA molecules control the behavior of genes to 
be the top scientific achievement of 2002. Funded in large part by 
grants from NIGMS, this ``Breakthrough of the Year'' research shows 
promise as the basis for new therapies to treat cancer, AIDS, and other 
diseases.
    As we look ahead to fiscal year 2004 and beyond, NIGMS is poised to 
help make possible even more ground-breaking advances in biomedical 
science. I would like to share with you some of our strategies for 
accomplishing this important mission.

               UNRAVELING THE 3-D STRUCTURES OF PROTEINS

    Fifty years ago, Drs. James Watson and Francis Crick made their 
famous discovery of the double-helix structure of DNA. This year, 
scientists will reach another milestone: the completion of a highly 
accurate sequence representing the entire set of genetic instructions 
encoded in human DNA. As the Human Genome Project achieves this 
landmark goal, its promise to usher in a new era of molecular-based 
medicine will depend on another, equally important undertaking: 
discovering all the proteins our genes make and the functions these 
cellular ``workhorses'' play in health and disease.
    Key to this ambitious effort is the unraveling of the complex, 
three-dimensional structures of proteins. Determining these structures 
can in turn reveal how proteins function and help scientists tailor the 
design of new drugs to treat diseases. NIGMS is the world's single 
largest supporter of research in structural genomics, a field dedicated 
to discovering the structures of proteins using sophisticated computer-
based methods.
    In fiscal year 2000, NIGMS launched the Protein Structure 
Initiative (PSI), with the goal of determining 10,000 protein 
structures in 10 years. The nine pilot research centers we currently 
support have made significant progress in developing tools for the 
high-throughput determination of protein structures and have begun to 
yield some promising results, with potential applications in 
biomedicine and beyond.
    In November 2002, for example, NIGMS-funded researchers at Argonne 
National Laboratory determined the structure of a protein knot-one of 
only a few such structures seen in nature, and the first found in a 
protein from the most ancient type of single-celled organism, an 
archaebacterium. The microbe that the newly discovered protein comes 
from is of interest to industry for its ability to break down waste 
products and produce methane gas.
    NIGMS is considering additional activities to help the centers 
reach their full capability, including a materials storage bank and a 
database for protein production and crystallization experiments. The 
production phase of the PSI, during which researchers will be rapidly 
deriving protein structures, will begin in fiscal year 2005.

        HARNESSING MATH & COMPUTERS TO SOLVE BIOLOGICAL PROBLEMS

    In addition to leading the way in structural genomics, NIGMS is 
also at another forefront: a shift in biomedical science often called 
the ``mathematization'' of biology. This shift represents a broadening 
of biologists' research focus from studying how individual biological 
molecules behave to investigating how a large number of molecules 
interact with one another. In order to model and predict these complex 
interactions, biomedical scientists are increasingly partnering with 
quantitative scientists, including mathematicians, physicists, computer 
scientists, and engineers. Together, they are applying their combined 
expertise to solve particularly challenging problems in biomedicine, 
such as understanding embryonic development, metabolism, cell growth, 
and cell death.
    To encourage more quantitative approaches in biological studies, 
NIGMS established Centers of Excellence in Complex Biomedical Systems 
Research. The first awards were for two center grants and seven 
planning grants to lay the groundwork for future centers, designed to 
foster a multidisciplinary research environment for develop ing 
innovative methods to solve biomedical problems. These centers will 
also lead the way in training the next generation of computational 
biologists.
    A good example of this teamwork is the recent work by NIGMS-funded 
researchers who have produced the first comprehensive ``script of 
life,'' describing the regulation of all the genes in yeast. Reporting 
in the journal Science in October 2002, Dr. Richard Young, a biologist 
at the Whitehead Institute for Biomedical Research, and Dr. David 
Gifford, a computer scientist at the Massachusetts Institute of 
Technology, detailed how they used advanced, high-throughput biological 
and computing technologies to do in weeks what would have taken years 
to achieve using traditional techniques.
    The mathematization of biology and its importance in modeling 
complex biological systems were also major themes at our Institute's 
``Visions of the Future'' meeting, held in September 2002. NIGMS 
invited visionary scientific leaders to identify the most important and 
emerging areas of biomedical research. A recurring topic of discussion 
was the need to develop mechanisms that encourage cooperative 
interactions among mathematicians, physicists, computer scientists, 
engineers, and biologists. Moreover, meeting participants stressed the 
need for more rigorous quantitative training of undergraduate and 
graduate students who are pursuing research careers in the life 
sciences.
    Such interaction and training were cited as keys to realizing some 
of science's grandest visions. These include the development of 
``virtual'' models--of cells, tissues, disease states, and ultimately 
entire organisms--as well as new imaging tools and methods for making 
``molecular movies'' of cellular machinery. Such technologies will help 
fill enormous gaps in our understanding of how molecules move in three 
dimensions and how they interact inside living cells in real time. 
Through its support of research and training in computational biology 
and other areas that cross traditional academic boundaries, NIGMS is 
uniquely positioned to help turn these visions into reality.

          GUARDING AGAINST INFECTIOUS DISEASES & BIOTERRORISM

    As concern grows over bioterrorism and the emergence of new 
infectious diseases, NIGMS is designing an initiative to address this 
threat using computational approaches and mathematical modeling. Such 
models will help predict the spread of microbes, the rate of disease 
progression in individuals, the effectiveness of different treatment or 
prevention strategies, and the community response to new infectious 
diseases. These predictions will, in turn, provide policymakers with 
critical information that will help them respond quickly to the threat 
of a new disease or bioterrorism attack.
    This new initiative follows on the footsteps of another successful 
NIGMS program--one dealing with the evolution of infectious diseases. 
Deadly viruses and bacteria can adapt to seemingly limitless 
environmental conditions by making rapid genetic changes, far outpacing 
our own ability to adapt. This microbial evolution renders previously 
effective drugs useless and creates a moving target for drug designers. 
However, by analyzing the evolution of infectious organisms, 
researchers now have a leg up on how to outwit potentially dangerous 
microbes.
    One application of this area of study is antibiotic resistance, an 
increasing problem throughout the world. Recently, NIGMS-funded 
researcher Dr. Barry G. Hall of the University of Rochester developed a 
computer simulation of microbial evolution. Dr. Hall determined through 
experiment which bacterial genes are most susceptible to changes that 
cause resistance to commonly used antibiotics. Using this approach, 
pharmaceutical companies could create drugs for which bacteria have no 
evolutionary escape route.
    NIGMS is also leading the way in supporting structural studies of 
infectious diseases. For example, the final piece of the anthrax 
puzzle--the structure of the third toxic protein responsible for the 
deadly effects of the anthrax bacterium--was discovered last year by 
Dr. Wei-Jen Tang of the University of Chicago. The toxin, edema factor, 
causes potentially lethal swelling and fluid buildup in the body. By 
completing the detailed, three-dimensional the structure of edema 
factor, Dr. Tang also found that the protein appears to be an ideal 
drug target, opening the door to a possible new compound to combat 
anthrax infection, as well as other bacterial diseases.

              BASIC RESEARCH: A VITAL RETURN ON INVESTMENT

    In closing, it is worth noting that our leading efforts in 
structural genomics, computational biology, complex biological systems, 
and multidisciplinary collaboration give NIGMS a pivotal role to play 
in the trans-NIH ``Roadmap'' initiatives. Through its partnerships with 
other NIH institutes and centers, NIGMS will help forge new pathways to 
discovery and research teams of the future.
    It is also important to emphasize that all of the scientific 
advances I have shared with you today resulted from investing in basic 
research on fundamental biological processes--the central mission of 
NIGMS. As administrators of federal research dollars, we are asked to 
show what we have done to ensure the best possible return on that 
investment, and to show how we plan to continue doing so in the future. 
I hope that the examples I have mentioned--from our Nobel Prize--
winning achievements to our cutting-edge initiatives-illustrate the 
tremendous value of basic biomedical research to the strength of our 
scientific workforce, the security of our nation, and the health of our 
people.
    Thank you, Mr. Chairman. I would be pleased to answer any questions 
that you may have.
                                 ______
                                 
                Prepared Statement of Dr. Glen R. Hanson

    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's budget request for the National Institute on Drug 
Abuse. The fiscal year 2004 budget includes $995,614 million, an 
increase of $34,496 million over fiscal year 2003 enacted level of 
$961,118 million comparable for transfers proposed in the President's 
request.

                            NIDA LEADERSHIP

    I have been very fortunate and privileged to serve as the Acting 
Director of the National Institute on Drug Abuse for the past year and 
a half during a time of burgeoning scientific advances that have 
dramatically increased our understanding of brain, behavior and 
addiction. I am extremely confident that the incoming Director for 
NIDA, Dr. Nora Volkow, will be a strong leader and advocate for drug 
abuse research. I am pleased to have this final opportunity to showcase 
some of NIDA's most exciting advances and discuss how these and other 
research findings are resulting in tangible benefits that will improve 
the Nation's health.

       PUBLIC/PRIVATE VENTURE YIELDS NEW MEDICATION FOR ADDICTION

    An important example of how NIDA-supported research is decreasing 
the tremendous economic and human costs associated with drug abuse and 
addiction, while meeting the national need for quality treatment, is by 
bringing a new medication to the clinical toolbox of health care 
professionals. Buprenorphine, approved by the Food and Drug 
Administration in October 2002, is the first medication ever available 
for the treatment of opiate dependence that can be prescribed and 
dispensed by qualified physicians in an office setting, rather than at 
a specialized addiction treatment clinic. The nearly 1 million people 
who suffer from heroin addiction will benefit from the historic 
collaborations that took place between legislators who passed the Drug 
Addiction Treatment Act of 2000, Federal agencies, and the private 
sector (Reckitt Benckiser Pharmaceuticals) to bring this new medication 
to market. Buprenorphine marks the second medication to come directly 
out of NIDA's relatively short investment in its Medications 
Development Program. Developing medications for other drugs of abuse, 
particularly stimulants like cocaine and methamphetamine, is a top 
priority for the Institute, as is our commitment to develop practical 
and more effective science-based behavioral therapies.

                NEW TARGETS FOR MEDICATIONS DEVELOPMENT

    Building on a series of discoveries regarding the effects of 
marijuana on the brain, researchers discovered a new neuromodulatory 
called the cannabinoid system, which is involved in pain regulation, 
memory, appetite, and addiction. This system was named after the active 
ingredient in marijuana, tetrahydrocannabinol. Researchers from NIDA's 
own intramural program have used a compound that blocks cannabinoid 
receptors to demonstrate that the mood altering and cardiac effects of 
marijuana in humans can be suppressed. Additionally, they discovered 
that the cannabinoid system may also be involved in relapse to other 
drug addictions. In animal models, this same blocking compound 
prevented drug-seeking for cocaine following exposure to two of the 
three conditions that typically trigger relapse in human addicts. The 
discovery of this new brain system has opened the door for the 
development of new treatments for addiction to a variety of drugs, 
including cocaine and alcohol, and may also prove useful for treating 
obesity and pain. As we continue to unravel the complexity of the brain 
and identify new systems, molecules, proteins, and genes that can be 
exploited for therapeutic development, the need for a repository or 
molecular library where this information can be stored and shared with 
other scientists increases. This is the goal of the proposed Molecular 
Libraries project in the trans-institute NIH Road Map Initiative. We 
hope to work with the pharmaceutical companies to more rapidly develop 
novel and even more effective therapeutic strategies for addiction and 
other brain diseases that have historically been extremely difficult to 
treat and control, and are often overlooked by pharmaceutical 
companies.

                          STRESS AND THE BRAIN

    We also are becoming increasing knowledgeable about the impact of 
stress on brain function. Stress can be a major factor in both the 
initiation of drug abuse and is known to be one of the most powerful 
triggers to relapse to drug abuse in former addicts. Nowhere was this 
more apparent than in a study published last year following the 
September 11th attacks in Manhattan. Twenty-nine percent of the 1,000 
respondents interviewed 1-2 months following the event reported an 
increase in substance use, with the highest rates in those reporting 
symptoms of Post-Traumatic Stress Disorder and/or depression. A study 
released just last month in the journal, Neuron, elucidated one of the 
ways in which stress and drugs of abuse produce a similar adaptation in 
the brain through an effect on dopamine neurons. As we progress in our 
understanding of the ways in which stress and drugs of abuse affect 
common mechanisms, we can develop prevention and treatment strategies 
that more effectively satisfy the needs of patients, particularly those 
who suffer from comorbid substance abuse and mental disorders.

         THE ROLE OF GENETICS AND THE ENVIRONMENT IN ADDICTION

    Powerful new technologies, such as microarrays, 3-dimensional brain 
mapping, and animal knockouts are accelerating the pace of science and 
helping us to identify the roles that genes play in addiction. One gene 
in particular (FAAH) produces an enzyme involved in the breakdown of 
the brain's natural cannabinoid compound. A recent study showed that a 
genetic variation in this gene was found more frequently in people who 
abused drugs compared to those who did not. As other genes that 
increase the risk of addiction are identified through NIDA's 
Vulnerability to Addiction Research Initiative, it becomes even more 
imperative that we understand how the environment can modify this risk. 
Basic research is giving us important insight into this complex domain 
of gene-environment interactions. A recent study conducted in monkeys 
using brain imaging techniques found that the animal's social 
environment can modify its neurobiology and ultimately its likelihood 
to self administer drugs of abuse like cocaine. When monkeys were 
housed together, the ones displaying dominant behavior were shown to 
have altered expression of D2 receptors, which are important components 
in the brain's reward pathway. They also were less prone to self 
administer cocaine (a model of cocaine abuse). This illustrates that 
the natural state of the dopamine system is altered by the environment, 
which in turn influences the likelihood of using drugs of abuse. Future 
studies which determine the interplay between genetic and environmental 
factors will be important in gaining further insight into the 
prevention and treatment of drug abuse and addiction.

             REDUCING TOBACCO USE BY FIGHTING THE ADDICTION

    Tobacco use is responsible for more that 430,000 deaths per year 
among adults in the United States, making it one of the Nation's top 
preventable causes of death. It is addiction to nicotine that continues 
to drive the use of tobacco, and why NIDA's expertise concerning the 
neurobiology of nicotine and the mechanisms of the addiction process, 
is so integral to the national effort to reduce this public health 
burden. NIDA supported research has already paved the way for a number 
of treatments, including behavioral therapies, nicotine-replacement 
approaches such as the patch and gum, and Zyban, that help people 
conquer their addiction. But we must accelerate our efforts to help the 
estimated 48 million people according to a 2000 Surgeon General Report 
who remain addicted to this drug. Capitalizing on new knowledge about 
the biological substrates and behavioral mechanisms of nicotine and 
tobacco addiction, NIDA has joined with other NIH institutes to launch 
a number of new activities to more rapidly translate tobacco addiction 
research into new treatments. NIDA is also supporting research that 
focuses on preventing adolescents from starting to smoke.

                    GOOD NEWS IN PREVENTION RESEARCH

    There is good news in the epidemiology and prevention arena. NIDA's 
long-standing annual Monitoring the Future Survey, which measures drug 
use among 8th, 10th, and 12th graders, showed substantial decreases in 
the overall use of all illicit drugs, as well as a reduction in the use 
of cigarettes, marijuana, club drugs, and alcohol in the past year. One 
of the most encouraging findings is the significant drop in the use of 
MDMA (Ecstasy), the abuse of which had been rising at alarming rates in 
recent years. We attribute these downward trends, in part, to our 
prevention and education efforts. As a by product of our dissemination 
of science-based information about all drugs of abuse, America's youth 
are able to weigh the facts about drugs and are making better health 
decisions. Understanding adolescent decision-making is an important 
research area being addressed in NIDA's prevention portfolio. By 
elucidating the cognitive expectancies of how an adolescent makes the 
initial and subsequent decisions to try or not to try drugs, we will 
gain new insight into how to develop interventions aimed at changing 
the actual decision to use drugs. Preventing the initial use of drugs 
and stopping the progression of drug use before it escalates to 
addiction are two targeted objectives of NIDA's National Prevention 
Research Initiative. The multi-disciplinary teams of basic researchers, 
community leaders, prevention specialists, clinicians, and health 
service providers who have been brought together as part of this 
Initiative will use the power of science to reduce drug use in the 
country.

     COMBATING HIV/AIDS, HEPATITIS DOMESTICALLY AND INTERNATIONALLY

    Our efforts to reduce the burden of drug abuse goes beyond our 
borders. Given the growing number of countries that report HIV and 
hepatitis C infection associated with drug injection behaviors, NIDA 
supports a strong research program that is yielding findings that are 
beneficial both domestically and internationally. In the absence of a 
vaccine or cure for AIDS, comprehensive HIV prevention strategies are 
the most cost effective and reliable approaches for preventing new HIV 
infections, and other bloodborne infections, such as hepatitis C. NIDA-
supported researchers are making progress in curtailing the spread of 
these diseases. NIDA researchers, using molecular biology techniques, 
have recently shown that new outbreaks of HIV infection among injection 
drug users are spreading along drug trafficking routes and spreading 
from drug users to non-drug using individuals through sexual 
transmission. Some of the victims of such transmission are homeless 
U.S. adolescents and AIDS orphans. Understanding how drug use related 
HIV transmission occurs is critical to the development of culturally 
specific behavior change strategies. NIDA remains committed to work 
with other Institutes and federal agencies to discover more effective 
ways to stop drug abuse-related spread of these infectious diseases and 
work towards transferring these evidence-based strategies to slow the 
spread of HIV and other related infections.

       CLINICAL TRIALS NETWORK DOES MORE THAN JUST TREAT PATIENTS

    HIV prevention interventions are some of the new protocols being 
developed for testing in NIDA's National Drug Abuse Treatment Clinical 
Trials Network (CTN). The CTN, which was established in 1999, provides 
a national infrastructure to bring science-based behavioral and 
pharmacological treatments for addiction into diverse patient and 
treatment settings across the country. NIDA added three new sites in 
the past year, which now allows our 17 centers or nodes to better serve 
patients across a wider geographic area, in fact through the 115 
community treatment programs involved in this endeavor we are serving 
patients in 27 states. Over 8,000 patients are expected to be enrolled 
in treatment protocols that are addressing the unmet needs of diverse 
populations, including adolescents, pregnant women, and women who 
suffer from Post-Traumatic Stress Disorder. Clinical trial networks for 
cancer and diabetes have been active for decades, but NIDA's efforts 
are the first ever to establish this model for addiction. Another first 
for the field, is the unprecedented efforts being taken to reduce the 
lag time between translating research discovery into practice. NIDA is 
working with the Substance Abuse and Mental Health Services 
Administration to disseminate science-based treatments into SAMHSA-
supported Centers and activities. Blending the expertise of 
researchers, practitioners, and service-oriented professionals is the 
hallmark of the CTN, and why the CTN has become more than just a way to 
get quality treatment. It is the conduit through which research meets 
practice.

                               CONCLUSION

    Reducing the adverse health, economic, and social consequences of 
drug abuse to individuals, families, and communities is the ultimate 
goal of our Nation's investment in drug abuse research. That goal is 
being met by NIDA.

                                 ______
                                 
               Prepared Statement of Dr. Richard J. Hodes

    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's budget request for the National Institute on Aging 
(NIA) for fiscal year 2004. The fiscal year 2004 budget includes 
$994,411,000, an increase of $1,342,000 over the fiscal year 2003 
enacted level of $993,069,000 comparable for transfers proposed in the 
President's Request. The NIH budget request includes performance 
information required by the Government Performance and Results Act 
(GPRA) of 1993. Prominent in the performance data is NIH's third annual 
performance report, which compared our fiscal year 2001 results to the 
goals in our fiscal year 2001 performance plan.
    There are today approximately 35 million Americans ages 65 and 
over, according to the U.S. Bureau of the Census. Thanks to 
improvements in health care, nutrition, and the overall standard of 
living, these men and women are more likely than ever before to be 
healthy, vigorous, and productive: A recent meta-analysis of 
demographic studies confirms that disability among America's elders has 
declined steadily over the past decade. More older Americans are able 
to participate in ``instrumental activities of daily living,'' such as 
performing household chores and managing their own medications, while 
fewer are experiencing limitations in basic physical tasks such as 
walking or climbing stairs. The prevalence of severe cognitive 
impairment also appears to be declining, although this finding needs 
verification.
    At the same time, diseases of aging continue to affect many older 
men and women, seriously compromising the quality of their lives. For 
example, more than half of all Americans over age 65 show evidence of 
osteoarthritis in at least one joint.\1\ Over half of Americans over 
age 50 have osteoporosis or low bone mass.\2\ Cardiovascular disease, 
cancer, and diabetes remain common among older Americans. And, 
according to the Alzheimer's Association, as many as 4 million 
Americans suffer from Alzheimer's disease (AD), the most common cause 
of dementia among older persons.
---------------------------------------------------------------------------
    \1\ See ``Handout on Health: Osteoarthritis,'' National Institute 
of Arthritis and Musculoskeletal and Skin Diseases, July 2002.
    \2\ See America's Bone Health: The State of Osteoporosis and Low 
Bone Mass in Our Nation. National Osteoporosis Foundation, February 
2002.
---------------------------------------------------------------------------
                     CONQUERING ALZHEIMER'S DISEASE

    We have made progress in several important areas of AD research. 
For example:
    We are improving our ability to diagnose AD early.--Scientists are 
developing and refining powerful imaging techniques that target 
anatomical, molecular, and functional processes in the brain. These new 
techniques hold promise of earlier and more accurate diagnosis of AD, 
as well as improved identification of people who are at risk of 
developing the disease. For example, researchers have developed a new 
method of functional magnetic resonance imaging (fMRI) based on oxygen 
use by the brain during rest. This technique permits visualization of 
signals from minute subregions of the hippocampus, a brain region 
important for learning and memory that shows degenerative changes in 
AD, and the researchers are using it to distinguish between hippocampal 
changes that are related to normal aging and those that may indicate 
the presence of neurodegenerative disease. Other researchers are 
working to improve our ability to image AD's characteristic amyloid 
plaques and neurofibrillary tangles in vivo, which will allow us to 
diagnose the disease with greater accuracy and more closely follow its 
progression. These and other NIA-funded neuroimaging studies support 
the broader goals of the molecular imaging component of the NIH Roadmap 
Initiative.
    We are developing new, more effective treatments and preventive 
interventions for AD.--Research into the underlying biology of AD is 
suggesting new ways to treat the disease or even prevent it altogether. 
For example, human stem cells, with their unique capacity to regenerate 
and give rise to many tissue types, are of particular interest in AD 
research because of their potential ability to generate new cells that 
could renew damaged brain tissue, replace dying neurons, or enhance the 
ability of the brain to respond to age-related impairments. Recent 
findings suggest that both human embryonic stem cells (hES), which can 
give rise to many cell types, and ``adult'' stem cells, which develop 
into a specific cell type, show promise for the eventual treatment of 
AD and other neurodegenerative conditions. Researchers have recently 
developed a method for inducing hES cells to differentiate into 
neurons. These newly-derived cells exhibit the properties of cells 
ordinarily found in the brain and central nervous system, suggesting 
that hES cells could provide a source for neural progenitor cells and 
mature neurons for therapeutic use. Investigators have also found that 
in the adult hippocampus, neural stem cells can give rise to functional 
neurons that can integrate effectively into existing neural circuits.
    NIA is currently supporting 18 AD clinical trials, seven of which 
are large-scale prevention trials. These trials are testing agents such 
as estrogen, anti-inflammatory drugs, and anti-oxidants for their 
effects on slowing progress of the disease, delaying AD's onset, or 
preventing the disease altogether. Other intervention trials are 
assessing the effects of various compounds on the behavioral symptoms 
(agitation, aggression, and sleep disorders) of people with AD. The 
design and implementation of all of these clinical trials will be 
carried out in the context of the NIH Roadmap initiative to enhance 
clinical research infrastructure and methodology.
    We are working to reduce the burden on caregivers of persons with 
AD.--Most Americans with AD are cared for at home by an adult child or 
in-law, a spouse, another relative, or a friend. For this reason, the 
AD ``patient'' is, in a sense, not only the person with the disease, 
but the entire family unit. The NIA's REACH Project (Resources for 
Enhancing Alzheimer's Caregiver Health), a large, multi-site 
intervention study aimed at family caregivers of AD patients, was 
designed to characterize and test promising interventions for enhancing 
family caregiving. Nine different social and behavioral interventions 
were tested, and investigators found that the combined effect of 
interventions alleviated caregiver burden, and that interventions that 
enhanced caregiver behavioral skills reduced depression. The second 
phase of the study, REACH II, combines elements of the diverse 
interventions tested in REACH into a single multi-component 
psychosocial behavioral intervention and is ongoing.

                   UNDERSTANDING THE BIOLOGY OF AGING

    We are continuing to advance our understanding of the molecular and 
cellular changes that underlie aging processes, with the goals of 
identifying the factors that affect the life span of an organism and 
using this information to develop interventions to extend life and 
delay the onset of disease and/or disability.
    Experiments in a number of animal models are providing valuable 
insights into mechanisms of longevity. Investigators recently created a 
transgenic mouse carrying a mutation in the Xpd gene, which codes for 
an enzyme involved in both repair of DNA damage and transcription of 
DNA into RNA (an important first step in gene activation). These mice 
appear normal at birth but age rapidly and live only about half as long 
as normal mice. This new mouse model will be useful for studying a 
number of aspects of aging, including the roles of DNA damage and cell 
death, as well as mechanisms by which the genome maintains itself and 
how such maintenance contributes to longevity.
    Researchers are also using animal models to identify interventions 
that might be useful in delaying aging. For example, in one recent 
study, fruit flies fed the chemical 4-phenylbutyrate throughout 
adulthood lived significantly longer than expected, with no negative 
effects on physical activity, stress resistance, or fertility. In 
addition, last year the NIA issued a Request for Applications (RFA) for 
the Aging Intervention Testing Program, a large-scale initiative to 
test intervention strategies that may slow the rate of aging in animal 
models. A number of unproven strategies are already in substantial and 
growing use by older Americans; positive results using such strategies 
in animals could lead to clinical trials to establish safety and 
efficacy in humans. An important secondary goal is to identify 
interventions that are not safe or are ineffective.
    Work in animal models is also leading to the identification of 
genes involved in regulation of the life span. In the tiny worm C. 
elegans, researchers used a sophisticated genetic screen to identify 
about 200 genes that cause an increase in longevity; many of these 
genes were related to the worm's mitochondria (cellular energy 
centers), while the exact function of many others remains unknown.
    Such findings in model systems, as well as our increasing 
understanding of genetic disorders such as Hutchinson-Gilford progeria 
syndrome that exhibit features of premature aging, suggest important 
roles for genes in human aging. Evidence for a genetic basis of human 
longevity was strengthened by the recent finding that siblings of 
centenarians have about half the risk of dying at every age compared 
with people who do not have a centenarian sibling. In the same study, 
the investigators found that brothers of centenarians were at least 17 
times more likely to reach the age of 100 themselves; sisters were at 
least 8 times more likely to reach 100 years of age.

                    REDUCING DISEASE AND DISABILITY

    Evidence of the beneficial effects of exercise on older people 
continues to increase. In a study last year, researchers assessed the 
results of a resistive strength training program on men and women in 
two age groups, 20-30 and 65-75. They found that the effects of the 
program did not differ between the two groups: Participants in both age 
groups increased strength and showed similar increases in muscle mass 
and in resting metabolic rates, which generally decrease with age.
    NIA is working to translate research findings in action through its 
highly successful campaign to encourage older people to exercise. Since 
the campaign was launched in 1998, NIA has distributed nearly one half-
million copies of its exercise guide and almost 60,000 copies of its 
companion video to the public. A Spanish-language version of the guide 
was published in January 2002, and over 50,000 copies were distributed 
last year.
    We are also working to reduce the troubling health disparities that 
still exist among different racial and ethnic groups. In one study of 
elderly heart attack patients, researchers found that black patients 
did not live as long after discharge from the hospital as white 
patients. Much of this disparity could be explained by the lower rate 
of use of certain cardiac procedures among black patients, suggesting 
that expanded use of effective procedures could substantially reduce 
racial differences in long-term survival.
    To address disability and disease in special populations, NIA 
implemented a major new study of health disparities among different 
racial, ethnic, and socioeconomic groups. The study, Healthy Aging in 
Nationally Diverse Longitudinal Samples (HANDLS), focuses primarily on 
cerebrovascular health, cardiovascular health, age-associated changes 
in cognition, and strength and physical functioning. Through this 
study, we hope to address hypotheses about aging and health disparities 
in minority and poor populations to understand the significance of 
environmental and genetic risk factors for disease. The pilot phase of 
HANDLS, in which investigators assessed the logistics and feasibility 
of this community-based study, was completed at the end of 2001, and 
the larger population-based phase of this study is scheduled to begin 
in late fall of 2003.
    Other areas of research interest include:
    Diabetes.--Last year, investigators in the multi-institutional 
Diabetes Prevention Program (DPP) reported that people who are at high 
risk for diabetes can sharply reduce their risk through a low-fat diet, 
and a moderate exercise regimen. This effect was most pronounced among 
study participants age 60 and over. Treatment with the drug metformin 
(Glucophage) also reduced diabetes risk among study participants, but 
for unknown reasons was less effective among older participants. With 
other participating NIH Institutes, we are continuing to follow up the 
DPP participants to determine long-term effectiveness of these 
interventions.
    Menopause.--Women approaching menopause may experience a variety of 
uncomfortable symptoms, but uncertainty remains over the safety of 
hormonal therapy due to reports of serious health risks related to some 
combinations of hormones. NIA-supported researchers are working to find 
effective treatments for the symptoms of menopause that do not increase 
risk of adverse effects.

                               CONCLUSION

    It is becoming increasingly obvious that old age need not be 
associated with illness, frailty, or disability. In fact, we have made 
tremendous progress against all of the major diseases and conditions of 
aging. However, much work remains to be done. NIA is committed to 
supporting high-quality research to address all aspects of aging, from 
conditions and diseases that primarily affect older people to physical, 
behavioral, and cellular characteristics of the aging process. As more 
Americans live longer, NIA will meet the challenges of our rapidly 
aging society by continuing and intensifying research that improves the 
health and well-being of older people.

                                 ______
                                 
               Prepared Statement of Dr. Thomas R. Insel

    Mr. Chairman, and members of the Committee, I am pleased to present 
the President's budget request for the National Institute of Mental 
Health (NIMH) for fiscal year 2004, a sum of $1,382 million, which 
reflects an increase of $42 million over the fiscal year 2003 enacted 
level of $1,340 million comparable for transfers proposed in the 
President's budget.
    In my statement, I will call to your attention the immense burden 
on our Nation of mental and behavioral disorders. In addition, in the 
context of a brief review of our research activities and 
accomplishments, I will suggest how NIMH's expertise in behavioral 
science and behavioral neuroscience are contributing to the Nation's 
capacity to prepare for and respond effectively to the psychological 
impact of bioterrorist attack.

                      THE BURDEN OF MENTAL ILLNESS

    Mental disorders are real illnesses that are mediated by the brain 
and can be diagnosed reliably and accurately. Thanks to the Nation's 
willingness to invest generously in research, highly effective 
treatments exist for most mental disorders; and recovery is a realistic 
and attainable goal for many people who have a mental disorder. Despite 
our research progress, our society faces a pressing need to strengthen 
the quality and accessibility of clinical services for mental disorders 
for all those who require such services. In keeping with our public 
health mission, NIMH assigns high priority to the task of moving 
information gained through research into the hands of providers, 
systems, patients, and families.
    The Surgeon General's Report on Mental Health noted that an 
estimated 5.4 percent of Americans adults have a serious mental 
disorder such as schizophrenia, major depression, and bipolar in a 
given year, and about 5- to 9 percent of children and adolescents 
suffer from mental and behavioral disorders that are sufficiently 
severe to cause academic, social, or family impairment. Research 
supported and conducted by NIMH has significantly strengthened the 
ability of the Nation's health care providers to treat and manage these 
disorders; still, the public health challenge posed by mental illness 
remains formidable, in large part because many serious mental disorders 
tend to strike in childhood, adolescence and young adulthood, and to 
persist across much of a person's lifetime.

        THE PRESIDENT'S NEW FREEDOM COMMISSION ON MENTAL HEALTH

    With the release of the final report of The President's New Freedom 
Commission on Mental Health scheduled for this Spring, efforts to 
translate our science into clinical service programs will assume added 
importance and urgency. The Commission was charged to identify specific 
examples of community-based care models that are demonstrably 
successful in achieving desired outcomes. In its interim report, the 
Commission noted that much can and is being done to improve the 
delivery of high quality mental health care. The Commission found, 
however, that the national mental health care system is hampered by 
fragmentation of services and limited access to effective treatments. 
We have worked closely with the Commission over the course of its 
study, and look forward to helping to implement the its 
recommendations.
    An ongoing collaboration between NIH and the Substance Abuse and 
Mental Health Services Administration (SAMHSA) anticipates the 
Commission's interest in ensuring that individuals in every region of 
the country have access to the best available treatments. NIMH, the 
National Institute on Drug Abuse, and the National Institute on Alcohol 
Abuse and Alcoholism have identified specific treatment and 
preventative interventions that have a strong scientific evidence base 
and we are working with SAMHSA officials as they develop plans to 
assist State agencies implement these interventions. Built into this 
initiative are processes designed to establish a systematic feedback 
loop that will enable researchers to draw on real world experiences 
with evidence-based practices in order to inform and guide future 
intervention research.
    Need clearly exists for NIMH to advise SAMHSA of completed research 
that will improve the quality of care available immediately. Still, 
opportunities have never been greater for fundamentally revamping our 
approaches to developing new clinical treatments and preventive 
interventions. New scientific knowledge about the brain and behavior, 
as well as the emerging science of genomics, promise to yield new 
treatments for mental disorders that ultimately will alter the delivery 
of mental health care in far-reaching ways.

            SEARCHING FOR SCHIZOPHRENIA VULNERABILITY GENES

    After many years of searching, the recent discoveries of several 
putative vulnerability genes for schizophrenia have been among the most 
noteworthy achievements of the past year. Schizophrenia is a 
genetically complex disorder, in which multiple genes are involved, but 
no single one of them is sufficient or necessary to cause the disease. 
Rather, multiple genes, interacting with environmental influences, lead 
to illness. One newly discovered gene, called G72, plays a role in 
regulating the activity of glutamate, an important excitatory 
neurotransmitter in the brain. This is intriguing because decreased 
glutamate activity appears to play a key role in negative, or deficit, 
symptoms of schizophrenia such as social withdrawal, a lack of 
motivation and expressiveness, and an inability to experience pleasure. 
It is interesting that several of the recently discovered genes 
believed to be associated with susceptibility for schizophrenia may 
function by interfering with neurotransmitters in the prefrontal cortex 
(PFC) and related brain regions. For example, another newly identified 
gene encodes an enzyme that terminates the activity of dopamine in the 
PFC. In work led by an NIMH scientist, this research has identified two 
alleles, or variants, of this gene; one of these has been shown in 
clinical studies to be associated with deficits in information 
processing and memory, again symptoms central to schizophrenia. These 
discoveries highlight the biological basis for schizophrenia and may 
ultimately yield both diagnostic and therapeutic breakthroughs.

                  SCREENING FOR DRUG DISCOVERY TARGETS

    One initial application of genetic discoveries will be to identify 
the various molecules they encode and then design medications that act 
on those molecules when they are implicated in various disorders. 
Molecular processes gone awry can serve as targets for medications 
designed to prevent, treat, or halt progression of a given condition. 
As part of an initiative included in the NIH Roadmap, NIMH is 
supporting research to generate a library of small molecules with novel 
actions that will interact with particular biological targets. 
Subsequent research will test these substances as candidates for the 
treatment of mental disorders as well as for their utility as 
diagnostic agents or research tools.

                                 AUTISM

    Autism represents an urgent and significant scientific and public 
health challenge that, given scientific opportunity and public concern, 
is the appropriate focus of multiple NIH Institutes. The reported 
incidence and prevalence of autism appears to be rising. Over the past 
two decades, estimates of prevalence have escalated from \1/10000\ to 
as many as \1/250\ (for autism spectrum) to \1/400\ (classic autism). A 
recent investigation by CDC in Brick Township, New Jersey, found a 
prevalence rate for autism of 4.0 per 1,000 children and a rate of 6.7 
per 1,000 children for the more broadly defined category of autistic 
spectrum disorders.
    A biologically based developmental disorder, autism is 
characterized by qualitative impairments in social interaction and both 
verbal and nonverbal communication and behaviors, resulting in a 
markedly restricted repertoire of activities. High quality clinical 
care and management of children with autism can exert a draining 
financial toll on families.
    Last year, NIMH accepted leadership of the internal NIH Autism 
Coordinating Committee (ACC), which operates in close communication 
with the larger Interagency Autism Coordinating Committee (IACC). Other 
NIH Institutes retain control over their own activities, such as the 
long-standing Collaborative Programs for Excellence in Autism (CPEAs), 
a network of sites funded by NICHD and NIDCD. In 2002, NIMH committed 
to be the primary funding source for the Studies to Advance Autism 
Research and Treatment (STAART) Centers program mandated by the 
Children's Health Act of 2000. The Institute awarded grants to develop 
STAART Centers, with co-funding provided by NINDS, NICHD, NIDCD, and 
NIEHS. Two Centers were awarded in fiscal year 2002, and six additional 
Centers are slated for funding in fiscal year 2003. This will complete 
establishment of the network, exceeding the mandate of at least five 
centers required by the Act.
    Our research is yielding significant dividends. A recent study 
found risperidone, one of a newer class of anti-psychotic medications, 
to be successful and well tolerated for the treatment of serious 
behavioral disturbance associated with autistic disorder in children 
aged 5 to 17. Also near completion is a study evaluating the safety and 
efficacy of methylphenidate (Ritalin) in treating overactivity, 
impulsivity, and distractibility in children with autism spectrum 
disorders.

                  PSYCHOLOGICAL IMPACT OF BIOTERRORISM

    In light of the maxim that ``the purpose of terror is to 
terrorize,'' prudence dictates that we use research not only to treat 
the consequences of terrorism, but also to help refine our ability to 
triage those individuals likely to be most susceptible to serious 
adverse neurobiological responses to a bioterroist attack and, to the 
extent possible, to ``innoculate'' the population against destabilizing 
or unwarranted anxiety or panic. Over many decades, NIMH has supported 
a robust behavioral science research portfolio that has informed us 
about many basic behavioral mechanisms, including those influencing 
group processes. More recently, we have supported studies that have 
examined the psychological impact of natural disasters such as floods 
and tornados, and the terrorist attacks in Oklahoma City in 1995 and on 
September 11, 2001. Behavioral science and clinical research not only 
provide a ``top-down'' systems-level context to help us understand what 
is happening at molecular and cellular levels in the brain in the face 
of overwhelming fear and anxiety, but also can help us to prepare for 
and treat the psychological and social consequences of such events.
    A key finding of this research to date is that people are very 
resilient--the vast majority of victims of mass disaster and terrorist 
attack do not develop a psychiatric disorder. For those individuals who 
do, the most frequent adverse outcome is post-traumatic stress 
disorder, or PTSD. This is a form of anxiety disorder that occurs after 
exposure to an extreme stressor in which an individual experiences, 
witnesses, or is confronted with actual or threatened death or serious 
injury to self or others. Given its prevalence, disabling impact, 
chronicity, and treatment resistance, PTSD represents a major public 
health concern. Through the research we have conducted, however, we are 
gaining an increasingly clear understanding of what variety of 
psychological and behavioral problems to expect in the event of an 
attack and the types of services that will be needed. We know that we 
should expect to see increases in requests for therapy and medications 
for common and troubling symptoms of fear, anxiety, hyperarousal, and 
sleep problems. We know that survivors--particularly those with PTSD 
and others who may have a comorbid, or co-occurring mental disorder--
actively use mental health services. In the event of a future attack, 
as we move beyond needs for first aid, housing, and food, the majority 
of those people who were directly affected will have need for 
supportive counseling and assistance with resuming normal activities 
such as household routines, school, and work. Research that has 
examined the use of mental health interventions speaks to the clinical 
significance of subjective distress even in subjects without recognized 
psychiatric disorders. We also have information about who is most 
likely to be at risk for developing longer-term problems and, thus, as 
people present to health, educational and social service programs for a 
variety of physical and mental health problems, it will be important to 
apply what we know with the aim of preventing such problems. I would 
also note that we also are drawing on behavioral science research 
involving coping in response to threat to advise individuals and 
communities how to anticipate and lessen the emotional burden caused by 
trauma. It is clear that the availability of accurate information, 
including information about health risk, for example, blunts the 
anxiety- and panic-provoking nature of unjustified speculation about 
risk and permits people to decide on action that they can take. 
Research on basic behavioral processes involved in decision-making, 
judgment, and health risk assessment--all involved in shaping 
attitudes, affect, and behavior--is very useful in shaping the messages 
we convey to our citizens.
    I will be pleased to answer any questions.

                                 ______
                                 
               Prepared Statement of Dr. Stephen I. Katz

    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's budget request for the National Institute of Arthritis 
and Musculoskeletal and Skin Diseases (NIAMS). The fiscal year 2004 
budget includes $502.778 million, an increase of $17.005 million over 
the fiscal year 2003 enacted level of $485.773 million comparable for 
transfers proposed in the President's request.
    The budget increases over the last few years have made a tremendous 
difference in the studies we have been able to launch, particularly in 
clinical research including clinical trials in a wide variety of 
diseases as well as the expansion of vital scientific infrastructure in 
a creative way. As stewards of these funds, we have worked with a wide 
range of advisers, both from the scientific community and from the lay 
public, to ensure that we target areas of greatest scientific 
opportunity. In addition, we worked to undertake studies that could 
either be done solely or better by the Federal government. I am pleased 
to be able to share highlights of some of the stories of progress and 
promise that have resulted from our investments in medical research.

                      PUBLIC/PRIVATE PARTNERSHIPS

    One of the priority areas in the new NIH Roadmap Initiative is the 
development of public/private partnerships. The NIAMS has had a number 
of positive experiences in this area, and I will mention two ongoing 
examples. The first is the Osteoarthritis Initiative. Our Institute 
partnered with the National Institute on Aging and several other NIH 
components as well as with three pharmaceutical companies in launching 
this public/private partnership aimed at developing clinical research 
resources that support the discovery and evaluation of biomarkers and 
surrogate endpoints for osteoarthritis clinical trials. This seven-year 
project is being undertaken by four clinical sites and one data 
coordinating center, and this consortium will likely serve as a model 
for future endeavors that link the public and private sectors.
    The second partnership involves the NIH and the Muscular Dystrophy 
Association (MDA). The NIH has been actively engaged in implementing 
the mandates of the MD-CARE Act, and has worked closely with 
representatives of the muscular dystrophy (MD) research and patient 
communities in this effort. Specifically, the NIAMS, NINDS, and NICHD 
have partnered to issue new research solicitations for MD cooperative 
research centers, and for developmental planning grants for future 
centers. In addition, we are developing an initiative to support the 
training of basic and clinical researchers to study muscular dystrophy. 
To underscore the importance of stimulating and supporting further work 
in this area, the NIH has established an MD Research Task Force, which 
includes NIH scientific staff, as well as researchers, clinicians, and 
patient representatives. This group will help ensure that we pursue all 
promising opportunities to boost MD research and training, and it will 
also complement the work of the newly established inter-agency Muscular 
Dystrophy Coordinating Committee, which was called for in the MD-CARE 
Act.

                            MUSCLE DISEASES

    One of the most active and productive areas within the Institute's 
research portfolio is in the muscular dystrophies--a group of genetic 
diseases characterized by progressive weakness and degeneration of the 
skeletal or voluntary muscles which control movement. Research advances 
from NIAMS investments in this area include: (1) the finding that 
people with facioscapulohumeral muscular dystrophy (FSHD) have an 
exclusive association with one of the two different forms of the 
chromosomal region linked to the disease. This work may lead to a 
better understanding of the instability of the genetic locus associated 
with FSHD. (2) the discovery of how to reverse muscle degeneration in a 
mouse model of Duchenne muscular dystrophy, a genetic disorder in which 
muscle cells become progressively more damaged and die. Scientists have 
devised a way to revitalize wasting muscle by using a special viral 
carrier to introduce the missing dystrophin gene into the diseased 
muscle tissue--a finding that could eventually lead to gene therapies 
for patients with Duchenne muscular dystrophy. (3) the report that a 
faulty gene is key to understanding myotonic dystrophy. The genetic 
defect affects the conductance of electrical signals, resulting in 
delayed muscle control. (4) the isolation of muscle-generating stem 
cells that can improve muscle regeneration and deliver the missing 
protein dystrophin to damaged muscles in a mouse muscular dystrophy 
model. These results signal that some of the major obstacles to stem 
cell transplantation may be overcome, resulting in more effective 
treatments for muscular dystrophy and other muscle-related diseases. 
and (5) the creation of a new animal model that has been labeled a 
``marathon mouse,'' which expresses an energy-metabolizing protein that 
increases the proportion of particular muscle fibers that give distance 
runners their muscular stamina. Further work in this area could benefit 
research efforts against muscle-wasting diseases like the muscular 
dystrophies.

                      SYSTEMIC LUPUS ERYTHEMATOSUS

    Some of the most promising research results in fur mission areas 
have come from the ability of researchers to apply the explosion of 
information in genetics and genomics. One example of this is the very 
recent research report that a particular genetic ``signature'' has been 
linked to the blood of patients with severe systemic lupus 
erythematosus (SLE or lupus). A team of scientists supported by the 
NIAMS, other parts of the NIH, and the private sector (the Minnesota 
Lupus Foundation and the Alliance for Lupus Research) has discovered a 
genetic ``signature'' present in some patients with lupus who develop 
such life-threatening complications as blood disorders, central nervous 
system damage, and kidney failure. These researchers analyzed thousands 
of genes in the blood of patients with lupus, and, surprisingly, 14 of 
the thousands of genes studied were linked to a subset of lupus 
patients with severe disease. These 14 genes are associated with a 
complex family of proteins involved in the regulation of immune 
responses, and these findings provide strong support for developing new 
therapies to block the affected pathways in patients with severe lupus, 
as well as for identifying patients most likely to benefit from these 
new therapies.
    I want to also mention an important new clinical trial that we 
launched in children with lupus. The trial is designed to test the 
efficacy of statins (cholesterol-lowering agents) in preventing or 
delaying progression of cardiovascular disease in children with lupus. 
This research study involves 20 centers from the Pediatric Rheumatology 
Research Network in establishing the largest cohort of pediatric lupus 
patients ever prospectively studied.

                BONE AND OTHER MUSCULOSKELETAL DISEASES

    One dimension of the NIH Roadmap Initiative is translational 
research, and we know that translating the results of basic bone 
biology research into therapies that prevent or treat musculoskeletal 
diseases can have a very significant impact on public health. 
Development and maintenance of a healthy skeleton depends on 
interactions between bone and bone marrow, blood vessels, and even the 
central nervous system. Understanding these complex interactions will 
depend on studies employing genetic and genomic tools, including NIAMS-
supported efforts in animal models that are expected to translate into 
insights guiding the development of new preventive and therapeutic 
approaches to conditions such as osteoporosis. In recent advances, a 
variety of pharmacological agents and biochemical factors, some already 
familiar in other contexts, has been found to have unexpected effects 
on bone mass. For example, the actions of the cholesterol-lowering 
drugs called statins, the hormone leptin (originally identified as 
important for controlling obesity), and nitric oxide (best known for 
its effects on the heart and blood vessels) all provide clues to ways 
that new therapies might improve bone health. In addition, studies of 
the genetics of bone mass are increasingly productive, including 
reports of a gene that was previously unsuspected of playing any role 
in bone emerging as a possible key to restoring bone in cases of 
osteoporosis.
    Research that has direct applicability to daily life of affected 
individuals has determined that limb reconstruction and amputation 
after trauma to the lower leg result in similar outcomes in terms of 
function. We anticipate that the findings of this study will help 
surgeons and patients make better informed decisions when choosing 
between reconstruction (limb salvage) or amputation of a limb that has 
been severely damaged. With a look to the future, a large United 
States/Canada cooperative project is now underway to resolve 
differences of opinion on the best way to repair the fracture of the 
tibia--the most common long bone fracture in the human body. Factors 
that will be considered in determining which of the groups being 
studied has a more successful outcome include how soon patients return 
to work and their general health status and quality of life. Finally, 
plans are underway for an NIH Consensus Development Conference on 
Primary Knee Replacement in December 2003 to address the issues that 
exist in this area, to review the current state of the science, and to 
identify directions for future research.

                             SKIN DISEASES

    NIAMS-supported researchers recently reported exciting and 
promising results from their gene therapy studies in the recessive form 
of the devastating blistering skin disease dystrophic epidermolysis 
bullosa. This disease is caused by the absence of a specific gene, and 
researchers used a particular enzyme as the base for gene transfer. The 
researchers were successful in stably integrating the DNA from the 
missing gene into genomes of cultured skin cells from four patients 
with this inherited skin disease. The skin that was developed using 
these cells displayed stable correction of the hallmark features of 
this disease. These results establish a potential practical approach to 
nonviral genetic correction of severe human genetic disorders that 
require stable genomic integration of large DNA sequences.
    The Institute has recently called on scientific experts and lay 
representatives to help us in three particular areas of skin diseases 
research: (1) In response to fiscal year 2002 Congressional language, 
the NIAMS sponsored the ``Workshop on the Burden of Skin Disease'' in 
September 2002, to discuss the elements that comprise the burden of 
skin diseases and their impact on public health and daily living; 
current knowledge and data-collection instruments, and how to access 
the data more effectively; and future data needs and instruments for 
facilitating the collection of the data. The recommendations from this 
workshop are being reviewed by the Institute to determine the need and 
path for future initiatives in this area. The lessons learned from this 
workshop can serve as a paradigm for other areas--all of which share 
the challenge of defining the burden of a disease on an individual, the 
family, the workplace, and society as a whole. (2) The NIAMS teamed 
with the National Alopecia Areata Foundation in sponsoring the Fourth 
International Research Workshop on Alopecia Areata in November 2002, 
bringing together investigators from around the country for an exchange 
of recent findings in alopecia areata and related fields of hair 
biology. Results of this workshop will guide future research in this 
field. (3) The Institute is planning a workshop on immune modulation in 
the treatment of skin diseases, which will include new treatments for 
psoriasis, atopic dermatitis, autoimmune bullous diseases, and other 
skin diseases. The workshop will focus on trying to understand how some 
new treatments are actually working so that we may better understand 
the mechanisms underlying these diseases.

                           HEALTH DISPARITIES

    In research related to health disparities, there are four efforts 
that I want to highlight: (1) The NIAMS continues to support the 
diversity initiative it has created and developed over the last few 
years--the Health Partnership Program, a collaborative community-based 
effort in Washington, D.C., that is directed at developing research 
programs to understand and address health disparities in rheumatic 
diseases in African American and Hispanic/Latino communities. (2) 
Differences have been documented in the damage caused by lupus in 
studies of Hispanic, African American, and Caucasian individuals with 
this disease. The proportion of patients who had any organ damage was 
higher among Hispanics than among the other two groups, confirming the 
greater negative impact of lupus among members of this ethnic group. 
The association of organ damage with poor coping skills was reported 
for the first time, and it suggests that approaches designed to modify 
patients' behaviors and attitudes to their illness could reduce the 
damage to the body caused by lupus. (3) Research suggests that women 
with lupus are at increased risk for both clinical osteoporosis and 
cardiovascular complications at a much younger age, and more aggressive 
control of the risk factors for these complications is needed to 
prevent these conditions in women with lupus. (4) Social experience has 
been shown to influence joint replacement decisions; that is, when 
people think about having a hip or knee replaced, knowing someone who 
has had the surgery may influence their decision. A recent study funded 
by the NIAMS and the Robert Wood Johnson Foundation suggested that one 
reason African Americans may be less likely than Caucasians to seek 
joint replacement surgery, a procedure that makes a significant 
difference in alleviating pain and improving function of severely 
affected individuals, is because they know fewer people who have had 
this procedure.

                               CONCLUSION

    We are proud of the advances that scientists supported by the NIAMS 
have achieved and we are excited about initiatives that we have 
launched. Patients and their families are looking to us with hope and 
anticipation for answers to what causes their diseases, as well as how 
their diseases can be better treated and even prevented. We are 
confident that public health in general as well as daily life for 
affected individuals in particular will benefit from NIAMS research in 
the extensive and diverse array of chronic diseases within our mission 
areas of bones, joints, muscles, and skin.
    I would be happy to answer any questions.

                                 ______
                                 
               Prepared Statement of Dr. Gerald T. Keusch

    The fiscal year 2004 budget includes $64,266,000, an increase of 
$2,073,000 over the fiscal year 2003 enacted level of $62,193,000 
comparable for transfers proposed in the President's request.

                       SCIENCE FOR GLOBAL HEALTH

    Thirty five years ago, the Fogarty International Center was 
established to honor the memory of Congressman John E. Fogarty of Rhode 
Island. The authorizing legislation, introduced by Representative 
Melvin Laird of Wisconsin, stated ``. . . the committee has provided 
funds to plan a lasting memorial to a man who for more than a quarter 
of a century worked tirelessly for a healthier America in a healthier 
world.'' (Congressional Record, House, May 25, 19867, p. 14062). It is 
my privilege to report to you, that for the past 35 years, the Fogarty 
International Center (FIC) has fulfilled this promise--Mr. Fogarty and 
Mr. Laird would be proud of their legacy. Today the FIC is an essential 
component of the DHHS and NIH response to global challenges in health, 
representing the nexus between science and diplomacy and promoting both 
at the same time. FIC is known and respected around the world for its 
critical role in promoting research and capacity building for global 
health.
    The research and training supported by FIC is a window to a 
brighter future for the low- and middle-income countries with heavy 
burdens of disease. While people in these countries typically suffer 
from high infant, child and maternal mortality rates, amplified 
manyfold by the threats represented by AIDS, TB, malaria and other 
seemingly intractable infectious diseases, increasingly these 
populations are now subject to the ravages of chronic disease and 
premature mortality represented by cardiovascular disease, diabetes, 
and cancer. All of these conditions limit societal productivity, 
economic growth, and stability. To this end FIC supports research to 
better understand the impact of improving health on economic 
development, political and social stability, and active participation 
in the global marketplace of the 21st century. Because economic growth 
invariably impacts on the environment, usually in an adverse manner, 
FIC has also developed a research agenda to improve our understanding 
of the impacts on population's health and individual's well-being 
related to sustainable economic development. These programs are crucial 
as we identify health care interventions that an improve both health 
and development.
    The programs of the FIC directly address five of the eight goals 
outlined in the United Nations Millennium Declaration, including 
eradication of extreme poverty (Goal 1), reducing child mortality and 
improving maternal health (Goals 4 and 5), combating HIV/AIDS, TB and 
malaria (Goal 6), and ensuring environmental sustainability (Goal 7). 
These goals are daunting, but not incapacitating. As U.N. Secretary 
General Kofi Annan has said, ``They are achievable, not by holding more 
world conferences, but by people in every country, coming together and 
taking action.'' This is precisely what FIC does every day. To maximize 
and leverage the impacts of FIC programs, the Center has collaborated 
extensively within the NIH, across the Department of Health and Human 
Services, and beyond, including other components of the Federal 
government, bilateral and multilateral agencies here and abroad, 
foundations, and international organizations such as the World Health 
Organization, The World Bank and the Regional Development Banks.

              STRENGTHENING THE GLOBAL CULTURE OF RESEARCH

    For scientists to come together and take action requires them to 
share a common culture of scientific ethos and values. This can only be 
accomplished in an environment in which rapid communication is 
possible, wherein scientific knowledge is readily available to all, and 
where research is conducted based on partnership and equity. When 
American scientists work across geographic boundaries in this manner, 
the beneficiaries are the collaborating scientists, science in general, 
the United States and foreign partner countries.
    FIC strengthens this ``global culture of research'' through a range 
of programs. The FIC International Bioethics Education and Career 
Development Award provides trainees with a strong background in ethics 
and an understanding of research. The cadre of thoughtful and 
knowledgeable people trained through this program will insure that 
internationally and United States-accepted ethical principles are 
upheld in studies around the world, including in poor nations. An 
additional component to strengthening a global culture of science is to 
ensure that technological advances made in one country are accessible 
to the greatest extent in all countries.
    FIC addresses the growing divide in the development and use of 
genetic technologies through the International Collaborative Genetics 
Research Training Program. FIC-upported training in the technology of 
modern genetics research is accompanied by a strong component of 
ethical, social, and legal considerations and focuses on the 
mplications of performing genetics research in low- and middle-income 
countries.
    The third pillar in support of the global culture of science is 
access to information, which is addressed by the International Training 
Program in Medical Informatics. This program enables U.S. institutions 
to support training in order to build the capacity of scientists in 
developing countries to access, utilize and construct computer-based 
tools to access and exchange information to advance biomedical research 
and public health. This program will recompete in fiscal year 2004. As 
a companion to this initiative, FIC in collaboration with the National 
Library of Medicine is embarking on additional programs to support and 
improve the editorial content of key biomedical research and health 
journals in developing countries, and to improve the quality and 
accuracy of reporting on medical research and health by developing 
country journalists, whether they are working in print, radio or 
television.
    As FIC works to strengthen the global culture of science through 
all its programs, to maximize the benefits of individual initiatives in 
fiscal year 2004 FIC proposes to pilot innovative International Glue 
Grants. These grants will provide resources to link together regional 
and national institutions in developing countries with their several 
U.S. partner institutions, taking advantage of the perspective of 
biomedical, clinical and behavioral and social scientists in creating 
new ways to explore old and emerging health problems. We expect the 
``glue'' will bring investigators together in a common framework for 
addressing critical issues, enabling these collaborators to work more 
cost-effectively and with greater productivity on critical challenges 
such as AIDS, maternal health, and impacts on health from environmental 
pollution.
    Support for the movement of junior researchers across borders is 
the fourth pillar of the broader effort to strengthen the global 
culture of research and science. FIC will continue to invest in the 
Global Health Research Initiative Program (GRIP), which provides 
resources for developing country scientists who trained in the United 
States to obtain, on a peer-reviewed merit-based system, funding to 
conduct research upon their return home and remain linked in 
collaborative research with their U.S. mentors. As a corollary to this 
program, FIC is also investing in career pathways in international 
research for young American investigators through the FIC International 
Research Scientist Development Award (IRSDA). The IRSDA supports junior 
U.S. scientists as they conduct research in the developing world on 
issues of global import, then provides additional opportunities and a 
``safety net'' on their return home. In addition, in fiscal year 2004, 
will bring the first crop of students of medicine, public health and 
allied medical sciences into a new program to provide a year of 
mentored clinical research training in a developing country 
collaborative research program. The rationale for this new program is 
to expose students as early as possible in their professional careers 
to research needs and prospects in the developing world as a means to 
encourage them to select global health challenges as long-term career 
pursuits. A partnership with the Ellison Medical Foundation, the 
Association of American Medical Colleges, the Association of Schools of 
Public Health and the FIC, the program will pair a U.S. student with 
one from the host country to train and participate in clinical research 
under the guidance of expert mentors from the United States and the 
foreign country who already work together on clinical research studies.
    A previously neglected area is that of gender and global health 
research. Not only may risk factors, disease progression, and response 
to treatment vary by gender, but societal responses based on gender may 
exclude women from accessing health care or may imbue them with stigma 
that adds significantly to the burden of disease. FIC is initiating two 
new programs to address these issues. First, the Stigma and Global 
Health research program, expected to be funded in fiscal year 2003, 
will support studies to better understand the exclusion of stigmatized 
populations from the benefits of medical care and participation in 
medical research. Importantly, it will identify interventions to 
address the major needs. Second, FIC, the NIH Office of Research on 
Women's Health, the Canadian Institutes of Health Research, and Harvard 
and Yale Universities are working with experts around the world to 
develop a framework for the inclusion of gender issues across the range 
of global research and training programs the Center and other science 
funding agencies support. Included in this initiative is an effort to 
enhance career development for women scientists from the developing 
world.

         CONTINUING TO INVEST IN COMMUNICABLE DISEASE RESEARCH

    FIC currently supports a broad program of research and training in 
AIDS, tuberculosis, malaria and other emerging infectious diseases. In 
fiscal year 2004 the Center will pursue these major global health 
problems in three ways, first through its continuing focus on AIDS, the 
greatest epidemic threat of our time, and second, through support of a 
comprehensive program, the Global Infectious Disease Training and 
Research Program (GLIDTR), to focus on infectious diseases that are 
predominately endemic in or impact primarily upon people living in 
tropical countries. Under the AIDS programs, a major new initiative 
will be fully launched with the awarding of the first set of 
comprehensive grants under the International Clinical, Operational and 
Health Services Research and Training Award for AIDS and TB (ICOHRTA-
AIDS/TB). This program has as its major goal the promotion of excellent 
clinical research in support of care of AIDS patients, along with the 
necessary operational and health services research to move new 
knowledge into practice as soon as possible. The GLIDTR is augmented by 
FIC/NIH enlarging investments in the Ecology and Infectious Diseases 
research program, a major collaboration between FIC and the National 
Science Foundation. This innovative program is oriented towards 
identifying predictive models for emergence of infectious diseases so 
that preventive strategies can be implemented before a new global 
calamity is unleashed on the world. Finally, FIC's Division of 
International Epidemiology and Populations Studies is conducting and 
coordinating research involving mathematical modeling of epidemic 
disease, whether due to events in nature or caused by humans, in an 
effort to better identify key questions and intervention points. 
Working closely with NIAID, NIGMS, and the Office of Public Health 
Emergency Preparedness at DHHS, FIC is coordinating work with leading 
academic mathematical modeling groups in the United States and abroad.

           EXPANDING INVESTMENTS IN NON-COMMUNICABLE DISEASES

    With the aging of populations worldwide, including in poor nations, 
along with changing ifestyle patterns and migration into cities, there 
is a growing recognition that the global burden of disease will 
increasingly include non-communicable diseases. FIC's current programs 
in this broad field address the burden of mental illness, the broad 
range of brain disorders across the life cycle, and the major epidemic 
of tobacco use and the inevitable epidemic of chronic pulmonary, 
cardiovascular disease and cancer that will follow. To complement this 
set of critical issues, FIC intends to explore ways to address the huge 
and growing burden of morbidity and mortality due to trauma and injury, 
whether intentional or un-intentional, such as road-traffic accidents. 
Areas of interest include training and research activities designed to 
better understand the body's systemic responses to major injury, 
fostering more rapid application of this knowledge to wound healing 
following trauma and burns, development of innovative low-cost and low-
maintenance prosthetic devices, integration of mental and physical 
rehabilitation into primary care for victims of trauma, and to develop 
and test effective cost-effective interventions.
    A complete description of the FIC Strategic Plan is available on 
the World Wide Web at http://www.nih.fic.gov/about/plan.html.

                               CONCLUSION

    Today, FIC, together with the Institutes and Centers at the NIH, is 
exerting leadership in global health research in important new ways, 
addressing critical global health problems while investing in the 
training of United States and foreign researchers who can, together, 
identify the solutions for tomorrow. As expressed by John E. Fogarty 
before his death in 1967, ``The alternative is that the United States 
will reduce its leadership role in furthering humanitarian programs, 
and may become more of a responder than a leader.''
                                 ______
                                 
               Prepared Statement of Dr. Raynard Kington

    Mr. Chairman, Members of the Committee: I am pleased to present the 
President's budget request for the Office of the Director (OD) for 
fiscal year 2004, a sum of $317,983,000, which reflects an increase of 
$44,031,000 over the comparable fiscal year 2003 appropriation. The OD 
provides leadership, coordination, and guidance in the formulation of 
policy and procedures related to biomedical research and research 
training programs. The OD also is responsible for a number of special 
programs and for management of centralized support services to the 
operations of the entire NIH.
    The OD guides and supports research by setting priorities; 
allocating funding among these priorities; developing policies based on 
scientific opportunities and ethical and legal considerations; 
maintaining peer review processes; providing oversight of grant and 
contract award functions and of intramural research; communicating 
health information to the public; facilitating the transfer of 
technology to the private sector; and providing fundamental management 
and administrative services such as budget and financial accounting, 
and personnel, property, and procurement management, administration of 
equal employment practices, and plant management services, including 
environmental and public safety regulations of facilities. The 
principal OD offices providing these activities include the Office of 
Extramural Research (OER), the Office of Intramural Research (OIR), and 
the Offices of: Science Policy; Communications and Public Liaison; 
Legislative Policy and Analysis; Equal Opportunity; Budget; and 
Management. This request contains funds to support the functions of 
these offices.
    In addition, the OD also maintains several trans-NIH offices and 
programs to foster and encourage research on specific, important health 
needs; I will now discuss the budget request for each of these trans-
NIH offices in greater detail.

                      THE OFFICE OF AIDS RESEARCH

    The Office of AIDS Research (OAR) coordinates the scientific, 
budgetary, legislative, and policy elements of the NIH AIDS research 
program. Our response to the epidemic requires a unique and complex 
multi-institute, multi-disciplinary, global research program. Perhaps 
no other disease so thoroughly transcends every area of clinical 
medicine and basic scientific investigation, crossing the boundaries of 
the NIH Institutes and Centers. This diverse research portfolio demands 
an unprecedented level of scientific coordination and management of 
research funds to identify the highest priority areas of scientific 
opportunity, enhance collaboration, minimize duplication, and ensure 
that precious research dollars are invested effectively and 
efficiently, allowing NIH to pursue a united research front against the 
global AIDS epidemic.
    Each year, OAR oversees the development of the comprehensive NIH 
AIDS-related research plan and budget, based on scientific consensus 
about the most compelling scientific priorities and opportunities that 
will lead to better therapies and prevention strategies for HIV 
disease. The Plan serves as the framework for developing the annual 
AIDS research budget for each Institute and Center; for determining the 
use of AIDS-designated dollars; and for tracking and monitoring those 
expenditures. OAR identifies scientific areas that require focused 
attention and facilitates multi-institute activities to address those 
needs. OAR coordinates, monitors and fosters plans for NIH involvement 
in international AIDS research and training activities. OAR supports a 
number of initiatives to enhance dissemination of research findings to 
researchers, physicians, patients and communities. The fiscal year 2004 
budget request for OAR is $60,942,000.

                THE OFFICE OF RESEARCH ON WOMEN'S HEALTH

    The Office of Research on Women's Health (ORWH) serves as the focal 
point for women's health research for the Office of the Director, to 
ensure that women are appropriately represented in biomedical and 
biobehavioral research studies supported by the NIH, and to develop and 
support biomedical careers. The report: An Agenda for Research on 
Women's Health for the 21st Century, provides the basis for the ORWH to 
collaborate with the scientific and advocacy communities to address 
scientific initiatives about women's health and sex and gender factors 
in health and disease. In fiscal year 2004, the OD budget request of 
$41,231,000 includes an increase of $808,000 over the fiscal year 2003 
enacted budget of $40,423,000 for the ORWH to continue stimulating new 
research and to implement innovative career development programs.
    Research priorities for women's health emphasize the importance of 
interdisciplinary collaboration, especially for chronic, multi-systemic 
conditions; prevention and elimination of high risk behaviors, such as 
overeating and physical inactivity, which contribute to morbidity and 
premature mortality of women; and reproductive health, including such 
gynecologic conditions as uterine fibroid tumors, and further exploring 
issues related to the menopausal transition, such as hormone therapy. 
The ORWH continues to partner with Institutes and Centers to monitor 
compliance with NIH policies for the inclusion of women and minorities 
in clinical research, and to ensure that analyses by sex/gender are 
addressed. The ORWH is witnessing exciting expansion of new research in 
its specialized centers of interdisciplinary research in women's health 
and sex and gender factors. The ORWH has also expanded its unique 
interdisciplinary career development program in women's health research 
that fosters the mentored development of junior faculty and assists 
them in bridging advanced training for junior investigators with 
research independence. In addition, the ORWH has now implemented a new 
Intramural Program on Research on Women=s Health to focus on NIH 
intramural women=s health and sex and gender comparison research.

         THE OFFICE OF BEHAVIORAL AND SOCIAL SCIENCES RESEARCH

    The NIH has a long history of funding health-related behavioral and 
social sciences research, and the results of this work have contributed 
significantly to our understanding, treatment, and prevention of 
disease. The Office of Behavioral and Social Sciences Research (OBSSR) 
furthers NIH's ability to capitalize on the scientific opportunities 
that exist in behavioral and social sciences research by providing 
leadership in identifying and implementing research programs in 
behavioral and social sciences that are likely to improve our 
understanding of the processes underlying health and disease and 
provide directions for intervention. OBSSR works to integrate a 
behavioral and social science approach across the programs of the NIH. 
The fiscal year 2004 OD budget includes $26,179,000 for OBSSR, an 
increase of $513,000 over the fiscal year 2003 appropriation.
    Many exciting scientific developments are occurring at the 
intersection of behavioral and social science research and biomedical 
research. OBSSR and several ICs are in the process of developing new 
approaches to train individuals to undertake a program of research that 
extends well beyond traditional disciplinary boundaries. One such 
initiative is a new postdoctoral program that would provide individuals 
trained in one discipline with formal course work and hands-on training 
in a second field. Collaboration between social and behavioral 
scientists and biomedical investigators is still relatively uncommon, 
in part, because traditionally trained social and behavioral 
researchers lack sufficient expertise in the biomedical fields and vice 
versa. The initiative will provide a mechanism for training 
investigators to work in interdisciplinary teams to tackle some of our 
most pressing health problems.
    OBSSR is also developing an initiative that will encourage 
investigators to expand on the current theoretical base of change 
processes and intervention models, to expand our understanding of how 
change, once achieved, is maintained over the long term. Maintaining 
behavior change over the long term appears as challenging, if not more 
so, than the initiation of behavior change. Past research efforts have 
typically focused on short-term behavioral change. However, other 
research indicates that relapse rates for addictive behaviors such as 
substance abuse and tobacco use are very high. Additionally, while the 
positive association between education and health has been well 
documented, there is a paucity of scientific information on the 
biological mechanisms and the causal pathways that underpin this 
association. OBSSR in collaboration with other ICs issued a Request for 
Applications to increase extramural research activity on this important 
scientific question.

                    THE OFFICE OF DISEASE PREVENTION

    The primary mission of the Office of Disease Prevention (ODP) is to 
stimulate disease prevention research across the NIH and to coordinate 
and collaborate on related activities with other federal agencies as 
well as the private sector. There are several other offices within the 
ODP organizational structure.
    The Office of Medical Applications of Research (OMAR) has as its 
mission to work with NIH Institutes, Centers, and Offices to assess, 
translate and disseminate the results of biomedical research that can 
be used in the delivery of important health services to the public. The 
Office of Disease Prevention (ODP) has several specific programs/
offices that strive to place new emphasis on the prevention and 
treatment of disease.
    In fiscal year 2004, the Office of Dietary Supplements (ODS) within 
ODP requests a budget of $18,778,000. It will continue to promote the 
scientific study of the use of dietary supplements by supporting 
investigator-initiated research in conjunction with other ICs at NIH 
and stimulating research through conduct of conferences and through 
presentations at national and international meetings. In its continuing 
efforts to inform the public about the benefits and risks of dietary 
supplements, the ODS expanded the International Bibliographic 
Information on Dietary Supplements (IBIDS) database to include a 
consumer-oriented search strategy. It has also disseminated a database 
devoted to federal funding of dietary supplement research, called 
CARDS, which is currently populated with data about the NIH investment 
from fiscal year 1999-2001. ODS publishes Fact Sheets about vitamin and 
mineral dietary supplements in collaboration with the NIH Clinical 
Center, as well as Fact Sheets about botanical supplements in 
conjunction with the National Center for Complementary and Alternative 
Medicine. ODS, in collaboration with the National Heart Lung and Blood 
Institute and other NIH ICs, has sponsored a systematic review of the 
relationship between omega-3 fatty acids and a series of clinical 
indications, particularly coronary heart disease. Several reports will 
be published in fiscal year 2003 and fiscal year 2004 based upon this 
review, which will serve as the basis for planning further NIH research 
on omega-3 fatty acids. To determine the future research studies of 
efficacy and safety of dietary supplements containing ephedra, ODS 
sponsored a systematic review of ephedra efficacy and safety, which has 
recently been completed. ODS has initiated work on a pre-clinical study 
of ephedra by the National Toxicology Program. Congressional language 
in the fiscal year 2002 and fiscal year 2003 appropriation reports 
directed ODS to enhance an ongoing collaboration for the development, 
validation, and dissemination of analytical methods and reference 
materials for botanical dietary supplements. ODS works with other 
partners in the public and private sectors to meet this objective. ODS 
supports the National Health and Nutrition Examination Survey (NHANES), 
conducted by the National Center for Health Statistics at the Centers 
for Disease Control and Prevention, in order to provide more 
information about dietary supplement use in the US population. This 
will inform future research about potentially important target 
populations, such as children, women, and the elderly. Funding is used 
to create and populate a database of dietary supplements, as well as to 
support the measurement of blood levels of key metabolites associated 
with dietary supplement use. In fiscal year 2003, ODS and USDA 
published the proceedings of a workshop that examined the emerging 
needs for dietary assessment, including supplement use, in national 
surveys such as NHANES. A key outcome has been to develop an 
analytically-based database of dietary supplement ingredients.
    Another component of ODP, the Office of Rare Diseases (ORD), 
develops and disseminates information to patients and their families, 
health care providers, patient support groups, and others and forges 
links among investigators with ongoing research activities in this 
area. The ORD supports workshops and symposia to stimulate research on 
rare diseases.
    To provide better and faster information, ORD, together with the 
National Human Genome Research Institute (NHGRI), established the 
Genetic and Rare Diseases Information Center to respond to requests for 
information about genetic and rare disorders. The fiscal year 2004 
budget request for ORD is $11,423,000.
    The ORD, supports together with NIH Institutes and Centers research 
on rare diseases. Approximately 25 million people in the United States 
are affected by an estimated 6,000 rare diseases. A ``rare disease'' is 
defined as a condition affecting fewer than 200,000 Americans. On 
November 6, 2002, the President signed the Rare Diseases Act of 2002 
(Public Law107-280). The purposes of this Act are to establish the 
Office of Rare Diseases in statute at the National Institutes of Health 
and to increase the national investment in the development of 
diagnostics and treatments for patients with rare diseases and 
disorders.

                    THE OFFICE OF SCIENCE EDUCATION

    The Office of Science Education (OSE) plans, develops, and 
coordinates science education programs to strengthen and enhance 
efforts of the NIH to attract young people to biomedical and behavioral 
science careers and to improve science literacy in both adults and 
children. The office's mission is to help people understand and use new 
knowledge uncovered by the NIH in pursuit of better health for 
everyone. The OSE works toward this mission by: creating programs to 
improve science education in schools (the NIH Curriculum Supplement 
Series); creating programs that stimulate interest in health and 
medical science careers (the new LifeWorks Web site); creating programs 
to advance public understanding of medical science, research, and 
careers; promoting NIH educational resources and programs; and advising 
NIH leadership about science education issues. All office programs 
target diverse populations including under-served communities, women, 
and minorities, with a special emphasis on the teachers of students 
from Kindergarten through grade 12. The OSE works closely with NIH 
institutes, centers, and offices on science education issues, and 
maintains the OSE Web site as a source of information about available 
resources and programs. http://science.education.nih.gov.
    The NIH Curriculum Supplements series are National Science 
Education Standards-based lesson plans that are distributed free to K-
12 teachers across the country. They incorporate the best of both 
science and education communities, and are intended to update science 
content and allow the teacher to incorporate the latest NIH research 
into classroom instructions. Life Works is a new OSE Web site created 
as a source of career information for students, teachers, counselors, 
and parents. The site will allow exploration of the educational 
requirements, knowledge, skills, and abilities required for over 100 
health and medical science careers. The fiscal year 2004 Budget request 
for OSE is $3,866,000.

                 LOAN REPAYMENT AND SCHOLARSHIP PROGRAM

    The NIH, through the Office of Loan Repayment and Scholarship 
(OLRS), administers the Loan Repayment and Undergraduate Scholarship 
Programs. The NIH Loan Repayment Programs (LRPs) seek to recruit and 
retain highly qualified physicians, dentists, and other health 
professionals with doctoral-level degrees to biomedical and behavioral 
research careers by countering the growing economic disincentives to 
embark on such careers, using as an incentive the repayment of 
educational loans. There are loan repayment programs designed to 
attract individuals to clinical research, pediatric research, health 
disparities research, and contraception and infertility research, and 
to attract individuals from disadvantaged backgrounds into clinical 
research. The AIDS, Clinical, and General Research Loan Repayment 
Programs are designed to attract investigators and physicians to the 
NIH's intramural research and research training programs. The NIH 
Undergraduate Scholarship Program (UGSP) is a scholarship program 
designed to support the training of undergraduate students from 
disadvantaged backgrounds in biomedical research careers and employment 
at the NIH. The fiscal year 2004 Budget request for OLRS is $6,843,000.

                              NIH ROADMAP

    The NIH Director is taking an innovative approach to accelerate 
fundamental discovery and translation of that knowledge into effective 
prevention strategies and new treatments-an effort referred to as the 
NIH Roadmap. The fiscal year 2004 budget request for the Office of the 
Director includes an increase of $35,000,000 for strategic ``roadmap'' 
initiatives. These funds will be allocated by the NIH Director to the 
Institutes and Centers to address critical roadblocks and knowledge 
gaps that currently constrain rapid progress in biomedical research. 
Three broad initiatives will be stimulated with these funds: (1) new 
pathways to discovery, which includes a comprehensive understanding of 
building blocks of the body's cells and tissues and how complex 
biological systems operate, regenerative medicine, structural biology, 
molecular libraries, nanotechnology, bioinformatics and computational 
biology, and molecular imaging; (2) research teams of the future, 
including multidisciplinary research and public-private sector 
partnerships; and (3) re-engineering the clinical research enterprise. 
These efforts will allow the NIH to rethink the infrastructure that is 
required to translate findings from the genomic era into front-line 
treatments and prevention strategies that benefit people in this 
country and abroad..
    Thank you for giving me the opportunity to present this statement; 
I will be pleased to answer questions.
                                 ______
                                 
                Prepared Statement of Dr. Claude Lenfant

    I am pleased to appear before this Committee once again on behalf 
of the National Heart, Lung, and Blood Institute (NHLBI). We are 
extremely grateful for the generous budget increases of recent years 
that have enabled us to capitalize on extraordinary research 
opportunities.

                        PROGRESS AND CHALLENGES

    A recent report in The New York Times (``Gains on Heart Disease 
Leave More Survivors, and Questions'') highlighted how far we have come 
in the battle against heart disease--and how far we have yet to go. The 
well-known good news is that heart disease death rates have been 
plummeting for decades, and serious disease manifests itself much later 
in life. The bad news is that an acute problem has become a chronic 
problem that affects millions of Americans--this is ``the endgame of 
the cardiovascular disease epidemic'' that we now confront.

                 CLINICAL RESEARCH AND THE NIH ROADMAP

    Our vigorous research effort is rapidly uncovering new knowledge 
and technologies that will undoubtedly lead to treatments undreamed of 
even 10 or 20 years ago. While they are being developed and tested, 
however, we must do our best to ensure that rigorous science guides 
appropriate use of more conventional treatments. Indeed, clinical 
research that has direct application to public health issues is a major 
focus of the NIH Roadmap that is currently being drawn and refined. The 
NIH investment in clinical research and, particularly, in clinical 
trials is absolutely critical if we are to provide health-care givers 
and their patients with science-based information to guide their 
decision-making. This is a role that the NIH is uniquely able to fill; 
indeed, it is a job that would never be undertaken without support from 
public funds. In this light, I am very pleased to mention some findings 
from recent clinical trials that have enormous practical significance 
for disease prevention and treatment.

                       BLOOD PRESSURE MEDICATIONS

    The benefits of treating hypertension are widely appreciated. 
However, the choice of a means to achieve blood-pressure lowering has 
been complicated in recent years by the arrival on the market of new 
drugs (e.g., calcium-channel blockers, angiotensin-converting-enzyme 
inhibitors, alpha blockers) that, while expensive, were thought to have 
advantages over older drugs. The ALLHAT (Antihypertensive and Lipid-
Lowering to Prevent Heart Attack Trial) compared these new drugs with a 
diuretic--one of a class of blood pressure-lowering drugs that has been 
used for many years and can be had for mere pennies a day. It found 
that the diuretic did at least as good a job as newer agents in 
preventing complications of hypertension--and a better job, according 
to some measures. The study was conducted in a variety of practice 
settings and its participants, all aged 55 and over, included high 
proportions of women, minorities, and persons with type 2 diabetes. 
Thus, the results are widely applicable to Americans with hypertension, 
who number about 50 million, according to the National Health and 
Nutrition Examination Survey.

                     POSTMENOPAUSAL HORMONE THERAPY

    The merit of conducting rigorous research to challenge widely held, 
but unproven, assumptions about treatment and prevention is illustrated 
even more starkly by recent studies of hormone therapy in 
postmenopausal women. When the NIH Women's Health Initiative was 
started more than a decade ago, belief in the manifold benefits of 
estrogen--and particularly its benefits with respect to heart disease 
prevention--was so widespread that some thought such a trial was 
neither feasible nor ethical. Thus, it was major news when the trial 
reported last summer that a widely used form of postmenopausal hormone 
therapy (estrogen plus progestin) is ineffective in reducing 
cardiovascular disease risk and appears, in fact, to be harmful. 
Estimates from U.S. Census data indicate that more than 40 million 
American women are postmenopausal, so the implications of this trial, 
in terms of both health and costs, are potentially very great.

                      TREATING ATRIAL FIBRILLATION

    Yet another example of a study that contradicted popular wisdom is 
the AFFIRM (Atrial Fibrillation Follow-up Investigation of Rhythm 
Management) trial. It compared a well-regarded rhythm-management 
approach to treating atrial fibrillation (an abnormal heart rhythm) 
with a rate-control strategy. The trial found that the purported 
benefits of the rhythm-management approach were nonexistent and, 
moreover, that the approach carried an increased risk of adverse drug 
effects. These findings are expected to alter fundamentally our method 
for preventing complications, most notably stroke, of this arrhythmia, 
which affects an estimated 2.3 million people in this country, 
according to data from the American Heart Association.

                    PREVENTING RECURRENT BLOOD CLOTS

    Finally, the PREVENT (Prevention of Recurrent Venous 
Thromboembolism) trial was recently halted ahead of schedule because of 
persuasive intermediate results. It found that long-term use of low-
dose warfarin (a blood thinner) to prevent the recurrence of two blood-
clotting disorders, deep vein thrombosis and pulmonary embolism, 
provided major benefits without significant side effects. As was the 
case with the ALLHAT study, this trial addressed a research question 
that would never have been pursued by industry, and identified an 
important use for an old, very inexpensive therapeutic agent.

         NEW RESEARCH TO ADDRESS CRITICAL PUBLIC HEALTH ISSUES

    Two of the most pressing public health priorities of today are 
obesity and diabetes, conditions that have become epidemic in modern 
America. Both are the object of NIH-wide multifaceted efforts; they 
are, moreover, the special focus of concerted NHLBI attention because 
their victims are inordinately susceptible to cardiovascular disease 
complications. The NHLBI is undertaking new programs in both areas, 
with the ultimate goal of reducing the toll of such complications.

                                OBESITY

    Innovative worksite interventions for preventing and controlling 
obesity in adults will be designed and tested. Although traditional 
obesity-control strategies have focused on the individual, the 
workplace constitutes a promising location for making positive, long-
lasting behavioral and environmental changes that may affect a broad 
range of adults. It is envisioned that researchers will consider a 
variety of approaches to make healthful foods available, affordable, 
and desirable; promote physical activity; and establish support systems 
that enable achievement and long-term maintenance of appropriate 
weight.
    A comprehensive research initiative on asthma and obesity will also 
be undertaken. Studies have found that body mass index is strongly and 
independently associated with risk of adult-onset asthma, and that 
excessive weight gain in elementary school greatly increases risk of 
developing asthma among young girls. Overweight also appears to 
contribute to asthma exacerbations and diminished pulmonary function. 
Experts from a variety of relevant disciplines believe that research 
conducted collaboratively by scientists with expertise in asthma and in 
body weight issues may yield important clues about hormonal, genetic, 
and mechanical factors that influence the relationship between these 
conditions. Stimulation of such collaboration is the goal of this new 
program.

                                DIABETES

    A major new clinical trial will test approaches to lowering risk of 
cardiovascular disease in adults with type 2 diabetes. The ACCORD 
(Action to Control Cardiovascular Risk in Diabetes) study will evaluate 
the effects of intense blood sugar control along with very aggressive 
control of blood pressure and lipids. Type 2 diabetes presents an 
enormous public health challenge; its many victims are highly 
susceptible to developing such serious consequences as heart attack, 
stroke, and limb amputation due to impaired circulation and an 
estimated 70 percent of them ultimately die of cardiovascular disease. 
More than 15 million Americans have diagnosed type 2 diabetes, and the 
number is expected to climb to 27 million by 2050; thus, if this new 
program uncovers a better treatment approach, its impact will be 
significant.
    The Institute is also working to develop a program to study the 
causes, prevention, and treatment of cardiovascular disease in the 
generally younger population of patients with type 1 diabetes. Such 
patients who have advanced microvascular complications suffer 
cardiovascular disease rates 10-20 times those of the general 
population, and there is an urgent need to identify effective 
approaches to prevent or postpone this complication. Undoubtedly, some 
common factors contribute to the risk of cardiovascular disease in both 
type 1 and type 2 diabetic patients, but the differences in 
pathophysiology between the two diseases suggest there may also be 
different factors. It is hoped that a closer look at existing data 
regarding such factors will form the basis for development of 
innovative preventive interventions.

                          SPARK II CONFERENCE

    Although this testimony has focused attention on programs and 
activities of immediate and obvious clinical relevance, I want to 
assure the Committee that the Institute is moving forward briskly on 
all fronts. This past October, we began revisiting a process (called 
SPARK, a reference to the expectation that it would ignite a new world 
of ideas) which had been first undertaken in 1998 to assist us in 
determining the best use of the funds that came our way as part of the 
doubling of the NIH budget. First, a working group of select scientists 
was assembled to assist in identifying important opportunities that the 
Institute should address over the next 3 to 5 years. Subsequently, a 
conference was held to obtain the views of representatives of three 
major professional societies associated with the mission of the NHLBI 
(i.e., the American Heart Association, the American Thoracic Society, 
and the American Society of Hematology). A research schema was 
developed that focused on five areas of opportunity: regenerative 
biology and replacement therapy, development and embryogenesis, 
immunology and inflammation, health promotion and disease prevention, 
and public health applications of genomics and proteomics. I expect 
that we will have much good news to report to the Committee in the 
upcoming years as the recommendations of SPARK II are implemented.

                            BUDGET STATEMENT

    The fiscal year fiscal year 2004 budget includes $2,868 million, an 
increase of $76 million over the fiscal year 2003 enacted level of 
$2,792 million comparable for transfers proposed in the President's 
request.
    I would be pleased to answer any questions that the Committee may 
have.
                                 ______
                                 
                 Prepared Statement of Dr. Ting-Kai Li

    I am pleased to present the President's budget request for the 
National Institute on Alcohol Abuse and Alcoholism (NIAAA) for fiscal 
year 2004. The fiscal year 2004 budget includes $430 million, an 
increase of $14 million over the fiscal year 2003 enacted level of $416 
million comparable for transfers proposed in the President's request. 
Alcohol is the third leading preventable risk factor for premature 
death in developed countries, according to the 2002 World Health 
Organization report. In the United States, alcohol misuse costs society 
about $185 billion each year.\1\
---------------------------------------------------------------------------
    \1\ National Institute on Drug Abuse and the National Institute on 
Alcohol Abuse and Alcoholism. The Economic Costs of Alcohol and Drug 
Abuse in the United States, 1992. Analysis by the Lewin Group, Harwood, 
H.; Fountain, D.; and Livermore, G. Bethesda, MD: DHHS, NIH, NIH 
Publication No. 98-4327 (September 1998).
---------------------------------------------------------------------------
    The reason alcohol takes such a heavy toll is that its potential to 
cause harm extends beyond alcoholism and behaviors that lead to fatal 
injuries, major problems in themselves. Alcohol is not only a 
psychoactive substance, but also a toxin that can damage any tissue or 
organ in the body, unlike illegal drugs. Alcohol's toxic actions cause 
or contribute to certain cancers, liver and pancreatic disease, brain 
damage, and disturbances of the immune and endocrine systems, among 
other conditions. But alcohol also presents a paradox. While heavy 
drinking substantially raises the risk of heart disease and stroke, 
studies suggest that moderate drinking appears to reduce them. Thus a 
major contributor to disease appears to have the potential to improve 
certain aspects of health.

                       VARIATION HOLDS THE ANSWER

    The explanation for the paradox lies not only in degree of drinking 
in terms of the quantity and the frequency of drinking, but also in 
differences in our biological make-up. When we can answer the question 
of why alcohol is harmful in some circumstances, but appears to be 
beneficial in others, we'll also be likely to find answers to other 
questions fundamental to our research: Why do only some of the people 
who drink, but not others, develop alcoholism or tissue damage? Why 
does the same medication result in sustained recovery from alcoholism 
in some people, but fail completely in others?
    The answers lie largely in variations in our genes and the hundreds 
of biochemical activities they influence in our cells and, ultimately, 
our organs and behaviors. Different individuals and different ethnic 
populations can have different gene variants to yield a four-fold 
difference in their metabolic and behavioral responses to alcohol.
    Much of our research is aimed at identifying and understanding: (1) 
the genes that influence how our organs and behaviors respond to 
alcohol, (2) the association of specific variants of these genes with 
specific alcohol-related outcomes, such as tissue damage or alcoholism; 
(3) patterns of variation in gene activity, protein activity, and 
metabolic activity with specific alcohol-related outcomes, and (4) how 
environmental factors interact with these biological factors to 
increase or decrease risk of alcoholism and alcohol-related problems.
    Findings from this research form the basis on which we develop and 
test pharmacological and behavioral strategies for prevention and 
treatment. Through studies in humans as well as animals, a high-risk, 
high-technology project currently underway is developing a biosensor 
that will help us understand vulnerability to alcoholism and organ 
pathology. This unobtrusive sensor will enable us to continuously 
measure and integrate over time levels of alcohol and, simultaneously, 
measure products resulting from alcohol metabolism in a number of 
bodily processes.
    One approach is an external skin sensor that periodically and 
imperceptibly inserts a probe smaller than a human hair into an 
individual subject's tissue or the fluid around it.
    Another is to implant a microchip sensor subcutaneously. The 
continuous data it generates will provide valuable information about 
metabolic patterns of vulnerability. Clinically, alcohol levels also 
will reveal whether patients are complying with treatment regimens, 
providing clues about which treatment strategies are most effective.

                         CLINICAL IMPLICATIONS

    Data from our basic research will enable us to do several crucial 
things. We will be able to provide clinicians with reliable 
biomarkers--laboratory tests--that will tell them which of their 
patients are biologically and/or genetically at risk of becoming 
alcoholic or of developing alcohol-induced tissue injury. Clinicians 
also will have the potential to predict which patients are biologically 
and/or genetically predisposed to respond to a specific medication for 
treatment of alcoholism, and which patients will respond to another.
    At the same time, this research is helping us to identify molecular 
targets for new medications to treat both alcoholism and alcohol-
induced organ damage, a pressing need in the clinical setting. As we 
follow the pathways from genes to physical and behavioral outcomes, 
we're asking where, within the many biochemical reactions that occur 
along the way, we can find the best molecular points at which to aim 
pharmaceuticals that block alcohol's actions. We also are asking if 
these points for intervention vary depending on variations in a 
person's constellation of genes, necessitating different medications or 
molecular targets for subtypes of the disorders.
    One such point for intervention is about to be tested in human 
clinical trials. Our scientists used several approaches to test a 
hypothesis that blocking a specific receptor on brain cells--the CB1 
receptor, a docking site for the brain's own version of marijuana-like 
substances called endocannabinoids--reduces desire for alcohol. In each 
approach, the CB1-receptor blocker (Rimonabant) reduced drinking. 
Pending results of the clinical trials, Rimonabant could become an 
important addition to our currently limited arsenal of effective 
treatments for alcoholism. We have identified another 16 compounds that 
are potential candidates for further development.
    Our research also can help us isolate the biological mechanisms 
that underlie alcohol's apparent beneficial effects. Since we don't yet 
have clinically useful biomarkers that tell us who can benefit from 
moderate alcohol use and who is at risk of alcohol-related problems, 
and because alcohol carries with it so many well-documented risks, a 
recommendation to drink moderately for those who do not drink would be 
irresponsible at this point. If we can isolate the mechanisms that 
underlie whatever benefits alcohol might have, we have a chance of 
designing pharmaceuticals that mimic the actions of these mechanisms, 
but don't have alcohol's many deleterious effects.

                             BRAIN RESEARCH

    Alcohol exerts its principal actions in the brain. It is here that 
heavy alcohol use results in brain-cell adaptations that lead to 
alcohol addiction. We're approaching this crucial area of brain 
research with our Integrative Neuroscience Initiative on Alcoholism 
(INIA). This initiative is extending beyond traditional models of 
collaboration to capture the potential of input from the many fields 
that necessarily contribute to alcohol research, including genetics, 
imaging, molecular biology, and behavior--each of which may use 
different methods and attach different significance to findings.
    At the scientific level, INIA has provided its investigators with 
technologies and standardized animal models which ensure that the 
significance of findings from each field are placed in the context of 
alcohol research. INIA collaborations are occurring not only across 
fields of research, but also across universities and organizations, 
nationally and internationally.
    More than that, INIA has created an operational structure that 
enables us to pursue the most productive research, relatively 
unencumbered by inflexible funding mechanisms. INIA's funding strategy 
allows us to pursue productive investigations as they emerge, to 
continue them, and to discontinue those that prove to be less promising 
or have reached their potential. In short, INIA has removed roadblocks 
to progress. This is enabling us to identify the structure and function 
of neural circuits, networks of brain cells that work in concert as 
intermediaries of alcohol's behavioral outcomes.
    Molecular imaging techniques are permitting INIA investigators to 
link alcohol-induced molecular responses with behaviors, in real time. 
Through computational biology, INIA researchers are creating models 
that predict how different brain structures and functions will respond 
to alcohol under different scenarios. This kind of research can help us 
determine optimal points for therapeutic intervention. A recent 
expansion of INIA will enable us to conduct translational research, to 
test whether neurobiological changes that occur in our animal models of 
alcohol-related behavior also occur in humans.

                           UNDER-AGE DRINKING

    Drinking by children and adolescents is a concern reflected not 
only in our research, but also in parents and the media. Young brains 
are still forming nerve-cell connections, and they appear to be more 
sensitive to the deleterious effects of alcohol. Researchers are 
investigating how alcohol affects this and other processes in the 
developing brain, and for how long. Early indications are that 
adolescents who have gone through alcohol addiction and withdrawal risk 
long-term deficits in learning ability and memory. Research also shows 
that people who begin drinking at young ages are much more likely than 
those who begin later to become alcoholic at a later point in life.
    Children and adolescents also are still developing decision-making 
capabilities, so important in formulating responses to environmental 
influences, such as peer pressure, that are powerful contributors to 
their choices about drinking. Almost 30 percent of 9th-12th graders 
surveyed report that they have had five drinks in a row at least once 
in the previous month.\2\
---------------------------------------------------------------------------
    \2\ Centers for Disease Control and Prevention, Youth Risk Behavior 
Survey. http://www.cdc.gov/nccdphp/dash/yrbs/2001/youth01online.htm
---------------------------------------------------------------------------
    An important question in alcohol research is how different drinking 
patterns affect risk of developing alcohol-related problems. Heavy, 
episodic drinking (sometimes referred to as ``binge drinking'') appears 
to be popular among some youth--notably college students, as newspaper 
headlines frequently attest. A study widely publicized in the media 
last year estimated that 1,400 college students die each year from 
alcohol-related causes and that 500,000 are injured.\3\
---------------------------------------------------------------------------
    \3\ Hingson, R.W.; Heeren, T.; Zakocs, R.C.; Kopstein, A.; 
Wechsler, H. Magnitude of alcohol-related mortality and morbidity among 
U.S. college students ages 18-24. Journal of Studies on Alcohol, 
63(2):136-144, 2002. (164269)
---------------------------------------------------------------------------
    In addition to our investigator-initiated research in this area, we 
have formed the Task Force on College Drinking, a collaboration between 
college presidents and scientists. The Task Force has released 
recommendations on prevention strategies, literature for various 
audiences, and a website, and has organized regional workshops. The 
Institute recently issued a research announcement calling for 
scientists with expertise in underage drinking to form rapid-response 
partnerships with colleges that request help. Episodic heavy drinking 
of alcohol has been ritualized and is an accepted part of life at 
certain celebratory events in our society, not only among youth, but 
also among adults. Among the questions we're asking are: How does this 
kind of drinking practice become ritualized in our society in spite of 
its deleterious consequences? How can we change the culture that leads 
to it?
    Meanwhile, our initiative on the biological mechanisms of 
adolescent alcohol abuse is using imaging techniques that correlate 
brain structure with function and behaviors, in addition to other 
techniques, to reveal how alcohol affects specific brain areas, in 
human and nonhuman primate and rodent animal model studies. We're also 
asking how developmental and environmental factors and the interplay 
between genes and environment affect youths' choices to drink and their 
physical and behavioral responses to alcohol.

                     PREVENTION AND RISK REDUCTION

    Alcohol prevention research is aimed at reducing the causes and 
consequences of alcohol abuse and alcoholism. For example, whether the 
relationship between early onset of drinking and subsequent alcoholism 
is one of cause and effect or the result of factors that predispose 
people to both those behaviors, and others, is unclear. Our 
investigators are studying this issue, and their findings will help us 
understand why people become alcoholic. Meanwhile, preventing youth 
from drinking and reducing the harm it causes are essential, not only 
because early onset drinking predicts subsequent alcoholism, but also 
because of the immediate harm that alcohol misuse can cause injury, 
violence, early introduction into the criminal justice system, legal 
repercussions, derailed scholastic careers, and death, to name a few.
    We are conducting studies that develop and test strategies to 
prevent drinking by youth of different ages and backgrounds. 
Particularly important among these are longitudinal studies that can 
tell us whether strategies that show promise among a given subgroup of 
youth, such as rural adolescents, are successful or can be adapted for 
others, such as urban youth. These studies examine the impact of a 
number of factors, such as school programs, parental and family 
influence, peer influence, alcohol advertisements, and community 
policies and practices.
    Prevention research at NIAAA also focuses on the general population 
and segments with unique needs. Among them are pregnant women (and 
their unborn children, who are at risk of fetal alcohol syndrome) and 
the elderly, who may be prone to depression and dangerous interactions 
between alcohol and prescription drugs. One of our initiatives is 
determining if community-based approaches successful in preventing 
alcohol-use disorders in the short-term can result in long-term 
prevention at different life stages.

                                OUTREACH

    Public and private partnerships are helping us send our prevention 
messages to the community. The Leadership to Keep Children Alcohol-
Free, a prevention campaign in which the Robert Wood Johnson Foundation 
has joined us, has recruited 33 governors' spouses to act as 
spokespersons.
    Other partners in our efforts to prevent under-age drinking include 
the National Highway Traffic Safety Administration, the Department of 
Justice, the Department of Education, and the Substance Abuse and 
Mental Health Services Administration. Our outreach efforts also target 
clinicians, including physician groups such as the National Hispanic 
Medical Association, and the National Medical Association, that serve 
special populations. A science-to-service program provides clinicians 
with information about current research, and links them with scientists 
who advise them on specific areas of practice, at the clinician's 
request. We work with States to engage their treatment providers and 
administrators. After exchanging information about our current research 
findings and the practitioners' obstacles to providing treatment, we 
place experts in temporary residencies in treatment programs that have 
identified specific areas of need. Medical schools generally aren't 
thorough in their coverage of alcohol-related problems, and we have 
produced a physician's guide to help fill the gap. Through these 
efforts, we promote the practical application of our research where 
it's most needed.
                                 ______
                                 
            Prepared Statement of Dr. Donald A. B. Lindberg

    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's budget request for the National Library of Medicine 
(NLM) for fiscal year 2004, a sum of $316,040,000, which reflects an 
increase of $9,334,000 over the fiscal year 2003 enacted level of 
$306,706,000 comparable for transfers proposed in the President's 
request.
    For more than 150 years one institution has been the nation's 
primary source of published medical information--your National Library 
of Medicine (NLM). Originally part of the Army, the Library became a 
civilian organization in the 1950s and a part of the NIH in the 1960s. 
Innovation in disseminating medical information has been a hallmark of 
the Library since the 19th century, including the first successful 
application of computers (40 years ago) to a large-scale bibliographic 
system. Today NLM not only maintains the world's largest collection of 
biomedical books and journals, but it has become, via the Web, a 
ubiquitous source of authoritative information for scientists, health 
professionals, and consumers around the world. Some half a billion 
searches of the various NLM databases are done each year.
    The NLM in the 21st century is distinguished especially by two 
features unknown to it just two decades ago: the institution has become 
the leading source of human genome information and at the same time an 
important source of nontechnical health information for the public. The 
proximate source of the information that makes both these features 
possible is the National Institutes of Health. The NLM, through the Web 
operations of its National Center for Biotechnology Information, 
receives more than a quarter million visitors a day seeking molecular 
biology information ranging from DNA sequences and protein structures 
to the related research literature. On the other hand, the extensive 
health information issued by the various NIH institutes and centers 
forms the backbone of the MEDLINEplus information service offered to 
the general public.
    An unusual aspect of the NLM's contemporary role that there is a 
direct connection between the Library's research and information 
programs and the defense against bioterrorism and medical and public 
health preparedness for disaster management and terrorist attack. To 
cite a few examples: genomics research databases for targeted 
development of drugs, vaccines, and other forms of treatment for such 
diseases as smallpox, anthrax, plague, Ebola, and cholera; informatics 
R & D related to terrorism and disaster management; training for health 
professionals in the use of pertinent information resources; developing 
experimental information resources targeted at first responders; and 
improving the information infrastructure so that vital data can be 
shared during a crisis. As to post-9/11 information services, NLM 
quickly placed pages on its Web site about post-traumatic stress 
disorder, biological and chemical warfare agents, anthrax, and other 
information related to bioterrorism.

             TOOLS FOR SCIENTISTS AND HEALTH PROFESSIONALS

    In its role as the world's largest medical library, the National 
Library of Medicine continues to provide access to the enormous 
literature of the health sciences, including even priceless historical 
treasures dating to the 11th century. Most medical researchers and 
health professionals have, directly or indirectly, availed themselves 
of the Library's services some time in their career; there are those 
who access MEDLINE/PubMed (to take one popular example) almost daily. 
Another heavily used information resource is GenBank (with DNA sequence 
data).
    MEDLINE is a database of 12 million references and abstracts to the 
world's medical literature published since the 1960s; PubMed is the 
Web-based retrieval system that makes this wealth of information freely 
and easily searchable to health professionals and others. MEDLINE/
PubMed is an evolving system. The database expands at the rate of about 
half a million records a year. Several years ago NLM introduced links 
between MEDLINE references and publisher websites so users could 
retrieve the full text of articles. Today, more than 3,000 of the 4,600 
publications indexed for MEDLINE have such links. Another element in 
the evolution of MEDLINE is converting information from the 1950s, 
MEDLINE form, so that valuable research data, on smallpox and 
tuberculosis to take just two pertinent examples, will be available to 
today's scientists. A recent improvement is a text version of PubMed 
for users who require special adaptive equipment to access the web. 
This has had the additional benefit of making the system much more 
friendly for those using hand-held devices.
    GenBank, on the other hand, is accessed primarily by scientists--
some 50,000 of them each day. It is a collection of all publicly 
available DNA sequences and is thus a key element in ensuring that the 
flood of data resulting from research around the world, including the 
Human Genome Project here at home, is available for further research 
and for further analysis and for gene discovery. GenBank is maintained 
by NLM's National Center for Biotechnology Information (NCBI) and now 
contains more than 15 million sequences and 29 billion base pairs from 
over 130,000 species. These are limited to chromosome maps, gene 
protein products, and other relevant genetic information for human and 
many smaller species.
    An increasingly popular NCBI service for the scientist and health 
professional is PubMedCentral. This is a digital archive of life 
sciences journal literature under which publishers electronically 
submit peer-reviewed research articles, essays, and editorials to be 
included. NLM undertakes to guarantee free access to the material; 
copyright remains with the publisher or the author. Creating ``digital 
archives'' is an important NLM responsibility in this electronic age.
    Electronic health data standards are also part of the information 
infrastructure of the 21st century. Such standards are needed for safe 
and effective health care, efficient clinical and health services 
research, and timely public health and bioterrorism surveillance. NLM 
plays an important role in HHS initiatives to promote standardization 
of electronic patient data by supporting the maintenance, distribution, 
and linking of key clinical terminologies within the Unified Medical 
Language System (UMLS) Metathesaurus. As a result, these clinical 
terminologies are available for use throughout the United States in 
clinical research databases, patient care, and public health 
surveillance. NLM is providing funding for the development, 
enhancement, and distribution of several clinically specific 
vocabularies. The UMLS Metathesaurus provides a common distribution 
vehicle for such vocabularies and a mechanism for linking them to 
HIPAA-mandated administrative code sets, basic research vocabularies, 
and thesauri designed to index the scientific literature. In addition, 
pilot projects for testing the use of the vocabulary in different 
settings will be critical for maximizing the benefit of electronic 
health data standards for improving patient safety, reducing costs, and 
enhancing effective information exchange to combat bioterrorism.

                  INFORMATION SERVICES FOR THE PUBLIC

    Since 1998, NLM has expanded its mission beyond serving health 
professionals and researchers to encompass providing high quality 
electronic health information services for the public. To serve this 
audience, the Library developed a new information resource, 
MEDLINEplus, a Web-based service that provides integrated access to the 
high quality consumer health information produced by NIH and HHS 
components and other reputable organizations. About 1.8 million unique 
visitors obtained health information from MEDLINEplus in January 2003. 
The main features of MEDLINEplus: 600 ``health topics,'' from Abdominal 
Pain to Yeast Infections, consumer-friendly information about thousands 
of prescription and over-the counter drugs, an illustrated medical 
encyclopedia and medical dictionaries, directories of hospitals and 
health professionals, a daily health news feed from the major print 
media, 150 interactive and simply presented tutorials (with audio and 
video) about diseases and medical procedures, and connections from the 
health topics to current clinical trials.
    Like MEDLINE, MEDLINEplus is a constantly evolving system. Links 
are checked daily and new health topics added weekly. A completely 
Spanish-language version of MEDLINEplus was introduced in 2002 and is 
receiving heavy use. Early in 2003 a prototype ``MEDLINEplus Go Local'' 
system was introduced in North Carolina, a joint effort of the 
University of North Carolina and the NLM. This system allows 
MEDLINEplus users access to ``NC Health Info,'' which contains links to 
local, county, and state health services in North Carolina and, 
conversely, users of NC Health Info can link into the detailed, 
authoritative health information about particular diseases and 
conditions in MEDLINEplus.
    The NLM casts a wide net in creating and promoting MEDLINEplus, 
working closely with the Public Library Association and other 
organizations not associated with NLM's mission, as well as with the 
4,700 member institutions of the National Network of Libraries of 
Medicine. Network librarians not only assist in identifying and 
evaluating information to be included in MEDLINEplus, but are of 
tremendous help in demonstrating MEDLINEplus locally and publicizing 
it.
    Another major consumer information resource, ClinicalTrials.gov, 
was developed by the NLM on behalf of the entire NIH in response to a 
mandate from Congress. The database provides patients and families 
access to information about clinical trials and opportunities to 
participate in the evaluation of new treatments. The site was launched 
in February 2000 and currently contains approximately 7,200 clinical 
studies sponsored by NIH, other Federal agencies, and the 
pharmaceutical industry.

                 NLM RESEARCH AND DEVELOPMENT PROGRAMS

    The Library is at the cutting edge of research and development in 
medical informatics--the intersection of computer technology and the 
health sciences. NLM has a program of grants and contracts to 
university-based researchers and also a cadre of in-house scientists in 
the Lister Hill National Center for Biomedical Communications and the 
National Center for Biotechnology Information. The Lister Hill Center 
sponsors many exciting communications research projects, such as those 
in telemedicine and the Visible Human Project. The NLM-supported ``A 
Clinic in Every Home'' is an especially promising telemedicine project 
for medically underserved rural Iowa residents to provide them with 
access to high quality health care. The expectation is that this system 
will both raise the quality of health care and lower costs. Another 
Lister Hill Center program is the initiative to fund projects that 
demonstrate the medical community's technical needs in using high-speed 
communications networks for critical healthcare applications, including 
computing in support of disaster management.
    The Visible Human Project comprises two enormous data sets, male 
and female, of anatomical MRI, CT, and photographic cryosection images. 
These data sets, licensed to more than 1,700 individuals and 
institutions in 43 countries, are being used in a wide range of 
educational, diagnostic, treatment planning, virtual reality, artistic, 
mathematical, and industrial applications. Projects run the gamut from 
teaching anatomy to practicing endoscopic procedures to rehearsing 
surgery. NLM's AnatLine is a web-based image delivery system that 
provides retrieval access (even from a home computer) to large 
anatomical image files of various parts of the Visible Human male 
thoracic region, such as the heart and stomach, including 3D images.
    The other major NLM component involved in R & D is the National 
Center for Biotechnology Information, noted above as the source of the 
GenBank database of DNA sequence information. NCBI is more than just 
assembler of genomic data, however. NCBI investigators have developed 
sophisticated computational tools such as the BLAST suite of programs 
that makes it dramatically easier for researchers to scan huge sequence 
databases for similarities, and to evaluate the resulting matches. 
Another NCBI product, Entrez, is an integrated database that allows 
users to easily and quickly search enormous amounts of sequence and 
literature information. The newest tool is the ``Reference Sequence 
Collection'' that is serving as a foundation for genomic research by 
providing a centralized, integrated, non-redundant set of sequences, 
including genomic DNA, transcript (RNA), and proteome (protein product) 
sequences, integrated with other vital information for all major 
research organisms. As genomic sequence data continues to accumulate 
and be made available in ingenious ways through the web, we can expect 
discoveries that promise future medical breakthroughs.
    NLM extramural programs have an important role in supporting R & D 
in biocommunications. One timely example is the early warning public 
health surveillance system developed at the University of Pittsburgh 
and recently demonstrated to the President. NLM's grant program also is 
a key supporter of NIH's ``Biomedical Information Science and 
Technology Initiative.'' The Library has expanded its support from 12 
to 18 training programs at universities across the nation to train 
experts to carry out research in general informatics and in 
bioinformatics. The NLM has recently augmented each of the training 
programs with a ``BISTI supplement'' and has also funded two planning 
grants that will eventually lead to the development of what are called 
National Programs of Excellence in Biomedical Computing.

                      SERVING SPECIAL COMMUNITIES

    The NLM has been working with the National Institute on Aging to 
create NIHSeniorHealth.gov. Accessible from MEDLINEplus, the new site 
contains information in a format that is especially usable by senior 
citizens. At present NIHSeniorHealth.gov contains information on topics 
like Alzheimer's and exercise for older adults, but it will soon be 
expanded to include more topics of special interest to seniors as other 
NIH institutes contribute to it. NLM is working on adapting special 
software that would allow the visually impaired to exercise control and 
hear Web pages read to them. This would also be a boon to some senior 
citizens.
    The National Network of Libraries of Medicine, noted above in 
connection with MEDLINEplus, places a special emphasis on outreach to 
underserved populations in an effort to reduce health disparities. For 
example, there are programs to assist in remedying the disparity in 
health opportunities experienced by such segments of the American 
population as African Americans, Latinos, Native Americans, senior 
citizens, and rural populations. One of the NN/LM outreach efforts 
involves a telemedicine ``connections'' program for Native Americans in 
the Pacific Northwest conducted through the Regional Medical Library at 
the University of Washington.
    Another highly successful NLM outreach program has been 
strengthening Historically Black Colleges and Universities so that they 
can train people to use information resources in dealing with 
environmental and chemical hazards. Under this program, faculty and 
students in more than 80 minority institutions have received such 
training. Through these schools, NLM is working to promote high-quality 
Internet connectivity and using technology for research and education.
    There are other NLM programs targeting groups of citizens with 
special health information needs. In the past several years, the 
Library has made more than 50 awards to continue its HIV/AIDS-related 
outreach efforts to community-based organizations, patient advocacy 
groups, faith-based organizations, departments of health, and 
libraries. This program supports local programs to improve information 
access for AIDS patients, the affected community, and caregivers. 
Emphasis is on providing information in a way meaningful to the target 
community, and may include training in information retrieval, sending 
interlibrary loans, and providing Internet access.
    NLM's efforts to reach special populations in need are not limited 
to the United States. An international partnership in which the NLM is 
a key player is the Multilateral Initiative on Malaria. NLM's mandate 
as leader of the Communications Working Group has been to leverage 
partnerships (at 13 installations) to create a malaria research network 
in Africa, enabling scientists there to have full access to the 
Internet and the Web as well as access to medical literature. The aim 
is to allow researchers, any time of the day or night, to have 
instantaneous Internet access that will enable them to send and receive 
e-mails, search for literature, interrogate databases, share files and 
images with colleagues, and generally move to a new and more efficient 
way of doing collaborative research.

                            FUTURE PROSPECTS

    NLM is responsible for acquiring, indexing, cataloging, and 
preserving the world's biomedical literature--in all languages and 
media--and for providing reference and research assistance and document 
delivery from this comprehensive collection. NLM also collects, 
processes and distributes genome sequence data through NCBI. Both of 
these core areas are experiencing unprecedented growth. The cost of 
purchasing the biomedical literature typically increases about 10 
percent per year, irrespective of general inflation, and the move to 
electronic publishing has not diminished this rate of increase. NLM 
uses advanced technology to improve the efficiency of its basic 
operations, and contractors currently perform the majority of 
activities required to provide NLM's basic services.
                                 ______
                                 
                Prepared Statement of Dr. Kenneth Olden

    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's budget for the National Institute of Environmental 
Health Sciences (NIEHS). The fiscal year 2004 budget includes 
$630,774,00, an increase of $17,358,000 over the fiscal year 2003 
enacted level of $613,416,000 comparable for transfers proposed in the 
President's request.

                              INTRODUCTION

    Voluminous literature derived from epidemiological studies as well 
as human and animal experiments has shown that environmental factors 
play an important role in human health and disease. That is, most 
complex diseases arise from the interplay between genetics, environment 
and behavior. However, understanding of these interactions has remained 
grossly descriptive and the molecular mechanisms elusive. But, thanks 
to the rare confluence of technology breakthroughs in genomics and 
proteomics and the rethinking and redirection of the environmental 
health sciences over the past decade, the link between the environment 
and human health and disease can now be investigated with more rigor 
and specificity. For example, the sequencing of the human genome and 
the development of high throughput technologies to monitor the 
expression of genes and proteins in response to specific environmental 
exposures has created an unparalleled opportunity to study gene-
environment interactions.

                            NEW INITIATIVES

    Breast Cancer and Environment Research Centers.--There is 
surprisingly little information on the development of the normal 
breast. The lack of knowledge about the biological and molecular 
mechanisms involved in normal breast development hinders our ability to 
identify environmental triggers of breast cancer. How can we identify 
early adverse changes in breast tissue if it is not known how the 
tissue normally develops? To fill this research gap, NIEHS is funding a 
consortium centers program that will provide new information on the 
normal growth and development of the breast and reproductive systems, 
evaluate the impact of environmental exposures on the breast, and 
explore potential times of increased sensitivity and vulnerability of 
breast tissue to environmental effects. These centers represent a 
collaborative effort with the National Cancer Institute.
    NIEHS is also continuing the effort to establish a cohort of 
unaffected sisters of breast cancer cases to clarify the gene-
environment interactions in this disease. This cohort can be used to 
examine breast cancer risk in relation to factors such as endogenous 
hormones, growth factors and environmental contaminants, and to study 
these factors jointly with genes to elucidate genetic modifiers of 
response.
    Toxicogenomics.--NIEHS developed the National Center for 
Toxicogenomics (NCT) to coordinate a nationwide research effort for the 
development of a toxicogenomics knowledge base. Toxicogenomics is a new 
discipline that studies how genes respond to environmental stressors or 
toxicants. It combines genetics (genomic-scale mRNA expression), 
proteomics (cell and tissue-wide protein expression), metabonomics 
(metabolite production) and bioinformatics with conventional toxicology 
to investigate the role of gene-environment interactions in health and 
disease. New molecular technologies, such as DNA microarray analysis 
and protein chips, can be used to measure the expression of thousands 
of genes and proteins, providing the potential to accelerate discovery 
of toxicant pathways and specific chemical and drug targets.
    When a person is exposed to a chemical, cells in the body may 
respond by switching on some genes and switching off others. The on/off 
pattern of various genes is different for different chemicals, creating 
a characteristic pattern or ``signature,'' which scientists hope will 
be useful in classifying chemicals and other stressors by their 
biological activity. This signature pattern would provide a means of 
predicting effects on human health from chemicals we currently know 
little about. Toxicogenomics seeks to use these signature gene 
expression patterns to go beyond the traditional toxicological tools of 
testing animals for adverse outcomes that might indicate toxicity.
    One aim of the NCT is to create a Chemical Effects in Biological 
Systems (CEBS) Database. The CEBS database will contain data on global 
gene expression, protein expression, metabolite profiles, and 
associated chemical/stressor-induced effects in multiple species. With 
such information, it will be possible to derive functional pathways and 
network information based on cross-species homology. Once sufficient 
high quality data have been accumulated and assimilated, it will become 
possible to predict the toxicity of an unknown chemical by comparing 
its gene and/or protein expression profile to compendia of expression 
profiles in the database. As the field of toxicogenomics evolves, 
toxicogenomics databases will begin to support predictive toxicology 
and hazard assessment. This will help scientists predict the 
toxicologic impact of suspected toxicants and calculate how much of a 
hazard these toxicants actually represent to human and environmental 
health.
    The pharmaceutical industry is making huge investments in this 
technology because of their interest in finding ways to speed up the 
process of toxicological assessment of new research and development 
products. Identifying molecular events that serve as precursors of 
adverse health outcomes early in the development process would 
eliminate much of the expense (estimated in the billions of dollars 
annually) associated with the development of new pharmaceutical 
products.
    Susceptibility to Environmental Exposures.--Although reference is 
made to the human genome, the concept of a single genome is misleading. 
Each individual's genetic makeup, with the exception of identical 
twins, is unique. While the genomes of individuals are 99.9 percent 
identical, the 0.1 percent variation leaves considerable room for 
individual differences among the approximately three billion nucleotide 
base pairs that make up the human genome. However, it should be 
emphasized that genes are not the only factors that contribute to 
differences in susceptibility to environmental exposures; age or stage 
of development, behavior, and general health or nutritional status can 
have a spectacular influence. Both the genetic and age/stage of 
development-related aspects of susceptibility are being addressed by 
NIEHS.
    Differences in susceptibility to environmental exposures had 
received little attention until NIEHS launched the Environmental Genome 
Project (EGP) and the Children's Environmental Health Research and 
Prevention Centers in 1998. There is now considerable evidence that 
hundreds of genes exist in the human genome that make some individuals 
more or less susceptible to the effects of pollutants or other 
environmental chemicals, contributing to everything from cancer to 
birth defects and Parkinson's Disease. The key objective of the EGP is 
to discover the alleles or genetic variants (called polymorphisms) that 
confer susceptibility or resistance.
    The Children's Environmental Health Research and Prevention Centers 
were developed, in collaboration with the EPA, to explore the 
relationship between the timing of exposure, the stage of development 
and susceptibility. Because of the rapid rate of growth and development 
of major organ systems (e.g., the lung, brain, and heart), children are 
thought to be particularly vulnerable to environmental toxicants. They 
can be more vulnerable than adults to adverse health outcomes, and the 
consequences of these adverse effects are sustained throughout life, 
making the reduction of childhood exposures a critical component of 
environmental public policy.
    We are also exploring the possibility of susceptibility studies in 
seniors. For a variety of reasons, older Americans are also more 
susceptible to environmental stress (e.g., the combination of poor air 
quality and extreme heat during the summer months). This important 
public health issue has received almost no attention, but dialogue is 
ongoing with the EPA and the National Institute on Aging about ways to 
include older Americans in more environmental health studies.
    Parkinson's Disease Research Consortium.--NIEHS created a 
Parkinson's Disease Consortium Centers Research Program in 2002 because 
we believe that a collaborative, multidisciplinary, multi-institutional 
approach is required to elucidate the complex interactions between 
genes and environmental factors likely to be involved in the 
development of this devastating disease. Collectively, the three 
centers that make up the consortium have expertise in basic 
neurosciences, human genetics, clinical research, and epidemiology, and 
long-standing collaborative interactions with the various non-profit 
organizations that represent patient advocates. These scientific 
disciplines were included in the consortium because a major impediment 
in Parkinson's Disease research has been that significant findings in 
one field were not readily disseminated among investigators in the 
other related fields. It is our intent to expand the Consortium Centers 
concept in 2004 to capture some of the outstanding activities not 
funded earlier.
    The knowledge and technologies developed in the Institute's EGP, 
the Mouse Genome Centers, and the National Center for Toxicogenomics 
will also be made available to this cohort of investigators as they 
become available. For example, new Parkinson's Disease susceptibility 
genes and new environmental risk factors are likely to be discovered, 
and new mouse models of the disease are likely to be created using gene 
``knockout'' and ``knockin'' technologies. These new resources will be 
invaluable to the Parkinson's Disease research community.
    The Development of Multidisciplinary Research Teams and Novel 
Technologies.--The solution to complex problems often requires the 
collective knowledge and experience of multiple investigators and novel 
approaches developed at the boundary of several disciplines. While the 
individual investigator approach remains the cornerstone of innovation 
of science and technology development, translation often requires a 
team approach. In fact, lack of infrastructure to support the 
development of multidisciplinary research teams is hampering our 
ability to realize the benefits of the nation's expenditures for 
biomedical research. While the NIH has invested in infrastructure to 
build maps of the human genome and develop technologies for genotyping 
and monitoring gene and protein expression, it is the deployment of 
these data bases and technologies to prevent human illness that has 
proven to be the most challenging.
    Also, the inadequacy of current analytical methods to investigate 
complex interactions involving genes, proteins and environmental 
factors has been a bottleneck in understanding the development of 
complex diseases resulting from such interactions. While high 
resolution structural analysis of proteins is critical for 
understanding molecular interactions between genes, or proteins and 
toxic chemicals, new technologies will be needed to determine how the 
latter disrupts structure and function of highly coordinated biological 
pathways or networks at the level of the cell and tissue. NIEHS has 
developed the Center Programs described here to catalyze the formation 
of multidisciplinary research teams to investigate gene-environment 
interactions using emerging expertise and technologies.

                                SUMMARY

    The data generated by the studies I have described will allow for a 
more rational approach of gauging environmental threats, and will 
reduce the need to rely on default assumptions in extrapolating results 
from animal models to humans and in setting exposure limits. These 
studies will also lead to the development of high throughput 
technologies that could both accelerate and reduce the costs of 
toxicity testing of pharmaceuticals and environmental xenobiotics. This 
approach to understand how genes and the environment interact shifts 
the focus of disease management from symptom-based classification to 
biological causation and prevention. The objective is to provide a 
database that will allow for the use of precursors or molecular markers 
in assessment of disease states.
                                 ______
                                 
                Prepared Statement of Dr. Audrey S. Penn

    Mr. Chairman and Members of the Committee, I am Audrey Penn, Acting 
Director of the National Institute of Neurological Disorders and Stroke 
(NINDS). I am pleased to present the President's budget request for 
NINDS for fiscal year 2004. The fiscal year 2004 budget includes $1,469 
million, an increase of $13 million over the fiscal year 2003 enacted 
level of $1,456 million comparable for transfers proposed in the 
President's request.
    The mission of NINDS is to reduce the burden of neurological 
disorders, that is, the many diseases that affect the brain, spinal 
cord, muscles, and nerves of the body. Neurological disorders cause 
enormous suffering and loss of life, often defying the best efforts of 
modern medicine. However, we are making progress in prevention and in 
treatment, derived from continuing advances in fundamental scientific 
understanding of the nervous system, which enhance the prospects for 
the future. Today I will touch on these points and concentrate on what 
NINDS is doing to expedite progress.

                  THE BURDEN OF NEUROLOGICAL DISORDERS

    Neurological disorders can compromise the complex thinking and 
emotions that make us human, the routine perception and movement that 
we take for granted, and even the control of bodily systems that are 
normally beneath our awareness. Diseases of the nervous system strike 
at every age. Some, such as stroke, chronic pain, epilepsy, and 
traumatic brain injury, are among the most common of all causes of 
death and disability. Hundreds of less common neurological disorders 
take an incalculable toll on patients and families too. Also demanding 
attention are substantial disparities in impact by ethnic group, 
gender, socioeconomic status, and geography.

                 PROGRESS AND PROSPECTS FOR THE FUTURE

    Progress in preventing and treating neurological disorders has been 
notable. As Dr. Zerhouni has testified previously, this year alone 
almost a quarter of a million fewer deaths from stroke will occur in 
the United States than would have been expected without advances in 
prevention--progress that represents the cooperative efforts of many 
groups, public and private. Prevention of nervous system birth defects, 
such as spina bifida, and genetic counseling for inherited disorders, 
such as Tay-Sachs disease, are also having a major impact on public 
health. The first acute treatments for ischemic stroke and spinal cord 
injury--though still far from adequate--have proven effective for 
reducing neurological damage. Immune therapies now reduce relapses and 
slow the progression of disability in multiple sclerosis. Surgical 
options employ implantable devices to compensate for brain circuits 
unbalanced by disease in Parkinson's disease and epilepsy. Enzyme 
therapies have brought the first successes in treating lipid storage 
disorders. Advances in molecular genetics and brain imaging are further 
augmenting clinicians' insights to diagnose and to guide therapy.
    Progress is gaining momentum, with an unprecedented variety of new 
treatment and prevention strategies under development: drugs to home in 
on the molecules that cause disease, stem cell therapies to replace 
lost nerve cells, neural prostheses to read control signals directly 
from the brain, immune tolerance approaches to prevent stroke, 
therapies to repair or replace defective genes, and behavioral 
interventions to encourage the latent ``plasticity'' of the brain and 
spinal cord toward self-repair. Each of these strategies relies upon 
remarkable advances in understanding how the normal nervous system 
works and what goes wrong in disease.
    A few findings from the past year illustrate this progress: 
Scientists studying genes discovered a mutation that causes a form of 
Charcot-Marie-Tooth disorder, a common disabling disease of peripheral 
nerves; pinpointed the site of a gene contributing to autism; and found 
clues about how a chromosome defect causes facioscapulohumeral 
dystrophy, a common form of muscular dystrophy. In animal models of 
human disease, themselves often the product of gene research, gene 
therapies have yielded encouraging results for neurofibromatosis, Fabry 
disease and Parkinson's. Scientists on the trail of cell therapies 
discovered that primitive precursor cells in the adult rat brain can 
respond to experimental damage by multiplying, migrating to the site of 
damage, and making new nerve cells, and that transplanted embryonic 
stem cells show promise in animal models of Parkinson's disease, 
stroke, and other disorders. Scientists focusing on the immune system 
found that a strategy, which suppresses immune reactions, prevents 
strokes in hypertensive rats; that an anti-cholesterol drug, the statin 
Lipitor, reduces symptoms in an animal model of multiple sclerosis; and 
that the gene defect in Batten disease may result in unexpected immune 
reactions, which could contribute to the devastating consequences in 
the brain. In research on drug treatments, the antibiotic minocycline 
slowed progression of amyotrophic lateral sclerosis in mice; the 
natural brain chemical inosine stimulated rewiring of the brain 
following stroke in rats; and coenzyme Q10 may slow progression of 
Parkinson's disease. Scientists studying new technologies developed a 
device that enabled rats to control a robot arm just by thinking about 
it; devised better ways to delivery therapeutic agents to the brain; 
used microarrays to monitor the activity of thousands of genes, 
yielding insights about brain tumors and multiple sclerosis; and for 
the first time, recorded activity of the human fetal brain in response 
to light, which may lead to better prenatal diagnostics.

                          EXPEDITING PROGRESS

    NINDS continues to rely on the insight and ingenuity of scientists 
and physicians throughout the nation to seek out scientific 
opportunities, propose research studies, and advise on promising ideas. 
Since Congress began the NIH budget doubling effort, the Institute has 
taken a more active role in directing research. Efforts are motivated 
by scientific opportunity, enabled by resources, guided by extensive 
and inclusive planning efforts, and quality-assured through peer 
review. Programs target specific diseases and cross-cutting 
opportunities to enhance the effectiveness of research. A few examples 
illustrate the wide range of activities:
    The NIH Parkinson's Disease Research Agenda is the pacesetter for 
disease-focused NINDS activities. The Agenda began in January 2000 with 
a working group that included Parkinson's disease researchers, patient 
advocates, industry representatives, and NIH scientific staff. Follow-
up meetings, most recently a July 2002 ``summit'' called by the NIH 
Director, have updated priorities to reflect the changing scientific 
landscape and to address roadblocks to progress. Since March 2000, the 
Parkinson's effort has included more than 20 solicitations, more than a 
dozen workshops, establishment of a network of Morris K. Udall Centers, 
major clinical trials, and funding of the Deep Brain Stimulation 
Consortium. The NINDS Office of Minority and Health Research is also 
leading a major effort to implement the NINDS Five Year Strategic Plan 
on Minority Health Disparities, and developing goals specific to 
neuroAIDS, stroke and epilepsy. Implementation of planning efforts in 
brain tumor, stroke, and epilepsy are also under way. Other initiatives 
are focusing on diseases such as autism, muscular dystrophy, and spinal 
muscular atrophy, and NINDS continues to support a variety of disease-
focused scientific workshops to assess current understanding, stimulate 
research interest, and foster collaborations.
    Re-engineering the research enterprise.--NINDS has designed and 
conducted pioneering clinical trials to test the safety and 
effectiveness of interventions to prevent and treat neurological 
disorders. In recent years, the Institute augmented clinical trials 
activities with new grant mechanisms for planning trials and for pilot 
trials; developed procedures and increased professional staff to 
optimize trial design and monitoring; and created a subcommittee of the 
NANDS Council to provide broad advice on priorities for clinical 
research, including trials. This year, NINDS is beginning to supplement 
ongoing clinical trials to capture genetic samples for a newly 
established DNA and cell line repository. For the future, the Institute 
is exploring options to create a network of physician-investigators to 
carry out clinical trials. Such a program might speed trials, minimize 
costs, enhance accessibility for patients, facilitate the recruitment 
of a diverse spectrum of participants, improve feasibility of trials 
for rare diseases, and accelerate the transfer of results to practice 
in community settings.
    A highlight of the clinical trials program is an innovative trial 
of neuroprotective drugs for Parkinson's disease, that is, drugs which 
slow disease progression rather than just temporarily improving 
symptoms. The Institute reached out widely to academia and industry, 
here and abroad, for suggestions of possible drugs, and developed a 
rigorous evaluation process, which has selected the most promising drug 
candidates. A network of more than 40 clinical sites, with central 
statistical and data coordination, has been established to carry out 
the trial. NINDS is working closely with voluntary groups to recruit 
patients. The first pilot studies may begin this spring.
    Translational research is another major focus of cross-cutting 
efforts. NINDS has a long history of translational research, which 
moves fundamental discoveries about the brain and disease toward 
therapies and clinical trials. Advances in neuroscience are yielding 
increasing opportunities for translation, and NINDS responded in July 
2002 by launching a comprehensive program to foster translational 
research. Essential to this program are peer review criteria tailored 
to the needs of translational research, milestone driven funding, and 
training a cadre of investigators to carry out translational research. 
The goal is to provide an environment where coalitions of basic 
scientists and clinicians can design and carry out preclinical studies 
required to bring therapeutic candidates to the point where clinical 
studies can begin.
    New pathways to discovery.--Several NINDS programs are exploring 
new avenues for discovery. NINDS has established a goal of identifying 
small molecules that are active in the nervous system and show promise 
as therapeutic candidates, diagnostic agents, or research tools. In 
2002, the Institute established a consortium to test more than 1000 
drugs, most previously approved by the U.S. Food and Drug 
Administration (FDA) for other conditions, against 29 rapid laboratory 
assays (tests) related to neurodegenerative diseases. The best 
candidate chemicals are moving to further testing in animal models 
through an NINDS supplement program. NINDS has also awarded a contract 
for a high throughput screening (HTS) center, and is soliciting 
proposals for the development of assays for HTS. HTS rapidly tests 
thousands of chemicals to find lead compounds for drug development. In 
another effort, a contract-based approach to therapeutics development 
for spinal muscular atrophy will test a new model that might apply to 
other diseases. The NIH Molecular Library Roadmap Project will speed 
the discovery process for drugs and chemical research tools by 
providing access to information databases and to potentially useful 
compounds. The Institute has also established a facility to provide 
researchers access to microarray technology, which allows simultaneous 
monitoring of the activity of thousands of genes in health and disease. 
Stem cell research remains a high priority for the Institute. NINDS has 
provided supplements for grantees to pursue stem cell research, and 
joined with other components of NIH in stimulating this research and 
targeting aspects critical for the nervous system. An NINDS intramural 
investigator will lead a new NIH facility to characterize the available 
approved lines of human embryonic stem cells.
    Research teams of the future.--Increasingly, progress against 
neurological disorders requires cooperation among multi-disciplinary 
teams of investigators. NINDS is enhancing the opportunities for team 
approaches with general programs to support common resources and 
specific initiatives tailored to areas such as Parkinson's disease, 
stroke, autism, muscular dystrophy, spinal cord injury and health 
disparities. The Institute is also addressing critical training needs 
in areas such as translational and clinical research. In the NIH 
Intramural program, the John Edward Porter Neuroscience Center will 
bring together scientists from ten NIH components that focus on the 
brain.

                               CONCLUSION

    Neurological disorders have always challenged the best efforts of 
medicine. The intricacy of the brain is awesome, its workings are 
elusive, and an extraordinary variety of disorders affect the nervous 
system. Furthermore, the brain and spinal cord are difficult to access, 
sensitive to intervention, and reluctant to regenerate following 
damage. However, building on advances in basic science, progress is 
improving peoples' lives, and prospects for the future are even more 
encouraging. We are working to engage the best minds in the nation and 
provide them with the resources they need to devise ways to prevent, 
treat, or, ultimately, cure neurological disorders. Thank you.
                                 ______
                                 
             Prepared Statement of Dr. Roderic I. Pettigrew

    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's budget request for the National Institute of Biomedical 
Imaging and Bioengineering (NIBIB). The fiscal year 2004 budget 
includes $282,109,000, an increase of $3,838,000 over the fiscal year 
2003 enacted level of $278,271,000 comparable for transfers proposed in 
the President's request.
    The NIBIB's mission is to lead the development and application of 
breakthrough technologies in the physical and engineering sciences to 
facilitate an improved fundamental understanding of complex biological 
processes. This research agenda will dramatically advance the Nation's 
health care by improving the detection, management, understanding and, 
ultimately, the prevention of disease. Health care and technology have 
long been linked in the United States. Today, cardiac pacemakers, 
mammograms, sustained release medications, and artificial hips are but 
a few examples of how biomedical imaging and bioengineering are 
transforming health care.
    In September 2002, I began my tenure as the first Director of the 
NIBIB. I assumed my role during a time when the landscape of conducting 
biomedical research is changing. It is this altered landscape, wherein 
the most efficacious medical advances depend on multidisciplinary 
findings obtained from researchers working together at the interface 
between the biological and quantitative sciences, that led to the 
creation of the NIBIB. This new environment, combined with recent 
budgetary increases, visionary predecessors, the rapid pace in 
technology development, and high-quality investigator-initiated 
research, has allowed the NIBIB-just in its second year of operation-to 
establish a strong research foundation on which to capitalize. To 
illustrate these points, my testimony will highlight recently achieved 
milestones, outline research plans and directions, and describe areas 
of progress and opportunity.

                         MILESTONES TO SUCCESS

    The NIBIB, the newest Institute at the National Institutes of 
Health (NIH), was established by law December 29, 2000, and received 
its first appropriation and grant funding authority in fiscal year 
2002, just 15 months ago. Since its establishment, NIBIB staff have 
achieved significant milestones. In fiscal year 2002 the NIBIB funded 
approximately 300 research applications, participated in approximately 
170 extramural symposia, planned 16 NIH-based symposia and workshops, 
served as lead on 5 trans-NIH initiatives, and collaborated on 4 trans-
NIH programs.
    Additional milestones have been achieved in fiscal year 2003. In 
January, the NIBIB held the first meeting of its National Advisory 
Council. The Institute has also built a solid research infrastructure 
through the release of numerous basic and applied research 
solicitations in promising areas of scientific investigation, including 
tissue engineering, advanced biomaterials, image-guided interventions, 
low-cost medical imaging modalities, biosensor technology, and cellular 
and molecular imaging.
    The NIBIB has successfully fostered extensive linkages and 
collaborations with other NIH Institutes and Centers, Federal agencies, 
academic institutions, private industry, and scientific societies. As 
examples, the NIBIB administers and participates in the Bioengineering 
Consortium (BECON), an NIH-wide consortium dedicated to promoting and 
coordinating bioengineering research across the NIH. The NIBIB and the 
National Science Foundation are collaborating with the National Academy 
of Engineering-a private, independent, nonprofit institution-on a 
project entitled ``Engineering and the Health Care System.'' This study 
focuses on ways to harness advances in engineering applications to 
improve health care delivery. The NIBIB will collaborate with the 
National Institute of Diabetes and Digestive and Kidney Diseases to 
develop a program for monitoring pancreatic insulin cell failure in 
diabetes. This would constitute a significant advance in diabetes 
research.

                      THE NIBIB RESEARCH PORTFOLIO

    In December 2002, the NIBIB officially launched its strategic 
planning process with an interactive workshop entitled ``Future 
Research Directions.'' This workshop helped identify high-priority 
research focus areas and associated high-impact projects and 
technologies that could contribute significantly to biomedical research 
and global healthcare needs. Areas identified as highly relevant to 
NIBIB's mission include image-guided interventions, cellular and 
molecular imaging, computational biology, biosensor technologies, 
optical imaging technologies, and regenerative medicine. The Institute 
is now poised to realize the promise within these areas of opportunity.

                         ADVANCED TECHNOLOGIES

    Biomedical imaging and bioengineering are interdisciplinary fields 
that require collaborations not only among imagers and engineers, but 
also with biologists, chemists, mathematicians, computer scientists, 
and clinicians of all specialties. Today, the imaging and engineering 
sciences are essential for improved understanding of biological 
systems, detecting and controlling disease, and enhancing human health. 
Recent advances in these fields have enabled the diagnosis and 
treatment of various diseases using increasingly less invasive 
procedures. Benefits associated with minimally invasive imaging 
applications include quicker and more accurate diagnoses leading to 
improved patient outcomes at reduced costs. Minimally invasive image-
guided interventions now serve as powerful tools in the operating room 
and can be applied to surgical procedures in urology, oncology, 
neurosurgery, ophthalmology, cardiology, and orthopedics. However, 
these techniques are in relatively early stages of development. A goal 
of the NIBIB is to further establish and validate minimally invasive 
image-guided therapies as standards for patient care and to support 
additional research in therapeutic areas where minimally invasive 
technologies do not yet exist. The NIBIB also has initiatives underway 
to encourage investigator-initiated research for tracking anatomical 
targets and instruments and for developing steerable devices, including 
catheters, endoscopes, and needles. A goal is to develop theses 
techniques so that they may be used to routinely identify disease at 
its earliest stages, even before symptoms arise. At that point, 
treatments can be instituted to cure the disease or preempt any serious 
consequences.
    The combination of image-guided therapies with genomics and 
proteomics, has given researchers the capacity to develop new molecular 
probes and targets for disease detection, and to immediately direct 
treatment to the diseased site. By studying how a person's genetic 
blueprint is expressed through proteins, and how these proteins differ 
in healthy and diseased cells, researchers will be able to develop 
therapies tailor-made for an individual. As a first step towards 
``personalized medicine,'' NIBIB researchers are investigating tiny 
``barcoded'' metal particles as a method for analyzing proteomes-the 
complete set of an organism's proteins. Advances in miniaturized 
devices not only have the potential to identify and characterize new 
proteins, but to advance the rapid screening of multiple compounds in 
the drug development process.
    Molecular imaging provides a way to monitor cellular activities in 
normal and diseased states. The development of novel imaging 
technologies, combined with new or enhanced probes that bind to defined 
cellular targets, will allow this technique to be more broadly applied 
to biomolecules that are known indicators of a diseased state, such as 
an enzyme that may be overexpressed in a specific tumor. For example, 
NIBIB researchers have developed artificial fluorescent agents, called 
quantum dots, that glow and act as cell markers when bound to certain 
cancer cells. Further testing of these agents in animal models of 
cancer will determine their utility as effective imaging agents for the 
early detection of cancer in humans.

                BIOINFORMATICS AND COMPUTATIONAL BIOLOGY

    Advances in bioinformatics and computational biology have been 
identified as one of the areas of greatest need, and one of the areas 
having the greatest potential for positive impact on the universe of 
medical science and health care. In recognition of the critical role 
these disciplines play in biomedical imaging and bioengineering, NIBIB 
supports fundamental research in computing technology, the targeted 
development and application of new biocomputing tools, and technologies 
that provide structural and functional data at the cellular level. 
Areas of NIBIB interest include the development of high performance 
computing and visualization methods applicable to the modeling of 
biological systems, the utilization of medical imaging data in 
computational modeling of biological systems and human physiology, the 
development of algorithms and software for the manipulation and 
analysis of imaging data, and computer modeling of tissue mechanics. 
Our goal is to advance an understanding of the integrated function of 
biological systems through the development and application of 
computational models, and to apply these models to the design of novel 
treatments and therapeutics. In support of this goal, a NIBIB 
researcher is developing a brain-computer interface (BCI) system that 
acquires and analyzes brain signals to create a communications channel 
directly between a person's brain and a computer. BCI technologies can 
allow people who are completely paralyzed to express wishes to 
caregivers and to use computer programs.

                  NANOTECHNOLOGY: SENSORS FOR MEDICINE

    The term nanotechnology is used to describe many types of research 
at the atomic, molecular, or macromolecular level-research where the 
characteristic dimensions are less than one-thousandth of the diameter 
of a human hair. Biosensors are nanoscale devices that detect, monitor, 
and transmit information about a physiological change, or about the 
presence of various chemicals, gases, or biological materials (bacteria 
and viruses). Laboratory diagnostics used in hematology, clinical 
chemistry, pathology, and microbiology already employ sensor 
technologies to perform simultaneous measurements for hundreds, maybe 
thousands, of substances in urine, blood, saliva, sweat, and 
interstitial fluids. The NIBIB has an active research program in sensor 
technologies and is expanding this area of research.
     Knowledge gained through NIBIB-supported advances in 
nanotechnology, particularly in the areas of biosensors and molecular 
imaging, will be further leveraged for the development of sensors that 
can be applied to other critical research areas. For example, NIBIB 
researchers are adapting highly sensitive and selective biosensor 
arrays to provide a fingerprint for the identification of harmful 
bacteria and environmental health hazards. Future NIBIB efforts being 
planned in nanotechnology and sensors focus on the development of low-
cost, miniaturized, integrated sampling detector systems for field use, 
including the development of systems that provide ``detect-to-warn'' 
capabilities, and that enable the rapid and accurate verification of 
exposure to harmful environmental agents.

             MULTIDISCIPLINARY RESEARCH TEAMS OF THE FUTURE

    The era of the solo independent investigator is passing. Our 
research culture must be redirected to the formation of teams that span 
academic departments and scientific disciplines. Their formation is 
critical to the development and validation of new technologies to aid 
in disease detection, treatment, and prevention. Therefore, a major 
goal of the NIBIB is to catalyze team science through initiatives that 
encourage multi-organizational and multidisciplinary teams. Programs 
differ from traditional NIH opportunities as they require collaborative 
efforts between quantitative and biomedical researchers. These will 
support institutional needs, infrastructure development, and the costs 
associated with making team science viable and attractive to academic 
institutions. Within a given area, specific clinical problems-such as 
our current effort to image pancreatic beta cell function in diabetes-
will be identified to serve as a catalyst to drive the formation of the 
research team. The value in catalyzing team science lies not only in 
strengthening research capacity, but in fostering the formation of 
research teams among disciplines where they previously have not 
naturally formed.
    In conclusion, the NIBIB is dedicated to promoting the development 
of emerging technologies and establishing opportunities that will 
encourage the necessary interdisciplinary collaborations to advance 
biomedical and global health care priorities. I would be pleased to 
respond to any questions that the Committee may have.
                                 ______
                                 
                 Prepared Statement of Dr. John Ruffin

    Mr. Chairman and members of the Committee: I am pleased to present 
the President's budget request for the National Center on Minority 
Health and Health Disparities (NCMHD) for fiscal year 2004, a sum of 
$192,724,000, which represents an increase of $7,010,000 over the 
comparable fiscal year 2003 appropriation.
    Despite improvements in the overall health of the general 
population, over the past decade, African Americans, Hispanics, 
American Indians, Alaska Natives, and Asians and Pacific Islanders the 
fastest growing communities in this country and the urban and rural 
poor, continue to suffer an unequal burden of death, disability, and 
disease.
    With the goal of addressing health disparities through science, the 
Congress enacted Public Law 106-525, the Minority Health and Health 
Disparities Research and Education Act of 2000, to establish the NCMHD. 
The mission of the Center is to promote minority health and to lead, 
coordinate, support, and assess the National Institutes of Health's 
(NIH) effort to ultimately eliminate health disparities. I am grateful 
to the Congress for its wisdom in creating the NCMHD so that America 
can be more responsive to its increasingly diverse and complex health 
and human services needs. And, I thank you for your ongoing support of 
the Center. I also want to thank Dr. Elias Zerhouni, Director of the 
NIH, and the Directors of the NIH Institutes and Centers (ICs) and 
Offices for all of their cooperation and continued commitment to making 
the elimination of health disparities a top priority for the NIH.
    In January 2003, the NCMHD celebrated its second anniversary. The 
staff at the NCMHD has been diligent, working hard to make the 
priorities envisioned for the Center by the Congress a reality. Today, 
I am happy to report to you the highlights of our accomplishments.

                  TRANS-NIH STRATEGIC PLAN AND BUDGET

    The NCMHD has worked together with the Director of the NIH and the 
Directors of the other ICs at the NIH, to develop the first 
comprehensive NIH Strategic Research Plan and Budget to Reduce and 
Ultimately Eliminate Health Disparities. This Plan, which was developed 
with substantial stakeholder input from the health disparities 
populations, has three main goals--research, research infrastructure, 
and community outreach through information dissemination and public 
health education. This is an evolving document, that will be updated 
each year, and it includes current NIH activities and future plans to: 
address the health disparities; build a culturally competent cadre of 
biomedical and behavioral investigators; and increase the number of 
minority clinical and basic medical scientists who are essential to the 
success of our efforts. The Plan will be posted for public comment on 
the NCMHD website at www.ncmhd.nih.gov.
   nih fiscal year 2001 annual report on health disparities research
    The NCMHD also collaborated with the other ICs to develop the NIH 
fiscal year 2001 Annual Report on Health Disparities Research, which 
highlights the NIH's activities, and describes the progress emanating 
from the NIH's research strategies, structures, processes, and programs 
to ultimately reduce and ultimately eliminate health disparities.

                             NCMHD PROGRAMS

    As authorized by the Congress, the NCMHD has established its three 
core programs, which have been successfully launched with substantial 
assistance from the other NIH ICs. The Centers of Excellence in 
Partnership for Community Outreach, Research on Health Disparities, and 
Training (Project EXPORT) Program supports the conduct of research, 
research training, and community outreach activities in the field of 
health disparities at Centers of Excellence. The Research Endowment 
Program is designed to build minority health and other health 
disparities research capacity at Health Resources and Services 
Administration (HRSA) Section 736 Centers of Excellence. The NCMHD has 
established two distinct extramural Loan Repayment Programs to increase 
the participation of health professionals in health disparities 
research and to increase the participation of individuals from 
disadvantaged backgrounds in clinical research. The Center also 
administers the Research Infrastructure in Minority Institutions (RIMI) 
Program to provide support for institutions that enroll a number of 
students from minority health disparity populations to develop and 
enhance their capacity and competitiveness to conduct biomedical or 
behavioral research. By expanding the infrastructure of institutions 
committed to health disparities research and supporting the education 
and training of racial and ethnic minorities, as well as the medically 
underserved, these programs will provide sustained effort aimed at 
eradicating health disparities.

                        NCMHD CO-FUNDED RESEARCH

    The NCMHD also supports research through collaborative agreements 
with other NIH ICs and HHS agencies, for example the: Racial and Ethnic 
Approaches to Community Health Program (REACH 2010) at the Centers for 
Disease Prevention and Control (CDC); Excellence Centers to Eliminate 
Ethnic/Racial Disparities Program (EXCEED) at the Agency for Healthcare 
Research and Quality; Jackson Heart Study at the National Heart, Lung 
and Blood Institute (NHLBI); Appalachia Cancer Network and Native 
Hawaiian Cancer Awareness Research & Training Network at the National 
Cancer Institute (NCI); National Latino and Asian American Study at the 
National Institute of Mental Health, and Tribal Epidemiology Centers 
Program at the Indian Health Service.
    Through these and many other co-funded projects the NCMHD works to: 
pilot new health disparities programs; improve recruitment and 
retention of racial and ethnic minorities in clinical trials; and 
provide competitive supplements to expand the focus of existing 
research programs.

                    NIH HEALTH DISPARITIES RESEARCH

    Along with the NCMHD, all of the ICs at the NIH actively support 
health disparities research within their categorical missions. Let me 
provide a few illustrative examples:
    The NHLBI supports the Jackson Heart Study, co-sponsored with the 
NCMHD, to address the cardiovascular health of African Americans; the 
Strong Heart Study, directed at cardiovascular disease risk factors and 
development in American Indians; the Multi-Ethnic Study of 
Atherosclerosis, which is examining the development and progression of 
subclinical disease in a multi-ethnic and predominately minority 
population; the Family Blood Pressure Program, which is identifying 
major genes associated with high blood pressure in a predominately 
African American population; studies aimed at identifying genetic and 
other biological factors that increase susceptibility to hypertension-
related injury and damage; and programs examining genetic factors 
associated with asthma in minority populations.
    To lead the NCI's efforts to examine the causes of cancer health 
disparities, develop effective and sustainable interventions to 
eliminate them, and actively facilitate their implementation across the 
cancer continuum, the NCI established the Center to Reduce Cancer 
Health Disparities. Among the NCI's other major initiatives are the 
expansion of public, private, academic, and community-based partners to 
increase enrollment of minorities in clinical treatment and prevention 
trials and to investigate the socioeconomic, cultural, health system 
related, and other causes of disparities in cervical cancer mortality. 
The NCI also has established interdisciplinary research Centers for 
Population Health and Health Disparities to better understand the 
interaction of determinants of cancer and the behavioral and biologic 
factors that contribute to them, and the Institute has expanded and 
improved the efficiency and utility of the Surveillance Epidemiology 
End Results Program on several fronts.
    The National Institute of Allergy and Infectious Diseases (NIAID) 
continues to focus on those research areas that have a major impact on 
health disparities by supporting: the Innovation Grant Program, which 
fosters exploratory investigator-initiated HIV vaccine research at the 
early stages of concept development; the Legacy Donor Registry Project, 
which supports efforts to increase organ donation in minority 
populations; Genetic studies in African-American kidney transplant 
recipients regarding tissue (organ) rejection; Autoimmunity Centers of 
Excellence, which evaluate immunotherapies for Systemic Lupus 
Erythematosus (SLE) and Scleroderma; the Inner City Asthma Consortium, 
which evaluates the safety and efficacy of promising immune-based 
therapies to reduce asthma severity and prevent disease onset in 
minority children in inner city dwellings; and Hepatitis C Cooperative 
Research Centers, which study factors that contribute to resistance to 
treatment in African Americans and disease outcome in Alaska Natives 
and Hispanics.
    The National Institute of Diabetes and Digestive and Kidney 
Diseases (NIDDK) has established its Office of Minority Health Research 
Coordination to help implement its strategic plan for health 
disparities. The Institute places high priority on supporting studies 
of many diseases, including type 2 diabetes, hepatitis C, and kidney 
disease, which disproportionately impact the health of minority 
populations. Recently the Diabetes Prevention Program showed that 
modest improvements in diet and exercise could dramatically decrease 
the incidence of type 2 diabetes in those at risk, the benefits of 
which extend to all racial and ethnic groups. American Indian and 
Alaska Native communities have the highest rates of diabetes in the 
world. Using the network of Tribal Colleges and Universities, the NIDDK 
Diabetes-Based Science Education in Tribal Schools Program is 
developing supplemental curricula for Tribal elementary, middle and 
high schools to instruct students about lifestyle changes that can 
dramatically reduce the risk of diabetes. The NIDDK also has initiated 
the National Kidney Disease Education Program, initially targeting 
cities with African-American populations showing high incidence of 
chronic kidney disease.
    Since the National Institute of Child Health and Human Development 
(NICHD) launched its national ``Back to Sleep'' campaign in 1994, the 
Sudden Infant Death Syndrome (SIDS) rate has fallen by more than 50 
percent. Even though the death rates from SIDS have declined at about 
the same rate for White and African-American infants, a 
disproportionate number of African-American infants are still lost to 
SIDS. To begin closing this gap, the NICHD enlisted the help of the 
Alpha Kappa Alpha sorority, the National Coalition of 100 Black Women, 
and the Women in the NAACP to conduct a series of ``summit'' meetings 
in three U.S. cities with high rates of African-American SIDS deaths. 
These summits will help develop strategies and create an infrastructure 
for establishing community-based programs to further reduce SIDS among 
African-American infants. The NICHD also is developing outreach 
activities and products that encourage American Indian/Native American 
communities to place babies on their back to sleep.

                               CONCLUSION

    The NCMHD is working together with the other ICs at the NIH to 
ensure that all Americans have an opportunity to lead long, healthy, 
and productive lives. I am grateful to the Congress for giving the 
Center a unique opportunity to bring together the expertise of health 
professionals, researchers, businesses, communities, academia, public 
health agencies, and government to eliminate health disparities. It's 
going to take all of us working together to build a healthy America.
                                 ______
                                 
               Prepared Statement of Dr. Paul A. Sieving

    Mr. Chairman an members of the Committee: I am pleased to present 
the President's budget request for the National Eye Institute (NEI) for 
fiscal year 2004. This budget includes $648 million, an increase of $16 
million over the fiscal year 2003 enacted level of $632 million 
comparable for transfers proposed in the President's request.
    It is my privilege to be here as the Director of the NEI and tell 
you about progress laboratory and clinical scientists are making in 
combating blindness and visual impairment and about the unique 
opportunities that exist in the field of vision research.

                           GLAUCOMA RESEARCH

    Glaucoma leads to blindness from damage to the optic nerve of the 
eye. Glaucoma is often, but not always, associated with increased 
pressure within the eye caused by inadequate drainage of aqueous humor, 
the fluid within the eye that nourishes the cornea and lens. Results 
from two important clinical trials were reported during this past year. 
Investigators conducting the Ocular Hypertension Treatment Study found 
that eye drops used to treat elevated pressure inside the eye can be 
effective in delaying the onset of glaucoma. The study identified 
several significant risk factors that were associated with the 
development of glaucoma in study participants. These included personal 
risk factors, such as older age and African descent, as well as ocular 
risk factors, such as higher eye pressure and certain characteristics 
of the optic nerve and cornea. These results mean that treating people 
at higher risk for developing glaucoma may delay or possibly prevent 
the disease.
    In a separate study researchers conducting the Early Manifest 
Glaucoma Trial, which was designed to compare the effect of immediate 
therapy to reduce pressure inside the eye with late or no treatment on 
the progression of newly detected open-angle glaucoma, found that 
progression was less frequent in the treated group (45 percent) than in 
the control group (62 percent), and occurred significantly later in 
treated patients. This finding demonstrates definitively that treatment 
to lower pressure inside the eye can slow glaucoma damage and 
subsequent vision loss.
    Continuing the progress in the genetics of glaucoma reported last 
year by the finding of a new gene mutation that caused a form of adult-
onset glaucoma, scientists recently reported identification of a human 
gene that is linked to a disease known as ``low-tension'' glaucoma. 
This form of glaucoma has the characteristic pattern of optic nerve 
degeneration but the elevation in pressure within the eye normally 
associated with this pattern of damage is not evident on clinical 
examination. The gene that was identified produces a protein that is 
expressed in a number of tissues including the brain and retina and is 
believed to have a significant neurological function. The 
identification of genes associated with glaucoma provides a tool to 
study the biochemical pathways leading to optic nerve degeneration, as 
well as giving insight into designing neuroprotective strategies. 
Additionally, NEI sponsored a meeting on ganglion cell and optic nerve 
degeneration that brought together laboratory and clinical scientists 
studying glaucoma and those studying other neurodegenerative diseases 
to explore common mechanisms of nerve cell damage and potential methods 
of protection.

                        RETINAL DISEASE RESEARCH

    The retina is the transparent, light-sensitive tissue that lines 
the back of the eye. Diseases and disorders of the retina and its blood 
vessels account for much of the blindness and visual disability in this 
country. An important barrier to therapeutic intervention in human 
retinal disease is the identification of the gene or genes that cause 
vision loss. Visual loss and the degenerative and other changes in the 
retina are largely linked to rod and cone photoreceptors, the light-
sensing nerve cells in the retina.
    Scientists have recently undertaken a comprehensive genetic 
analysis of rod photoreceptors, the most abundant sensory neuron in the 
retina, in order to identify all the possible genes expressed in these 
cells. Rod cells play an essential role in the visual pathway and may 
be especially vulnerable to any genetic defect involving the retina or 
other visual centers. For many identified retinal disease genes, a 
photoreceptor gene is mutated and its product is altered due to the 
mutation. Work is progressing on completing a database that will 
simplify the identification of candidate retinal disease genes, and 
many new genes in rod photoreceptors have already been identified.
    Scientists have identified a mutation in a gene on the X chromosome 
that normally is associated with a form of retinitis pigmentosa (RP) 
that causes a progressive loss of rod photoreceptors in the peripheral 
retina and results in blindness in adulthood. This mutation was also 
reported to cause a unique type of degeneration in the macula, in a 
particular family. Further study may help us understand how this 
mutation specifically targets the macula and causes this unique loss of 
cones. This may lead to an understanding of the mechanisms of damage in 
other forms of macular degeneration and perhaps to the development of 
the means to prevent this type of damage to the macula.
    The NEI is also funding studies on ocular albinism, a set of 
hypomelanotic diseases and conditions that are characterized by 
deficient cellular production of the pigment melanin. Deficiency in 
this pigment causes a cosmetic loss of ocular and skin pigmentation, 
but more importantly, it limits the development of vision in infants 
and children by fundamentally altering the connections between the eye 
and the brain. Recently the OA1 gene, which is associated with most 
cases of the disease, was identified. The form of the disease 
associated with OA1 is an X-linked or hereditary blinding eye disease 
that primarily affects boys at an early age. Although the cause or 
causes are unknown, misrouting of the neurons that go from the retina 
to the brain is involved. Understanding the causes of the abnormal 
neural cell axon guidance in ocular albinism may help us understand the 
fundamental neurobiology that underlies this disease and represents an 
important research initiative for the NEI.

                        CORNEAL DISEASE RESEARCH

    NEI-supported scientists have also made progress against blinding 
diseases of the cornea. The cornea is the transparent tissue at the 
front of the eye that plays an important role in refracting or bending 
light to focus visual images sharply on the retina. Because the cornea 
is the most exposed surface of the eye, it is especially vulnerable to 
damage from injury or infection. One such infection is ocular 
onchocerciasis, commonly known as river blindness. Although river 
blindness is rare in developed countries, it is the second leading 
infectious cause of blindness in the world. This infection occurs when 
a nematode worm infects the cornea. Researchers have found that 
development and growth of the worm depends on a bacterium that lives 
within it. They found that the blindness associated with the infection 
was due to the reaction of the patient's immune system to the bacterium 
and not to the worm. The scientists discovered that an antibiotic that 
killed the bacterium also caused the death of the worm but without 
causing blindness. Further development of this treatment could 
revolutionize treatment of river blindness throughout the developing 
world.

                           CATARACT RESEARCH

    Although cataract treatment in this country is one of the most 
successful of all surgical procedures, development of non-surgical 
approaches to preventing or treating cataracts remains an important 
area of research, because of the potential that it holds for reducing 
costs to the Medicare system and improving the quality of life of our 
senior citizens. A cataract is an opacity of the eye's normally clear 
lens that interferes with vision. Age-related cataract formation is 
believed to result from the complex effects of aging on normal 
physiological processes. Because the end-result, cataract formation, is 
in most cases far removed in time from the initial insult, exacting a 
cause and effect relationship has been difficult. Lens transparency 
results from the very high concentration of soluble proteins, the 
crystallins, within a specialized lens fiber cell. During aging and 
cataract formation, soluble lens crystallins tend to combine or 
aggregate into large complexes that cause light to scatter. NEI-
sponsored researchers have found that alpha-crystallin, which normally 
protects the lens by binding to other proteins, may itself become the 
vehicle for the aggregate formation that accelerates cataract 
formation. Additional research in this area may provide the means for 
clinicians to intervene prior to the formation of a clinically evident 
cataract.
    Other scientists are attempting to determine the genes that control 
one of the earliest events in the development of the eye, the 
development of the lens. Scientists studying lens development have 
identified a master gene that controls the expression of a number of 
other critical genes. Two of these critical genes that have recently 
been discovered. Without these two genes, the development of the lens 
is stopped and crystallin-synthesizing cells fail to form. These 
findings add to our understanding of the overall control of lens and 
eye development and may ultimately enhance our knowledge of the 
molecular basis of congenital diseases of the eye, thereby opening the 
possibility of future interventions.

         STRABISMUS, AMBLYOPIA, AND VISUAL PROCESSING RESEARCH

    The most frequent causes of vision loss in our children are 
strabismus, a misalignment of the eyes, and the development of 
amblyopia, or lazy eye. Strabismus results in diseases in which visual 
processing is abnormal. Amblyopia can result from this misalignment or 
from unequal refraction between the eyes. NEI-supported scientists have 
found that eye drops used to treat amblyopia work as well as the 
standard treatment of patching the eye. This research finding may lead 
to better compliance with treatment and improved quality of life in 
children with this eye disorder. Patients continue to be followed in 
this study to better assess the long term effects these treatments have 
on visual acuity.
    Recent work by NEI-sponsored researchers has helped our 
understanding of nerve cell regeneration. Following injury or disease, 
neurons in the central nervous system (CNS) have a limited regenerative 
capacity, unlike nerve cells in the peripheral nervous system.
    Nerve cells typically have two types of extensions that arise from 
their cell bodies. Axons are normally quite long and extend over 
considerable distances. Dendrites are much shorter and extend short 
distances from the cell body. The inability of CNS neurons to 
regenerate is due to the failure of their axons to re-grow. These 
scientists found that axon growth may be due to a factor within the 
nerve cell itself rather than in the surrounding environment and may be 
regulated by signals from other nerve cells. Further research may allow 
discovery of the signals that switch neurons back to the axonal growth 
mode to repair damage to nerve tissue from injury or disease.

                           HEALTH DISPARITIES

    Scientists recently reported the prevalence of glaucoma in a 
population-based study conducted among 4,774 Mexican American adults 
residing in two communities in Arizona. Glaucoma prevalence rates have 
been reported previously for white and African American adults, but no 
similar studies have been conducted among the U.S. Hispanic population. 
The prevalence of open-angle glaucoma in this Mexican American 
population was intermediate between the high rates reported for African 
Americans and the lower rates reported for whites. Of those diagnosed 
with glaucoma, only 38 percent were aware they had the disease. The 
prevalence of glaucoma increased rapidly with age and was the leading 
cause of bilateral blindness in this population. This information will 
allow health educators to create additional glaucoma awareness 
campaigns to increase awareness of the importance of glaucoma treatment 
in the Mexican American population, thereby allowing eye care providers 
to identify and treat those at greatest risk so that blindness can be 
prevented.

                          PROGRAM INITIATIVES

    Diabetic retinopathy is a potentially blinding complication of 
diabetes characterized by the uncontrolled growth of fragile new blood 
vessels in the retina that may leak fluid and blood threatening vision. 
It is the leading cause of new cases of blindness in working age adults 
in the United States. Macular edema secondary to diabetic retinopathy 
is also a major cause of visual loss in patients with diabetes. The NEI 
is developing a clinical research network of core centers and 
participating clinics that will help satisfy the need to evaluate 
promising new approaches to treat diabetes induced retinal disorders 
and to investigate other approaches as they become available. This 
network approach will provide a framework for rapid initiation of 
important studies, efficient use of pooled clinical expertise in idea 
generation and protocol development, and efficient use of central 
resources for data management, quality control, and endpoint 
evaluation.
    The NEI is also planing to increase the pace of research in age-
related macular degeneration (AMD) prevention and treatment by 
supporting a wide array of laboratory and clinical studies. AMD is the 
leading cause of severe vision loss in older persons in the United 
States, and it will have an increasingly important social and economic 
impact as the population ages. These studies may range from pilot work 
to the establishment and implementation of clinical research networks. 
It is anticipated that a network approach to AMD clinical research will 
hasten development of the more successful therapies for the treatment 
or prevention of AMD.
    The NEI is also undertaking a major effort to reinvigorate the 
intramural research program and enhance resources to neurodegenerative 
and genetic forms of vision loss. Ocular genetics research has 
demonstrated that many common eye diseases have complex genetic and 
environmental etiologies that must be understood before innovative 
biological treatments can be designed. NEI is working on a new 
laboratory program devoted to complex human eye disease to hasten 
progress in this area.
    Mr. Chairman that concludes my prepared statement. I would be 
pleased to respond to any questions you or other members of the 
committee may have.
                                 ______
                                 
               Prepared Statement of Dr. Allen M. Spiegel

    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's budget request for the National Institute of Diabetes 
and Digestive and Kidney Diseases (NIDDK) for fiscal year 2004, a sum 
of $1,670,007,000, which reflects an increase of $66,846,000 over the 
comparable fiscal year 2003 appropriation. The fiscal year 2004 budget 
comprises $1,820 million which includes $150 million ($100 million in 
fiscal year 2003) for the Special Appropriation for Research on Type 1 
Diabetes through Public Law 107-360. The NIDDK transfers some of these 
to other institutes of the NIH and to the CDC. Adjusted for these 
mandatory funds, this is an increase of $48 million over the fiscal 
year 2003 enacted level of $1,622 million comparable for transfers 
proposed in the President's request. The NIH budget request includes 
the performance information required by the Government Performance and 
Results Act (GPRA) of 1993. Prominent in the performance data is NIH's 
second annual performance report, which compared our fiscal year 2002 
results to the goals in our fiscal year 2002 performance plan.

                            OBESITY RESEARCH

     I appreciate the opportunity to testify on behalf of the NIDDK, 
which supports research on a wide range of chronic, debilitating 
diseases. Many of these diseases, including type 2 diabetes, 
nonalcoholic fatty liver disease, gallstones, end-stage kidney disease, 
and urinary incontinence, are caused, directly or indirectly, by 
obesity. Data from the Centers for Disease Control and Prevention 
documents that obesity is growing at an alarming rate in both adults 
and children, and that it disproportionately affects minorities. Recent 
results from the Framingham Heart Study indicate that obesity cuts six 
to seven years off of life, comparable to the effects of smoking. The 
2001 Surgeon General's Call to Action to Prevent and Decrease 
Overweight and Obesity reports that each year, it costs this country an 
estimated $117 billion in health care related expenditures.
    We must approach obesity, not as a cosmetic or moral problem, but 
rather as a health problem. To address this problem, research is vital, 
and the NIDDK and the National Institutes of Health are formulating a 
bold and coordinated research plan. Obesity and its associated diseases 
result from complex interactions of biologic and environmental factors. 
The environmental factors include social, demographic, and economic 
changes that encourage people to eat more food than necessary to meet 
their energy requirements, and discourage physical activity that would 
increase their energy expenditure. These environmental factors 
disproportionately affect individuals who are biologically more 
susceptible to becoming obese and to develop obesity-associated 
diseases.
    Tremendous progress has been made recently in understanding the 
biologic basis of obesity, and I will cite just a few examples. We now 
understand better how appetite is controlled through newly discovered 
hormones such as ghrelin and PYY. They are produced by the stomach and 
small intestine, and signal the brain, respectively, to increase and 
decrease appetite. Blood levels of ghrelin peak just before meals, and 
peaks are significantly higher in obese individuals who have lost 
weight by dieting, perhaps explaining why sustaining weight loss is so 
difficult. Bariatric, or gastric bypass, surgery is being increasingly 
performed in the United States, and part of its effectiveness in 
achieving sustained weight loss may be explained by the recent finding 
that ghrelin levels are suppressed by some forms of the surgery. 
Blocking the action of ghrelin is thus a potentially attractive target 
for drug development
    Similar advances are being made in understanding how the body 
decides whether and where to metabolize or store fat. Discovery of 
hormones such as leptin and adiponectin secreted by fat have shown that 
fat signals to brain, liver, and muscle to regulate fuel metabolism and 
response to insulin. Such discoveries help explain how obesity leads to 
insulin resistance and type 2 diabetes, and offer new ways of treating 
or preventing obesity-associated disorders. Epidemiologic results and 
clinical studies show that differences in distribution of body fat may 
also be important in determining which individuals develop obesity-
associated disorders.
    Progress in behavioral research provided the basis for the 
lifestyle intervention of our Diabetes Prevention Program (DPP), which 
revealed that participants who lost 5 to 7 percent or more of their 
body weight and who performed at least 150 minutes of physical activity 
per week reduced their risk of developing type 2 diabetes by 58 
percent. We are conducting a follow-up DPP Outcomes Study to assess the 
durability of the DPP interventions in preventing diabetes, and to 
determine whether the interventions reduce cardiovascular disease. Our 
Look AHEAD: Action for Health in Diabetes clinical trial is testing the 
effect of sustained weight loss on prevention of cardiovascular disease 
in obese individuals who already have type 2 diabetes.
    To further sharpen the NIDDK's obesity research efforts, I recently 
announced creation of a new Office of Obesity Research within the NIDDK 
that is bringing together expertise in our Division of Diabetes, 
Endocrinology, and Metabolic Diseases, and our Division of Digestive 
Diseases and Nutrition, both of which have important input to obesity 
research. This new group is framing initiatives across a wide range of 
obesity research areas to address the epidemic of obesity, from the 
fundamental biologic aspects to the behavioral and environmental. 
Examples include a study of the life cycle of the fat cell directed at 
discovery of novel targets for treatment of obesity and associated 
metabolic disorders. In order to address obesity-associated diseases 
such as type 2 diabetes, we will expand our Diabetes Genome Anatomy 
Project to include genetic analysis of all the major organ systems 
affected by diabetes and its complications . We are helping re-engineer 
the clinical research enterprise by creating a new Bariatric Surgery 
Clinical Research Consortium (BSCRSC). The BSCRC will develop a common 
data collection protocol to accelerate clinical research and progress 
in understanding the development of severe obesity and its 
complications, as well as understanding the risks and benefits of 
bariatric surgery as a treatment method.
    In behavioral research, we have begun a clinical trial to develop 
effective strategies to prevent type 2 diabetes in children. This 
initiative focuses on school-based primary prevention programs to 
decrease risk factors for type 2 diabetes and lower the incidence of 
the disorder. We are supporting research to translate the results of 
the highly successful Diabetes Prevention Program, into clinical 
practice for prevention of type 2 diabetes in individuals and 
communities at risk. Of particular interest will be interventions that 
focus on underserved and minority populations disproportionately 
affected by the disease. Given the environmental influences fueling the 
obesity epidemic, we are encouraging research to study promising 
interventions that would target environmental factors contributing to 
inappropriate weight gain in children, adolescents and adults. We are 
asking investigators to partner with community organizations or 
businesses, such as schools, supermarkets, restaurants, churches, 
community groups, and worksites to develop interventions that could 
potentially be translated into larger-scale interventions.
    These are just some of the ways we are encouraging research to 
combat obesity and its co-morbid conditions. We believe NIDDK and NIH 
research is our best hope for stemming the tide of this epidemic. Why? 
Because we stand poised, given new information about the human genome 
and the advent of new research tools to determine the biologic and 
genetic factors that make one person more (or less) susceptible to 
obesity than another. Why is this important? Because it should allow 
targeted obesity prevention and allow the development of new kinds of 
drugs and therapies that should be more successful in preventing weight 
gain and in helping people lose weight and to sustain weight loss. Tied 
to this is improved research-based behavioral approaches to weight loss 
and maintenance. In addition, NIH research ultimately will provide the 
scientific basis for policy decisions on needed changes in 
environmental factors that affect diet, nutrition, and physical 
activity. Obesity is a complex problem requiring a multi-disciplinary 
research approach if we are to reverse this ominous threat to our 
nation's health.

                                DIABETES

    Approximately one million Americans suffer from a type of diabetes 
that is not obesity-related. Rather, type 1 diabetes involves immune 
destruction of the insulin-producing beta cells of the pancreas. We are 
vigorously pursuing cutting-edge research opportunities for prevention 
of type 1 diabetes through our TrialNet, and for treatment and cure of 
type 1 diabetes through support of the field of regenerative medicine. 
One example of the latter is our Beta Cell Biology Consortium, which 
brings together multi-disciplinary teams of investigators with 
expertise in pancreatic development, beta cell biology, stem cell 
biology, and bioinformatics. Through such collaborative research 
programs, we are laying a solid foundation for the future development 
of innovative, cell and regenerative growth factor therapies for 
diabetes and other debilitating diseases. Increased understanding of 
beta cell biology should also improve our ability to develop 
noninvasive, functional imaging technology that would, for example, 
help monitor type 1 diabetes prevention trials.

                              HEPATITIS C

    The hepatitis C virus is the cause of the most common form of end-
stage liver disease in the United States. We recently held a Consensus 
Development Conference on the management of hepatitis C that 
recommended directions for future research, and led to development of 
initiatives that are encouraging further basic and clinical research on 
hepatitis C, research on management of hepatitis C in people with 
chronic kidney disease, and research on new therapies for children with 
hepatitis C. From such research should emerge more effective forms of 
treatment and prevention.

                       GASTROINTESTINAL DISEASES

    We are bolstering our research activities across the full spectrum 
of gastrointestinal (GI) diseases, ranging from celiac disease, in 
which a known dietary factor triggers intestinal damage in genetically 
susceptible individuals, to functional GI disorders such as irritable 
bowel syndrome. Our strong research portfolio in inflammatory bowel 
disease (IBD) is paying dividends. A recent clinical trial reported 
that a recombinant monoclonal antibody that blocked the action of 
certain cell adhesion molecules could be used to reduce the symptoms 
and improve quality of life of patients with Crohn's disease, an 
inflammatory bowel disease. The NIDDK supported the basic research 
underpinning this exciting work, providing another example of the 
critical role of NIH research in the development of therapies for human 
disease. Our IBD Genetics Research Consortium aims to identify genes 
associated with increased risk of developing Crohn's disease and 
ulcerative colitis. The long-term goal is to increase molecular 
understanding of IBD so as to facilitate development of novel therapies 
and new diagnostic methods.

                             KIDNEY DISEASE

    We are addressing the sharp rise in end-stage renal disease (ESRD) 
by supporting research on the causes, treatment, and prevention of the 
major forms of kidney disease leading to ESRD. The discovery that the 
proteins encoded by the polycystic kidney disease (PKD) genes are 
localized to cilia (hair-like projections) in kidney tubular cells 
demonstrates the rapid progress in understanding the pathogenesis of 
the major cause of inherited ESRD. Results from some of our major 
kidney disease trials have significant implications for clinical 
practice. Our African American Study of Kidney Disease and Hypertension 
(AASK) showed that angiotenson-converting enzyme inhibitors, compared 
with calcium channel blockers, slowed kidney disease progression by 36 
percent, and drastically reduced the risk of ESRD by 48 percent in 
patients who had at least one gram of protein in the urine, a sign of 
kidney failure.
    The Institute's HEMO clinical trial recently showed that the 
standard recommended hemodialysis dosage and filters are adequate for 
reducing morbidity and mortality in ESRD patients, and that increasing 
dialysis dose using a conventional three times per week regimen does 
not provide greater benefit to patients. However, the important 
question now is the duration and frequency of dialysis. We therefore 
have planned clinical trials to compare conventional dialysis with more 
frequent dialysis in patients with ESRD. We also have launched a 
prospective epidemiological study of children with chronic kidney 
disease to determine the risk factors for decline in kidney function, 
and associated morbidities such as impaired neurocognitive development, 
cardiovascular disease, and growth failure.

                           UROLOGIC DISEASES

    Our major clinical trial on Medical Therapy of Prostate Symptoms 
(MTOPS) recently demonstrated that two drugs commonly used to treat 
benign prostatic hyperplasia (BPH), finasteride and doxasozin, are 
significantly more effective at preventing symptomatic BPH incidence 
and progression when given in combination. Samples collected during the 
MTOPS trial will be used by our new MTOPS Prostate Samples Analysis 
Consortium to discover and validate biologic markers for detection and 
risk assessment of BPH.
    Our Bladder Progress Review Group report provides a strategic plan 
for future bladder research. We are already implementing the report's 
recommendations on interstitial cystitis (IC), a debilitating, chronic 
syndrome of urinary urgency, frequency, and pelvic pain, by encouraging 
basic research pertinent to IC, the ultimate goal being the development 
of reliable diagnostic tools, and new and effective disease treatments 
and prevention.
    Mr. Chairman and Members of the Committee, these are just a few 
examples of our many research advances and initiatives. I would be 
pleased to answer any questions.
                                 ______
                                 
              Prepared Statement of Dr. Stephen E. Straus

    I am pleased to present the President's fiscal year 2004 budget 
request for the National Center for Complementary and Alternative 
Medicine (NCCAM). The fiscal year 2004 budget includes $116,202 
million, an increase of $2.9 million over the fiscal year 2003 enacted 
level of $113,302 million comparable for transfers proposed in the 
President's request.

                              INTRODUCTION

    Arthritis, depression, menopause, cancer . . . for millions of 
Americans, these and other health concerns are not being adequately 
addressed through conventional medicine. Many are turning outside the 
medical mainstream to approaches that embrace the whole person--mind, 
body, and spirit. From acupuncture to dietary supplements, 
complementary and alternative medicine (CAM) approaches are affordable 
and accessible, but largely untested. Under NCCAM's leadership, 
researchers are applying the tools of modern science to discover which 
CAM practices work, why and how they work, and whether they are truly 
safe. Exploring CAM through rigorous science will lead to the 
integration of proven CAM practices with conventional medicine, thus 
improving the lives of all Americans.

       STANDARDIZATION & CHARACTERIZATION OF DIETARY SUPPLEMENTS

    Dietary supplements, one of the most popular categories of CAM 
practices, are used by 10 percent of American adults.\1\ Many consumers 
use dietary supplements with the expectation that they are effective in 
the self-treatment and prevention of disease and the promotion of 
wellness and, further, with the assumption that they are safe. Under 
the law, supplements are classified as foods and not held to the same 
rigorous standards as drugs.
---------------------------------------------------------------------------
    \1\ Hanyu NI, Catherine Simile and Ann M. Hardy, ``Utilization of 
Complementary and Alternative Medicine by United States Adults: Results 
From the 1999 National Health Interview Survey,'' Medical Care, Vol. 
40, No. 4, pp. 353-358.
---------------------------------------------------------------------------
    Research supported by NCCAM indicates that Americans who take 
ginseng on a regular basis cannot rely on the label to accurately 
reflect the product's contents. After examining 25 commercial ginseng 
products, one NCCAM grantee recently reported that, the concentrations 
of ginseng differed by as much as ten-fold from the label. The lack of 
standardized dietary supplements is not only an issue of consumer 
safety; it is also an issue for researchers who need to protect their 
patients and work withwell-characterized and standardized products to 
scientifically and accurately examine study their purported benefits.
    NCCAM's recent experience with PC SPES, a patented mixture of eight 
herbs, is an example of the other vexinganother problem with some 
dietary supplements contamination. In 2001, thousands of men with 
advanced prostate cancer in America tookwere taking PC SPES. Based on 
encouraging early clinical results, NCCAM was supporting four research 
studies, including a clinical trial, to determine the safety, efficacy, 
and mechanism of action (i.e., how it works) of PC SPES. In February 
2002, the California Department of Health Services and the Food and 
Drug Administration reported that PC SPES was contaminated with 
undeclared prescription drug ingredients. This finding led the 
manufacturer to recall the product and subsequently cease its 
operations. NCCAM immediately put its studies on hold and convened 
meetings with scientists, prostate cancer specialists, patients, and 
industry representatives to determine howif a ``cleaner'' an 
uncontaminated product could be made available to the publicreenter the 
marketplace and the research pipeline, allowing the research to resume. 
As part of this strategya result of these meetings, NCCAM resumed its 
laboratory studies of the cellular and molecular biology of PC- SPES 
and pronounced declared its interest in resuming clinical trials once 
an unadulterated, fully characterized, and standardized product is 
available.
    NCCAM is taking several steps is taking several stepsto address the 
critical issue of product standardization and quality. Among the top-
selling products in the dietary supplement industry are products like 
echinacea (Echinacea purpurea), taken to prevent and treat colds, milk 
thistle (Silybum marianum), taken to treat chronic hepatitis and 
cirrhosis, and feverfew (Tanacetum parthenium), taken to lower fevers. 
All of these products have shown promise in small uncontrolled studies; 
however, each has problems with standardization, precluding their full 
and objective study. NCCAM is making awards under using the Small 
Business Innovative Research (SBIR) program to obtain well-
characterized and standardized clinical-trial-grade materials of these 
supplements. This investment in high-quality productsessential first 
step will be followed by studies to define the optimal dose of each 
product. To implement this second step, in 2004, NCCAM plans toplans to 
establish a Dietary Supplement Standardization and Characterization 
Center (DSSCC), which willto serve as a resource for the analysis of 
dietary supplements, especially botanical products, before they are 
used in clinical trials.

       DETERMINING THE MECHANISMS OF ACTION OF CAM INTERVENTIONS

    While pursuing innovative approaches to ensuring the safety of its 
clinical trial products, NCCAM continues to support basic and clinical 
studies NCCAM continues to support basic and clinical studies. The 
central objective of many of these studies is to examine the mechanisms 
of action underlying various CAM therapies. In 2002, for example, 
NCCAM-supported researchers conducted an important body of research on 
alternatives to conventional hormone therapy--an area of obvious 
interest for millions of menopausalwomen who are seeking safe and 
effective alternatives to conventional hormone therapy for relief of 
menopausal symptoms and related conditions. Specifically, scientists 
are using in vitro systems to examine how some popular dietary 
supplements act on biochemical pathways responsive to estrogen. Others 
are examining the estrogenic activity and specific mechanisms of 
estrogen receptor regulation of a Chinese herbal extract; identifying 
the active compounds of black cohosh (Cimifuga racemosa) and red clover 
(Trifolium pratense); and investigating the range and mechanisms of 
action of two plant-based estrogens, genistein and diadzein, and 
extracts of soy on immune function. These studies will clarify what 
biochemical effects supplements might have on women and indicate which, 
if any, are worthy of testing in a clinical trial.
    Building on the results of a detailed scientific review that NCCAM 
conducted with the Agency for Healthcare Research and Quality on the 
popular dietary supplement, S-Adenosyl-L-Methionine (SAMe), the Center 
is also supporting mechanistic projects on the mechanisms of action of 
SAMe that are consistent with the findings of the report associated 
with key areas identified by the report. One grantee is using cultured 
cells to better characterize the biochemistry of liver injury and what 
role SAMe may play in preventing liver damage. Another investigator is 
using a mouse model of hepatitis and liver cancer to study the role of 
SAMe in regulating liver cell growth and death.
    A trio of studies indicate that Ginkgo biloba may provide multiple 
levels of protection to neural tissues and contribute to the body of 
evidence explaining how Ginkgo may be beneficial in preventing the 
onset of dementia. NCCAM-supported investigators reported that a 
standardized Ginkgo extract protects cells from oxidative stress and 
apoptosis (programmed cell death). Using model systems to study the 
factors that regulate cell death, the investigators showed that the 
Ginkgo extracts increase the lifespan of the worm, Caenorhabditis 
aenorhabditis elegans, protect cultured neural cells from undergoing 
programmed death, and hinder an early step in the biochemical processes 
leading to neurodegeneration.
    In fiscal year 2003, NCCAM made several awards as part of the 
initiatives it launched with NIH partners to elucidate the underlying 
biological pathways of the placebo effect and to reveal factors 
important for eliciting the placebo effect in clinical practice 
setting. The Center designated mind-body medicine as a priority 
research area in fiscal year 2003, recognizing the potential 
contributions to prevention and treatment of chronic diseases that 
could be made by interventions based on evidence from innovative 
psychophysiological research. NCCAM will enhance the support for 
research into the mechanisms of mind-body medicine. Most recently, 
NCCAM joined other NIH partners to solicit applications from 
institutions poised to advance research on mind-body interactions and 
health. The Center also designated mind-body medicine as a priority 
research area in fiscal year 2003, recognizing the potential 
contributions to prevention and treatment of chronic diseases that 
could be made by interventions based on evidence from innovative 
psychophysiological research.

          EVALUATING CAM THERAPIES IN RIGOROUS CLINICAL TRIALS

    A chief goal of the basic and preclinical research NCCAM supports 
isbasic and preclinical research to test therapies for eventual use in 
clinical trials with the ultimate objective being to translate safe and 
effective therapies into widespread practice. Another purpose ofIn 
addition, NCCAM-supported clinical trials is to test CAM products 
already being widely used by the public. Ultimately, NCCAM wants to 
answer the central question: ``does it work?''
    In 2002, NCCAM announced the results of its first large-scale 
clinical trial. The trial evaluated a one product containing St. John's 
wort (Hypericum perforatum) product, a popular herbal remedy for 
depression, as a treatment for major depression of moderate severity 
and found it to be ineffective as compared to placebo. Although the 
results of this trial were negative showed that St. John's wort is not 
effective for this type of depression, the outcome provided 
practitioners and patients alike with valuable data. In addition, the 
outcome informed researchers who are testing St. John's wort as a 
treatment for less severe forms of depression. NCCAM is following-up on 
this finding by co-funding a new trial to test St. John's wort as a 
treatment for minor depression, a less severe but very common type of 
depressive illness. The trial begins this year and will enroll 300 
patients at three sites nationwide.
    Because CAM products and practices are already used by millions of 
Americans, NCCAM supports relatively morea higher percentage of 
clinical research than all of the other NIH Institutes and Centers. As 
part of its clinical research portfolio, the NCCAM extramural research 
program is already supporting 12 ongoing large-scale clinical trials 
with other NIH Institutes and Centers. These trials include the largest 
ever herbalstudy of Ginkgo biloba for the prevention of dementia a 
critical study given the aforementioned body of evidence that exists 
regarding Ginkgo's potential protective effects. The list also includes 
the largest ever studieslargest ever study of dietary supplements 
(selenium and vitamin E), involving 30,000 men, for the prevention of 
prostate cancer. In fiscal year 2002, NCCAM cosponsored the first large 
clinical trial to test chelation therapy as a treatment for coronary 
artery disease. Also in fiscal year 2002, the NCCAM Intramural Research 
Program initiated its first clinical trial, which is evaluating 
electroacupuncture in reducing the severe nausea experienced by many 
children following intensive cancer chemotherapy. NCCAM is taking 
actionactive to ensure the quality and safety of NCCAM-supportedits 
clinical trials.
    In 2002, the Center established the Office of Clinical and 
Regulatory Affairs to help plan, coordinate, and monitor NCCAM-
supported clinical trials. All of these activities reflect NCCAM's rich 
investment in and commitment to clinical research.

       BUILDING RESEARCH INFRASTRUCTURE AND INTELLECTUAL CAPITAL

    The success of NCCAM's future research endeavors is contingent upon 
depends on the availability of skilled investigators in both the 
conventional and CAM research communities. Toward this end, NCCAM is 
supporting dozens of mentored and independent trainees, from the pre-
doctoral level through mid-career and senior faculty members. In 2002, 
NCCAM made institutional training and clinical research career awards 
to CAM institutions and joined the new NIH-wide loan repayment program 
with awards to two junior practitioner-investigators, marking a series 
of ``firsts'' for NCCAM.
    In addition to its support ofinvestment in training programs, NCCAM 
continues to support a robust research centers program, providing a 
critical CAM research infrastructure. In 2002, NCCAM sought to 
strengthen its centers program by convening sought to strengthen its 
centers program by cing an expert panel to evaluate the program's 
current structure and objectives. The panel recommended a more flexible 
approach to supporting future centers research. This new approach, 
which employs a mix of funding and research mechanisms, will ideally 
expand ideally the participation among investigators with varying 
degrees of research expertise at both CAM and conventional institutions 
in a multi-disciplinary fashion. Implementation of this strategy began 
in fiscal year 2003 and will continue through fiscal year 2005.

                               CONCLUSION

    NCCAM has made remarkablesignificant progress in its first 4 years. 
Between fiscal year 2000 and fiscal year 2001, the number of people 
enrolled in NCCAM-supported clinical research projects doubled. The 
Center, in a partnership with other NIH Institutes, launched some of 
some of the largest clinical studies of CAM therapies ever conducted. 
NCCAM took pro-activesteps to improve the safety and efficacy of its 
clinical research studies and the quality of the information 
disseminated to the public about CAM therapies. Finally, the Center 
increased its level of support to researchers who are applying cutting-
edge scientific tools to study the most promising CAM approaches to the 
most important public health challenges facing our nation. I look 
forward to keeping you and the American public apprised of NCCAM's 
future activities and accomplishments.
                                 ______
                                 
              Prepared Statement of Dr. Lawrence A. Tabak

    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's budget request for the National Institute of Dental and 
Craniofacial Research (NIDCR) for fiscal year 2004. The fiscal year 
2004 budget includes $382,396,000, an increase of $11,254,000 over the 
fiscal year 2003 enacted level of $371,142,000 comparable for transfers 
proposed in the President's Request.

                  MOLECULAR MEDICINE ENTERS THE MOUTH

    When molecular biologists discuss the future of medicine and 
dentistry, many foresee a day when health care professionals will 
possess the technological tools to dust a patient's cells, like a 
detective dusts for fingerprints, and pull up a ``molecular 
fingerprint'' of the activity inside. This fingerprint will allow them 
for the first time to examine the patterns within the cells for 
disease-causing abnormalities in the genes, proteins, and protein 
networks. Based on these specific biological clues, doctors will have 
far more detailed information at hand to make a correct diagnosis and 
perhaps one day tailor a person's care to treat the specific molecular 
defects that underlie the disorder.

                          SALIVARY DIAGNOSTICS

    Scientists have long recognized that our saliva serves as a 
``mirror'' of the body's health, in that it contains the full 
repertoire of proteins, hormones, antibodies, and other molecular 
analytes that are frequently measured in standard blood tests. The 
Institute recently launched a major research effort that, in keeping 
with the National Institutes of Health (NIH) Roadmap initiative, seeks 
to identify and address major cross-cutting biomedical challenges, and 
will further develop needed technologies and create the first 
comprehensive baseline catalogue of all proteins found in oral fluids 
of healthy individuals. The NIDCR envisions that this basic research 
could one day translate into miniature, hi-tech tests, or so called 
``labs'' on a silicon chip, that rapidly scan oral fluid for the 
presence or absence of multiple proteins linked to various systemic 
diseases and conditions. Ultimately, this approach could be used for 
real-time health surveillance--rapidly identifying persons most at risk 
at the earliest moments of detectable change in key diagnostic markers.

          THE GENOMICS AND PROTEOMICS OF PERIODONTAL DISEASES

    Although ``molecular medicine'' is still in its infancy, the NIDCR 
continues to help lay its basic intellectual foundations. The tools of 
molecular medicine offer promising new strategies for addressing oral 
infectious diseases such as periodontitis. These conditions begin when 
bacteria colonize a ``biofilm'' that forms on the surface of teeth. 
Many of these microorganisms remain uncultivated and only recently have 
some of these bacteria been identified by their molecular fingerprints. 
Some of these bacteria are highly virulent; they elaborate noxious 
substances that damage hard and soft tissues of the mouth. Furthermore, 
oral bacteria can trigger an immune response that often proves 
destructive both within the mouth and elsewhere in the body. Indeed, 
recent studies with animal models and epidemiologic surveys have linked 
periodontal diseases with pre-term delivery and low birth weight.
    With the advent of more powerful research tools, NIDCR supported 
scientists will now be able to assemble a molecular ``parts list'' of 
all the genes and proteins involved in periodontal diseases. For the 
first time, a detailed understanding of the microbial and host 
signaling pathways that are activated or deactivated during periodontal 
disease progression will be mapped. This represents an important step 
in defining new therapeutic targets to overcome one of the most 
prevalent infectious diseases of humankind.

                           TISSUE ENGINEERING

    The NIDCR continues to invest heavily in regenerative medicine, 
with a strong interest in engineering new bone to repair dental and 
craniofacial wounds and birth defects. Of particular interest are adult 
bone marrow stromal stem cells, the natural progenitors that create the 
body's bone-forming cells. In recent years, scientists have envisioned 
healing bone fractures by inserting these cells directly into the 
wound. The adult stem cells would replicate in the wound, create 
millions of new bone cells, and heal the fracture rapidly and 
efficiently. As appealing as this approach is, however, technical 
challenges have emerged to slow the research. One of the most 
formidable obstacles is the discovery that adult bone marrow stromal 
stem cells stop growing soon after they are introduced into cell 
culture and quickly lose their ability to form new bone. Because 
hundreds of thousands of stem cells are required to heal even a minor 
bone fracture, scientists have been hard pressed to generate an 
adequate supply of these precursors.
    For the first time, NIDCR scientists and grantees reported that 
they have more than doubled the life span of adult bone marrow stromal 
stem cells, under laboratory conditions, by incorporating the 
catalytic, or active, component of a much-studied enzyme called 
telomerase, termed the hTERT gene, into the stem cells. This was 
particularly interesting because hTERT is the catalytic, or active, 
component of a much studied enzyme called telomerase. Telomerase has 
been shown to counter the shortening of telomeres, the tips of 
chromosomes, by triggering a chemical reaction that adds new base pairs 
to them and extends the life of the cell. In follow-up animal studies, 
the scientists found that the newly formed bone, generated from the 
stem cells, had all of the hallmarks of normal bone--including 
organized collagen fibers and various mineral components.

                           SJOGREN'S SYNDROME

    The NIDCR is also applying tissue engineering strategies to 
Sjogren's syndrome, a relatively rare condition that affects over one 
million Americans. The syndrome is caused when the immune system 
mistakenly attacks various parts of the body, often including cells 
that produce saliva. When this occurs, people develop chronically dry 
mouths, which can impair their ability to taste and swallow as well as 
lead to oral disease. While studies are ongoing to pinpoint the root 
cause of this condition, NIDCR continues to explore the possibility of 
developing an artificial salivary gland, an approach that one day could 
help to restore adequate levels of saliva for Sjogren's patients.
    In studying Sjogren's syndrome, one of the major barriers always 
has been logistical. People with the syndrome are scattered throughout 
the country, and scientists are sometimes uncertain about how to find 
them. To ensure that researchers have access to sufficient numbers of 
Sjogren's patients with well defined clinical histories and relevant 
biological samples, NIDCR will support the first international registry 
of Sjogren's patients. The registry will be crucial in tracking the 
incidence and natural history of the condition. It also will allow 
NIDCR to launch more rapidly the necessary clinical trials to evaluate 
promising diagnostic and therapeutic leads as they emerge. NIDCR also 
plans to identify biomarkers--genes, proteins, or even protein 
networks--which will allow early diagnosis, determination of disease 
progression, and stratification of high risk individuals. By developing 
a battery of sensitive and highly specific diagnostic and prognostic 
biomarkers, critical molecular information will be available to more 
accurately diagnose and treat Sjogren's syndrome, a long-held hope of 
many Americans affected by this condition.

                             PAIN RESEARCH

    For the past four decades, the NIDCR has been one of the key 
players at NIH in the study of the basic biology and treatment of pain. 
While current analgesic drugs help many ease discomfort, millions of 
others have pain management needs that remain completely or partially 
unmet. Nearly all available analgesics were developed based on overly 
simplified, linear models of pain transmission. Recent advances show 
that pain transmission is a far more dynamic process that often 
involves multiple routes, or pathways. Each pathway integrates a 
convergence of molecular signals, then relays them along their own 
specific, hard-wired routes to the brain. The research challenge is to 
define the molecular details of these multiple routes of pain 
transmission with the aim of increasing the repertoire of pain 
management strategies.
    In keeping with the NIH Roadmap initiative, progress is now being 
made in defining the biological pathways and networks of pain. For 
example, a group of NIDCR grantees have discovered several biological 
factors that influence pain perception. This multidisciplinary team 
focuses its research on developing novel, real-time imaging techniques 
that track the mu-opioid system, a specific type of protein receptor in 
the brain that researchers have long suspected triggers a dampening of 
the pain. In a seminal study published last year, the team confirmed 
the role of the mu-opioid system in enhancing a person's tolerance of 
pain. According to the research team, this marked the first study ever 
that combined prolonged pain with simultaneous brain scan monitoring of 
the mu-opioid system and self-reported pain ratings of human 
volunteers.
    The group found that the onset and slow release of jaw muscle pain 
(that mimics, in part, the symptoms of individuals suffering from 
Temporomandibular muscle and joint diseases and conditions) over 20 
minutes caused a surge in the release of endorphins, naturally produced 
chemicals that bind to the mu-opioid protein receptors that are 
displayed on the surface of brain cells. Once the endorphins activated 
the receptors, the volunteers said they felt a reduction in pain and 
emotions related to the sensation. Specific brain regions--especially 
those that play a role in emotional responses or that help to process 
signals from the body's sensory systems--had the greatest increase in 
endorphin levels. The research also revealed major variations among 
volunteers in baseline and pain-induced levels of opioids. The 
scientists noted that their results establish that people vary both in 
their capacity to produce mu-opioid receptors and in their ability to 
release the anti-pain chemicals themselves. This variability appears to 
determine the emotional and sensory aspects of a painful experience and 
might explain why some people react to pain differently. It may also 
help to explain why some people are more prone to chronic pain 
conditions or do not benefit from certain anti-pain medications.
    The group and its collaborators have published two important 
followup studies. In the first study, the scientists observed that, at 
matched levels of pain intensity, men and women differ in the degree 
and direction of the mu-opioid response in distinct areas of the brain. 
In particular, men had greater activation of mu receptors in specific 
regions of the brain--the anterior thalamus, ventral basal ganglia, and 
amygdala. Women, conversely, had reductions in the resting levels of 
these receptors when they experienced pain in the nucleus accubens, an 
area of the brain previously associated with hyperalgesic responses to 
the blockage of these receptors.
    In the second study, the scientists focused on a gene that produces 
a key enzyme involved in the mu-opiod system. The group found that 
people who inherit an extremely common variation in the gene have a 
lower natural threshold of pain than those who were born without the 
variation. The scientists speculated that the variant gene encodes a 
slightly altered enzyme that functions somewhat differently than the 
normal enzyme, leading to lower brain levels of pain-killing 
endorphins. This finding highlights the growing recognition that pain 
treatment should be customized to meet the specific needs of individual 
patients.
    Because of the mouth's unique role in the human body, NIDCR is well 
positioned to make key contributions to the future of molecular-based 
medicine--not only in alleviating oral conditions but also toward 
improving systemic health. This Institute's continued contributions 
represent hope for millions of Americans today, as well as improved 
health and quality of life for generations to come.
                                 ______
                                 
            Prepared Statement of Dr. Judith L. Vaitukaitis

    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's budget request for the National Center for Research 
Resources (NCRR) for fiscal year 2004, a sum of $1,053,926, a decrease 
of $84,738,000 from the fiscal year 2003 enacted level of $1,138,664 
comparable for transfers proposed in the President's request.
    Infrastructure is at the heart of NCRR. For more than 40 years, it 
has been NCRR's mission to develop and support essential research 
resources that strengthen and enhance research environments for health-
related studies. NCRR provides the nation's scientific community with 
access to broad-ranging resources, including animal models, advanced 
technologies, research facilities, and clinical research centers that 
explore new approaches for diagnosing, treating, and preventing human 
disease.
    To be responsive to emerging needs, NCRR works in trusted 
partnership with the biomedical research community, with other NIH 
institutes and centers, and, in some cases, with other Federal agencies 
and private sector organizations. In anticipation of emerging needs, 
NCRR in recent years has funded construction of biocontainment 
laboratories for the study of dangerous infectious agents; islet cell 
resources to explore novel therapies for diabetes; and creation of 
transgenic animals that enhance understanding of human disease.
    Scientists today are exploring biomedical problems of enormous 
complexity. Some of the nation's most pressing health concerns can best 
be addressed through multidisciplinary research teams, which integrate 
technologies and expertise from a variety of fields. NCRR, with its 
cross-cutting mission, is ideally positioned to facilitate this 
evolving approach. Today I will outline NCRR's plans for meeting the 
ever-changing infrastructure needs and describe just a few of the 
research advances enabled through NCRR-supported research 
infrastructure.

                         ADVANCED TECHNOLOGIES

    NCRR has a long history of developing and enhancing access to new 
technologies. Magnetic resonance imaging, mass spectrometry, 
synchrotrons for crystallography and optical imaging are just a few of 
the now-indispensable tools that NCRR supported in their infancy, 
primarily through the nationwide network of Biomedical Technology 
Resource Centers. NCRR must remain positioned to ensure that innovative 
technologies are developed and accessible before research progress is 
compromised.
    Novel insights into the prevention or treatment of disease will 
arise from synthesis of massive amounts of molecular, genetic, and 
biologic data. To take advantage of these rich sources of information, 
researchers need new bioinformatics tools and approaches to selectively 
retrieve, analyze, and interpret data stored in many different formats 
and at different levels of aggregation in locations spread across many 
sites. Tool development, including new database architecture, is needed 
to manipulate large data sets with data object entries that vary 
markedly in size and complexity. Seamless integration of information 
across these data sources is a major research challenge.
    NCRR has begun to address such issues through its Biomedical 
Informatics Research Network (BIRN). The test bed encompasses diverse 
locations nationwide. The initial development of BIRN focuses on 
generating several robust technologies, computational tools, and 
communications networks. These networks simplify and facilitate the 
sharing of scientific expertise, technologies, and data. BIRN currently 
provides links, via Internet2, among several General Clinical Research 
Centers and Biomedical Technology Resource Centers. NCRR now plans to 
extend the scope of these networked resources by connecting all NCRR-
supported research resource centers to Internet2, which will enhance 
nationwide access to databases, bioinformatics tools, and enabling 
resources for clinical and basic research in a second test bed that 
will concentrate on infrastructure for clinical research.
    In another facet of the BIRN development, NCRR will work in concert 
with other NIH components to expand the advanced technologies used or 
developed for BIRN and apply them to build a National Electronic 
Clinical Trials and Research network, called NECTAR. This effort will 
include designing a web-based approach for entering clinical data, 
developing advanced tools for integrating datasets, and enabling 
manipulation of complex datasets from remote sites. Initial development 
of the NECTAR network will focus on therapeutic development networks, 
particularly for the treatment of rare diseases. Ultimately, the tools 
developed for NECTAR may be readily scaled up for larger 
investigations, including collaboratories.
    With today's multifaceted studies, biomedical scientists 
increasingly depend on a systems approach that integrates, for example, 
advanced technologies for macromolecular structures, structure-based 
drug design, novel technologies to discern the gene-gene interactions 
and molecular imaging. To enable such studies, NCRR proposes to develop 
and support comprehensive research resource centers equipped with 
state-of-the-art technologies and a team of investigators with wide-
ranging but complementary expertise. These comprehensive centers, which 
may provide remote access to resources, will allow investigators to 
characterize the thousands of proteins expressed by the human genome. 
Scientists will be positioned to address fundamental questions that 
cannot be answered by examining one protein at a time. Such 
``postgenomic'' studies may provide clues to complex disease-related 
processes that may be prevented or arrested with novel interventions.

                 MODEL DEVELOPMENT AND GENETIC MEDICINE

    NCRR is also at the forefront in developing nonhuman models and 
tools for genetic medicine. In recent years, numerous gene-targeting 
and transgenic studies have produced a wealth of information on gene 
function and their role in development, aging, and disease processes. 
But the enormous volume of collected data is often unwieldy and 
difficult to analyze. NCRR will enhance this promising area of research 
by supporting a national network of resources to systematically 
classify and characterize genetically altered animal models and to 
support the development of new technologies to rapidly phenotype new 
mutants. With the decoding of the human genome and development of new 
technologies, biologic models may help unravel the causes and identify 
cures for such complex diseases as diabetes, hypertension and cancer.
    The mouse has gained new prominence in biomedical laboratories now 
that scientists can readily modify the animal's genome to create 
transgenic and ``knockout'' 1models of human disease. In 1999, NCRR 
established the Mutant Mouse Regional Resource Centers to expand the 
nation's capacity for preserving specialized mice and distributing them 
to biomedical researchers. Because of the program's success and value 
to the scientific community, NCRR now plans to extend the scope of the 
mouse resource centers to an international level. Collaborations will 
be established with Mutant Mouse Resources at sites in Europe and 
Japan, thereby minimizing unplanned duplicative efforts on a global 
scale.
    NCRR also proposes to initiate a network of Mutant Rat Regional 
Resource Centers--similar to the successful mouse network--to import, 
validate, cryopreserve, and distribute mutant rats to investigators 
globally. Up to three rat resource centers will be established along 
with a complementary informatics center to design and maintain a 
database of relevant data for each mutant rat included in the network, 
and mantain a dedicated Internet linkage among the Centers to provide 
investigators access the information on validated mutant rat models 
within the network's collection and relevant information a centralized 
web site and database.
    Research using swine models has expanded significantly over the 
past five years, resulting in the need for animal production, 
appropriate husbandry and care, and genetic technologies related to 
pigs. In 2002, an NCRR-supported research team at the University of 
Missouri succeeded in creating the world's first ``knockout'' pigs--the 
gene function is altered so that the gene can no longer add specific 
sugars to the outer surface of liver cells, which, in turn, decreases 
the immune-mediated tissue rejection response. The knockout pigs 
represented a first step toward developing genetically engineered swine 
suitable for cross-species transplantation, or xenotransplantation, 
into humans. NCRR proposes to establish a National Swine Regional 
Resource Center with the capacity to import, cryopreserve, 
characterize, maintain, and distribute well-characterized specific-
pathogen-free swine strains. The Resource Center will also have an R&D 
component to enhance the research scope and expertise of investigators 
there.

                  PREVENTION, DIAGNOSIS, AND TREATMENT

    NCRR is also an ardent supporter of clinical research. The 
nationwide network of General Clinical Research Centers (GCRCs) 
provides a collection of research resources and professional research 
staffing for conducting state-of-the-art clinical research and career 
development programs to develop independent investigators. GCRCs are 
encouraged to reach out to investigators at nearby institutions without 
GCRCs and provide access to the resources of the GCRCs. NCRR also funds 
clinical research centers at minority institutions.
    To address the public's concern about the safety of clinical 
research, NCRR implemented the Research Subject Advocate (RSA) program 
to assure that research conducted on NCRR-supported GCRCs and minority 
clinical research sites are in compliance with Federal laws, 
regulations and policies. Research Subject Advocates work closely with 
research subjects to help them understand the research project for 
which they agreed to participate and also work closely with clinical 
investigators to apprise them of their ethical responsibilities to 
research subjects. The RSA organizes workshops to inform investigators 
about the several local and Federal regulations and policies that 
relate to clinical research. Because of the enthusiastic institutional 
responses to the Research Subject Advocate program, NCRR proposes to 
begin phasing in support for RSAs for all NIH-supported patient-
oriented research at GCRC host institutions.
    In addition, NCRR intends to support research to identify factors--
for example, biologic, economic or cultural--which lead to health 
disparities and how to modulate for eliminate those factors in racial 
and ethnic minority Americans. Through establishing dedicated 
Comprehensive Centers for Health Disparities Research, NCRR support 
will develop the clinical research skills and translational research 
capacity of students, postdoctoral research fellows and faculty at 
minority medical schools. NCRR also will continue to encourage 
multidisciplinary collaborations among minority institutions and 
institutions with established research programs to not only accelerate 
the development of independent clinical research investigators but also 
to enhance our understanding of the factors that contribute to health 
disparities and how to negate them.

                    ENHANCEMENT OF RESEARCH CAPACITY

    NCRR's purview is research infrastructure, in the broadest 
interpretation of the term. Insight leading to novel research 
approaches to prevent, treat or ameliorate disease will result from 
synthesis of massive amounts of molecular, genetic, and biologic data. 
Seamless integration of information across these data sources is a 
major research challenge.
    NCRR will expand the advanced technology used or developed for the 
neuroscience testbed for BIRN to build a National Electronic Clinical 
Trials and Research (NECTAR) network. This effort will include 
designing a web based data entry approach for clinical trials and other 
types of clinical research, development of a host of other tools, 
including advanced grid technology to integrate datasets and develop 
tools to manipulate these datasets at distributed sites. The NECTAR 
network will generate heterogeneous data types which have distinct or 
unique requirements for data collection, storage, integration, and 
analysis. Initially this phase of the NECTAR network development will 
focus on therapeutic development networks, particularly in rare 
diseases. The tools developed at this stage may be readily scaled up to 
include, for example, collaborative clinical research across wide 
geographic sites, primary care physician clinical trial networks, other 
provider networks, and private sector partners. This infrastructure 
will constitute the foundation for a nation wide NECTAR-BIRN to 
accelerate the rate for which health research advances at the bench 
reach patients who are the intended benefactors of biomedical research.
    The BIRN allows access to databases, bioinformatics tools, scalable 
computing up to the teraflop level, research resources for clinical, 
animal and basic research; it also includes federated databases, web-
based data collection for clinical trials and access to virtual 
laboratories for crystallography, magnetic resonance imaging, electron 
microscopy. This cyberspace-based network will be intertwined with a 
``ground-based'' network of technology-based resources. The 
complementary networks will continue to evolve with technologic needs 
and research complexities. Similarly, technologies and resources 
networked for human, animal and basic research will also evolve across 
this national infrastructure for land-based and cyber-spaced networks. 
In essence, as research problems become more complex, infrastructure to 
facilitate that research must undergo a paradigm shift.
    The Institutional Development Award (IDeA) program includes two 
subprograms to strengthen the research infrastructure among 23 states 
and Puerto Rico to improve their research competitiveness for NIH grant 
awards. The two infrastructure-building programs--Centers of Biomedical 
Research Excellence (COBRE) and the Biomedical Research Infrastructure 
Network (BRIN)--have been in place for three and two years, 
respectively. In that short time span, preliminary observations are 
extremely encouraging. Between 1997 and 2002, the application rate for 
NIH grants increased 16 percent--but the number of competitive NIH 
grant awards increased 37 percent. The IDeA programs' impact has 
resulted from providing support for modern laboratories and research 
equipment, recruitment established investigators to lead the research 
effort as well as to mentor graduate students and junior faculty to 
become independent investigators. There has been a spinoff to small 
industry as well. For example, a faculty member of the COBRE in West 
Virginia has invented a microfludics chip (``lab on a chip'') that will 
enable researchers to analyze and identify proteins more rapidly, an 
innovation that may lead to new diagnostic strategies and treatments. 
Both the COBRE and BRIN programs are enthusiastically embraced by 
students, mentor-faculty, and institutional leadership. In fiscal year 
2004 the NCRR will develop new COBRE research centers and will develop 
a follow-on program to the BRIN, initially funded as a planning grant, 
to capitalize on statewide networks to facilitate biomedical research 
efforts at undergraduate institutions and to further enhance the 
pipeline for promising baccalaureate and graduate students in fields 
relevant to biomedical research.
    Finally, NCRR will further strengthen institutional biomedical 
research infrastructure and also design specific programs to develop 
the research skills of graduate students and junior faculty in both 
basic and clinical sciences at RCMI and IDeA institutions. Programs 
will be designed to enhance early career scientists to transition from 
a mentored research environment to an independent research career to 
bolster the collective research capacities of this subset of 
institutions. To continue to address the shrinking pool of clinical 
investigators, NCRR plans to expand and extend the successful 
Institutional Mentored Clinical Research Scholars (CRS) Program to 
include a consortium of minority medical schools associated with the 
Research Centers in Minority Institutions (RCMI) program. This cohort 
of investigators will be included in a dedicated network to foster 
their research through the Clinical Research Infrastructure initiative.

                               CONCLUSION

    In conclusion, the health-related advances of tomorrow will depend 
on the availability of essential, shared research resources, including 
nonhuman models, advanced technologies, and tools for exploring new 
diagnostics, therapies, and preventive strategies. NCRR is poised to 
provide these essential resources to the biomedical community. As we 
have for more than 40 years, NCRR remains committed to providing the 
enabling tools and technologies that advance biomedical science and 
improve the health of our nation's citizens. In collaboration with the 
National Science Foundation, Internet2, and investigators from several 
universities, NCRR has become a major supporter for upgrading the 
infrastructure for health-related research focusing on development of a 
bioinformatics tool box, a more efficient clinical trials system and 
use Internet2 interface for the several tools and algorithms for data 
visualization, efficient clinical trials networks and development of 
grids for security, computation, and data storage.
    My colleagues and I will be happy to respond to any questions you 
may have.
                                 ______
                                 
              Prepared Statement of Dr. Jack Whitescarver

    Mr. Chairman and Members of the Committee, I am pleased to present 
the President's budget request for the AIDS research programs of the 
NIH for fiscal year 2004, a sum of $2,869,858,000 an increase of 
$122,395,000 above the comparable fiscal year 2003 appropriation.
    The NIH represents the largest and most significant public 
investment in AIDS research in the world. It supports a comprehensive 
program of basic, clinical, and behavioral research on HIV infection 
and its associated opportunistic infections and malignancies that will 
lead to a better understanding of the basic biology of HIV, the 
development of effective therapies to treat it, and the design of 
better interventions to prevent new infections. Perhaps no other 
disease so thoroughly transcends every area of clinical medicine and 
scientific investigation, crossing the boundaries of the NIH 
institutes. The Office of AIDS Research (OAR) plays a unique role at 
the NIH. OAR coordinates the scientific, budgetary, and policy elements 
of the NIH AIDS program, supported by nearly every Institute and 
Center; prepares an annual comprehensive trans-NIH plan and budget for 
all NIH-sponsored AIDS research; facilitates NIH involvement in 
international AIDS research activities; and identifies and facilitates 
scientific programs for multi-institute participation in priority areas 
of research.

                         THE WORLDWIDE PANDEMIC

    HIV has already infected more than 60 million people around the 
world. According to a new CIA report, ``The HIV/AIDS pandemic continues 
to spread around the world at an alarming rate, and the number of 
people with the disease will grow significantly by the end of the 
decade, as it becomes more geographically diffuse. By 2010, we estimate 
that five countries of strategic importance to the United States--
Nigeria, Ethiopia, Russia, India, and China--collectively will have the 
largest number of HIV/AIDS cases on earth.'' A recent article in 
Foreign Affairs magazine stated, ``The spread of HIV/AIDS through 
Eurasia, in short, will assuredly qualify as a humanitarian tragedy--
but it will be much more than that. The pandemic there stands to 
affect, and alter, the economic potential--and by extension, the 
military power--of the region's major states . . . Over the decades 
ahead, in other words, HIV/AIDS is set to be a factor in the very 
balance of power within Eurasia--and thus in the relationship between 
Eurasian states and the rest of the world.'' Dramatic increases in HIV 
infection also are occurring in Eastern Europe, Central Asia, Latin 
America, and the Caribbean. An article in the New York Times recently 
reported another dimension to the epidemic: ``As a result of HIV, the 
worst-hit African countries have undergone a social breakdown that is 
now reaching a new level: African societies' capacity to resist famine 
is fast eroding. Hunger and disease have begun reinforcing each 
other.''

                           THE U.S. EPIDEMIC

    The Centers for Disease Control and Prevention (CDC) recently 
reported that more people were diagnosed with AIDS in 2001, the latest 
year for which reliable statistics are available, than the previous 
year, or any year since 1998. After years of sharp declines, thanks 
largely to successful treatment with new antiretroviral therapies 
(ART), this report indicates a reversal in cases of AIDS in the U.S. 
Further, CDC reported that the rate of new HIV diagnoses, which had 
remained stable since 1990, also appears to be increasing. New HIV 
infections rose a striking 8 percent between 1999 and 2001, based on 
data from 25 states with mandatory HIV reporting, which does not 
include the two highest prevalence states of New York and California. 
HIV infection rates continue to climb among women, racial and ethnic 
minorities, young homosexual men, individuals with addictive disorders, 
and people over 50 years of age. In addition, use of ART has now been 
associated with a series of side effects and long-term complications 
that may have a negative impact on mortality rates. The appearance of 
multi-drug resistant strains of HIV presents an additional serious 
public health concern. According to CDC reports, approximately one 
quarter of the HIV-infected population in the United States also is 
infected with Hepatitis C virus (HCV). AIDS affects African Americans 
and Hispanics disproportionately. According to CDC figures through 
December 2001, approximately 64 percent of newly infected women are 
African American and 17 percent are Hispanic. Among newly infected men, 
approximately 43 percent are African American and 20 percent are 
Hispanic. This expanding and evolving U.S. epidemic presents new and 
complex scientific challenges.

              COMPREHENSIVE AIDS RESEARCH PLAN AND BUDGET

    To address these compelling scientific questions, the OAR develops 
an annual comprehensive trans-NIH AIDS research plan and budget, based 
on the scientific priorities and opportunities that will lead to better 
therapies and prevention strategies for HIV infection and AIDS. The 
planning process is inclusive and collaborative, involving the NIH 
Institutes, as well as eminent non-government experts from academia, 
industry, foundations, and AIDS community representatives. The Plan 
serves as the framework for developing the annual AIDS research budget 
for each Institute and Center, for determining the use of AIDS-
designated dollars, and for tracking and monitoring those expenditures.
    The Plan establishes the NIH AIDS scientific agenda in the areas 
of: Natural History and Epidemiology; Etiology and Pathogenesis; 
Therapeutics; Vaccines; and Behavioral and Social Science. In addition, 
the plan addresses the cross-cutting areas of: Microbicides; Racial and 
Ethnic Minorities; Women and Girls; Prevention Science; International 
Research; Training, Infrastructure, and Capacity Building; and 
Information Dissemination. In consultation with the Director of NIH, 
the OAR determines the total annual AIDS research budget. Within that 
total, the OAR establishes the AIDS research budgets for each NIH 
Institute and Center, in accordance with the priorities and objectives 
of the Plan, at each step of the budget development process up to the 
Conference Committee. To accomplish this, OAR consults regularly with 
the Institute and Center Directors. This process allows the OAR to 
ensure that NIH AIDS research funds will be provided to the most 
compelling scientific opportunities, rather than a distribution based 
solely on a formula.
    OAR plays a crucial role in identifying scientific areas that 
require focused attention and facilitating multi-Institute activities 
to address those needs. OAR fosters this research through a number of 
mechanisms, such as designating funds and supplements to jump-start or 
pilot program areas, sponsoring workshops or conferences to highlight a 
particular research topic, and sponsoring reviews or evaluations of 
research program areas to identify research needs.
    The overarching priorities that continue to frame the NIH AIDS 
research agenda are: prevention research to reduce HIV transmission, 
including development of vaccines, microbicides, and behavioral 
interventions; therapeutics research to develop simpler, less toxic, 
and cheaper drugs and drug regimens to treat HIV infection and its 
associated illnesses, malignancies, and other complications; 
international research, particularly to address the critical needs in 
developing countries; and research targeting the disproportionate 
impact of AIDS on minority populations in the United States. All of 
these efforts require a strong foundation of basic science, the bedrock 
of our research endeavor.

                NEW CHALLENGES IN THERAPEUTICS RESEARCH

    While multiple ART drug combinations continue to successfully 
reduce viral load and restore immune responses in many HIV-infected 
individuals, these regimens also can result in serious toxicities and 
side effects, single- and multiple drug-resistance, and other 
complications which make them unacceptable for some individuals. These 
side effects and complications appear to be increasing as HIV-infected 
individuals continue on drug regimens. More deaths occurring from liver 
failure, kidney disease, and cardiovascular complications are being 
observed in this patient population. NIH-sponsored research efforts 
continue to develop better antiretroviral drugs and treatment regimens 
that demonstrate less toxicity, activity in viral and cellular 
reservoirs, reduced development of drug resistant virus, improved 
pharmacodynamics and pharmacokinetics, easier compliance, and lower 
cost.
    While the incidence of certain opportunistic infections (OIs) and 
malignancies has decreased with the advent of ART, the number of cases 
of TB, multiple drug resistant TB, and other coinfections such as 
Hepatitis B virus and Hepatitis C virus has increased. The development 
of practical and affordable treatment regimens against HIV coinfections 
and endemic diseases in developed and developing nations is an NIH 
priority.

                          PREVENTION RESEARCH

    NIH supports a comprehensive approach to HIV prevention research 
that includes contributions from the biomedical, behavioral, and social 
sciences. Our biomedical prevention research priorities include the 
development of vaccines, topical microbicides, strategies to prevent 
mother-to-child transmission-including a better understanding of risk 
associated with breast-feeding-and management of sexually transmitted 
diseases (STDs). NIH also supports behavioral research strategies, 
including interventions related to drug and alcohol use. Efforts 
continue to identify the most appropriate intervention strategies for 
different populations and sub-epidemics in the United States and around 
the world. As a result of increased NIH funding, many new approaches to 
HIV vaccines are being pursued. Although production of candidate 
vaccines for clinical study has proceeded slowly, at least 10 new 
candidate vaccines will enter Phase I trials in the next 2 years. 
Several new combinations of products, which are expected to provide 
better immune responses, also will be tested in Phase I or II trials. 
The Dale and Betty Bumpers Vaccine Research Center, located on the NIH 
campus, recently launched the first Phase I clinical trial of a multi-
clade, multi-gene vaccine candidate.

                         INTERNATIONAL RESEARCH

    To address the increasing urgency of the AIDS pandemic, the OAR 
established an initiative and strategic plan for global research on 
HIV/AIDS and has significantly increased research efforts in the past 
several years to benefit resource- and infrastructure-poor nations. NIH 
supports a growing portfolio of research conducted in collaboration 
with investigators in developing countries. Results of this research 
benefit the people in the country where the research is conducted, as 
well as people affected by HIV/AIDS worldwide. Critical to the success 
of these international studies are foreign scientists who are full and 
equal partners in the design and conduct of collaborative studies. To 
that end, NIH also supports international training programs and 
initiatives that help build infrastructure and laboratory capacity in 
developing countries where the research is conducted.

                          women and minorities
 
   Women experience HIV/AIDS differently from men. NIH research has 
demonstrated that women progress to AIDS at lower viral load levels and 
higher CD4 counts than men. Women also experience different clinical 
manifestations and complications of HIV disease. These findings may 
have implications for care and treatment of HIV-infected women, 
particularly with ART. There are many research questions that remain 
unanswered about specific characteristics of women and girls that might 
play a role in transmission, acquisition, or resistance to HIV 
infection during different stages of the life course.
    In many U.S. urban centers, HIV seroprevalence rates mimic those 
found in some developing nations. These findings, along with the 
resurgence of STDs and associated high-risk behaviors, demonstrate the 
need for comprehensive strategies to decrease HIV transmission in 
affected vulnerable populations, and improve treatment options and 
treatment outcomes. OAR is directing increased resources toward 
research to develop new interventions that will have significant impact 
on these groups. These include interventions that address the co-
occurrence of other STDs, hepatitis, drug abuse, and mental illness; 
and interventions that consider the role of culture, family, and other 
social factors in the transmission and prevention of these disorders in 
minority communities. NIH is making significant investments to improve 
research infrastructure and training opportunities for minorities and 
will continue to ensure the participation of minorities in AIDS 
clinical trials, as well as in natural history, epidemiologic, and 
prevention studies. OAR has provided additional funds to projects aimed 
at increasing the number of minority investigators conducting 
behavioral and clinical research; targeting the links between substance 
abuse, sexual behaviors, and HIV infection; increasing outreach 
education programs targeting minority physicians and at-risk 
populations; and expanding the portfolio of population-based research. 
One of these projects is a series of Training and Career Development 
Workshops that provide minority investigators with an opportunity to 
learn more about available NIH funding mechanisms and to meet and 
network with senior minority investigators who receive significant 
levels of NIH funding.

                                SUMMARY

    The human and economic toll of the AIDS pandemic is profound. It 
requires a unique response that is complex, comprehensive, multi-
disciplinary, and global. The NIH role in this response is fundamental 
and unprecedented. The diverse AIDS research portfolio demands 
scientific coordination and management of research funds to enhance 
collaboration, minimize duplication, and ensure that precious research 
dollars are invested in the highest priority areas of scientific 
opportunity. The nation's investment in AIDS research is reaping even 
greater dividends, as AIDS research is unraveling the mysteries 
surrounding many other infectious, malignant, neurologic, autoimmune, 
and metabolic diseases.
    The authorities of the Office of AIDS Research allow NIH to pursue 
a united research front against the global AIDS epidemic. We are deeply 
grateful for the continued support this Committee has provided to our 
efforts.

                            ACTING DIRECTORS

    Senator Specter. Thank you very much, Dr. Zerhouni.
    Are there any other institutes which have acting directors 
at the present time?
    Dr. Zerhouni. Yes. We have three institutes this minute. 
NIGMS, the General Medical Science Institute is--the Acting 
Director is Dr. Judy Greenberg. And she is with us today.
    Senator Specter. And when do you expect to have a permanent 
director there?
    Dr. Zerhouni. Senator, I have worked--the top priority for 
my first year was to complete all six--I mean, to fill all six 
vacancies for the six institutes that were vacant within the 
year. So I expect that, I hope on my first anniversary that all 
institutes will have new directors that have acting directors 
today.
    Senator Specter. Dr. Zerhouni, the subcommittee would 
appreciate knowing a little more about your efforts there. 
There is an inevitable sense that a full-time director with 
that authority is necessary to move an institute along at top 
speed. So would you submit to us in some detail, in writing, 
your expectations and the progress and keep us informed as to 
how you are doing on full-time directors for those institutes?
    Dr. Zerhouni. I will certainly do. And I agree with your 
views on that.
    [The information follows:]

                    Progress on Full-Time Directors

    Mr. Chairman, I consider the selection of outstanding, highly 
qualified scientist-administrators as directors of the various 
institutes to be among my highest priorities. Over the past eleven 
months, I have filled three of the vacancies for Directors of 
Institutes at NIH and have appointed:
    Dr. Thomas Insel, Director, National Institute of Mental Health
    Dr. T. K. Li, Director, National Institute on Alcohol Abuse and 
Alcoholism
    Dr. Nora Volkow, Director, National Institute and Drug Abuse
    Two other vacancies remain and I and my staff are working very hard 
to complete the searches so that I can make appointments:
  --The search for the Director, National Institute of Neurological 
        Disorders and Stroke has been prolonged, unfortunately. It 
        started in March, 2001 and, after careful consideration, the 
        leading candidate withdrew and took a position at a 
        pharmaceutical company in November, 2001. The vacancy 
        announcement was re-issued and a slate of three highly 
        qualified candidates was sent forward, all of whom were 
        interviewed by the Acting Director, NIH between late February 
        and March, 2002. A candidate was offered the position at the 
        end of March, accepted verbally and subsequently, withdrew in 
        early April 2002.
      Upon my assuming the Directorship of NIH, I discussed the 
        situation with my senior staff and decided to reconstitute the 
        search committee, and solicit applicants myself. This resulted 
        in several new applicants and consideration of several previous 
        candidates. Five candidates were interviewed and as of the time 
        of submission of this response, I am in active discussion with 
        my selectee. I anticipate that I will be able to name a 
        Director for NINDS within a very short time.
  --The search for the Director, National Institutes of General Medical 
        Sciences was initiated in mid-March, 2002. The search committee 
        interviewed a total of ten candidates between late September, 
        2002 and February, 2003. Of the group, I and my senior staff 
        have interviewed three during March and early April and 
        anticipate conducting one more interview. I anticipate that a 
        selection will be made in the next month.

                          SALIVARY DIAGNOSTICS

    Senator Specter. Dr. Zerhouni, one of the questions which 
we characteristically ask is the question about what progress 
is being made on major ailments and what could be done with 
greater funding. And it is obviously a very difficult question. 
It may be an impossible question when we ask when will a cure 
be found for Parkinson's. I choose Parkinson's because 5 years 
ago there were estimates that Parkinson's would be cured within 
5 years.
    Nobody can hold you to a cure time. But we would be 
interested in your projection on where you see NIH heading on 
the ailments to give us some projection as to what your 
expectations are. We understand that it is not possible to be 
scientifically precise. And then to tell us what more you can 
do with increased funding, what level of funding on the 
specific ailments would enable you to project an earlier time 
and by how much.
    Our colleagues in the Congress are very goal-oriented. And 
even questions which are really not answerable with precision 
are pursued. So to the extent that you could give us some ideas 
on those questions, the subcommittee would be very 
appreciative.
    Let me turn to Dr. Lawrence Tabak of the Dental Institute 
on a question which has recently come to the attention of the 
subcommittee on the presence of a cancer-related protein in 
saliva that could result in more acute, less costly ways to 
diagnose breast cancer in women. The question, Dr. Tabak, is, 
how much is being requested in the budget to pursue this line 
of research? And do you have any plans to conduct clinical 
trials in this area?
    Dr. Tabak. Thank you for the question, Senator Specter. In 
this current fiscal year, NIDCR is expending approximately $7 
million in the general area of salivary diagnostics. And for 
the next fiscal year, we hope to spend approximately $1.5 
million more to continue in this effort.
    Senator Specter. $1.5 million?
    Dr. Tabak. Yes, sir, that is correct.
    Senator Specter. What is the total budget of your 
institute?
    Dr. Tabak. Currently, it is $371 million, sir.
    Senator Specter. Does this new test pose real promise to 
give an easier, better diagnosis of breast cancer?
    Dr. Tabak. This and other salivary diagnostic tests do 
offer a great deal of promise, sir. The test to which you are 
referring, as you know, was worked out at the University of 
Mississippi. It is a test which recognizes a protein which can 
be found both in blood and saliva. But because of the ease of 
detection and the ease of sample collection in saliva, we feel 
that there are certain advantages for the saliva-based test.
    Senator Specter. Dr. Tabak, if you allocated more than $1.5 
million, do you think you could get a faster result on this 
important test?
    Dr. Tabak. Certainly, sir, resources are always welcome. 
But there is a point at which basic information needs to be 
gathered. And until that basic information is obtained, it 
would be premature to expend additional funds in a particular 
area.
    Senator Specter. Are you saying that is the maximum amount 
that can be efficiently spent on that research?
    Dr. Tabak. In terms of bringing this work to a full-blown 
clinical trial, sir, I think it would be premature. What we are 
now doing is termed phase-one trials to begin to understand 
whether or not this test is both accurate and efficacious. Once 
that base information is obtained, sir, then it would be 
appropriate to go on to larger scale trials.
    Senator Specter. Thank you.
    Senator Murray.
    Senator Murray. Thank you very much, Mr. Chairman.

                           PEDIATRIC RESEARCH

    Dr. Zerhouni, when you were confirmed, you and I talked 
about pediatric research. And I wanted to ask you today about 
any progress you have made. I think we have made a lot of 
progress on reducing gender bias, but I am still deeply 
concerned that we have not made much progress on making sure 
that we are looking at everything in terms of what happens to 
children.
    Can you give us an update on your pediatric research 
initiative?
    Dr. Zerhouni. Well, as you know, the pediatric research 
initiative is guided by a major document that we have been 
following in terms of implementation. There is no doubt in my 
mind that pediatric research is a priority, continues to be a 
priority. We have to also invest and continue to invest in the 
multiple areas of pediatric research.
    We are, for example, invested in terms of talent and 
developing talent and training capabilities for pediatric 
research. We are continuing to make investments in many of the 
pediatric diseases separately. For example, we have increased 
our investment in muscular dystrophy or increased our 
investment in spinal muscular atrophy. And in every category we 
have a disease-specific plan.
    But in terms of the overall investments in pediatric 
research, we need to integrate the pediatric research agenda 
within not just the NICHD Institute, which is primarily 
responsible for pediatric research, but all institutes.
    So I think it is work in progress. I think we are making 
good progress. But we will continue to consider that a 
priority, realizing as well, Senator, that many of the changes 
we need to make relate to these priority areas that I 
described--multidisciplinary teams that should invest in 
pediatric research, clinical research networks. For example, 
the Office of Rare Diseases is looking at establishing networks 
across the country to look at these rare diseases that tend to 
affect children.
    So we are looking at a multi-pronged approach and a 
strategic approach in pediatric research.

                     FUNDING OF RESEARCH PRIORITIES

    Senator Murray. Dr. Zerhouni, as you well know, there is a 
lot of misunderstanding about NIH research dollars. There is 
kind of this assumption out there that NIH only funds 
politically correct diseases or that you have to have a high-
profile celebrity in order to secure any NIH funding. And I 
know this subcommittee under Senators Specter and Harkin have 
really resisted any efforts to earmark NIH dollars by disease. 
We can express our thoughts through report language.
    But could you explain for us how you establish the 
priorities for NIH funding and what criteria is used in 
evaluating research applications?
    Dr. Zerhouni. Certainly, Senator. This is a question that 
is a recurring theme, especially when any particular area feels 
underserved. So that when we look at the decisionmaking 
process, we realize that there are fundamentally several 
factors that come into play. One, the first and foremost is the 
burden of the disease as we know it through epidemiological 
studies. And second, the predicted future burden of disease.
    For example, just as a matter of example, you look at 
diabetes and the rise in expenditures in diabetes, it parallels 
what we predict the burden of disease in diabetes is going to 
be. When you look at obesity research, we are now investing at 
an accelerated pace in obesity research because of the 
prediction. Even though when you look at the disease burden, 
per se, you cannot really decide that this is the only factor 
that you should look at, because the second factor is, have we 
made enough scientific advances to invest in the particular 
area with results that are likely to occur?
    So we look fundamentally at the investments in terms of, A, 
the burden of disease; B, the priority setting in terms of 
science. And we get advice in that context for many more 
sources than any. I am very impressed with the fact that NIH 
receives advice from 21,000 advisors every year on every single 
condition that we face.
    So the process is not an easy one to consider. But clearly, 
the patient advocacy groups are also interested in looking at 
how we invest. And my gratitude goes to you, because I think 
earmarking would not be a good direction for setting scientific 
priorities at NIH. And we try to avoid that and try to not be 
politically correct, as you state.
    Senator Murray. Well, I think it is really important to 
keep talking about how you set your criteria to the general 
public, because we do have a misperception constantly that if 
you get a high-profile person, that you get more funding. And 
so it makes it harder on us. And, as I said, Senator Specter 
has done a really good job managing that. But it is very 
difficult.
    I think it is important that we base it on science. So I 
appreciate your comments.
    Thank you, Mr. Chairman.
    Senator Specter. Thank you, Senator Murray.
    Dr. Zerhouni, I broach the subject of some delicacy now, 
which has already been communicated to you. Last year the 
Senate figure was cut by $25 million because the conference 
committee concluded that to reach the doubling, which was an 
astronomical figure, was more than sufficient. We have an 
enormous number of complaints from other research agencies 
about, candidly, the favoritism that NIH gets. And we have 
fought those battles out.
    We have heard from a number of people about directors of 
the institutes who have said that certain grants could not be 
applied or certain research could not be undertaken because the 
budget was cut and have attributed the $25 million reduction, 
which was not a cut at all, because there was an increase of 
more than $3.7 billion to the NIH budget.
    It would be amazing, I think, to many of you ladies and 
gentlemen, how fast the information travels from what you may 
tell someone who is applying for a grant or you may tell 
someone who is concerned about more research right back to my 
ears. You would be surprised.
    The advent of this very, very heavy increase in funding for 
NIH, which has come from this subcommittee, has had the 
reverberating effect of having this subcommittee contacted by 
many, many, many people, which had not been the case before we 
took up the cause of increasing the NIH grant. So if you do not 
want to make some allocation or you do not want to make a grant 
or you do not want to undertake some research, if you say it is 
because you got a cut in your budget, that is going to come 
back to the Congress.
    We hope you do not ever have a cut in your budget. But bear 
in mind that these people--and I know you have a good sense of 
this yourself--feel so very intently about these subjects, 
very, very emotional, when you have a child with one of these 
maladies, it is just the edge of the ledge. And I know that you 
dedicated men and women are well aware of that. But I thought 
it important to make a quasi-public statement. I have not said 
very much on the subject in the brief remarks I have just made.
    Let me turn now to the question of stem cell research. And 
I would like to direct this question to Dr. James Battey of the 
Deafness Institute and also to Dr. Allen Spiegel of the 
Diabetes and Digestive and Kidney Institute. Last September, 
this subcommittee held a hearing regarding the implementation 
of the Federal stem cell policy. And as you all know, back on 
August 9, 2001, President Bush articulated a modification of 
Federal policy to allow Federal funding on existing stem cell 
lines.
    At the September 25, 2002 hearing, Dr. Curt Civin stated, 
``Embryonic stem cell research is crawling like a caterpillar, 
while NIH has listed eligible lines in its registry at 78. Only 
a tiny fraction of these lines are accessible and only to those 
persistent and patient enough to jump through a series of hoops 
and endure lengthy waits. I am still waiting to receive my 
first stem cell line.''
    Dr. Battey and then Dr. Spiegel, what steps has NIH taken 
to help people like Dr. Civin and other scientists gain access 
to embryonic stem cell lines? And how many are now accessible?

                  ACCESS TO EMBRYONIC STEM CELL LINES

    Dr. Battey. The process of scaling up an embryonic stem 
cell derivation to the point where it can be distributed as a 
high-quality, well-characterized cell line takes about a year 
from start to finish. It is an expensive, time-consuming, 
technically demanding process that requires enormous care to 
maintain the cells in their state of pluripotency, which means 
their ability to differentiate into many different cell types, 
as well as to remain continuously self-renewing.
    To facilitate this very expensive and time-consuming 
process, the NIH has awarded infrastructure grants awards to 
eight suppliers that have derivations on the NIH stem cell 
registry. And I am pleased to tell you, Mr. Senator, that 
between the September hearing and the hearing today, if you had 
a research laboratory and wanted to order cell lines, in 
September you could have ordered five such cell lines. And 
right now, you could order 11 lines today.
    That effort is continuing to expand. And we expect that 
increasing numbers of cell lines will be widely available and 
actively shipped to the research community over the next 6 
months to a year.
    Senator Specter. How many stem cells are currently 
available?
    Dr. Battey. You could order 11 lines today.
    Senator Specter. Is that sufficient for the research which 
people want to undertake?
    Dr. Battey. At this point in time, the fundamental 
challenge in the human embryonic stem cell research arena is a 
basic research challenge. It is a challenge to understand what 
growth factors, transcription factors, and other molecules 
regulate the ability of embryonic stem cells to differentiate 
into one cell type versus another. It is an understanding of 
the interaction between the host and the transplanted cell that 
allows that cell to persist for a long time within the host and 
to function correctly.
    It is a challenge to understand how you control the cell 
cycle division of the cell, because once it is transplanted 
into a host, you do not want it to continue to be self-renewing 
in the same way that it was in the laboratory before it was 
transplanted.
    These basic research questions are readily addressable with 
the cell lines that are currently available and will become 
available within the next few months to a year.
    Senator Specter. Do we have sufficient stem cell lines for 
the research that people want to undertake?
    Dr. Battey. We have sufficient cell lines to embrace the 
basic research challenge that is in front of us today.
    Senator Specter. Well, is there some facet besides the 
``basic research challenge,'' which is in front of us today?
    Dr. Battey. The major questions that confront the stem cell 
research community today can be addressed with the cell lines 
that are available.

                    STEM CELL INFRASTRUCTURE AWARDS

    Senator Specter. Dr. Spiegel, would you care to amplify on 
Dr. Battey's answer?
    Dr. Spiegel. I would be happy to. Thank you, Senator 
Specter.
    Some general comments to amplify on what Dr. Battey said 
would include the provision of support through so-called 
infrastructure awards to the providers of these human embryonic 
stem cell lines. NCRR is funding the majority of these 
infrastructure awards. NIDDK is funding two of them. And this 
provides support to allow the distribution of these cells 
because they are very, very difficult to grow.
    Several NIH institutes have combined to provide training 
courses. As Dr. Battey has emphasized, one of the rate-limiting 
steps here is bringing new investigators into the field. It is 
not trivial to learn how to grow human embryonic stem cells. 
And these training courses are directed at that.
    A further example, which again comes out of the NIH Stem 
Cell Task Force, for which Dr. Zerhouni appointed Dr. Battey 
the Chair and on which I am pleased to serve, is an intramural 
NIH facility, which will be under Dr. Ron McKay and the 
Neurology Institute with extramural investigators as advisors. 
This effort will be comparing and looking critically at the 
different available human embryonic stem cell lines to provide 
information that is critical before investigators order them to 
work on in their own lab.
    Let me then just briefly speak on NIDDK specifically. 
NIDDK, like many of the other NIH institutes, has invested 
heavily in all aspects of stem cell research. So-called adult 
stem cell research, animal stem cell research, because animal 
models are very important, as well as human embryonic stem cell 
research. The aggregate figure for fiscal year 2002 for NIDDK 
was $58.3 million.
    One particular new initiative that we undertook, based on a 
trans-NIDDK planning group was so-called stem cell genome 
anatomy projects. These span the entire spectrum of the NIDDK 
mission so that we have projects directed at understanding the 
development of cells in the bone lineage, which we do with the 
Arthritis Institute, in the gastrointestinal and liver lineage, 
in the urology and the kidney lineage, and then so-called 
hematopoietic stem cells.
    One of our most important initiatives relating specifically 
to Type 1 and Type 2 diabetes is the so-called beta cell 
biology consortium. Of course, it is the beta cell that makes 
insulin, which is lacking in Type 1 diabetes and deficient in 
Type 2 diabetes. This consortium is looking at every avenue of 
approach to the development of these critical cells.
    Thank you.

                   STEM CELLS AND MOUSE FEEDER CELLS

    Senator Specter. Dr. Spiegel, what about the research to 
isolate stem cells without the use of mouse feeder cells?
    Dr. Spiegel. Currently, to my knowledge, although there 
have been reports from industry about the ability to grow human 
embryonic stem cells absent mouse feeder cells, the lines that 
are in use or available that Dr. Battey referred to do use 
mouse feeder cells. As Dr. Battey emphasized, this is not 
hampering the ability to do the basic research that we need to 
do to really be able to understand how we can trigger in a very 
organized and efficient way the development of these cells into 
various therapeutic possibilities.
    Senator Specter. Is it not true that research without the 
use of mouse feeder cells is indispensable, necessary to use 
those stem cells in humans?
    Dr. Spiegel. I totally agree. The comment that I was going 
to make is that a critical intermediate step before anyone 
should contemplate--in terms of safety and every other 
consideration--going into human trials, would be animal models, 
from small animal models and eventually to non-human primate 
models. Here, too, the mouse feeder layer issue is not rate-
limiting.
    But, you are certainly correct that to go into human 
trials, there would be issues that would have to be addressed 
in terms of possible mouse viruses and other contaminating 
proteins.
    Senator Specter. Should not those issues be addressed now 
by NIH?
    Dr. Spiegel. I think that that is an important issue. I 
think that, in terms of the available lines, there are 
important technical developments that can be undertaken that 
are critical to understand what the factors are that these 
mouse feeder-layers are eliciting that are necessary to keep 
the human embryonic stem cells from differentiating 
spontaneously. That is really the critical issue for which they 
are used.
    I believe that the kind of research that is being done, 
research that we can support, will very much address those 
kinds of issues. That is, after all, the goal, to really 
understand how to trigger development along a pathway that we 
want, and yet to prevent spontaneously differentiation. And 
such growth factor and other signaling research is being 
undertaken.
    Dr. Battey. If I could, Mr. Senator. Dr. Spiegel----
    Senator Specter. Wait just a minute. I find that very 
interesting, if not totally understandable. But what about the 
basic question of having some research without the use of mouse 
feeder cells? Do you not think that would be a pretty good idea 
with all you are doing? How many millions did you say you were 
spending?
    Dr. Spiegel. The total figure for NIDDK for fiscal year 
2002 was $58.3 million.
    Senator Specter. Well, why not some research without the 
mouse feeder cells? If they are to be used in humans, you are 
going to have to move in that direction.
    Ladies and gentlemen, what I want to be sure about, and I 
cannot quite accomplish it in this hearing today, is that we 
are not making any political decision, that you are making 
scientific decisions. That is what we expect from you 
scientists. That is why we are putting up $27 billion, which is 
a very, very big public trust.
    Do you want to say something more, Dr. Battey?

                           MOUSE FEEDER CELLS

    Dr. Battey. I just wanted to add to what Dr. Spiegel said. 
The first challenge to getting rid of the mouse feeder layer is 
figuring out what the mouse feeder layer is providing to the 
embryonic stem cells to render them able to differentiate into 
many different cell types and be self-renewing. And there is 
active research efforts to identify the factors that allow 
these cells to remain in that state. And when those factors are 
known and understood, we will be in a position to attempt to 
grow these cells absent a mouse feeder layer.
    Senator Specter. Dr. Penn, let me direct a question to you 
with respect to spinal muscular atrophy, a genetic motor neuron 
disease characterized by the wasting away of skeletal muscles. 
It is the leading killer of infants and toddlers. Twenty-five 
thousand Americans have the disease with up to 1,000 new babies 
born with the disorder each year.
    While there is a transitional research program, we are 
concerned about how effectively it is being put into operation. 
When spinal muscular atrophy was selected for this transitional 
research program--when was SMA selected for this transitional 
research program? And when will the first grants be awarded?
    Dr. Penn.

                    SPINAL MUSCULAR ATROPHY RESEARCH

    Dr. Penn. Yes, Senator. Spinal muscular atrophy actually is 
the leading genetic cause of infant mortality. It is not always 
lethal--there are three or four forms of it. In one form, it is 
really deadly to babies. But in several others, adults can grow 
and function and live with this disease.
    Spinal muscular atrophy, we feel, is a great scientific 
opportunity, because we not only know the genetic defect, but 
we know something about how to try to render this disease 
perhaps not cured, but to help it by dealing with the genetic 
defects. And therefore, we did decide to move this disease 
toward treatments, and I must say with a lot of help from the 
voluntary agencies, as well as the Muscular Dystrophy 
Association. And this is actually part of an institute-wide 
effort to move in what we call translational research, dealing 
with the basic mechanisms of a disease and then going to 
treatments.
    So we do have a brand-new way of pursuing working toward 
trying these treatments and doing clinical trials. We will go 
to the point of an investigational new drug application with 
FDA. And it has taken time to do this properly. This is so new 
that we have worked very hard to make it--to have a really 
excellent product.
    Actually what we are going to do is have a contractor issue 
subcontracts. And the subcontracts will be directed at the 
group of investigators out there that have done wonders to 
figure out what is going on with this disease since the gene 
was identified in 1995.
    So we will not be issuing grants. The contractor will 
actually call for subcontracts. We expect the whole group of 
investigators to come in for these. There will then be let a 
contract. And they will have to achieve milestones. It is not 
so much reporting on what you--yes, reporting on what you have 
done. You have to achieve something.
    There are drugs, actually drugs, that could be used in this 
disorder. And one of our intramural investigators, who is 
internationally recognized in these areas, is trying one of 
these drugs right now. But he is only working on cell lines 
from the patients. Again, we have to be very careful about 
using some of these things and moving to human beings.
    It has taken time. But we are issuing--we have issued the 
requests for proposals for this contract. And we expect to have 
this move by the end of the summer.
    Senator Specter. Dr. Penn, the question is, when was SMA 
selected for this transitional research program?
    Dr. Penn. Over a year ago. It took a year and a half to get 
it to this point.
    Senator Specter. Well, when will the first grants be 
awarded?
    Dr. Penn. The first subcontracts, sir, will be awarded, I 
would say, this winter.
    Senator Specter. When?
    Dr. Penn. This winter, sir.
    Senator Specter. Why is it taking so long?
    Dr. Penn. To do it properly and to get our intramural 
program up and running with it and to make sure that we develop 
and design this whole program so that we would have a really 
excellent result.
    Senator Specter. Well, why does it take almost 2 years, Dr. 
Penn?
    Dr. Penn. As I said, sir, this is something brand-new for 
us. It is a contract-based program. And it has taken 2 years.
    Senator Specter. It is something brand-new, but it is a 
contract-based program.
    Dr. Penn. It is brand-new for us. And we have--we are going 
to have a steering committee made up of the experts, both 
academic and----
    Senator Specter. You are going to have a search committee?
    Dr. Penn. A steering committee, sir, to run----
    Senator Specter. You are going to have a steering 
committee?
    Dr. Penn. For it to run----
    Senator Specter. Has the steering committee been appointed?
    Dr. Penn. It is being appointed right now.
    Senator Specter. Why does that take so long?
    Dr. Penn. Well, we had not gotten to that phase of the 
exercise.
    Senator Specter. Well, why have you not gotten to that 
phase?
    Dr. Penn. It just took this long to do this properly. It 
took this long----
    Senator Specter. Dr. Zerhouni, would you take a look at 
that and submit in writing----
    Dr. Zerhouni. Yes, Senator.
    Senator Specter [continuing]. What has happened?
    Dr. Zerhouni. I have looked----
    Senator Specter. I would like to have--but I am not going 
to take it up now.
    Dr. Zerhouni. Fine.
    Senator Specter. I would like to have precise answers as to 
when the program was adopted, as you call it a translational 
research program.
    Dr. Zerhouni. Understood.
    Senator Specter. And when a steering committee is adopted. 
And this subcommittee wants to examine whether there is an 
appropriate sense of urgency. It certainly has not satisfied a 
lot of parents whose children have this ailment.
    Dr. Zerhouni. I will respond directly to you on the record, 
sir.
    Senator Specter. Okay. We would appreciate it, if you 
would.
    [The information follows:]

                        Spinal Muscular Atrophy

    The NIH is committed to accelerating research toward finding a 
treatment for SMA, and fully appreciates the sense of urgency expressed 
by the parents of children with this disease, as it does the concerns 
of the parents of children affected by the scores of other neurological 
disorders--many of which are genetic and are often disabling or lethal. 
The NINDS recently launched a comprehensive program designed to 
encourage and support translational research for all neurological 
disorders. By translational research, I mean the process of applying 
insights and discoveries from basic scientific inquiry to the treatment 
or prevention of disease; the emphasis is on those activities focused 
on bringing therapeutic strategies to readiness for clinical testing.
    The specific, contract-based, SMA translational project to which 
you refer is in addition to all the other funding opportunities that 
are currently available for SMA research. It will use a performance-
based contract mechanism to allow rapid funding of translational 
research, in a milestone-driven process, to identify treatments for 
SMA. The NINDS presented the idea for this program to its National 
Advisory Neurological Disorders and Stroke Council in February 2002.
    The primary contract for the SMA project, which we expect to award 
on or about September 30 of this year, will provide overall scientific 
direction and organizational support for the program. A Steering 
Committee, drawn from academia, industry, the public, and NIH, will 
guide the program and play an integral oversight role for the 
Contractor throughout the project. A working group of the Council, 
including members of the proposed Steering Committee, will develop 
detailed recommendations for a plan for research on promising 
therapeutic strategies for SMA, such as drug development, gene therapy 
and stem cell therapy. The plan will address all the steps required, 
ultimately, to develop an IND--Investigational New Drug--application. 
The implementation of the research plan will be finalized by the 
Contractor, with guidance from the Steering Committee. The Steering 
Committee will assist the Contractor in evaluating success in 
accomplishing milestones, and in developing additional calls for 
research proposals as needed. Because the role of the Steering 
Committee is so integral to, and defined by, the contract, it would 
have been premature to establish its membership in advance of the 
publication of the statement of work in the request for proposals (RFP) 
for the SMA program; this RFP was issued on April 22, 2003. 
Importantly, efforts to recruit the Steering Committee are well 
underway, and there will be detailed recommendations for the research 
plan ready for presentation to the Council in September; calls for 
research projects can be issued in October 2003, shortly after the 
contract is awarded, and research projects should be underway by 
February 2004.
    The SMA translational program is not just a novel program for SMA, 
but also for the NINDS. The aim is to develop treatments that will be 
tested in people, and we hope this effort will serve as a model for 
expediting therapy development for other disorders. This program will 
require a significant investment of resources; the contract will be 
awarded for four years, and NINDS intends to fund the research 
subcontracts at a level of $4.5 million per year, which we anticipate 
will fund up to approximately ten research subcontracts per year. The 
NINDS intramural program will be involved throughout the process, 
providing expertise in neurogenetics and SMA, and will be equipped to 
rapidly initiate Phase I/II clinical trials when appropriate. For all 
of these reasons, careful planning has been essential.

    Senator Specter. Senator Harkin.
    Senator Harkin. Thank you, Mr. Chairman. I have an interest 
in SMA, also. I have met with families in Iowa about this. And 
I am concerned, as Senator Specter, that the leading cause of 
infant mortality is something that----
    Senator Specter. You ladies and gentlemen would be amazed 
with how many families we have met with with SMA and the other 
ailments.
    Senator Harkin. Yes. I started meeting with them maybe a 
couple years ago in Iowa or something. And this is something I 
had not even known about before. And now I just--now we find 
out that it is the leading cause of infant mortality. And we 
just have not done that much research on it. So I agree with 
you, we have to push hard on that. We have to get this thing 
moving. And I do not know why it has not by now. So I agree 
with the chairman on this, that we have to find out about that.
    Senator Specter. Well, there is one fellow who suffers from 
Parkinson's, who has an hourglass. Whenever he sees me, he 
turns the hourglass. And the ticking sands are going through 
the hourglass on every hour of his life. And these parents come 
to us with SMA and other ailments.
    I am about to go through a fairly long list of questions. 
We are going to take a little more time today, because we want 
to know what the sense of urgency is as to how these issues are 
being addressed.
    These people come to us and say, you are giving NIH all the 
money. What is happening? I do not like to hear talk of long 
periods of time on appointing steering committees.
    Senator Harkin.
    Senator Harkin. Thank you again, Mr. Chairman.
    I understand that you, in my absence--I was unavoidably 
absent from here a little bit--that you did cover the issue of 
stem cell research. And I just again want to buttress what you 
have said and hope that we can move ahead aggressively in this 
area, too. I understand that has been covered. So I will not go 
into that.
    The only thing that I just wanted to cover with you, Dr. 
Zerhouni, was just basically broader picture of the funding of 
NIH. We, as you know, basically just finished the doubling over 
5 years. Senator Specter and I are both, with his leadership 
and with my support, starting to get on another pathway of 
trying to get it up to a tripling, that is, from what we 
started in 1998.
    To maintain that level, it seems to me we are going to have 
to have somewhere in the neighborhood of about 7 or 8 percent a 
year, if I am not mistaken, increases. And it is my 
understanding, also, that just to maintain and kind of keep 
doing what we are doing, we are going to need somewhere in that 
level of funding. And yet the budget request this year is a 2.5 
percent request.
    So how can we keep from falling back from what we have 
done? And how can we continue to move ahead with a fairly 
aggressive level of expansion of NIH basic research at 2.5 
percent, or 2.6 percent, I guess it is?
    Dr. Zerhouni. Thank you.
    Senator Harkin. I mean, my point is, you asked for 2.6 
percent.

        SUSTAINING RESEARCH PROGRAMS ON MODEST BUDGET INCREASES

    Dr. Zerhouni. Thank you for your question. This is a very 
important consideration. Because one of the issues that we have 
to match with the concept of doubling is why are we doubling? 
And what are we trying to accomplish? And I think one of the 
issues that I raised was that we have evolving challenges. We 
have in fact stimulated in our country an incredible change in 
the way we do biomedical research. And we are in the transition 
phase in terms of understanding the new methods of research and 
the new teams that need to do this research.
    When you look at the 2004 budget, I worked very hard with 
the administration, with the Department, and with the Office of 
Management and Budget, when you look at the 2.6 percent 
overall, and we worked so that the effect on our research would 
be about 7.5 percent overall. And the reason for that is 
because we have essentially used one-time expenditures that 
related to building the infrastructures that we needed for 
biodefense research and other one-time items and reinvested it 
in research.
    So for 2004, the impact on the research portfolio in terms 
of growth is greater than the 2.6 percent, Senator.
    Senator Harkin. Well, I want to delve into that. In fiscal 
year 2003, Congress funded more than $300 million for 
extramural construction with allergies and infectious diseases, 
bioterrorism.
    Dr. Zerhouni. $375 million.
    Senator Harkin. $375 million?
    Dr. Zerhouni. Yes.
    Senator Harkin. I think you can argue that was probably a 
one-time expense.
    Dr. Zerhouni. Correct.
    Senator Harkin. But if I look at the extramural facilities 
renovation and construction program, going back just the last 
few years, this is an ongoing funding stream that this 
committee has funded, under different chairmanships here. We 
have all been supporting extramural construction and 
renovation. We know that some of the labs around the United 
States are deficient. They need to be upgraded. I am sure 
Senator Specter has visited, as I have. And so we embarked on 
this, also, a few years of making a funding stream every year 
available.
    So how can you say that this is a one-time expense? I could 
see saying that the $300-and-some million that we put in last 
year was a one-time expense for bioterrorism. But we have an 
ongoing extramural renovation and construction program that 
last year was $119 million, aside from that $300-and-some 
million. It was $110 million the year before. Now it was $75 
million a year for a few years before that. But then we bumped 
it up, because we saw the need out there. And now in fiscal 
year 2004, we are requesting zero dollars.
    To me, that is not a one-time expense. It is an ongoing 
commitment that we have to rebuild and modernize our laboratory 
infrastructure in the United States.

             FUNDING COMMITMENT TO EXTRAMURAL CONSTRUCTION

    Dr. Zerhouni. For the 2004 year, what we tried to do was to 
preserve and maintain the momentum in what is the most critical 
resource, and that is people applying for grants and getting 
support so that the teams of the scientists that we have 
stimulated continue to be stimulated. So we had to make hard 
choices, Senator. And that is one of them.
    Senator Harkin. But if we make the choice here to continue 
to fund extramural construction, then you will not have that 
money for research, will you? It will be down to 2.6 percent.
    Dr. Zerhouni. That is----
    Senator Harkin. If we keep the level of funding----
    Dr. Zerhouni. In each category the same per year, you are 
correct. You are correct, Senator.
    Senator Harkin. Dr. Zerhouni, are you advising us that we 
should zero out all funding for renovation and building of 
laboratory facilities?
    Dr. Zerhouni. For the year 2004, because of the portfolio 
of construction that we had to do and that we had to continue 
to fund, we thought that the best strategy to maintain the 
research momentum so that we can invest it in programs that 
relate to diseases was to make that choice and----
    Senator Harkin. For next year.
    Dr. Zerhouni. For next year. Correct.
    Senator Harkin. Well, then, Dr. Zerhouni, let me carry this 
one step further. The President's budget documents call for a 
1.9 percent increase in 2005, a 2 percent increase in 2006, and 
2.2 percent in 2007. So carrying this logic forward, then for 
the next 3 years, we will be asked to zero out any funding for 
extramural construction and renovation, if that is the case. So 
it may be so next year. We may be looking at 4 or 5 years 
here----
    Dr. Zerhouni. Right.
    Senator Harkin [continuing]. Of zeroing out any--I do not--
I can only speak for myself, but to me that is unacceptable. We 
cannot do that. And so I just--you know, this idea that somehow 
we are going to squeeze out of this and get a 7 percent for 
basic research and to make sure we keep the grant funding going 
out at that level, it does not square with what we have to do 
with extramural construction.
    So I--maybe you might do it 1 year. I do not think you can. 
I think we just cannot go to zero funding for 1 year. We can 
cut out the $300-and-some million, because that was a one-time 
expenditure for bioterrorism. But then there is the underlying 
program that I do not think that we can cut out. So I just 
wanted to make that point. I know what you are trying to do, 
but I do not think it fits. And we are simply going to have to 
come up with that extra money. And I am going to keep proposing 
that the President has to put that in his budget next year.
    Thank you, Dr. Zerhouni.
    Thank you, Mr. Chairman.
    Senator Specter. Thank you, Senator Harkin.
    Dr. Zerhouni, I am going to go over a series of questions. 
We have been asked to have separate hearings on many of the 
institutes. And that is not possible, given all of the 
difficult schedules. We have been asked to have a separate 
hearing on tuberous sclerosis, where scientists have reportedly 
isolated the genes responsible for this disease that affects 
all of the body's organs.
    I would like you to submit in writing and in some detail 
how much NIH is currently investing in research on tuberous 
sclerosis, and how that research is being coordinated among the 
various institutes involved.
    [The information follows:]
                       Tuberous Sclerosis Complex
    The NIH reported actual funding for tuberous sclerosis research in 
fiscal year 2002 was $6.1 million; the fiscal year 2003 estimated 
funding is $6.4 million. While the National Institute of Neurological 
Disorders and Stroke--NINDS--is the lead institute for research on 
tuberous sclerosis complex, TSC, several other institutes conduct and 
support TSC research, which is reflective of the multiple organs 
affected. The National Cancer Institute--NCI; the National Heart, Lung, 
and Blood Institute--NHLBI; and the National Institute of Diabetes and 
Digestive and Kidney Diseases--NIDDK, support TSC research. Funding by 
Institute is summarized in the table that follows:

----------------------------------------------------------------------------------------------------------------
                                                                                Fiscal years
                                                           -----------------------------------------------------
                                                              2002  actual     2003  estimate    2004  estimate
----------------------------------------------------------------------------------------------------------------
NCI.......................................................          $638,000          $657,000          $677,000
NHLBI.....................................................         2,140,000         2,279,000         2,336,000
NIDDK.....................................................           717,000           700,000           700,000
NINDS.....................................................         2,596,000         2,803,000         2,859,000
OD........................................................            30,000  ................  ................
                                                           -----------------------------------------------------
      Total...............................................         6,121,000         6,439,000         6,572,000
----------------------------------------------------------------------------------------------------------------

    The systems affected in TSC are quite distinct, and therefore, much 
of the research supported may be unique to a particular institute's 
mission, for example, NINDS to investigate the development of epilepy 
and autism in children with tuberous sclerosis; NCI for studies to 
examine what causes skin tumors to develop in patients with TSC; and 
NHLBI to study the molecular and cellular basis for the development of 
lymphangioleiomyomatosisL--AM--a severe destructive lung disease, in 
patients with tuberous sclerosis complex. However, we recognize the 
value in tracking and coordinating the TSC research that NIH supports, 
as well as identifying potential partnering opportunities, and on this 
NINDS has the lead. Coordination is achieved in many ways, not the 
least of which is regular communication among the program directors who 
manage the TSC portfolio in each institute. In addition, NINDS is 
coordinating input from several institutes, extramural researchers, and 
the advocacy community in developing the NIH research plan for tuberous 
sclerosis. For example, program staff from NIDDK and the National 
Institute of Arthritis and Musculoskeletal and Skin Diseases--NIAMS--
participated in the September 2002 NINDS-sponsored workshop on TSC 
research, the proceedings of which are providing the framework for the 
research plan, and these institutes, along with the National Institute 
of Child Health and Human Development--NICHD, NHLBI, and NCI, are being 
consulted in the development of the NIH TSC research plan.

    Senator Specter. There is another subject matter of 
scleroderma, where there has been a tremendous amount of 
interest. And there is significant vascular and autoimmune 
components to scleroderma. And the question is whether there 
are other institutes, aside from the National Institute of 
Arthritis, Musculoskeletal, and Skin Disorders or the National 
Heart, Lung, and Blood Institute, that you would recommend 
scleroderma researchers pursue to find experiments aimed at 
finding a cure.
    Since the leading cause of death in scleroderma patients is 
through pulmonary hypertension and its effects on heart 
function, should grants on pulmonary hypertension that 
encompass issues unique to scleroderma patients be directed 
at--and this question goes to Dr. Katz and Dr. Lenfant. Should 
those research grants be directed at NHLBI, instead of NIAMS?
    These questions are so complicated that I have to read 
them, which is not my style.
    What do you think, Dr. Lenfant? Are you willing to defer 
that to another agency, or should they be directed to your 
agency? I would appreciate as much brevity as you can bring 
here, because there are quite a few more questions. And we need 
to finish this hearing by 11. Actually, we need to finish this 
hearing by 10:45.

                          SCLERODERMA RESEARCH

    Dr. Lenfant. Senator, in view of the complexity of this 
condition, I think the research must be conducted by the two 
institutes. And it is so happens that Dr. Katz and I work very 
well on many conditions besides this one. And I am quite 
confident that this cooperation, should it continue, it will be 
the best way to handle that condition.
    Senator Specter. How are you doing, Dr. Lenfant, on finding 
a cure for scleroderma?
    Dr. Lenfant. Scleroderma, or systemic sclerosis, is of 
considerable interest to the NHLBI because of the lung problems 
that so often accompany it. Indeed, 8 out of 10 patients with 
scleroderma eventually develop some degree of lung disease, and 
interstitial pulmonary fibrosis (scarring) is now the leading 
cause of death among such patients. Since 1999, the NHLBI has 
supported the Scleroderma Lung Study, a clinical trial to 
evaluate treatment with cyclosphosphamide, a drug that has 
effects on inflammation and the immune system. The goal is to 
determine whether cyclophosphamide helps stabilize or improve 
measures of lung function; the trial will also assess changes 
in quality of life, activity, and shortness of breath. A 
positive outcome of this trial would be of great importance by 
offering a scientific basis for treatment. Similarly, a 
negative result, demonstrating no benefit from cyclophosphamide 
therapy, would provide an important basis for avoiding a 
hazardous and expensive therapy that is now being used in many 
patients.

                              SCLERODERMA

    Senator Specter. Dr. Katz, how close do you think you are 
coming to finding a cure for scleroderma?
    Dr. Katz. We are pursuing every scientific opportunity 
possible in scleroderma research and working with the community 
as well as with our colleagues at NHLBI in this area, which 
includes pulmonary fibrosis. We are pursuing research on blood 
vessel abnormalities genetic controlled fibrosis, as well as 
other genetic dimensions of scleroderma. So we are pursuing----
    Senator Specter. Is it a realistic question to ask you how 
close you are to a cure?
    Dr. Katz. Yes, sir. It is a realistic question.
    Senator Specter. Can you give me a realistic answer?
    Dr. Katz. I cannot give you a date, if that is what you are 
looking for. But I----
    Senator Specter. Can you give me a time frame, a ballpark?
    Dr. Katz. I would hope that in the next 5 years we will 
have some better information on the complexity of this disease.
    Senator Specter. Sometime within the next 5 years we would 
have better information on the complexity of the disease.
    Dr. Katz. Right.
    Senator Specter. I would like you to supplement that in 
writing, focusing on my question, please.
    Dr. Katz. I would be happy to.
    [The information follows:]

                              Scleroderma

    I am very pleased to tell you that research on scleroderma is at a 
very important and promising juncture. We have a solid foundation of 
grants in our portfolio, we have very powerful research tools to apply 
to scleroderma, and we are building on significant research advances in 
our understanding of scleroderma. Examples of recent advances include 
identifying a genetic marker for scleroderma in two populations; basic 
research that identified defective microfibrils in cultured fibroblasts 
from people with scleroderma; and the determination that the risk of 
having scleroderma increases significantly (on the order of 10 to 27 
times) if a family member has scleroderma. These are just highlights of 
progress. With a look to the future, I am very optimistic that within 
the next 5 years we will have much better information on the complexity 
of scleroderma. My optimism is based on the multi-pronged approach that 
we have taken in research on scleroderma, including the ongoing, 5-
year, multicenter clinical trial that is seeking to determine the 
efficacy of oral collagen in the treatment of scleroderma; the funding 
that the NIAMS provides for two Specialized Centers of Research focused 
on scleroderma that will enhance translational research; support for 
the National Family Registry for Scleroderma that will provide vitally 
important information on the genetic/family dimensions of this 
disorder; and the outcomes of the 10 new research grants that the NIAMS 
funded in fiscal year 2001 as the result of a special solicitation. We 
can expect that research findings will begin to emerge from these 
grants over the next few years and will contribute significantly to our 
understanding of the complexity of scleroderma. In addition, I would 
note that scleroderma is an autoimmune disease, and the knowledge base 
in this area is progressing at a rapid pace. Findings that we learn 
from one autoimmune disease can be very useful in informing us about 
other autoimmune diseases. So if we look broadly, advances in genetics 
and autoimmunity will accelerate the pace of progress in scleroderma 
and many other diseases. We know that medical research is an 
investment, and I believe that the investments we have made over the 
last few years will provide critical, key pieces of the multi-
dimensional, challenging puzzle that scleroderma represents.

    Senator Specter. Dr. Zerhouni, we are having a lot of 
comments on the Muscular Dystrophy Care Act, which called for 
the creation of multiple centers of excellence, signed into law 
in 2001. That was before your watch. The subcommittee on three 
occasions has said that a minimum of three such centers should 
be funded. A request for proposals has finally gone out to 
organize the centers. But the only assurance of the scientific 
community is that two centers will be funded.
    I would like you to submit in writing an answer to the 
question, why only two? And what funding level is projected for 
these centers?
    [The information follows:]

                           Muscular Dystrophy

    The NIH has been actively engaged in implementing the mandates of 
the MD-CARE Act, including efforts to establish research centers for 
muscular dystrophy. Specificially, in the Fall of 2002, the NIH issued 
two Requests for Applications (RFAs) in this area. The first solicited 
applications for up to three awards for Muscular Dystrophy Cooperative 
Research Centers, and the second solicited applications for up to five 
awards for Developmental Planning Grants for future centers. During 
fiscal year 2003, following peer review, we will make grant awards in 
response to these two RFAs; the number of grants actually awarded, up 
to the specified numbers, will depend on scientific merit. In fiscal 
year 2004, we plan to re-issue the RFA for Cooperative Research 
Centers, and expect to fund up to two additional meritorious centers in 
fiscal year 2005. Subject to the number of applications we receive and 
the results of scientific peer review, the combined solicitations could 
result in funding up to a total of five MD cooperative centers.
    We anticipate that the total costs for each center will be 
approximately $1.5 million for 5 years. If the combined solicitations 
result in funding a total of five MD cooperative centers, the total 
costs of all centers for 5 years is estimated at $37.5 million.

    Senator Specter. A question to the Cancer Institute to be 
responded to by Dr. von Eschenbach. On June 21, 2001, we held a 
hearing on blood cancers. And Dr. Klausner, then the Director 
of the Cancer Institute, testified that Gleevec has shown 
remarkable results in treating chronic leukemia. The question 
is: Why is Gleevec only effective on this particular form of 
cancer? And in what specific ways would Federal funding of stem 
cell research expedite the treatment and cures of blood cancer?

                                GLEEVEC

    Dr. von Eschenbach, would stem cells be helpful there, stem 
cell research?
    Dr. von Eschenbach. Thank you, Senator. As you are well 
aware, there has been a great deal of research with regard to 
adult stem cells, and particularly in their application 
therapeutically in support of the treatment of blood cancers. 
The issue of Gleevec, that is a very important story. Because 
one of the wonderful things that we have seen as a result of 
the progress made in using a drug like Gleevec, targeted to a 
specific genetic defect in leukemias, the understanding of how 
that drug works in that pathway is now being extended to a 
whole variety of other cancers. Gleevec is being used in 
prostate cancer and it is being used in other childhood 
cancers. So the return on investment of Gleevec is going far 
beyond the blood cancers.
    Senator Specter. Dr. Insel, the prevalence of autism is 
increasing, with the disease affecting, as we understand it, 
some 500,000 people in this country at a cost of $13 billion 
annually. Autism advocates are requesting the NIH expand its 
research portfolio as well to finance a tissue bank program 
that would enhance resources and provide centralized tracking 
of research projects among all autism research participants.
    What are your plans to develop a tissue bank? And how much 
has autism research increased since the NIH doubling began?

                            AUTISM RESEARCH

    Dr. Insel. Thank you, Senator. The interest in the autism 
tissue bank has increased greatly in the last few months. We 
held a workshop just in the last 6 weeks, bringing----
    Senator Specter. Greatly? Greatly?
    Dr. Insel. Yes.
    Senator Specter. How much?
    Dr. Insel. In terms of the interest? There is a wide----
    Senator Specter. Increase in funding is the question.
    Dr. Insel. I was saying interest in the tissue bank. The 
workshop that we held 6 weeks ago brought in people from around 
the country who are experts in autism. There is a plan to roll 
out the specifics at the next Interagency Autism Coordinating 
Committee meeting.
    Senator Specter. Is a tissue bank now being developed?
    Dr. Insel. We anticipate it will be public by July, the 
first week in July.
    Senator Specter. And how much has autism research 
increased?
    Dr. Insel. In 1998, the NIH budget for autism was 
$26,889,000. In 2002, it was $73,850,000.
    Senator Specter. Dr. Fauci, let us come back to smallpox 
one more time. The Federal Government is not recommending 
vaccination for the public. But HHS has stated that it will try 
to accommodate members of the public who want to be vaccinated. 
As the program is projected this year, the public has two 
options. First, enrolling in ongoing clinical trials; or 
second, for those who want to be vaccinated but who do not meet 
the trial criteria, HHS has proposed that it will allow 
vaccinations under an investigational new drug approach, which 
will require informed consent.
    Now this is because the new vaccine has not yet been 
licensed. Once the new vaccine is licensed in 2004, concluding 
that it will be at that time, the only way the public will be 
able to get it is from HHS.
    My question to you is, vaccination for the general public 
is at the impetus of the individual. Do you think this is 
sufficient, or should there be a national vaccination strategy 
for the general public as opposed to waiting for the individual 
to come forward?

                      NATIONAL VACCINATION PROGRAM

    Dr. Fauci. Mr. Chairman, given the current threat 
assessment, I think a national vaccine program for the general 
public, beyond just someone coming and asking for it, is not 
necessary at this time. The first priority, as you know, is to 
vaccinate the core smallpox response team and ultimately the 
first responders.
    But given the current threat assessment, if we get that 
core group vaccinated, which we hopefully will, then in the 
event of an attack, the logistic capability of vaccinating 
anyone who is within the range of a contact would be much 
easier than it is right now. So the combination of the 
Department of Homeland Security and HHS have come to the 
judgment that we do not need to implement a pre-event program 
for the general public at this time.
    Senator Specter. Dr. Fauci, I hope you are right.
    Dr. Fauci. I hope so.
    Senator Specter. We have gone back and forth. We have had 
quite a number of hearings on the subject. We have talked about 
our grandchildren. There is no precise, cannot be a precise, 
evaluation of what the risk is of a smallpox attack, try to use 
that as a biological warfare weapon. People who have taken the 
vaccine with some bad results. People do not like the risk. 
Pretty tough to undertake a risk from the vaccination when 
there is no identifiable risk of bioterrorism in the field.
    Dr. Fauci. Right.
    Senator Specter. But at the moment, the policy is sort of--
perhaps it is not drifting along, but it is pretty hard to 
formulate it with precision. But I respect your conclusion that 
the policy has been thought through. And you have decided to do 
no more. But we all hope you are right that we do not find a 
bioterrorism attack and insufficient cautions having been 
taken.
    Dr. Fauci. Excuse me, sir. In the event of an attack, there 
is a response capability that we are building on right now that 
would very likely, almost certainly, be able to protect the 
country. The reason that the program has not been recommended 
for the public is because the threat assessment of an attack is 
balanced against the known toxicities of the currently 
available Dry Vax, and it is felt that a preemptive total 
vaccination of the Nation is not necessary.
    This will change if one of two things happen. If the threat 
assessment changes and we feel the threat is greater. And what 
we are striving for in the next couple of years is a smallpox 
vaccine that has many fewer toxicities or adverse events. If we 
had the attenuated vaccine at the current time, I believe there 
would be a good deal more flexibility in the broad general 
recommendations for the general public.
    Senator Specter. Well, thank you very much, ladies and 
gentlemen. This is the longest hearing we have had in awhile. 
We are into the third hour. And it is hard to attract the 
attention of Senators for very long around here, given the 
problem of the war in Iraq and what we are going to do with 
North Korea and how we are going to handle the Middle East and 
what we are going to do with terrorism and what we are going to 
do with double taxation of dividends, probably the foremost 
question on the minds of everybody in this room today. I mean, 
not the foremost question on the minds of everybody in this 
room today.
    We appreciate what you are doing. There are going to be 
questions submitted for the record. And when Senator Taylor 
calls you up and brings issues to your attention, she is 
speaking for the whole Congress. She does not speak for just 
herself.
    She does not speak just for me. She does not speak for 
Senator Harkin and me or this subcommittee or the full 
Appropriations Committee or the Senate. She speaks for the 
whole Congress.
    We have become a lightning rod for inquiries and demands. 
You have no idea how many irate parents we see, or irate 
children we see for interest in their parents. So if we convey 
a sense that we are looking for a greater sense of urgency, if 
you get that message today, you are right. But we do know that 
you are in the trenches doing very, very important work. And we 
have a tougher issue now than we have ever had before on 
finding the money for NIH and the CDC. But we are going to plug 
away. And we look for your continued success.

                     ADDITIONAL COMMITTEE QUESTIONS

    There will be some additional questions which will be 
submitted for your response in the record.
    [The following questions were not asked at the hearing, but 
were submitted to the Department for response subsequent to the 
hearing:]

        Questions Submitted to the National Institutes of Health
              Questions Submitted by Senator Arlen Specter

                           PANCREATIC CANCER

    Question. Director von Eschenbach, this Subcommittee has taken a 
keen interest in the status of pancreatic cancer research at your 
Institute. Pancreatic cancer is the now the 4th leading cause of cancer 
death for men and women in this country. It also has the highest 
mortality rate making it the cancer you are most likely to die from, if 
you are diagnosed with this disease, because of the lack of reliable 
diagnostics.
    I would like for you to update the Subcommittee on the status of a 
number of pancreatic cancer initiatives:
    Last year's report expressed the strong intent of this Committee 
that the NCI fund at least five Pancreatic Cancer Specialized Program 
of Research Excellence (SPORE) grants by fiscal year 2004. Will you be 
following the Committee's intent--as expressed in last years report 
language--to fund five Pancreatic Cancer SPORE Grants by fiscal year 
2004?
    Answer. In fiscal year 2004 NCI expects to fund three pancreatic 
cancer SPORE grants. The NCI announced a special initiative to enhance 
and promote translational research in pancreatic cancer and received 
fourteen pancreatic SPOREs applications. Thirteen of these applications 
were reviewed by a Special Emphasis Panel following general peer-review 
principles established by the NIH. Only three of these SPORE 
applications were found to have sufficient scientific merit to be 
considered for funding by the NCI. No definitive decisions can be 
presented at this time since our funding recommendations will undergo a 
second level of review by the National Cancer Advisory Board at the 
next meeting in June 2003. We anticipate these three meritorious 
applications will be funded as P20 Development awards. We are hopeful 
these preliminary programs will jump start the field and serve as a 
foundation to develop additional strong researchers and programs in 
this field.
    Question. How many of the meritorious individual projects from non-
funded SPORE Grants and program project applications does the NCI 
intend to fund in fiscal year 2004?
    Answer. Four projects from the remaining applications were 
considered by the peer review as highly scientifically meritorious. 
These applications will be recommended for submission to our R01 grant 
mechanism for individual funding.
    Question. I compliment the NCI's past efforts to increase the 
paucity of researchers through extending the payline for grants that 
were 100 percent relevant to pancreatic cancer. I understand that this 
initiative may have been the single most important action taken by the 
NCI to finally give pancreatic cancer the support that it needs, yet it 
was discontinued after just one year. Why was this important payline 
initiative discontinued?
    Answer. Extending the payline for applications that were 100 
percent relevant to pancreatic cancer enabled the NCI to fund only 
three additional pancreatic cancer research projects in fiscal year 
2002. The NCI discontinued the extended payline for pancreatic cancer 
applications in fiscal year 2003 and agreed to use a mechanism for 
exception funding to include grants that meet only 50 percent 
relevancy. The NCI remains firmly committed to increasing the amount of 
research focused on pancreatic cancer. Therefore, the NCI is granting 
pancreatic cancer applications higher priority for exception funding, 
even those with only 50 percent relevance to the disease. We are 
hopeful that this mechanism will significantly increase the number of 
meritorious grants that will impact on pancreatic cancer.
    Question. Do you have plans to reinstate this extended payline, and 
what are the estimated costs to continue it for a period of five years?
    Answer. Since extending the payline for pancreatic cancer 
applications reduced the number of better scoring applications that the 
NCI could fund, the NCI does not intend to reinstate the extended 
payline. This decision is not made on basis of cost but rather a 
strategic effort to encourage meritorious research relevant to 
pancreatic cancer.
    Question. If not, how do you intend to develop the critical mass of 
researchers needed for pancreatic cancer?
    Answer. In its recently released strategic plan for addressing the 
recommendations of the Pancreatic Cancer Progress Review Group (http://
prg.cancer.gov/pancreatic/pancreatic.pdf), the NCI lays out a multi-
faceted approach for developing a critical mass of pancreatic cancer 
researchers. The Institute has implemented some of the strategies in 
the plan already. These include:
  --Granting special consideration to pancreatic cancer applications 
        beyond the payline, even those with only 50 percent relevance 
        to the disease.
  --Soliciting and promoting applications for SPOREs in pancreatic 
        cancer. The top-scoring applications will undergo a required 
        second level of review by the National Cancer Advisory Board in 
        June.
  --Informing investigators of new funding opportunities in areas of 
        particular relevance to pancreatic cancer, such as host-tumor 
        interactions, the tumor microenvironment, and nanotechnology 
        development for early detection.
    NCI plans to put additional strategies in place in fiscal year 2003 
and fiscal year 2004, but actual implementation will depend upon a 
final determination that these strategies are feasible and sound, and 
the receipt of high-quality applications from the research community. 
These strategies include:
  --Expanding the Transition Career Development Award (K22) to extend 
        the funding period and include all scientists.
  --Increasing the number of pancreatic cancer research mentors through 
        the National Research Service Award program.
    Question. It is my understanding that the NCI is continuing to make 
good on its commitment to implement the report of the Pancreatic Cancer 
Progress Review Group (PRG)--which is a national agenda for the 
research needed on pancreatic cancer. I have been told that since the 
PRG Report came out in February 2001, the NCI has been moving forward 
to implement the suggestions raised in the report, and that most 
recently the NCI has developed a ``Strategic Plan for Addressing the 
Recommendations of the Pancreatic Cancer Progress Review Group'' to 
further detail and prioritize the research needed on this disease. With 
the President's proposed NIH increase of roughly 2.6 percent for fiscal 
year 2004, how many of the strategies identified in the ``NCI Strategic 
Plan'' can actually be put into place next year, and which ones do you 
plan to implement?
    Answer. The NCI has already implemented some of the strategies in 
its pancreatic cancer plan. These strategies include:
  --Granting special consideration to pancreatic cancer applications 
        beyond the payline, even those with only 50 percent relevance 
        to the disease.
  --Soliciting and promoting applications for Specialized Programs of 
        Research Excellence (SPOREs) in pancreatic cancer.
  --Funding the development of new pancreatic cancer mouse models.
  --Funding phase 1 and phase 2 studies for chemoprevention of 
        pancreatic cancer.
  --Holding a state-of-the-science meeting on management of pancreatic 
        cancer symptoms.
    NCI plans to put additional strategies in place this year and next, 
but actual implementation will depend upon a final determination that 
these strategies are feasible and sound, and the receipt of high-
quality applications from the research community. These strategies 
include:
  --Funding the development of nanotechnologies that use small samples 
        for early detection of pancreatic cancer.
  --Identifying markers for early detection of pancreatic cancer 
        through NCI's Center for Proteomics.
  --Funding research on normal pancreas biology and pathogenesis of 
        pancreatic cancer (with NIDDK).
  --Expanding NCI's cohort consortium to include pancreatic cancer.
  --Supporting large case-control studies in HMOs to improve 
        understanding of pancreatic cancer risk factors.
    Question. I know the request was made before you came to the NCI, 
but in the fiscal year 2002 report, this Committee specifically 
requested that the NCI develop a professional judgment budget due April 
1, 2002 for research on pancreatic cancer for the next five years. The 
goal here was to ascertain how much the NCI is actually spending on 
pancreatic cancer and compare the current funding level to what is 
actually needed to make some inroads on this disease, which has a 99 
percent mortality rate, making it the cancer you are most likely to die 
from, if you are diagnosed with this disease. While I am delighted to 
hear that movement is being made on the findings of the Pancreatic 
Cancer Progress Review Group, we have not received the Five-Year 
Professional Judgment Budget to implement these recommendations. When 
might we receive it?
    Answer. Over the past several years, NCI has convened Progress 
Review Groups (PRGs) on several types of cancer, and the reports 
generated by these groups have formed the basis of expanded and 
intensified research in these areas. Completed PRG reports have 
identified gaps in research in breast, prostate, colo-rectal, brain, 
pancreatic, hematologic, lung, and gynecologic cancers. As with all 
other PRGs, NCI developed an implementation plan to move forward with 
the recommendations for pancreatic cancer research in a prioritized 
fashion. This was done with participation by outside scientists and 
advocates who also participated in the PRG itself.
    NCI announced a 10-point plan of action that allows NCI to take 
immediate steps to address the gaps in pancreatic cancer research. Some 
strategies have already been implemented such as granting special 
consideration to pancreatic cancer applications beyond the payline and 
funding Specialized Programs of Research Excellence (SPOREs) in 
pancreatic research. The plan's approach involves expanding existing 
programs, as well as developing new initiatives. Additional strategies 
are being considered, including funding the development of mechanisms 
for early detection and expanding proteomics research.
    We estimate that we will spend $38 million on pancreatic cancer 
research in fiscal year 2004. The preparation of a Professional 
Judgement Budget will take into account the implementation of these 
programs and their expected expenditures and increases over the next 
five years. Subsequent initiatives will be included in a rolling 
forward budget plan as reflected in our Bypass Budget.

                          PROTEMOMIC PATTERNS

    Question. In last years report, this Committee encouraged the NCI 
to ``rapidly identify predictive proteomic patterns relevant to 
pancreatic cancer'' and ``to develop and implement methods for rapid 
case ascertainment.'' Can you please provide us with the status of 
progress in both of these areas including what has been developed and 
implemented?
    Answer. The body's 30,000 or so genes carry the blueprint for 
making proteins, of which all living matter is made. Each protein has a 
particular shape and function that determine its role in the body. NCI 
has an extensive research program in proteomics, the study of protein 
shape, function, and patterns of expression, in hopes of developing 
better prevention, screening, and treatment options.
    There has been a joint effort including the Food and Drug 
Administration (FDA), the NCI Clinical Proteomics Program, and 
Correlogic Systems Inc. which has brought together two scientific 
disciplines: proteomics and artificial intelligence computer programs.
    Last year, there was an exciting announcement that with a 
preliminary diagnostic test, which could be completed in 30 minutes 
using blood that can be obtained from a finger stick, researchers were 
able to differentiate between serum samples taken from patients with 
ovarian cancer and those from unaffected individuals. Further study is 
continuing to confirm the sensitivity and accuracy of this technique as 
a diagnostic tool. The hope is that by combining the proteomic approach 
with other methods of ovarian cancer diagnosis, such as ultrasound, its 
accuracy can be further improved. This new diagnostic concept is 
potentially applicable to any type of disease and is now being tested 
on pancreatic, prostate, lung and breast cancer.
    NCI has made significant progress in the early detection of 
pancreas cancer using serum proteomic patterns. We are pleased to have 
already made progress in the application of this technology to 
pancreatic cancer. Scientists tested 350 plasma samples from the 
University of Minnesota. The sample groups were (a) unaffected, (b) 
diabetes only, (c) pancreatitis only and (d) pancreatic cancer. NCI 
researchers discovered a serum proteomic pattern that was greater than 
95 percent sensitive and specific in the classification of pancreas 
cancer compared to the other non cancer groups. Currently there is no 
other reliable test for pancreas cancer. We are now moving forward to 
validation of these preliminary results in a larger population of 
patients with and without pancreatic cancer. At the same time we are 
applying this technology to other cancers. If validated in larger 
series serum, proteomics could constitute a new approach to the early 
diagnosis of pancreatic cancer.

                  COMPREHENSIVE CANCER CENTER PROGRAM

    Cancer is a disease that affects families of all backgrounds in all 
parts of the country. However, cancer affects more families in my state 
than most others. We hold the unfortunate distinction of ranking among 
the top five in the nation in rates of multiple myeloma and oral, 
prostate, pancreatic, and esophageal cancer. We are also not far behind 
in regard to cervical and larynx cancer.
    Through the significant investment this Subcommittee has made in 
cancer research, we have enabled scientists from across the country to 
expand our basic understanding of cell growth and death and to develop 
effective forms of treatment and prevention. Much of this work was 
accomplished in NCI-designated comprehensive cancer centers. I am 
troubled that these centers tend to cluster in the Northeast and along 
the Pacific Coast, and bear little correlation to cancer incidence or 
mortality rates. In fact, only three of the fifteen states with the 
highest cancer mortality rates have a comprehensive cancer center. 
While we should continue to fund the best and brightest in their 
efforts to find cures for cancer, I believe the current concentration 
of comprehensive cancer centers deprives us of gaining valuable 
knowledge in the parts of the country where cancer is most prevalent.
    Question. Director Zerhouni and Director von Eschenbach, I would 
like to hear your plans for how you intend to grow the comprehensive 
cancer center program and how you intend to ensure that areas with high 
cancer rates receive the full attention of these centers.
    Answer. At the present time, NCI has 60 clinical and comprehensive 
cancer centers. They have a wide geographic distribution and leverage 
the extraordinary talents and resources of major medical centers. These 
spheres of influence go far beyond their geographic location as a 
Center of Excellence of cancer treatment.
    Over the years, the NCI has worked closely with a number of smaller 
institutions in underrepresented areas through the P20 planning grant 
program. At the present time, six centers are recipients of planning 
grants. Four of these are in states that currently have no cancer 
center and a fifth serves a primarily minority population. We are 
developing mechanisms to promote consortium centers in areas where one 
institution does not have the capability to apply independently, with 
concordant revision of NCI requirements to accommodate their unique 
structure. In at least one state, such a consortium has received 
legislative support and funding.
    The NCI's Special Populations Network program is establishing a 
robust and sustainable infrastructure to promote cancer awareness 
within minority and medically underserved communities, and launching 
more research and cancer control activities aimed at specific 
population subgroups. The current Special Populations Networks consists 
of 18 projects in 15 states across the United States. Initial projects 
were begun after funding was awarded in April 2000 to groups that 
addressed ways of building relationships between large institutions and 
community groups. During the first year, cancer awareness projects were 
implemented in the community and project plans were developed. In the 
second and third years, partnerships between the project and NCI 
sponsored groups should enhance minority training and minority 
participation in cancer trials. In the last two years of these awards, 
full-fledged investigator-initiated research grant applications will be 
developed based on the initiative projects.
    The NCI is also considering other options to improve access of 
patients in underserved areas to the benefits of cancer research. One 
such concept is that of a Regional Enhancement and Cancer Community 
Health (REACH) initiative, which would pair smaller institutions in 
these areas as formal partners with existing NCI designated centers for 
collaborative research activities and delivery of cutting edge care. As 
currently envisioned, this would involve providing small grants to the 
smaller centers for encouragement of research, as well as some form of 
NCI designation. An additional alternative might be to provide moderate 
support for the existing affiliate networks already established by the 
centers. These networks are primarily focused on clinical care but 
additional support could be provided to specifically foster the more 
extensive delivery of clinical trials into the community setting.
    Finally, through the emphasis of the NCI on the ``Discovery, 
Development, Delivery'' continuum, we anticipate that links between 
existing Cancer Centers, their affiliates and partners in research, and 
the state, municipal and private organizations within their communities 
will continue to expand. These links, once firmly established, should 
result in a more unified approach to the conquest of cancer, and a more 
uniform delivery of the benefits of cancer research into the community. 
NCI is actively seeking mechanisms to foster both the vertical 
integration (i.e. from the cancer centers through the community layers 
they serve) and the horizontal integration (i.e. across cancer centers 
and a nationwide network of public and private partners) of the 
benefits of cancer research.

                           SJOGREN'S SYNDROME

    Question. Some progress has been made regarding Sjogren's syndrome 
at the NIAID. However, the NIAMS conducts research on closely related 
diseases such as lupus, scleroderma and rheumatoid arthritis. Are you 
conducting research on Sjogren's syndrome and are you coordinating this 
research with other Institutes at the NIH?
    Answer. In collaboration with the NIAID and the NIDCR, the NIAMS 
supports research on Sjogren's syndrome and other autoimmune diseases 
that ranges from basic science investigations to genetic studies to 
prevention research. The NIH Autoimmune Diseases Coordinating 
Committee, of which the NIAMS is an active member, helps ensure the 
coordination of effort among various Federal and private entities that 
conduct autoimmunity research, education, and outreach. The NIAMS funds 
work to better understand the molecular basis of autoimmune diseases 
such as Sjogren's syndrome; to identify genes that predispose 
individuals to autommunity; and to develop animal models which will 
provide insights into the human form of diseases such as Sjogren's.

                           STEM CELL RESEARCH

    Concerns have been raised by some in the scientific community that 
not all NIH institutes are aggressively pursuing a stem cell research 
agenda.
    Question. Would you please submit for the record how each of your 
institutes and centers has been implementing the embryonic stem cell 
research policy?
    Answer. In November 2001, NIH issued NOT-OD-02-005 Notice of 
Criteria for Federal Funding of Research on Existing Human Embryonic 
Stem Cells (hESCs) and Establishment of NIH Human Embryonic Stem Cell 
Registry. This notice describes how federal funds can be used to 
support research in human embryonic stem cells that meet the criteria 
established by the President. This Notice also references the NIH Stem 
Cell Registry--a registry that only lists those human embryonic stem 
cell lines that meet the eligibility criteria. All NIH institutes 
comply with points described in the Notice and for those that support 
human embryonic stem cell research, only support human embryonic stem 
cell research that uses cell lines listed on the NIH Stem Cell 
Registry. In addition, NIH has a Stem Cell Implementation Committee 
with representatives from the NIH Institutes that assists with 
implementation. This Committee works in tandem with the NIH Stem Cell 
Task Force to ensure that policy and major research initiatives are 
communicated to all Institutes and provide a means for inter-Institute 
cooperation and exchange.
    Complimenting these NIH-wide implementation efforts are many 
Institute-specific Program Announcements (PAs), Requests for 
Applications (RFAs), scientific workshops, and outreach efforts to 
encourage and support research on human embryonic stem cells. The NIH-
wide and Institute-specific initiatives are described for each 
Institute with portfolios relevant to human embryonic stem cells:
    The National Institute on Aging (NIA) is encouraging and supporting 
research on human embryonic stem cells through a number of Program 
Announcements, Requests for Applications, Requests for Proposals, and 
workshops. NIA is co-sponsoring with other NIH Institutes PA 02-054 
Short-Term Courses in Human Embryonic Stem Cell Culture Techniques, PAR 
02-023 Human Embryonic Stem Cell Research Resource Infrastructure 
Enhancement Award, and PA-02-025 Plasticity of Human Stem Cells in the 
Nervous System. In addition, PAR 03-056 NIA Pilot Research Grant 
Program specifically encourages stem cell research pilot projects and 
NIA has issued a Request For Proposal (RFP) 260-03-16 on 
Characterization of Human Embryonic Stem Cell Lines to establish a 
contract to develop, maintain, and distribute data on the properties of 
undifferentiated human embryonic stem cell lines. The NIA intramural 
program is supporting one of the six intramural labs conducting 
research on human embryonic stem cells. Within NIA, a Stem Cell Working 
Group meets regularly to disseminate policy information on receipt, 
tracking, review and administration of grants involving human embryonic 
stem cell lines, as well as to plan and implement activities involving 
support of human embryonic stem cell research. In May 2003, NIA is 
hosting a meeting on Stem Cells and Aging to promote exchange and 
enhance research among NIA stem cell research grantees.
    The National Institute on Alcohol Abuse and Alcoholism (NIAAA) is 
encouraging research on human embryonic stem cells and has issued an 
RFA 02-010 on Alcohol and Stem Cells that encompasses research 
objectives that include human embryonic stem cell research.
    The National Institute of Allergy and Infectious Diseases (NIAID) 
is working to ensure that the scientific community has every 
opportunity to advance research into the potential of human embryonic 
stem cells in accordance with federal policy. NIAID is co-supporting 
with other NIH institutes PA 02-054 Short-Term Courses in Human 
Embryonic Stem Cell Culture Techniques and PAR 02-069 Career 
Enhancement Award for Stem Cell Research. In addition, new research 
grant mechanisms are available to support human embryonic stem cell 
research: PA 02-038 NIAID-Investigator-Initiated Small Research Grants 
(R03) and PAS-02-160 Application of Exploratory/Developmental 
Technologies to NIAID-Funded Research (R21). NIAID also accepts and 
supports requests for administrative supplements to add human embryonic 
stem cell research to an existing NIAID grant.
    The National Institute on Arthritis and Musculoskeletal and Skin 
Diseases (NIAMS) is encouraging research on human embryonic stem cells 
through several Program Announcements and Requests for Applications 
with research objectives that could encompass the use of human 
embryonic stem cells. These initiatives include: PA 03-009 High Risk 
Rheumatic And Musculoskeletal And Skin Diseases Research; RFA 02-003 
Basic And Applied Stem Cell Research For Arthritis And Musculoskeletal 
Diseases; PA 02-136 Precursor Cells in Skeletal Muscle Repair and 
Hypertrophy; and PAR 02-030 NIAMS Small Grant Program for New 
Investigators. In addition, administrative supplements to an existing 
NIAMS grant may be requested for the addition of studies of human 
embryonic stem cells.
    The National Institute of Biomedical Imaging and Bioengineering 
(NIBIB) is fully aware of the policies and procedures governing the 
funding and use of human embryonic stem cell research and takes the 
necessary steps to keep grantees informed. Scientific workshops are 
held and talks are presented to a wide variety of audiences in academia 
and private industry, concerning tissue engineering, biomaterials, 
sensors and other areas of research that may include human embryonic 
stem cells. Recent outreach efforts included presentations at a PGH 
Engineering Tissue Growth meeting and at a meeting for BEACON, a 
bioengineering consortium in New England. At every appropriate outreach 
opportunity, human embryonic stem cells research policy is delineated 
to current and potential researchers. Training workshops for current 
and potential grantees address this issue as well. The NIBIB currently 
has two Requests for Applications, RFA 03-09 Development of Advanced 
Biomaterials and RFA 03-010 Research Opportunities in Tissue 
Engineering that request grant applications related to tissue 
engineering, which may include human embryonic stem cell research.
    The National Cancer Institute (NCI) actively encourages research on 
human embryonic stem cells and widely disseminates NIH policies and 
procedures to grantees. In addition, NCI is co-sponsoring with other 
NIH institutes supporting the Program Announcement, PAR 02-054 Short-
Term Courses in Human Embryonic Stem Cell Culture Techniques, which 
provides funding to develop, conduct, evaluate, and disseminate short-
term courses on laboratory research techniques for human embryonic stem 
cell lines.
    The National Institute of Child Health and Human Development 
(NICHD) actively encourages and supports research on human embryonic 
stem cells. The Institute has implemented the embryonic stem cell 
research policy through the issuance of special NICHD initiatives in 
the form of Requests For Applications, Program Announcements and 
Notices that include embryonic stem cells as potential targets for 
research. These include: RFA 02-018 Female Health and Egg Quality; RFA 
02-029 Specialized Cooperative Centers Program in Reproductive 
Research; PA 01-005 Reproductive Genetics; NOT 03-005 NICHD 
Administrative Supplements for Human Embryonic Stem Cell Research. 
NICHD is also co-sponsoring with other NIH Institutes two program 
announcements: PAR 02-054 Short-Term Courses in Human Embryonic Stem 
Cell Culture Techniques, and PAR 02-023 Human Embryonic Stem Cell 
Research Resource Infrastructure Enhancement Awards to help build the 
infrastructure and capacity to disseminate human embryonic stem cells 
eligible for federal research support. In addition, NICHD funded the 
first formal training course on human embryonic stem cells that was 
held at the Jackson Laboratory, Bar Harbor, Maine in August 2002. NICHD 
has also conducted numerous outreach presentations at scientific 
meeting on opportunities for NICHD research support for human embryonic 
stem cell research.
    The National Institute on Drug Abuse (NIDA) sponsored a two-day 
meeting ``Stem Cells--Opportunities for Drug Abuse Research'' where 
developmental and general neuroscientists were brought together to 
pursue the link between drug abuse research to stem cell research and 
to provide input to NIDA about research directions in this area of 
endeavor.
    The National Institute on Deafness and Other Communication 
Disorders (NIDCD) is encouraging investigator-initiated projects on 
high risk/high impact research and administrative supplements to 
facilitate scientists that would like to pursue preliminary work in 
stem cell research. NIDCD is sponsoring RFA 02-003 on Cellular Repair 
Studies of the Auditory and Vestibular Systems. In addition to these 
research initiatives, the NIDCD Director currently serves as the Chair 
of the NIH Stem Cell Task Force, a group of high-ranking scientists 
from a number of NIH Institutes with expertise in the research area of 
human embryonic stem cells. NIDCD also provides staff support to the 
activities of the Task Force. The purpose of the Task Force is to 
identify obstacles to moving the stem cell research agenda forward and 
to develop strategies to overcoming these challenges.
    The National Institute of Dental and Craniofacial Research (NIDCR) 
encourages and supports research on human embryonic stem cells in 
studies on oral, dental, and craniofacial development and the 
development stem cell-based treatments for the repair and regeneration 
of orofacial structures that have been compromised by congenital 
disorders, diseases, and injuries. In addition, the Institute co-
supports PAR 02-054 Short-Term Courses in Human Embryonic Stem Cell 
Culture Techniques.
    The National Institute of Diabetes and Digestive and Kidney 
Diseases (NIDDK) has disseminated NIH policies and procedures to 
grantees through development of a web-based Investigator's Guide to 
Human Embryonic Stem Cell Research. In addition to encouraging and 
supporting investigator-initiated research, NIDDK has a number of RFAs 
and PAs with research objectives that could encompass the use of human 
embryonic stem cells. This list includes: PA 01-129 Innovative and 
Exploratory Research in Digestive Diseases and Nutrition; PA 02-127 
Pilot and Feasibility Program Related to the Kidney; PA 01-128 Pilot 
and Feasibility Program in Hematological Diseases; PA 01-093 NIDDK 
Expanded Awards for SBIR at NIDDK; and, PA 02-008 Pilot and Feasibility 
Programs in Diabetes Endocrinology and Metabolism. Also, NIDDK is co-
supporting with other NIH institutes research training and 
infrastructure initiatives targeting the needs of human embryonic stem 
cell research. These initiatives include: PAR 02-023 Human Embryonic 
Stem Cell Research Resource Infrastructure Enhancement Awards; PA 02-
054 Short-Term Courses in Human Embryonic Stem Cell Culture Techniques; 
and, PAR 02-069 Career Enhancement Award for Stem Cell Research.
    The National Institute of Environmental Health Sciences (NIEHS) 
actively encourages research on human embryonic stem cells and has 
established a stem cell research emphasis area to encourage research on 
organ toxicology with potential for regenerative intervention/
prevention technologies. Also, the Institute has initiated working 
discussions with biotechnology companies to promote their development 
of programs in human liver stem cell research to address the major 
public health organ transplantation issues leading to liver failure. In 
addition, the Institute held a scientific meeting in November 2002 
entitled ``Stem Cells: Scientific Progress and Future Research 
Directions'' that discussed the potential of human stem cell research 
both globally and with respect to the environmental health sciences 
mission of NIEHS. This spring, NIEHS is co-sponsoring the ``Frontiers 
in Human Embryonic Stem Cells Research Training Course and a sequel 
symposium entitled ``Embryonic Cell Biomedicine: The Journey from Mice 
to Patients'' both of which will be held at the University of 
Pittsburgh.
    The National Institute of General Medical Sciences (NIGMS) 
encourages and supports research on human embryonic stem cells. In 
fiscal year 2002, NIGMS supported a ``Workshop on the Basic Biology of 
Mammilian Stem Cells'' that included key scientists in the field of 
human embryonic stem cells. Based on this workshop, NIGMS developed the 
RFA 03-003 Exploratory Center Grants for Human Embryonic Stem Cell 
Research. In addition, NIGMS issued a Notice 03-002 for Administrative 
Supplements for Human Embryonic Stem Cell Research and is co-supporting 
with other NIH institutes the Program Announcement PAR 02-054 Short-
Term Courses in Human Embryonic Stem Cell Culture Techniques.
    The National Heart, Lung, and Blood Institute (NHLBI) actively 
encourages and supports research on human embryonic stem cells through 
a number of Program Announcements, Requests for Proposals, and 
workshops. NHLBI has invited research applications encompassing human 
embryonic stem cell research through the following: PA 02-017 
Innovative Concepts and Approaches to Developing Functional Tissues and 
Organs for Heart, Vascular, Lung, and Blood Applications; PA 02-018 
Basic Research on Mesenchymal Cell Biology; PA 02-019 Research on Stem 
Cell Biology and Cell-based Therapies for Heart, Lung, Blood, and Sleep 
Disorders; and PAR 03-063 NHLBI Competitive Supplements for Human 
Embryonic Stem Cell Research. Also, the Institute announced NOT 02-009 
NHLBI Administrative Supplements for Human Embryonic Stem Cell Research 
that resulted in the support of several administrative supplements to 
current grantees to include research on human embryonic stem cells. In 
addition, NHLBI is co-sponsoring several initiatives with other NIH 
institutes including: PA 02-025 Plasticity of Human Stem Cells in the 
Environment of the Nervous System; PAR 02-069 Career Enhancement Award 
for Stem Cell Research; PAR 02-023 Human Embryonic Stem Cell Research 
Resource Infrastructure Enhancement Award; and, PA 02-054 Short Term 
Courses in Human Embryonic Stem Cell Culture Techniques for which NHLBI 
serves as the coordinator and designated administrative contact for all 
resulting grants. NHLBI also is sponsoring BAA 03-06 and RFP 03-07 for 
Somatic Cell Therapy Processing Facilities and Administrative Center 
that could involve human embryonic stem cells and assist in preparing 
the cells for clinical research. In addition, the Institute also 
sponsored an ``NHLBI Working Group: Cell-Based Therapies for 
Regenerative and Reparative Medicine--Vision, Scope, and Directions'' 
in May 2002 that addressed the area of embryonic stem cells, including 
their future therapeutic potential.
    The National Institute of Mental Health (NIMH) disseminates NIH 
policies and procedures to grantees through development of a web page 
on NIMH Support for Stem Cell Research. In addition to encouraging 
investigator-initiated research on human embryonic stem cells, NIMH is 
co-sponsoring two Program Announcements with other NIH Institutes: PAR 
02-023 Human Embryonic Stem Cell Research Resource Infrastructure 
Enhancement Award and PA-02-025 Plasticity of Human Stem Cells in the 
Nervous System. In addition, NIMH sponsored a satellite symposium at 
the Society for Neuroscience Meeting (November 2002) on ``Neuroscience 
Opportunities in Human Embryonic Stem Cell Research: An International 
Perspective'' and is co-sponsoring an up-coming scientific workshop on 
``American-Swedish Network for Stem Cell Biology and Neural Repair'' 
currently scheduled for September 2003.
    The National Institute of Neurological Disorders and Stroke (NINDS) 
actively encourages and supports research on human embryonic stem 
cells. The Institute has developed an NINDS Stem Cell website to update 
investigators about NIH policy, funding opportunities, upcoming 
meetings, and other relevant information. In addition, NINDS is 
sponsoring PAR 02-139 NINDS Cooperative Program in Translational 
Research and co-supporting with other NIH Institutes PA 02-025 
Plasticity of Human Stem Cells in the Environment of the Nervous System 
and PA 02-054 Short-Term Courses in Human Embryonic Stem Cell 
Techniques. The Institute has issued several Notices requesting 
applications for administrative supplements: NOT 02-007, NOT 02-010, 
NOT 03-002 NINDS Administrative Supplements for Research on Human Stem 
Cells. These Notices have resulted in support of several administrative 
supplements that allow current grantees to include and pursue research 
on human embryonic stems. Also, NINDS co-funded four conferences 
focused on stem cell research: 8th International Conference on Neural 
Transplantation and Repair; International Society for Stem Cell 
Research Meeting; Conference on Stem Cells: Origins, Fate and 
Functions; and, Gordon Research Conference on Neural Development.
    The National Center for Research Resources (NCRR) actively 
encourages and supports research on human embryonic stem cells. NCRR 
co-supports PAR 02-023 Human Embryonic Stem Cell Research Resource 
Infrastructure Enhancement Award and serves as coordinator and 
designated contact for all the human embryonic stem cell infrastructure 
grants. In addition, the Institute is supporting a Infrastructure 
Awardees Meeting in June 2003 that will involve all current 
infrastructure awardees in an exchange about obstacles and progress to 
date in developing the respective eligible cells lines for distribution 
to the scientific community.
    The Fogarty International Center (FIC) has been active in 
conducting outreach with foreign sources of eligible human embryonic 
stem cell lines. FIC has coordinated the interests of the NIH with the 
U.S. Department of State and respective U.S. Embassies to establish 
dialogues with eligible stem cell providers in India, Israel, Sweden, 
Australia, and South Korea. These efforts have significantly 
contributed to the five NIH infrastructure awards made to-date to 
eligible foreign sources.
    Question. Please share with us the steps NIH has taken to create a 
positive environment for human embryonic stem cells and the researchers 
seeking cures using this promising research tool?
    Answer. Over the past 20 months, the NIH has undertaken a number of 
new initiatives to enable the field of human embryonic stem cell 
research to move forward:
    Train new investigators to culture and work with human embryonic 
stem cell lines. Currently, there is a limited pool of scientists with 
the hands-on experience needed to reliably perform experiments using 
approved human embryonic stem cells. To address this need, the NIH 
issued a Program Announcement soliciting applications for ``Short Term 
Courses in Human Embryonic Stem Cell Culture Techniques.'' Five 
applications were received in October 2002, subsequently reviewed and 
plans are underway to make awards to all five applications. In 
addition, to assist mid-career investigators in their efforts to 
initiate research studies, the NIH issued the Program Announcement. 
``Career Enhancement Award in Stem Cell Research.'' These grants will 
provide salary support as well as some support for other research 
costs, to allow scientists to join an established research group 
working with approved human embryonic stem cells for six to twenty-four 
months.
    Provide support to scale up and characterize human embryonic stem 
cells eligible for Federal funding and increasing accessibility to 
these lines. In early Winter 2001, many of the 71 independent human 
embryonic stem cell derivations listed on the NIH Human Embryonic Stem 
Cell Registry were in the early phases of development and had not been 
expanded or characterized to the point where they could be readily 
distributed to the research community. Expanding and characterizing 
cells derived from human embryos are time- and resource-consuming 
processes. To help make these cells available to the research 
community, the NIH issued a Program Announcement, ``Human Embryonic 
Stem Cell Research Resource Infrastructure Enhancement Awards'' to 
provide support to allowable sources of human embryonic stem cells to 
scale up and distribute cell lines to investigators seeking such lines. 
The first Infrastructure grant was awarded in April 2002. To date, 
eight such awards have been issued. As a consequence of this support 
the number of cell lines available for widespread distribution has 
grown from a single cell line in Spring 2002 to eleven cell lines at 
present, with more anticipated in the near future.
    Provide assistance to the research community wishing to use human 
embryonic stem cell lines in navigating the intellectual property 
rights (IPR) and licensing agreements or material transfer agreements 
that needed to be obtained with the owners of the cell lines. The human 
embryonic stem cells available for Federal funding are owned by private 
sources, not by the Federal Government. A U.S. patent exists for human 
embryonic stem cell lines and the techniques used to develop such 
lines. NIH negotiated a memorandum of understanding with the patent 
holder (WiCell Research Institute) in September 2001, as well as with 
several other sources for the use of their cells. While the NIH can 
only develop such agreements for the NIH intramural research program, 
the terms of these agreements require the provider to offer the cells 
under no more stringent terms to other investigators using federal 
funds to conduct non-commercial research.
    Encourage established investigators to initiate research projects 
involving human embryonic stem cells. In an effort to help established 
investigators begin experiments using human embryonic stem cells, the 
NIH announced the availability of Administrative Supplements to 
existing NIH grants. These supplements are supporting collection of 
preliminary data that will lead to investigator-initiated research 
grant applications whose major focus is research using human embryonic 
stem cells. To date, 42 supplements have been awarded. In addition to 
these supplements, the NIH is currently supporting 13 investigator-
initiated grant awards and additional applications will be considered 
for funding during the remainder of 2003, and in years ahead. Six NIH 
Intramural laboratories are currently engaged in research using human 
embryonic stem cell lines.
    Establish an NIH Human Embryonic Stem Cell Characterization Unit. 
The research community has expressed a need for information on the 
characteristics of the available cell lines, to allow scientists to 
select which lines are most suitable for their intended experiments. To 
address this important need, the NIH intramural program is creating a 
Stem Cell Characterization Unit. The mission of this unit is to provide 
reliable and standardized data derived from assays performed on human 
embryonic stem cell lines available to be shipped to the research 
community. Performing these assays in a single laboratory will allow a 
direct side-by-side comparison to be made among the cell lines that are 
available for shipment, and will facilitate comparison with adult stem 
cells. These data will arm the scientific community with peer reviewed 
information about the properties of available lines, so scientists can 
make an informed choice when ordering one or more of the available cell 
lines. Data will be posted on a stem cell web site as soon as they have 
been validated. The assays performed by this Unit will be overseen by a 
Steering Committee comprised of leading stem cell biologists in both 
the extramural and NIH Intramural Research community. In a 
complementary effort, the Mammalian Gene Collection at NIH has 
established contracts to construct cDNA libraries from several human 
embryonic stem cell lines, and to perform expressed sequence tag (EST) 
sample sequencing from these libraries. These libraries will be made 
available to the research community, and all sequences will be 
deposited into readily accessible public databases.
    Provide support for multidisciplinary teams of investigators to 
define the properties and potential of human embryonic stem cells. The 
research community also articulated the need for multidisciplinary, 
multi-investigator teams of researchers to explore the growth and 
maintenance, biochemical and molecular properties, and other unique 
properties of human embryonic stem cells. In response to a June 2002 
workshop sponsored by the National Institute of General Medical 
Sciences, a Request for Applications to support exploratory center 
grants has been issued. These awards are intended to lead to Research 
Centers within three years of funding the exploratory center award.
    Establish NIH Stem Cell Task Force. In August 2002, the NIH Stem 
Cell Task Force was established to oversee and coordinate the trans-NIH 
activities involving human embryonic stem cells, as well as other types 
of stem cells. Comprised of leading NIH scientists with expertise in 
stem cell research, the Task Force will continue to monitor the state 
of this rapidly evolving science, identifying barriers to research 
progress and addressing the needs of the research community.
    Update NIH Stem Cell Web Site. The NIH continues to serve as a 
resource for stem cell information by hosting a web site. Scientists 
have access to information on stem cell funding opportunities sponsored 
by NIH. The web site also includes the NIH Human Embryonic Stem Cell 
Registry, which lists the eligible cell lines that are available for 
shipping to researchers.
    Host NIH Stem Cell Symposium. The NIH plans to showcase its 
scientific progress in human embryonic stem cell research by sponsoring 
a scientific conference at NIH on June 12, 2003. The symposium will 
feature a morning plenary session with presentations from NIH-supported 
researchers and an afternoon session will feature workshops and poster 
sessions.
    Question. How many RFAs related to human embryonic stem cell 
research has your institute sponsored and cosponsored?
    Answer. Currently NIH has issued nine Requests for Applications 
(RFAs) related to human embryonic stem cell research. One RFA invites 
applications for multiple P20 Exploratory Grants that will support 
multi investigator teams to conduct research using human embryonic stem 
cells. Sponsored by the National Institute of General Medical Sciences 
(NIGMS), this RFA encourages and enables basic biologists with little 
or no prior hESC experience to work with hESC and establish the utility 
of hESC as a model system by supporting the development of an 
institutional infrastructure for research using hESC; encouraging 
research on the growth and maintenance requirements of hESC; 
identifying biochemical and molecular markers of hESC; stimulating 
research that will lead to a better understanding of the unique 
properties of hESC; and supporting pilot projects that exploit the 
advantages of hESC as a model system to further the study of 
fundamental research problems.
    Additional RFAs related to hESC research include:
  --Innovative Concepts and Approaches to Developing Functional Tissues 
        and Organs for Heart, Vascular, Lung and Blood Applications. 
        These exploratory and developmental grants are sponsored by the 
        National Heart, Lung and Blood Institute (NHLBI).
  --Basic and Applied Stem Cell Research for Arthritis and 
        Musculoskeletal Diseases, sponsored by the National Institute 
        of Arthritis and Musculoskeletal and Skin Diseases (NIAMS).
  --Stem Cells in Development/Repair of Orofacial Structures, sponsored 
        by the National Institute of Dental and Craniofacial Research 
        (NIDCR).
  --Basic Research on Mesenchymal Cell Biology, sponsored by the 
        National Institute on Aging (NIA) and National Heart, Lung, and 
        Blood Institute (NHLBI).
  --Comprehensive Programs in Beta Cell Biology sponsored by the 
        National Institute of Diabetes and Digestive and Kidney 
        Diseases (NIDDK).
  --Cellular Repair Studies of the Auditory and Vestibular System, 
        National Institute on Deafness and Other Communication 
        Disorders (NIDCD).
  --Research on Stem Cell Biology and Cell-Based Therapies for Heart, 
        Lung, Blood, and Sleep Disorders (NHLBI)
  --Stem Cell Research for Alcohol related Disorders, National 
        Institute on Alcohol Abuse and Alcoholism (NIAAA)
    Question. How many Program Announcements related to human embryonic 
stem cell research has your institute sponsored or cosponsored?
    Answer. The Following Program Announcements related to hESC have 
been issued by NIH:
  --Short Term Courses in Human Embryonic Stem Cell Culture Techniques 
        are supported by 11 NIH Institutes. Five awards will be made in 
        Spring 2003.
    The 11 Institutes supporting the short-term courses are:
  --National Heart, Lung, and Blood Institute (NHLBI)
  --National Cancer Institute (NCI)
  --National Center for Research Resources (NCRR)
  --National Institute of Allergy and Infectious Diseases (NIAID)
  --National Institute of Child Health and Human Development (NICHD)
  --National Institute of Dental and Craniofacial Research (NIDCR)
  --National Institute of Diabetes and Digestive and Kidney Diseases 
        (NIDDK)
  --National Institute of General Medical Sciences (NIGMS)
  --National Institute of Mental Health (NIMH)
  --National Institute of Neurological Disorders and Stroke (NINDS)
  --National Institute on Aging (NIA)
  --Career Development Awards which are sponsored by NIDDK, NIAAA, 
        NINR, NIAID and NHLBI. The announcement was made in March 1, 
        2002 and expires in June 1, 2005. The purpose of these awards 
        is to provide mid-career investigators with training to use 
        hESC in their research.
  --Plasticity of Human Stem Cells in the Nervous System sponsored by 
        NINDS, NIA, NIMH and NHLBI. The purpose of this Program 
        Announcement is to study the fundamental properties of all 
        classes of human stem cells, and to confirm, extend, and 
        compare the behavior of human stem cells that are derived from 
        different sources and ages or exposed to different regimes in 
        vitro and in vivo.
    Question. How much funding has been provided for human embryonic 
stem cell research in each of fiscal years 2001 and 2002?
    Answer. In fiscal year 2001, no funding was provided for human 
embryonic stem cell research and $10.7 million was provided for fiscal 
year 2002.
    Question. Approximately how much funding is your institute planning 
to provide for human embryonic stem cell research in fiscal year 2003?
    Answer. NIH estimates $17.1 million will be provided for human 
embryonic stem cell research in fiscal year 2003.
    Question. Please explain your plans to expand funding within your 
institutes for human embryonic stem cell research over the next three 
years?
    Answer. Investigator-initiated research is the foundation of grants 
supported by NIH. To date, NIH is supporting only 13 investigator-
initiated research grants using human embryonic stem cells but NIH 
anticipates a substantial number of applications over the next three 
years as this field of research matures and more scientists receive 
stem cell biology training through various training courses, such as 
the NIH-supported short-term training courses mentioned above or 
through training offered directly by eligible providers of human 
embryonic stem cells. Upon completion of the training, it is expected 
that scientists will address the basic research questions that need to 
be answered for the field to move forward before being used for human 
therapies: What are the molecular pathways that govern stem cell 
differentiation to a specific cell type? How can stem cell growth be 
regulated? How can stem cells be safely transplanted and how is cell 
rejection prevented? How long will the stem cell transplant continue to 
function? Can animal models be developed to test the efficacy of stem 
cells?
    Question. Please identify any administrative or program hurdles 
that are impeding your institute from maximizing the potential of human 
embryonic stem cell research in helping your institute achieve its 
mission?
    Answer. Currently, the rate limiting step of hESC research is the 
lack of well-trained investigators. NIH has taken steps to remedy the 
situation by funding five short term training courses for up to three 
years starting in fiscal year 2003. In addition, career enhancement 
awards to train scientists in the lab culturing techniques and growth 
methods for hESC are currently being offered for mid-career scientists 
who are interested in learning to work with hESCs. In addition, NIH is 
supporting short-term training courses to teach scientists cell 
culturing techniques. Currently, WiCell, UCSF and ES Cell International 
are providing additional stem cell training, independent of the NIH-
supported short term training courses. NIH has awarded infrastructure 
grants to providers of hESCs which allows them to grow and culture the 
federally approved cell lines, making more cells available to the 
research community. This will enable scientists to gain easier access 
to the eligible stem cell lines. In June, the NIH is sponsoring a 
symposium to showcase NIH supported hESC research. The symposium is 
attracting worldwide interest. NIH believes that these activities will 
assist in attracting new investigators to the field and alleviate the 
current shortage of trained investigators.
    Question. Several scientists have suggested to the Subcommittee 
that NIH should create new funding mechanism to support human embryonic 
stem cell research, given that this is such a new area of science. Are 
you considering creating a mechanism that requires less preliminary 
data?
    Answer. In an effort to help established investigators begin 
experiments using human embryonic stem cells, the NIH is issuing 
Administrative Supplements to existing NIH grants. These supplements 
are supporting collection of preliminary data that will lead to 
investigator-initiated research grant applications whose major focus is 
research using human embryonic stem cells. In addition, NIH is 
providing other funding mechanisms that are used to support high risk/
high impact research as a means for generating preliminary data. Also, 
the NIH Center for Scientific Review has implemented processes to 
facilitate the peer review of human embryonic stem cell grant 
applications. One example is informing scientific review administrators 
about this new field of research and the preliminary data, which is 
often part of an application or may be lacking in some grant 
applications and should not be considered a penalty.
    Question. If so, when can we expect this to be announced? If not, 
how do you plan to spur this field?
    Answer. NIH is currently implementing these initiatives. In 
addition, NIH is undertaking other initiatives to spur this new 
research field by enabling eligible stem cell providers to scale up 
cells for shipping, providing easier access of stem cells to 
researchers, becoming a source of information to the scientific 
community on stem cell characteristics, and providing a forum for 
scientists to share their data through a stem cell research symposium.

                           CLINICAL RESEARCH

    Question. Most of this type of research takes place at academic 
health centers, many of which are struggling financially. I also note 
that you want to re-establish the Biomedical Research Support Grant 
program to help support academic health centers. Are you requesting 
funds for that purpose in this budget?
    Answer. No funds are requested in fiscal year 2004 to re-establish 
the Biomedical Research Support Grant (BRSG) program.
    Question. For the record, would you provide the Subcommittee with a 
description of how that program would work, and how much money it would 
take to adequately support the program.
    Answer. No funds are requested in fiscal year 2004 to re-establish 
the Biomedical Research Support Grant (BRSG) program.
    Question. How much does NIH devote to translating basic research 
into improved health care for the patient?
    Answer. An integral component of NIH's mission is to communicate 
research results both to the lay public and health professionals. NIH 
works in partnership with many different organizations to communicate 
scientific results and health information to the medical research 
community, health care providers, patients, and the general public 
across the nation. NIH communicates basic research findings through 
publication in professional journals and by distributing news releases 
to the science and general media. NIH scientists speak to reporters to 
explain the significance of the research and put it into the broader 
context of making progress against disease. Some examples of the 
translation of research findings from bench-to-bedside that are 
provided below:
  --In 2001, the National Institute of Neurological Disorders and 
        Stroke (NINDS) launched a multi-faceted public education 
        campaign to educate people about how to recognize stroke 
        symptoms and to call 911 to get to a hospital quickly for 
        treatment. Know Stroke: Know the Signs, Act in Time includes: 
        public service advertising for radio, television and print; as 
        well as consumer education materials that include an award-
        winning 8-minute film, brochures, and posters. Because stroke 
        attacks the brain, a stroke patient often cannot act alone to 
        call 911 and seek medical treatment. Bystanders are integral to 
        acting quickly and getting stroke patients to the hospital.
      To date, the campaign materials have derived excellent results. 
        The television PSA garnered more than 87 million viewer 
        impressions and hundreds of thousands of dollars worth of free 
        broadcast time; the radio PSAs received more than 46,000 
        broadcasts on 272 stations; the airport dioramas were placed in 
        117 airports, in cities such as Atlanta, Dallas, Denver and 
        Baltimore and received more than 800 million annual 
        impressions; billboard advertising focused in the Southeastern 
        United States, known as the Stroke Belt, averaged more than 
        800,000 daily impressions for the months they were placed; bus 
        side advertising placed in 10 markets resulted in more than 
        115,000,000 over the course of three months; a matte service 
        article has generated more than 2 million impressions and about 
        15,000 requests for Know Stroke brochures, and the consumer 
        education materials developed for the campaign have been 
        requested by thousands of nursing homes, hospitals, senior 
        centers and other organizations. Many of these activities have 
        been done in partnership with the American Stroke Association, 
        a division of the American Heart Association, and the National 
        Stroke Association, the two largest voluntary organizations 
        serving stroke patients and their families.
  --The National Diabetes Education Program (NDEP), established in 
        1995, is a federally-sponsored initiative that involves public 
        and private partners to improve the treatment and outcomes for 
        people with diabetes, to promote early diagnosis, and to 
        prevent the onset of type 2 diabetes. The National Institute of 
        Diabetes and Digestive and Kidney Diseases (NIDDK) of the 
        National Institutes of Health (NIH) and the Division of 
        Diabetes Translation of the Centers for Disease Control and 
        Prevention (CDC) jointly sponsor the program with the 
        participation of over 200 partner organizations. The Program's 
        target audiences include people with diabetes and their 
        families, with special attention to Hispanics/Latinos, African 
        Americans, Asian Americans, Pacific Islanders, and American 
        Indians, people at risk for type 2 diabetes, especially those 
        with pre-diabetes, health care providers, health care payers, 
        purchasers, and policy makers. The program's main initiatives 
        include the ``Control the ABCs of Diabetes'' campaign to 
        promote the link between cardiovascular disease and diabetes 
        and the importance of controlling blood glucose, blood pressure 
        and cholesterol, and the ``Small Steps, Big Rewards. Prevent 
        type 2 Diabetes'' campaign, designed to promote the message 
        that diabetes can be prevented to the 16 million Americans with 
        pre-diabetes, a condition that puts them at high risk for 
        developing type 2 diabetes.
  --Co-sponsored by NIH and organizations such as the Maternal and 
        Child Health Bureau, the American Academy of Pediatrics, the 
        SIDS Alliance, and the Association of SIDS and Infant Mortality 
        Programs, the ``Back to Sleep'' National Public Health 
        Education Campaign has resulted in a 50 percent relative 
        decrease in the rate of Sudden Infant Death Syndrome since its 
        launch in 1994. This campaign is directed at mothers and family 
        members of young infants, the professionals responsible for 
        their care, and the public in general.
  --The National Eye Health Education Program (NEHEP) has established 
        public and professional education programs to help promote 
        public awareness on how to prevent vision loss. The NEHEP 
        comprises more than 50 public and private organizations, which 
        plan and implement eye health education programs. The NEHEP has 
        created educational kits on glaucoma and diabetic eye disease 
        for health professionals and community leaders. The kits 
        provide information and materials to educate people at high 
        risk about eye health and the need for regular dilated eye 
        exams. The NEHEP also has launched four national public service 
        campaigns. Materials and messages of the campaigns have been 
        tailored to high-risk populations.
  --The National Heart, Lung, and Blood Institute supports several 
        long-standing national programs that rely the cooperative 
        efforts of its partners to educate the lay public and health 
        professionals about preventing and treating some of the major 
        chronic diseases of our time. The National High Blood Pressure 
        Education Program (NHBPEP) is a cooperative effort among 
        professional and voluntary health agencies, state health 
        departments, and many community groups interested in 
        hypertension prevention and control. At the core of the program 
        is the NHBPEP Coordinating Committee, composed of 
        representatives from 38 national professional, public, and 
        voluntary health organizations and 7 federal agencies. The 
        program aims to reduce death and disability related to high 
        blood pressure through programs of professional, patient, and 
        public education. The National Cholesterol Education Program 
        (NCEP) was established to raise awareness and understanding 
        about high blood cholesterol as a risk factor for coronary 
        heart disease (CHD) and the benefits of lowering cholesterol 
        levels as a means of preventing CHD. The NCEP Coordinating 
        Committee, with its membership of more than 40 partner 
        organizations representing major medical and health 
        professional associations, voluntary health organizations, 
        community programs, and governmental agencies, helps bring 
        cholesterol information to a wide audience. The National Asthma 
        Education and Prevention Program (NAEPP) was initiated to 
        address the growing problem of asthma in the United States, 
        particularly among children, African Americans, and the 
        elderly. Through its Coordinating Committee, composed of 
        representative from 43 partner organizations from professional 
        medical and health associations, public and voluntary health 
        organizations, and federal agencies, the NAEPP works to raise 
        awareness that asthma is a serious chronic disease, ensure 
        recognition of symptoms, and ensure appropriate diagnosis and 
        effective control of asthma.

                           CLINICAL RESEARCH

    Question. I have a copy of your ``road map'' for streamlining the 
process of taking research from the laboratory to the bedside. Is this 
still in the planning stages or have you implemented it?
    Answer. A national effort, led by NIH, to re-engineer the clinical 
research enterprise is being planned at this time. In the course of 
developing this key agency priority, the Director, NIH convened a two-
day meeting to develop a plan to identify the critical roadblocks and 
knowledge gaps that constrain rapid advances, and to conceptualize and 
develop far reaching solutions to build the sophisticated clinical 
research enterprise of the future.
    In January 2003, meeting participants developed a plan to re-
engineer the clinical research system over next 10 years. They 
recommended creation of: (1) National Clinical Research Networks, which 
would accrue data on clinical outcomes and quality of care at the point 
of service; provide an infrastructure for rapid initiation of large 
clinical trials; and inform patients and consumers; (2) a Translational 
Research Infrastructure which would facilitate the transfer of clinical 
research findings to the front lines of clinical care-and back; and (3) 
a Clinical Research Workforce which is diverse, well trained, and 
capable of collaborating optimally in cross-disciplinary teams.
    Since that time, NIH workgroups on translational research, clinical 
networks and clinical training have been reviewing, consolidating, 
harmonizing, prioritizing, and determining the fiscal implications of 
the myriad recommendations to NIH to emerge from the Clinical Research 
Roadmap Meeting. Workgroups are actively taking into account key 
national priorities, scientific opportunities, feasability, timing, and 
resources. Draft suggestions for implementing the key recommendations 
for streamlining and updating the clinical research enterprise are 
being considered by agency leadership. The NIH Director, in 
collaboration with Institute and Center Directors, will make the final 
determination of which of the many key directions will be most likely 
to yield the most substantial benefits to the health of the American 
people over the course of the next century. Once agreement is reached 
amongst the NIH Institutes and Centers, operational plans and a 
timeline will be devised for implementing the new clinical research 
infrastructure. We look forward to keeping you up to date as these 
priorities develop.
    Question. One of the items in this road map calls for establishing 
``a natural home within NIH for clinical trials of medical 
importance.'' Last year, the Subcommittee encouraged you to establish 
an Office of Clinical Research to provide a central focus. So we seem 
to be on the same wave length. Where does that stand?
    Answer. NIH views clinical research, which focuses on the causes 
and consequences of disease in human populations, as the key link in 
the pathway from basic research to improvements in health. This area of 
research includes the development of new technologies, mechanisms of 
human disease, therapeutic interventions, clinical trials, 
epidemiologic and behavioral studies, and outcomes and health services 
research. We concur with your strong interest in ensuring the 
advancement of clinical research. In recent years, the NIH appreciably 
expanded its clinical research program; for example, by establishing 
both intramural and extramural clinical research fellowship programs 
targeted to medical and dental students at the NIH; expanding the 
resources available for the diverse needs of the clinical research 
community, including attention to inpatient, outpatient, and critical 
care clinical research; and investing heavily in Patient-Oriented 
Research Career Development Awards, Mid-Career Investigator Awards in 
Patient-Oriented Research, Graduate Training in Clinical Investigation 
Awards, and Clinical Research Curriculum Awards. In addition, the NIH 
Loan Repayment Program has been expanded to include health 
professionals engaged in clinical research funded by non-profit 
support.
    In an unprecedented effort to be responsive to the many and varied 
research priorities advanced by different stakeholders--practicing 
physicians, the pharmaceutic and biotechnology industries, researchers, 
health plans, and patient groups, the NIH Director has convened a 
series of Roadmap meetings with extramural and intramural scientists 
and the Institute and Center Directors to explore the scientific 
challenges in clinical research and the roadblocks to progress. As a 
result of the recommendations to emerge from these meetings, the NIH is 
moving forward to re-engineer the clinical research enterprise, and to 
develop innovative solutions to ensure the promise of a viable 21st 
century clinical research enterprise.
    The development of any new organizational entity at this juncture 
in the agency's deliberations would stimulate premature closure 
pertaining to this complex issue affecting all NIH Institutes and 
Centers. As we continue to develop the NIH clinical research roadmap 
plan, we look forward to keeping the committee apprised of our progress 
in implementing these goals as this groundbreaking process continues to 
unfold.

                        INCREASED STIPEND LEVELS

    In March 2001, NIH announced a commitment to increase stipend 
levels for Kirschstein research training awards:
    The NIH supports higher stipends for NRSA recipients and therefore 
announces tentative targets of $25,000 for graduate and $45,000 for 
entry-level postdoctoral stipends. Future budget requests will 
incorporate 10 to 12 percent stipend increases until these targets are 
reached. After attainment of these targets, the real value of stipends 
will be maintained with annual cost-of-living adjustments.
    Question. The Administration's fiscal year 2004 budget departs from 
this commitment. Can you comment on the rationale for this change in 
policy?
    Answer. The change came about through recommendations included in a 
2000 National Academy of Sciences report. In fiscal year 2003 the 
Senate Appropriations Committee and the Conference Committee reports 
asked NIH to comment on that report. The NIH remains committed to the 
stipend targets described in our responses on that report. The request 
for funds to cover a 4 percent increase in fiscal year 2004 will permit 
the NIH to continue to increase stipends.

                  APPOINTMENT OF STUDY SECTION MEMBERS

    Question. What role should the Administration have in the 
appointment of NIH study section members?
    Answer. NIH operates study section and appoints study section 
members primarily based on the scientific expertise needed for review 
of applications assigned to the specific scientific review committees. 
Technical evaluation and advice regarding the scientific merit of the 
proposed research requires that the advising panel has the appropriate 
collective scientific expertise. The Federal Advisory Committee Act, 
which regulates establishment and operation of NIH study sections, also 
requires that committees be ``balanced'' and not ``inappropriately 
influenced by the appointing authority.'' Trained NIH scientists who 
develop these committees have the skills and experience to ensure this 
balance and the presence of the appropriate scientific expertise so as 
to achieve fair and rigorous reviews. In addition, NIH attempts to 
ensure diversity (of race and ethnicity, gender, geographic 
distribution, small and large institutional affiliation, public and 
private institutional affiliation, academic and small business, etc.) 
on study sections.

                          FULLY FUNDED GRANTS

    Question. In the Administration's fiscal year 2004 budget request 
for NIH, 322 new grants are ``fully-funded,'' that is, rather than 
receiving funding over the 3 or 4-year lifespan of the grants, all 
funding for these grants would be disbursed in fiscal year 2004. Is my 
understanding is that this is a pilot or test that is being pushed by 
the Office of Management and Budget correct?
    Answer. Certain grant programs, such as the Academic Research 
Enhancement Awards (AREA), and the James A. Shannon awards, have always 
been fully funded. In fiscal year 2004, NIH will increase the number of 
fully funded grants. NIH will undertake a study to determine the type 
of grants that can reasonably be fully funded from both the point of 
financial stewardship and scientific accountability. Other categories 
of grants may also be proposed for full funding.
    Question. If this is to be a test, by what criteria will the 
success of full funding be judged?
    Answer. Factors include ensuring grantee accountability for the use 
of Federal funds and the availability of funds for new researchers with 
new ideas.
    Question. Currently, as grants are funded over a four-year cycle, 
there is annual oversight of the research being performed as non-
competing continuations are awarded. Will there be less oversight if 
the grants are fully-funded at one time?
    Answer. The overall institutional compliance responsibilities are 
the same for grants that are fully funded. As noted above, NIH 
currently has two long-standing award programs that are ``fully 
funded.'' For example, the Academic Research Enhancement Awards (AREA) 
program provides for a three -year-award to AREA-eligible institutions. 
AREA recipients are required to submit an annual progress report to 
NIH.
    Question. As a researcher and research administrator, what is your 
view of fully-funded grants?
    Answer. As a researcher, there are advantages with fully-funded 
grants in that one can plan a research project with full knowledge and 
control of the entire amount of the grant award. Thus, one can better 
plan and manage the budget for personnel, equipment and resources as 
these are needed to meet the milestones of the project. As a research 
administrator, full funding could provide additional flexibility in 
managing future year commitments made to NIH researchers.
    Question. Are there upsides or downsides that OMB, the Department 
or the Congress might not be aware of?
    Answer. When determining the type of grants that can reasonably be 
fully-funded, NIH will consider financial stewardship and scientific 
accountability, NIH's goal of supporting stable numbers of new grants, 
impact on research priorities supported through other mechanisms of 
support, and the impact on new researchers entering the research arena.

                           TRAINING STIPENDS

    Question. In March of 2001, NIH adopted a policy of increasing 
training stipends by 10 percent a year until appropriate stipend levels 
are reached. In fiscal year 2002 and fiscal year 2003, the 
Administration has chosen to ignore NIH's policy and request 
significantly lower increases for training stipends than are necessary, 
and the Appropriations Committee has had to take action to ensure that 
stipends were increased. Here we are in fiscal year 2004, and the 
Administration has once again underfunded training stipends. What is 
NIH's view of the need for a 10 percent increase in fiscal year 2004?
    Answer. The NIH remains committed to the stipend targets of $25,000 
for predoctoral and $45,000 for entry level postdoctoral Kirschstein--
NRSA recipients as identified on April 30, 2001. The 10 percent annual 
increases specified in the 2001 NIH statement would have permitted us 
to reach the indicated targets by fiscal year 2006. The indicated 
targets could still be achieved at 4 percent annual increases, albeit 
not until 2011, by which point they would need to be adjusted to 
account for changes in the cost-of-living.
    Question. What are the numbers of students supported and at what 
levels?
    Answer. Based on distribution of research training positions to 
various career levels in fiscal year 2001, we estimate that the 
positions funded in fiscal year 2004 will be filled according to the 
following table.

  REQUESTED FISCAL YEAR 2004 KIRSCHSTEIN--NRSA TRAINEES AND FELLOWS BY
                            LEVEL OF TRAINING
                     [Full-time training positions]
------------------------------------------------------------------------
                                                             Fiscal year
                                                 Number of    2004 est.
                 Career level                    positions     stipend
                                                                levels
------------------------------------------------------------------------
Predoctoral...................................       10,046      $19,631
Postdoctoral:
    Years of experience:
        0.....................................        1,339       33,629
        1.....................................        1,163       35,498
        2.....................................          818       40,494
        3.....................................          704       42,273
        4.....................................          842       44,032
        5.....................................          783       45,803
        6.....................................          449       47,574
        7.....................................        1,053       49,588
                                               -------------
          Total Postdocs......................        7,151
                                               =============
          Total Full-Time Training Positions..       17,197
------------------------------------------------------------------------

    Question. Is it your view that stipends are adequate and that we 
have enough high-quality students in the pipeline?
    Answer. As indicated in my previous response, the NIH believes that 
Kirschstein-NRSA stipends should be adjusted upward to $25,000 and 
$45,000 for predoctoral students and entry-level postdoctorates, 
respectively. Stipends are not being adjusted to influence the supply 
or the quality of students in the pipeline. Based on recent studies, 
the health-related sciences continue to attract highly motivated 
students that score very well on national, standardized tests. Stipends 
are being adjusted upward as recommended by the National Academy of 
Sciences in recognition of increases in the cost-of-living and because 
of the high level of education and professional skills involved in 
biomedical research.
    Looking at this budget proposal, I am reminded of those slow motion 
films of crash tests for cars. My suspicion is that, under the 
Administration's proposal, we are taking a $27 billion dollar research 
enterprise and driving it into a brick wall at 60 miles an hour. Fiscal 
year 2004 is the instant that the car's bumper hits the wall, the crash 
dummies in the car are just starting to be thrown forward, and perhaps 
the hood is starting to buckle. I fear that in fiscal year 2005 and 
beyond we may well ``total'' the NIH. I didn't double the NIH over the 
past five years so that we could drive it into a brick wall.

                      EMBRYONIC STEM CELL RESEARCH

    Question. Please discuss how human embryonic stem cell research 
fits into the mission of the NCI. Has NCI been actively encouraging 
research on human embryonic stem cell research in order to advance your 
mission?
    Answer. Currently, NCI has not received any research grant 
applications relating to human embryonic stem cell research. We do 
believe that we will see basic research applications in the future.
    NCI has an extensive commitment to the field of stem cell biology, 
including both adult and animal embryonic stem cells. This research is 
important in expanding our fund of knowledge that can be applied to 
future human embryonic stem cell research. The Institute has publicized 
to all of our grantees by listserv announcements the current applicable 
NIH policies and procedures. In fiscal year 2002, NCI spent a total of 
$95 million in both animal and human adult stem cell research. NCI has 
also provided vital resources to the research infrastructure through 
its Mammalian Gene Collection program. This program works with the 
source of stem cells, such as the program at the University of 
Wisconsin-Madison, to create public resources for full-length cDNA and 
genomic libraries of human ES cell lines. In addition, NCI also 
participates in the NIH task force and implementation team that are 
facilitating interactions with the scientific communities.
    Question. What is NCI doing to provide investigators with the 
training necessary to maximize the potential of these cells?
    Answer. In fiscal year 2002 NCI supported training and education 
programs for investigators to acquire the skills and techniques 
necessary to grow and maintain the human embryonic stem cell (hSEC) 
lines. NCI provided co-funding support to NHLBI for the T15 short 
courses in hESC culture techniques. The total funding provided was 
$50,000 per year, divided among the five (5) successful applications. 
These five awards were made to training programs to help establish the 
workforce necessary to pursue this research field. These awards will 
develop, conduct, evaluate, and disseminate short-term courses on 
laboratory research techniques for human embryonic stem cell lines. The 
courses will include hands-on experience to improve the knowledge and 
skills of biomedical researchers to maintain, characterize, and utilize 
human embryonic stem cells in basic research studies. The courses will 
improve the skills of biomedical researchers in the maintenance of 
human embryonic stem cells in culture and their application of this 
research tool in basic research studies. The long-term objective of the 
courses is to increase the number of researchers who have both 
knowledge and skills in the use of human embryonic stem cells in basic 
research.

                         REGENERATIVE MEDICINE

    Question. Regenerative medicine is an area of research that could 
be shared by government, academia and industry--a true public-private 
partnership. Can you outline for the Subcommittee how regenerative 
medicine fits into your plan for the NIH research agenda?
    Answer. Regenerative medicine involves collaboration between 
several research fields--stem cell biology, biomolecules/biomaterials, 
and tissue engineering; and involves several scientific disciplines--
medicine, biology and bioengineering. NIH places a high priority on 
supporting regenerative medicine research and is bringing together 
several working groups to identify research obstacles and address 
research opportunities for regenerative medicine especially in 
application to stem cell biology and biomolecules/biomaterials. This 
process will serve todevelop an NIH roadmap for regenerative medicine 
with the goal of attracting more scientists to this emerging 
multidisciplinary field that has the potential of revolutionizing 
health and quality of life of millions of people.
    Recent advances in stem cell research have spurred new interest in 
the field of regenerative medicine. Before new therapies using human 
embryonic stem cells (hESC) can proceed to the clinical phase, much 
basic research must be conducted. There is a need for validating the 
long-term stability of hESCs in culture and after transplantation, 
understanding cell cycle control and cell specialization, and 
evaluating cell-host interactions. In response to these needs, the NIH 
Stem Cell Task Force is convening a working group with representatives 
from government, academia and industry to develop recommendations about 
what steps NIH could take to help improve or develop supporting 
technologies and research tools in basic research of hESC biology. 
Topics for discussion would include assessing the needs for supporting 
supplies, materials, reagents, databases with broad public access; 
assessing needs, progress, and opportunities for characterization 
studies, genomic, and proteomic approaches to better define stem cell 
lines; determining protocols for directed differentiation of stem 
cells; and recommending needs for enhancing research tools to the Task 
Force.

                          SALIVARY DIAGNOSTICS
 
   Early detection offers the best hope for cure for many serious 
diseases. However, many of the existing ways of diagnosing disease can 
be difficult, invasive, time-consuming, and expensive, so that by the 
time people have a test done, it may be already too late. I understand 
that saliva as a diagnostic tool is a promising area of research for 
addressing this issue.
    Question. Is there, in the 2004 budget, an investment in this area 
of research and if there is, how much are you budgeting for saliva 
research?
    Answer. We need to improve methods for detecting and diagnosing 
disease in the early stages. Unfortunately, there are also many 
barriers to effective diagnosis. Current methods, like blood tests and 
imaging technologies, are often uncomfortable, invasive, and expensive. 
Some diagnostic methods also carry risks themselves. Currently many 
diagnostic tests do not allow for real time monitoring of the state of 
health or disease because testing can take days or even weeks to 
complete.
    One of the most promising lines of research for diagnostic testing 
involves the use of saliva. Like blood and urine, saliva can be used to 
detect and measure many compounds in the body. Unlike blood and urine, 
saliva is easy to collect in a physically non-invasive manner, and the 
mouth is accessible for continuous monitoring. The science of microchip 
technology is evolving so rapidly that it is possible to envision the 
day when a microchip could be attached to a patient's tooth and be 
capable of continuously monitoring not only specific disease conditions 
but also an individual's overall health status.
    NIH is using its resources to make this vision a reality. In fiscal 
year 2002, NIDCR funded a series of grants to develop strategies to 
measure and analyze multiple substances in saliva quickly and 
simultaneously. Working in partnership with colleagues in industry and 
academia, these grantees are using microchip technology to develop 
diagnostic tests for a variety of conditions. As these studies are 
completed, follow-up research will be conducted to determine the 
efficacy of these new tools.
    NIDCR will spend an estimated $9.0 million in fiscal year 2004 on 
salivary diagnostics research.
    Question. Is saliva being used for HIV diagnosis?
    Answer. A number of companies have been working on saliva tests to 
measure antibodies to HIV. However, the sensitivity and specificity is 
lower than desired, mostly due to the fact that saliva contains low 
levels of immunoglobulin G. Thus, two companies are using mucosal 
transudate, the fluid that naturally seeps from the soft tissues of the 
mouth, as a diagnostic medium. The existing systems are really 
collection devices. The sample is sent to a laboratory, and the results 
are obtained after a week or two. Both companies, however, have 
developed rapid tests that are pending FDA approval for use in the 
United States. One company received FDA approval on Jan. 31, 2003 for a 
rapid test that utilizes a finger stick (i.e., blood sample) and 
provides results in 20 minutes. The same company also has an 
application before the FDA that uses the same technology with a sample 
of oral mucosal fluid. FDA approval of the oral mucosal rapid test is 
expected by the end of 2003.
    Question. I hear people talk about the need to develop an ``HIV 
rapid test''. Can you explain what that is and are you close to 
accomplishing that?
    Answer. An ``HIV rapid test'' implies that it can be conducted on 
site within a very short time frame without the need for specialized 
equipment or trained laboratory personnel. The NIDCR is working to make 
this vision a reality. In fiscal year 2002, the Institute funded 
several grants to develop technologies to measure and analyze multiple 
substances, including HIV, in saliva. Working in partnership with 
colleagues in industry, national laboratories and academia, these 
grantees are focusing their efforts on developing ``labs on a chip'', 
miniaturized systems about the size of a credit card for the detection 
of HIV and other substances. These technologies will allow real-time 
analysis of a large number of proteins (including antibodies to HIV), 
nucleic acids (DNA, RNA) and small molecules (e.g., drugs, metabolites) 
in oral fluids. The development of these technologies would permit 
fast, highly sensitive and accurate diagnosis of HIV in small amounts 
of saliva. To date, grantees at the University of Washington and the 
University of Pennsylvania working in partnership with industry have 
developed miniaturized prototypes for immunoassays of substances in 
blood. This technology is currently being adapted for the rapid 
diagnosis of HIV antibodies in saliva. Once these technologies are 
developed, they will need to be validated prior to widespread use.

           CLINICAL TRIALS RESEARCH IN DENTAL AND ORAL HEALTH

    This Committee appreciates the need to support definitive, high-
quality clinical trials. We understand that such trials are especially 
critical in dental and oral health, where large numbers of Americans 
continue to suffer from oral diseases and disorders.
    Question. Are there clinical trials in the area of oral health that 
need to be conducted?
    Answer. Continuing scientific progress in oral health has created 
opportunities for state-of-the-art clinical trials to determine the 
effectiveness of new treatment approaches and to broaden our 
understanding of the link between oral health maintenance and overall 
health. For example, new clinical trials are underway to assess the 
effectiveness of periodontal treatment on control of systemic health 
conditions such as preterm birth. The NIDCR has taken several steps to 
increase the number of applications and awards for high-quality 
clinical trials and to enhance the oral health research community's 
capacity to conduct such trials.
    Question. And what plans does NIH have to respond to this need?
    Answer. As support for clinical trials in oral health has expanded 
from about $10.8 million in fiscal year 2000 to nearly $18 million in 
fiscal year 2002, NIDCR instituted a new process designed to better 
assist investigators to develop and conduct clinical trials. The 
Institute has given priority to Phase III clinical trials that are 
likely to have a major impact on public health policy and/or clinical 
practices, and that will provide important new information to 
practitioners and consumers.
    NIDCR recently reorganized its extramural programs to delineate 
more clearly and to focus more prominently on the development and 
management of clinical trials and recruited additional program staff 
with expertise in clinical trials. Furthermore, a new, defined path for 
clinical trial applications has been established, which will assist 
investigators in developing and conducting trials. NIDCR has given the 
highest priority to Phase III clinical trials with the potential for 
high public impact. In addition, the Institute is using a variety of 
funding mechanisms to strengthen the scientific workforce through 
expanded training in clinical trial methods. The extramural community 
has been very positive about these program enhancements, as reflected 
in the increased number of applications and funding for clinical 
trials.

                          SMA RESEARCH BUDGET

    Question. What is the budget for SMA basic research for fiscal year 
2003 and fiscal year 2004?
    Answer. The NIH total estimated funding for Spinal Muscular Atrophy 
(SMA) is $7,351,000 in fiscal year 2003 and $11,489,000 in fiscal year 
2004.

                   SMA TRANSLATIONAL RESEARCH BUDGET

    Question. As a result of promising breakthroughs in basic research 
along with the severity and incidence of this disease in newborns and 
infants, NIH has selected SMA as a model for translational research. 
What is the budget for translational research for SMA in fiscal year 
2003 and fiscal year 2004?
    Answer. To enhance our current research efforts on SMA, we 
anticipate awarding a contract for the SMA translational project on or 
about September 30, 2003. The contract will be awarded for four years, 
and the research will be conducted as subcontracts. The NINDS intends 
to fund these research subcontracts at a level of $4.5 million per 
year, which will support up to ten research subcontracts.

          IMPLEMENTATION OF SMA TRANSLATIONAL RESEARCH PROGRAM

    Question. Please provide specific details on your plan of action 
for implementing SMA translational research?
    Answer. The NINDS has developed a performance-based contract 
approach to allow rapid funding of translational research in a 
milestone-driven process to identify treatments for SMA. The members of 
the steering committee, selected by the NINDS Director and drawn from 
academia, industry, the public, and NIH, are in the process of being 
identified and recruited; they will guide the program and play an 
integral role throughout the project. During the Summer of 2003, a 
working group will develop recommendations for a detailed plan for 
research on promising therapeutic strategies, such as drug development, 
gene therapy and stem cell therapy, which will address all steps 
ultimately required to develop an IND-Investigational New Drug-
application, the formal procedure usually required before a treatment 
can be tested in people. The primary contract for the SMA project will 
provide overall scientific and organizational support. Subcontracts 
will support individual research projects, which will be highly-
targeted and milestone-driven, as is often the case in industry. The 
steering committee will evaluate progress toward the specified 
milestones and prepare calls for additional subcontracts to do the next 
steps along each therapy development pathway, as appropriate. The NINDS 
intramural program, which has substantial expertise in SMA and other 
neurogenetic disorders, will play an integral role throughout this 
effort, and is capable of performing early phase clinical trials when 
these become appropriate.

                OVERSIGHT OF SMA TRANSLATIONAL RESEARCH

    Question. Who has been appointed within the NINDS to oversee and 
execute the SMA translational research project? What mechanisms are in 
place to review the process of the project on an ongoing basis with NIH 
leadership and Congress?
    Answer. Dr. Jill Heemskerk, an NINDS Program Director, will be the 
Project Officer for the SMA contract. She will receive advice from the 
steering committee and other NINDS staff. To allow optimal management 
and monitoring of research progress by the steering committee, projects 
will be short-term, goal-directed, and milestone-driven. The steering 
committee will review research progress at biannual oversight meetings; 
advise the Contractor in assessment of research milestones; and advise 
on strategies for overcoming difficulties in research progress.
    Institute staff have briefed Dr. Zerhouni extensively about the 
project and will continue to do so. We have responded to many questions 
about the project, by letter and phone, from members of Congress, and 
will continue to keep Congress informed.

            TIMELINE AND PLAN FOR SMA TRANSLATIONAL RESEARCH

    Question. Please provide a timeline and strategic plan for the 
implementation of the translational research project and identify any 
potential roadblocks?
    Answer. In December 2002, NINDS published a notice on the 
``Collaborative Program to Accelerate SMA Therapeutics Development'' in 
the NIH Guide to Grants and Contracts to help develop the statement of 
work and a request for proposals. A March 23, 2003 notice in Federal 
Business Opportunities announced that the formal request for proposals 
will be issued in April, and a similar notice appeared in the NIH Guide 
on April 8th. We expect to award the primary contract on or about 
September 30, 2003. Subsequently, calls for proposals for highly-
targeted research sub-projects will be issued quickly, and initial 
research projects should be underway in January or February 2004. 
Importantly, efforts to establish the steering committee are underway, 
and a working group should have detailed recommendations for research 
plans ready by the end of the summer, in time to begin issuing calls 
for specific research and development projects once the contract is 
awarded.
    With regard to roadblocks, the project depends, of course, on 
receiving proposals that are sufficiently scientifically meritorious so 
that we can responsibly fund them. The most serious obstacles to 
success, however, are scientific. It is important to keep in mind that 
developing effective treatments for neurogenetic diseases such as SMA 
is very much on the frontier of medicine. There are very substantial 
scientific difficulties that must be overcome to develop a treatment 
for SMA.

               PROMOTING AWARENESS OF AND RESEARCH ON SMA

    Question. What is NINDS doing to solicit grant applications? What 
workshops and conferences have been organized this year and next year 
to increase awareness of SMA and promote research funding 
opportunities?
    Answer. We are using both grant and contract mechanisms to enhance 
research on SMA. SMA research funding at NINDS increased by 21 percent 
from fiscal year 2001 to fiscal year 2002; SMA funding grew by more 
than 500 percent from fiscal year 1998--$945,000--to fiscal year 2002--
$5.6 million. This reflects in part the stimulus provided by an NIH 
workshop and a request for applications--RFA--on SMA and amyotrophic 
lateral sclerosis--ALS--in Spring 2000. Much of the growth, however, 
arises from the increased scientific opportunities, and reflects the 
strength of the traditional investigator-initiated grant process in 
responding to new avenues for progress. Given the state of the science, 
we expect grant applications in SMA will continue to increase.
    The translational project in SMA that I described is contract-
based. In December 2002, NINDS published a notice on the 
``Collaborative Program to Accelerate SMA Therapeutics Development'' in 
the NIH Guide for Grants and Contracts to help develop the statement of 
work and Request for Proposals--RFP--for this program. On March 23, 
2003 and April 8, 2003 NINDS published notices in Federal Business 
Opportunities and the NIH Guide, respectively, that the RFP will be 
released in April.
    Other efforts include an NINDS consortium, developed through a 
solicitation, to screen all FDA approved compounds for activity against 
neurodegenerative diseases, which included a test specific to SMA. The 
Institute has a program to rapidly provide supplemental funding for 
testing candidate treatments that emerge from this, or other efforts, 
in rodent models. Through a solicitation, the NINDS has also 
established a high throughput drug screening facility and called for 
proposals for disease assays, specifically listing SMA among those 
disease assays being sought. In recent years, we have offered 
solicitations in several cross-cutting areas that may provide results 
that are relevant to SMA, focused on areas such as gene therapy for the 
nervous system, neural stem cells, and pediatric neurological diseases. 
The NINDS is also assisting voluntary groups in organizing a scientific 
conference for Spring 2004 that will, among other goals, help inform 
biotechnology companies and the pharmaceutical industry about 
opportunities to develop therapies for SMA.

           PROMOTING PROFESSIONAL AND PUBLIC AWARENESS OF SMA

    Question. Please identify other NIH institutes and federal agencies 
that NINDS is working with to promote professional and public awareness 
of the disease. Please describe the programs that are being developed 
with a timeline and list of objectives?
    Answer. The NINDS has an SMA public information page with links to 
advocacy organizations, relevant clinical studies, and research 
literature. The National Library of Medicine also has an information 
page for SMA with many useful links. In addition, scientific workshops 
and the variety of research solicitations addressing or referencing 
SMA, as well as program staff contacts, provide outreach to the 
professional community. There are a number of voluntary health advocacy 
groups focused on SMA that undertake extensive activities to inform the 
public and the research community, as is appropriate to their role, and 
we have cooperated with these groups in various ways.

              STATUS AND COSTS OF CLINICAL TRIALS FOR SMA

    Question. What is the status of clinical trials for promising SMA 
treatments?
    Answer. The NINDS is funding a grant to lay the groundwork for 
clinical trials in SMA by developing a consortium of investigators and 
by validating appropriate outcome measures. However, at this time we 
need to emphasize translational research to bring potential treatments 
to the point where clinical trials are warranted. The NINDS is 
addressing this need in several ways. The contract-based translational 
research project for SMA is, of course, an important part of that 
effort.
    Question. What is the estimate cost per trial?
    Answer. Estimating the cost of trials and the possibilities of 
partnering with industry depend on the specific drugs or other 
therapies that might be tested, so we are not yet at the point 
scientifically where I can give a specific answer.
    Question. For FDA approved drugs, what efforts have been made to 
partner with the manufacturer of these drugs?
    Answer. We also support a consortium of investigators to screen FDA 
approved drugs for potential use against neurodegenerative diseases, 
including SMA. We have recently developed a high-throughput drug 
screening facility as well, and called for proposals to develop 
disease-specific tests, including those focused on SMA. In addition, 
the NINDS intramural program will be capable of conducting clinical 
trials on candidate therapies that emerge from these or other efforts.

             ADDITIONAL RESOURCES REQUIRED FOR SMA RESEARCH

    Question. What additional resources are necessary to execute the 
SMA translational research project? What additional resources do you 
require to increase the focus of SMA research at the NIH?
    Answer. We believe we have the resources to execute the SMA 
translational project at this time. This and all other efforts against 
SMA depend on the response of the research community to these efforts. 
The substantial increases in funded research on SMA over the last few 
years reflect exciting scientific advances, which have brought 
increases in the scientifically meritorious proposals we receive from 
investigators, which is very encouraging. The growth also reflects our 
commitment to addressing this terrible disease.

             DUCHENNE MUSCULAR DYSTROPHY--NICHD INVOLVEMENT

    Question. Duchenne Muscular Dystrophy is the world's most 
prevalent, lethal childhood genetic disorder. Only in the past year has 
the Child Health Institute at NIH had any involvement in this disease. 
Has the Child Health Institute devoted any specific, significant 
resources to this disease?
    Answer. Since the passage of the MD-CARE Act, the NICHD has 
partnered with the National Institute of Neurological Disorders and 
Stroke (NINDS) and the National Institute of Arthritis and 
Musculoskeletal and Skin Diseases (NIAMS) to support the Muscular 
Dystrophy Cooperative Research Centers and the Developmental Planning 
Grants for Muscular Dystrophy Research Centers. In addition, over the 
past five years, NICHD, although it does not have primary 
responsibility for muscular dystrophy research, has sponsored an active 
portfolio of grants concerned with the muscular dystrophies, muscle 
pathophysiology and other neuromuscular disorders. NICHD, along with 
other NIH Institutes, also has an active role on both the NIH MD 
Research Task Force and the MD Coordinating Committee.
    In addition, through the NICHD-sponsored network of Mental 
Retardation and Developmental Disabilities Research Centers, resources 
created under this network have been used to conduct research in some 
topics related to muscular dystrophy. The National Center for Medical 
Rehabilitation Research within NICHD has also sponsored research on 
muscle and neuromuscular disorders including such topics as the effect 
of stress on dystrophic muscle and the role of strength on child 
mobility. Finally, the Intramural research program at NICHD has for 
several years had a research focus on understanding muscle 
pathophysiology.

          DUCHENNE MUSCULAR DYSTROPHY--CONGRESSIONAL PRIORITY

    Question. Funding for DMD is approximately \1/2500\ of the NIH 
budget. This committee has held a hearing on the subject; strong report 
language has been attached to the Labor/HHS appropriation for three 
years in a row; a comprehensive muscular dystrophy authorization bill 
has been signed into law. Is the spending of NIAMS, NINDS, and other 
institutes consistent with the congressional priority that has been 
identified for this disease?
    Answer. Yes, NIH's funding of muscular dystrophy research is 
consistent with Congressional priorities. Indeed, from fiscal year 2000 
to fiscal year 2002, NIH funding for muscular dystrophy--MD--research 
has more than doubled. In fiscal year 2000, NIH funding for MD was 
$12.6 million; NIH funding increased to $21.0 million in fiscal year 
2001 and to $27.6 million in fiscal year 2002. Funding for DMD during 
the same period also increased from $7.0 million in fiscal year 2000 to 
$12.4 million in fiscal year 2002.

                   MD-CARE ACT--CENTERS OF EXCELLENCE

    Question. The Muscular Dystrophy CARE Act called for the creation 
of multiple Centers of Excellence, and was signed into law in 2001. 
This committee on three occasions has said that a minimum of three such 
Centers should be fully funded. I understand an RFP has finally gone 
out to organize the Centers, but the only assurance to the scientific 
community is that two Centers will be funded. Why so few? What funding 
level is assumed for these Centers?
    Answer. The NIH has been actively engaged in implementing the 
mandates of the MD-CARE Act, including efforts to establish research 
centers for muscular dystrophy; the Act did not provide for a specific 
number of Centers. Specifically, in the Fall of 2002, the NIH issued 
two Requests for Applications--RFAs--in this area. The first solicited 
applications for up to three awards for Muscular Dystrophy Cooperative 
Research Centers, and the second solicited applications for up to five 
awards for Developmental Planning Grants for future centers. During 
fiscal year 2003, following peer review, we will make grant awards in 
response to these two RFAs; the number of centers actually funded, up 
to the specified numbers, will depend on scientific merit. In fiscal 
year 2004, we plan to re-issue the RFA for Cooperative Research 
Centers, and expect to fund up to two additional meritorious centers in 
fiscal year 2005. Subject to the number of applications we receive and 
the results of scientific peer review, the combined solicitations could 
result in funding up to a total of five MD cooperative centers. Direct 
costs for the research centers can be a maximum of $1 million per 
center per year, for five years.

                       MD-CARE ACT--CBO ESTIMATES

    Question. The MD-CARE Act was scored by CBO two years ago to cost 
$54 million over four years. Apparently there was a minor increase in 
funding during the past year, but it is exceptionally difficult to see 
that this Act is going to be fully funded at the current pace of NIAMS/
NINDS activity. What are the prospects for full funding of this Act?
    Answer. The Congressional Budget Office--CBO--estimated that 
implementing the MD-CARE Act--including aspects that are the 
responsibility of other HHS components--would cost $4 million in fiscal 
year 2002 and $56 million over the five year period of fiscal years 
2002 through 2006. Of this amount, the costs of the NIH activities and 
of the MD Coordinating Committee, which was established by the Act, 
were estimated at $2 million in fiscal year 2002, and at $28 million 
total over the fiscal year 2002 to fiscal year 2006 period. From fiscal 
year 2001 to fiscal year 2002, NIH actual funding for muscular 
dystrophy research increased from $21.0 million to $27.6 million, an 
increase of $6.6 million or 31.4 percent--considerably more than the 
CBO estimate for fiscal year 2002. Budget estimates for fiscal year 
2003 suggest that NIH muscular dystrophy funding would increase another 
13.8 percent this fiscal year to an estimated $31.4 million. While this 
trend of increasing support for MD research is dependent upon future 
scientific opportunities and meritorious applications, it should be 
evident that the NIH is fully committed to implementing the MD-CARE 
Act, and to defining and advancing the MD research agenda.

                       MUSCULAR DYSTROPHY--CINRG

    Question. Has NIH ever funded translational research into muscular 
dystrophy--in particular, has NIH ever subsidized the only human 
clinical trials network (the Cooperative International Neuromuscular 
Research Group, or CINRG) that is testing pharmacological approaches to 
delay the progression of this disease?
    Answer. The CINRG, with the Children's National Medical Center as 
its coordinating center, conducts a multicenter clinical trials program 
to investigate the most promising treatments for DMD and related 
disorders. NIH currently funds a number of researchers who serve as 
principal investigators at participating centers for these clinical 
trials. In addition, NINDS has supported clinical trials on muscular 
dystrophy through both its intramural and extramural programs, and 
welcomes proposals for translational and clinical research aimed at 
delaying the progression of MD and related neuromuscular diseases.
    Translational research, by which we mean the process of applying 
ideas, insights, and discoveries generated through basic scientific 
inquiry to the treatment or prevention of human disease, is a high 
priority for the NIH. The emphasis in translational research is 
squarely on projects focused on the identification and pre-clinical 
testing of new therapeutics. The Muscular Dystrophy Cooperative 
Research Centers will promote side-by-side basic, translational, and 
clinical research, and will be designed to accelerate the translation 
of fundamental advances to the clinic. In addition, in July 2002, NINDS 
initiated a comprehensive program designed to encourage and support 
translational research for all neurological disorders, complemented by 
specific initiatives in areas such as drug discovery, gene therapy, and 
stem cells. Translational research is also an area of focus in the 
ongoing NIH Roadmap initiative.

                  MUSCULAR DYSTROPHY--NIH COORDINATION

    Question. DMD is untreatable and incurable, and has, throughout 
history, taken the lives of children in their teenage years. Because of 
the extraordinary burdens placed on families of children with this 
disease, most of the benevolence on this affliction goes to subsidize 
care, not research. While DMD is the#1 genetic child killer, it 
afflicts one out of 3,500 boys, which is not a threshold high enough to 
attract private drug money. Hence NIH research is the leading hope for 
this generation of sufferers. Yet only in the past year has NIH created 
a muscle biology study group--the only one devoted to the study of the 
largest organ of the body, out of 110 study groups in all of NIH. 
Scientific interest in this disease for years had been dampened and 
frustrated because of this structural flaw. Congress on repeated 
occasions has suggested that NIH coordinate its activities, and begin 
to fund this disease commensurate with others--on the basis of 
prevalence, severity, need, and scientific opportunity. Yet the process 
of securing adequate funding in this area has been painfully, 
tortuously slow--testing the limits of congressional patience and 
willingness to entrust the Institutes alone to designate funding 
priorities. What assurance can you give that this will change?
    Answer. NIH has already taken numerous steps to coordinate its 
activities with regard to muscular dystrophy. In early 2002, NIH formed 
the Muscular Dystrophy Research Task Force to help guide efforts to 
intensify research on muscular dystrophy. The Task Force is made up of 
physicians, scientists, NIH professional staff, and representatives of 
voluntary health organizations with a focus on muscular dystrophy. The 
purpose of the group is to help NIH add new capabilities to the 
national effort to understand and treat muscular dystrophies, without 
duplicating existing programs. The Task Force has met twice already--in 
May 2002 and January 2003.
    In September 2002, NINDS, NIAMS, and NICHD jointly issued the 
request for applications--RFA--``Muscular Dystrophy Cooperative 
Research Centers--MDCRC,'' and in November 2002, issued another RFA, 
``Developmental Planning Grants for Muscular Dystrophy Research 
Centers.'' These centers will constitute a cohesive program, the MDCRC 
Program, operating under guidelines for NIH cooperative agreements. The 
centers will promote cooperation and coordination of activities and 
resources across the entire MD research community.
    Coordination of MD research and education activities across the 
entire MD community will also be greatly enhanced by the formation of 
the Muscular Dystrophy Coordinating Committee--MDCC, as called for in 
the MD-CARE Act. The MDCC has broad representation from a number of HHS 
agencies, including the CDC, FDA, and HRSA as well as other government 
agencies, MD advocacy organizations, and the public, with an interest 
in MD research and education. The MDCC is tasked with developing a plan 
for conducting and supporting research and education on muscular 
dystrophy through the national research institutes. This plan is to be 
developed within a year of the establishment of the MDCC and will 
further enhance the coordination of activities and funding 
opportunities relevant to MD across NIH.

                   MUSCULAR DYSTROPHY--NIAMS EFFORTS

    Question. What is the NIH doing to ensure an integrated research 
approach regarding Muscular Dystrophy? What specific corporate 
processes exist to ensure research synergies and research success? 
Please provide for the record NIAMS efforts in these regard.
    Answer. The NIH has a strong and growing interest in research on 
muscular dystrophy, and a number of collaborative efforts illustrate 
this commitment. Over the past few years, several NIH Institutes, 
including the NIAMS and NINDS, have partnered to support scientific 
meetings and research initiatives designed to advance the field of 
muscular dystrophy research. Projects funded as a result of these 
efforts include work on several forms of the disease, including the 
Duchenne, facioscapulohumeral, myotonic, and limb-girdle dystrophies. 
To underscore the importance of expanding and intensifying programs in 
this field, the NIH has established a Muscular Dystrophy Research Task 
Force, which includes NIH scientific staff, as well as researchers, 
clinicians, and patient representatives. This group will help ensure 
that we pursue all promising opportunities to enhance muscular 
dystrophy research and training. It will also complement the work of 
the newly established inter-agency MD Coordinating Committee, which was 
mandated by the MD-CARE Act. Among other NIH Institutes, the NIAMS has 
a very active role on both the Research Task Force and the Coordinating 
Committee.

               DUCHENNE MUSCULAR DYSTROPHY--``ROADMAPS''

    Question. Are the specific Science and Technology ``roadmaps'' 
established for diseases such at Duchenne Muscular Dystrophy? What are 
the disciplines involved? If so, for the record, please provide these, 
demonstrating how they integrate multidisciplinary sciences and 
technology efforts.
    Answer. The ``Roadmap'' Action Plans being developed by Dr. 
Zerhouni, with input from a broad range of NIH staff and extramural 
scientific experts, are not disease or discipline specific, but rather 
take a cross-cutting approach to identify scientific challenges and 
roadblocks to progress. The ``Roadmap'' Action Plans will focus on 
facilitating and accelerating multi-disciplinary aspects of basic, 
translational, and clinical research. It is likely that several of 
these areas will be applicable to research on DMD. With regard to 
muscular dystrophy research overall, the MD Coordinating Committee--
MDCC--is tasked with developing a plan for conducting and supporting 
research and education on muscular dystrophy through the national 
research institutes. This plan will be developed within a year of the 
establishment of the MDCC.

               MUSCULAR DYSTROPHY--TRANSLATIONAL RESEARCH

    Question. Has the NIH ever considered a technology maturity 
assessment methodology akin to the NASA technology readiness levels or 
TRLs? Outline for the record the means and process for determination of 
transition from laboratory science to clinical trial?
    Answer. As was mentioned before, translational research--the 
transition from laboratory science to clinical trial--is the process of 
applying ideas, insights, and discoveries generated through basic 
scientific inquiry to the treatment or prevention of human disease. 
There are rigorous criteria and procedures, which are unique to medical 
science, for determining when it is appropriate to begin a clinical 
trial. At the present time, the NIH is in the midst of developing 
Roadmap Action Plans that will identify opportunities and roadblocks, 
as well as establish goals, in cross-cutting, multidisciplinary areas 
such as translational research. We expect that, as these needs are 
addressed over the next several years, the rate of successful 
translation of scientific advances into clinical trials will increase.

                      MD-CARE ACT--IMPLEMENTATION

    Question. Outline the specific steps and associated timetime that 
the Department of Health and Human Services and NIH have been on to 
fully implement the provisions of the MD-Care Act of 2001. The 
Congressional Budget office scored the MD Care Act act approximately 
$54 million for implementation. What are the total resources that NIH 
has dedicated to implementation of this Act currently reflected in the 
fiscal year 2004 President's Budget Submission? Please provide for the 
record fiscal year 2002 and fiscal year 2003 obligations and 
expenditures for muscular dystrophy. Please indicate by institute by 
form of MD, to include, Duchenne, Becker, Limble-Girdle etc.
    Answer. In September 2002, NINDS, NIAMS, and NICHD jointly issued 
two RFAs related to establishing the MD Research Centers provided for 
in the Act. The RFA for ``Muscular Dystrophy Cooperative Research 
Centers,'' will establish research centers, each of which will bring 
together expertise, infrastructure and resources focused on major 
questions about muscular dystrophy. In November 2002, another 
solicitation was issued for ``Developmental Planning Grants for 
Muscular Dystrophy Research Centers.'' These capacity-building grants 
are targeted to investigators who are not yet ready to compete to 
establish a muscular dystrophy research center, but would like to do so 
eventually.
    With respect to the MD Coordinating Committee called for in the 
Act, the public members of the MDCC have been appointed as of April 20, 
2003. Nine of the 10 Federal agency members have been designated by the 
Secretary, HHS, and it has been recommended that the DOD be invited as 
a member of the MDCC, based on the establishment in fiscal year 2003 of 
muscular dystrophy research as a project within the DOD's Defense 
Health Program. Committee members have been contacted about scheduling 
the first meeting, which is expected to be held in July.
    The NIH has also been expanding and intensifying its efforts in MD 
research. In fiscal year 2002, NIH funding for MD was $27.6 million. 
Estimated NIH funding for MD research in fiscal year 2003 is $31.4 
million and $32.4 million in the President's fiscal year 2004 Budget. 
The funding by institute follows:

----------------------------------------------------------------------------------------------------------------
                                                                                    Fiscal year
                                                                 -----------------------------------------------
                                                                   2002  actual   2003  estimate  2004  estimate
----------------------------------------------------------------------------------------------------------------
NHLBI...........................................................      $1,099,000      $1,170,000      $1,200,000
NINDS...........................................................       9,843,000      12,327,000      12,589,000
NICHD...........................................................         599,000         600,000         600,000
NIA.............................................................       1,265,000       1,300,000       1,330,000
NIAMS...........................................................      11,081,000      12,000,000      12,450,000
NHGRI...........................................................       2,253,000       2,413,000       2,502,000
NCRR............................................................       1,438,000       1,631,000       1,679,000
                                                                 -----------------------------------------------
      NIH.......................................................      27,578,000      31,441,000      32,350,000
----------------------------------------------------------------------------------------------------------------

    The NIH funding for Duchenne MD was $12.4 million in fiscal year 
2002, and the estimated funding for fiscal year 2003 is $13.7 million. 
The reported funding for Duchenne MD in fiscal year 2002, fiscal year 
2003, and fiscal year 2004, by institute follows:

----------------------------------------------------------------------------------------------------------------
                                                                                    Fiscal year
                                                                 -----------------------------------------------
                                                                   2002  actual   2003  estimate  2004  estimate
----------------------------------------------------------------------------------------------------------------
NINDS...........................................................      $4,050,000      $4,373,000      $4,459,000
NIA.............................................................       1,265,000       1,360,000       1,400,000
NIAMS...........................................................       4,571,000       5,000,000       5,200,000
NHGRI...........................................................       2,160,000       2,312,000       2,398,000
NCRR............................................................         384,000         430,000         454,000
 OD.............................................................  ..............         200,000  ..............
                                                                 -----------------------------------------------
      NIH.......................................................      12,430,000      13,675,000      13,911,000
----------------------------------------------------------------------------------------------------------------

              MUSCULAR DYSTROPHY RESEARCH--INFRASTRUCTURE

    Question. What are the specific NIH ``infrastructure'' shortfalls 
associated with MD research? (ie. RDT&E equipment, laboratory 
equipment, facilities, facility improvements) Please list any unfunded 
requirements by institute.
    Answer. The NIH's Muscular Dystrophy Research Task Force has 
identified a number of infrastructure priorities, including the need 
for multidisciplinary training programs to ensure a steady pipeline of 
MD researchers; the importance of developing better animal models for 
MD; the need to enhance bioinformatics and imaging resources; and the 
need for tissue repositories, DNA samples, and cell lines that can be 
used by the MD research community. Some of these needs will be 
addressed through the Muscular Dystrophy Cooperative Research Centers 
that NIH is planning to fund over the next few years, while others may 
require novel partnerships with industry and MD voluntary 
organizations.

           MUSCULAR DYSTROPHY RESEARCH--COOPERATION WITH DOD

    Question. Is there any relationship or cooperative research 
activities with the Department of Defense regarding muscle or 
myopathies? Between NIAMS and DOD? Or any other institute and DOD?
    Answer. NIAMS is aware of the Department of Defense's (DOD) 
involvement in muscular dystrophy research, as reflected in the fiscal 
year 2003 DOD Appropriation for the Defense Health Program--Public Law 
107-248--in that area. As a result, NIH is recommending that the 
Secretary of HHS solicit a nomination for a DOD representative to the 
Muscular Dystrophy Coordinating Committee. This will help to foster the 
communication and cooperation between DOD and NIH with regard to MD 
activities.

                  MYOPATHIES RESEARCH--NIAMS AND NASA

    Question. In similar fashion, is there any cooperative RDT&E 
between NIAMS and NASA on muscle, muscle wasting, or myopathies? Is 
there any significant relationship to human physiology of flight, 
especially for long-duration manned space flight? Have NIH institutes 
made use of any data from NASA regarding muscle preservation with long-
duration space flight? Please provide for the record.
    Answer. Research cooperation between NIAMS and NASA can be traced 
at least to the early 1990's, highlighted by a 1990 meeting entitled, 
``The Effects of Space Travel on the Musculoskeletal System'' and a 
program announcement, which resulted in several grants. In 2000, NASA 
and a number of NIH institutes--including NIAMS--collaborated on the 
program announcement, ``Earth-Based Research Relevant to the Space 
Environment,'' to encourage research applications related to biomedical 
effects of space flight on humans, including the effects of gravity on 
the musculoskeletal system. Thus far, the announcement has resulted in 
the award of at least one NIAMS grant, a project which may provide 
insights into the use of resistance exercise as a countermeasure to the 
loss of muscle and bone that occurs during space flight.

            DUCHENNE AND BECKER DYSTROPHIES--CLINICAL TRIALS

    Question. What is the status of potential clinical trials on 
Duchenne and Becker dystrophies? Are these efforts fully funded in the 
fiscal year 2004 President's Budget Submission? Where is this in NIAMS 
research priorities for fiscal year 2004 and the outyears? Please 
provide for the record the current status of research on systematic 
delivery of the dystrophin gene? What are the specific impediments to 
gene therapy in DMD/Becker? What resources are reflected in the fiscal 
year 2004 PB for these efforts? Provide a comprehensive list of the 
``critical technical issues'' associated with efficiency of systemic 
delivery.
    Answer. Although much promising research is being done in animal 
models of muscular dystrophy, significant work remains before the 
science progresses to the level where major clinical trials in humans 
are safe and appropriate. Recent progress in developing simple and 
effective tests that detect more accurately the precise genetic defects 
in forms of muscular dystrophy may help advance clinical research in 
this area. By establishing a correct genetic diagnosis, we can identify 
potential gene replacement strategies, and more accurately estimate 
risks in families with a history of the disease. In addition, the NINDS 
has recently funded a pilot clinical trial that will test whether the 
common antibiotic gentamicin has therapeutic potential for patients 
with both the Duchenne and limb-girdle forms of muscular dystrophy. 
This trial may provide new insights that will help shape the course of 
future clinical studies in this area. Other clinical trials are 
currently under development.
    One potential avenue to pursue, gene therapy, which uses vectors 
such as viruses to deliver a replacement for the defective gene, is 
seeing some success in the mouse. Current issues in muscular dystrophy 
gene therapy include obtaining vectors in significant numbers, 
effective gene delivery to affected muscles, and prevention of immune 
reactions to the vector itself. NIH also supports promising work in 
animal models on the therapeutic properties of muscle stem cells to 
devise potential new approaches for treatment of MD. Discussions by the 
NIH Muscular Dystrophy Research Task Force are expected to address 
these issues.

         DUCHENNE AND BECKER DYSTROPHIES--RESEARCH INITIATIVES

    Question. What specific research initiatives exist regarding the 
neuropsychological aspects of DMD/Becker? What resources and institutes 
are associated with this effort?
    Answer. NIH realizes the importance of studying and integrating 
research on all aspects of a disease--from the physiological to the 
psychological. NIH has supported research and invites proposals on the 
neurocognitive and neuropsychological aspects of DMD. More broadly, 
four NIH Institutes--NINR with NIAMS, NICHD, and NINDS--in May 2002, 
issued a solicitation on ``Increasing Quality of Life in Mobility 
Disorders.'' This initiative seeks applications for grants to study the 
psychosocial aspects of conditions with limited mobility, which could 
include DMD. These psychological consequences may include anxiety, 
depression, social isolation, and lowered self-esteem. In February 
2003, NINDS also issued a Request for Information for a contract that 
NINDS is considering to develop a coordinated approach to defining and 
measuring quality of life in neurological disorders. Patients' social 
and psychological condition, as well as mental well-being, are among 
the parameters that may be measured. In addition, NINDS funds very 
basic studies on the effects of MD-related proteins in brain function. 
These studies may provide the basis for developing studies on 
neuropsychological aspects of MD.
    The Muscular Dystrophy Coordinating Committee, which is tasked with 
developing a research and education plan for muscular dystrophy, has 
broad representation from a number of HHS agencies, such as the CDC, 
FDA and HRSA, as well as other government agencies such as the 
Department of Education. This will ensure that all aspects of MD, 
including the neuropsychological aspects of the disease, are considered 
in developing the research and education plan.

       DUCHENNE AND BECKER DYSTROPHIES--PHARMACOLOGIC APPROACHES

    Question. What specific pharmacologic approaches to DMD/Becker are 
currently being pursued by NIH and NIAMS? What are the resource 
implications and institutes involved?
    Answer. Several years ago, NIAMS-funded scientists successfully 
used the common antibiotic gentamicin to restore the function of the 
missing protein dystrophin in mouse models of DMD. More recently, the 
NINDS has funded a pilot clinical trial that will test whether 
gentamicin has therapeutic potential for patients with both the 
Duchenne and limb-girdle forms of muscular dystrophy. This trial may 
provide new insights that will help shape the course of future clinical 
studies in this area. The NINDS is also supporting work in mouse models 
to test the efficacy of the protein biglycan as a potential therapy for 
Duchenne muscular dystrophy. In addition, early advances involving 
enzyme inhibitors and growth factors could eventually lead to new 
pharmacologic treatments.
    The NICHD has established a Pediatric Pharmacology Research Unit 
Network which could prove to be a resource for developing 
pharmacological approaches in this area.

               DUCHENNE AND BECKER DYSTROPHIES--STEROIDS

    Question. Has the NIH developed a consensus statement regarding 
steroids in DMD/Becker? What is the progress here and target dates for 
such a statement? How is NIAMS participating in this?
    Answer. In the spring of 2000, several NIH Institutes, including 
NIAMS and NINDS, sponsored a scientific workshop on ``Therapeutic 
Approaches for Duchenne Muscular Dystrophy.'' The goals of this 
workshop were to address key questions in improving treatments for DMD, 
and identify areas of needed scientific knowledge, impediments, and 
critical next steps to promote effective therapies. One of the areas 
covered in the workshop was the use of steroids in treating DMD 
patients, specifically the lack of guidelines for use and concerns 
about side effects in children. Subsequent to this workshop, the 
American Academy of Neurology--AAN--charged a Practice Parameters 
Committee with looking at this treatment approach and developing 
clinical guidelines. The AAN is expected to publish these guidelines in 
the next few months.

               MD CARE ACT--COOPERATIVE RESEARCH CENTERS

    Question. The MD Care Act mandated the creation of coordinated 
research centers in muscular dystrophy research, and suggested a budget 
of $54 million. Would you verify for the record that the NIH has indeed 
responded to this by requesting applications for ``Muscular Dystrophy 
Cooperative Research Centers?'' Additionally, please detail your goal 
of funding 2 to 3 centers at the cost of $1 million direct costs each 
for 5 years a total of about $15-21 million over 5 years. Is this 
currently reflected in the fiscal year 2004 President's Budget Submit?
    Answer. The CBO estimate of $56 million for implementation of the 
MD-CARE Act encompasses more than just the creation of research 
centers; it is an estimate for implementing all aspects of the Act, 
including those outside of NIH.
    As one of the first steps in implementing the Act, NIH issued two 
requests for applications related to Muscular Dystrophy Research 
Centers. In September 2002, NIH issued an RFA entitled ``Muscular 
Dystrophy Cooperative Research Centers,'' to establish research 
centers, each of which will bring together expertise, infrastructure 
and resources focused on major questions about muscular dystrophy. In 
fiscal year 2003, following peer review and selection of applications 
of the highest merit, NIH will fund up to three centers. In November 
2002, NIH issued a second RFA for ``Developmental Planning Grants for 
Muscular Dystrophy Research Centers.'' These grants, which will be 
awarded in fiscal year 2003, are targeted to investigators who are not 
ready to establish a muscular dystrophy research center but would like 
to do so eventually. Since the President's fiscal year 2004 budget 
reflects commitments from awards made in fiscal year 2003, the Centers 
are reflected in the fiscal year 2004 budget.
    In fiscal year 2004, we plan to reissue the RFA for Cooperative 
Research Centers, and expect to fund up to two additional meritorious 
centers in fiscal year 2005. Direct costs for the research centers can 
be a maximum of $1 million per center per year, for five years.

            MD COOPERATIVE RESEARCH CENTERS--RESOURCE CORES

    Question. The committee understands that a second round of 
competitive awards is anticipated in late 2004, with funding shared 
between NINDS, NICHD, and NIAMS. Please outline for the record the 
concept of ``Scientific Research Resource Cores.'' Does this include 
the Muscular Dystrophy Cooperative Research Centers grant mechanism? 
Does this initiative ensure that the very best support infrastructures 
are present and enable the nation-wide muscular dystrophy research 
community some advantage?
    Answer. In fiscal year 2004, we plan to re-issue the RFA for 
Muscular Dystrophy Cooperative Research Centers, and expect to fund up 
to two additional centers in fiscal year 2005. At present, NIAMS and 
NINDS are committed to funding centers of the highest scientific merit 
through this follow-up initiative. The Scientific Research Resource 
Cores that will be funded as part of these new centers are expected to 
serve the national muscular dystrophy research community, in addition 
to supporting research within the centers. These resource cores will 
foster multidisciplinary collaborations across departments at a single 
institution, as well as among investigators at several institutions, 
through the sharing of novel research tools. Examples of scientific 
cores include, but are not limited to, tissue and DNA repositories, 
medical imaging, special animal facilities, and bioinformatics. 
Investigators at the cooperative research centers are expected to 
promote the use of the core facilities among researchers within the 
parent institution and among scientists at other institutions.

             MD RESEARCH RESOURCE CORES--ACCESS AND FUNDING

    Question. A successful competitive clinical trial network could 
accept clinical trials for promising therapeutic approaches from 
muscular dystrophy investigators that are not formally part of one of 
the two or three funded MDCRCs. Likewise, a successful gene vector or 
stem cell core facility could produce these critical reagents for 
laboratories throughout the country. Is the potential increased work 
load of a successful Scientific Research Resource Cores planned to be 
funded by the NIH via administrative supplements? Please outline your 
plans and the funding profiles for record for fiscal year 2004 and the 
outyears.
    Answer. It is expected that an MDCRC will be able not only to 
accommodate the research ideas and needs of participating scientists, 
but also to be responsive to other muscular dystrophy research 
enterprises that may not have direct connections to the center. 
Cooperation is a key part of the MDCRC's name; the centers are designed 
to both foster research, and to share knowledge and resources with the 
muscular dystrophy community at large.
    In fiscal year 2004, we plan to reissue the RFA for Cooperative 
Research Centers, and expect to fund up to two additional meritorious 
centers in fiscal year 2005. Direct costs for the research centers can 
be a maximum of $1 million per center per year, for five years. The 
Scientific Research Resource Cores will be funded as part of these 
centers. In general, administrative supplements are awarded to already 
funded researchers in response to identified needs and opportunities 
within the scope of the original grant award. Since the center grants 
have not yet been awarded, any discussion of supplements would be 
premature.

                MD COOPERATIVE RESEARCH CENTERS--FUNDING

    Question. It appears that innovative and novel mechanisms that they 
have put into place for executing the congressionally directed muscular 
dystrophy cooperative research centers. Please outline for the record 
the anticipated funding levels and implementation dates for three 
competitive centers, and evidence of implementation of the innovative 
Scientific Research Resource Cores via administrative supplements.
    Answer. As stated in the recent solicitations for muscular 
dystrophy cooperative research centers and for developmental planning 
grants for future centers, the NIH expects to fund up to three research 
centers and up to five planning grants in fiscal year 2003. In fiscal 
year 2004, we plan to re-issue the RFA for Muscular Dystrophy 
Cooperative Research Centers. Direct costs for the research centers can 
be a maximum of $1 million per center per year, for five years. The 
Scientific Research Resource Cores, which will be funded as part of 
these new centers, are expected to serve the national muscular 
dystrophy research community, in addition to supporting research within 
the centers.

                     NIH TUBEROUS SCLEROSIS FUNDING

    Question. How much is NIH currently investing in research on 
tuberous sclerosis complex (TSC)?
    Answer. The NIH reported actual funding for TSC research in fiscal 
year 2002 was $6,121,000. The fiscal year 2003 estimated funding is 
$6,439,000.

             INVESTMENT IN TUBEROUS SCLEROSIS BY INSTITUTES

    Question. Since tuberous sclerosis can affect all of the body's 
organ systems, which institutes are currently supporting this research, 
and how much is each institute investing?
    Answer. The National Cancer Institute--NCI; National Heart, Lung, 
and Blood Institute--NHLBI; National Institute of Diabetes and 
Digestive and Kidney Diseases--NIDDK; and National Institute of 
Neurological Disorders and Stroke--NINDS support TSC research. Funding 
by Institute is summarized in the table that follows.

----------------------------------------------------------------------------------------------------------------
                                                                                    Fiscal year
                                                                 -----------------------------------------------
                                                                   2002  actual   2003  estimate  2004  estimate
----------------------------------------------------------------------------------------------------------------
NCI.............................................................        $638,000        $657,000        $677,000
NHLBI...........................................................       2,140,000       2,279,000       2,336,000
NIDDK...........................................................         717,000         700,000         700,000
NINDS...........................................................       2,596,000       2,803,000       2,859,000
OD..............................................................          30,000  ..............  ..............
                                                                 -----------------------------------------------
      Total.....................................................       6,121,000       6,439,000       6,572,000
----------------------------------------------------------------------------------------------------------------

              COORDINATION OF TUBEROUS SCLEROSIS RESEARCH

    Question. Has there been any attempt to coordinate research on 
tuberous sclerosis among the institutes involved?
    Answer. Yes. The Program Director at NINDS who manages the TSC 
research portfolio is in regular contact with his counterparts at other 
Institutes. In addition, program staff from the National Institute of 
Arthritis and Musculoskeletal and Skin Diseases--NIAMS and NIDDK 
participated in the September 2002 NINDS-sponsored workshop on TSC 
research, and these institutes, along with the National Institute of 
Child Health and Human Development--NICHD, NHLBI, and NCI, are being 
consulted in the development of the NIH TSC research plan.

              TUBEROUS SCLEROSIS RESEARCH PLAN AND REPORT

    Question. On September 19-22, 2002, NIH, the Office of Rare 
Disorders and the Tuberous Sclerosis Alliance sponsored a research 
conference entitled New Perspectives in Tuberous Sclerosis Complex. In 
the fiscal year 2003 Senate report the Committee asked to receive a 
progress report on efforts to develop a research plan. When can we 
expect to receive this report, and how will it affect future research 
on tuberous sclerosis?
    Answer. In response to a joint resolution of Congress, passed in 
2001, NIH is preparing a five-year TSC research plan. Efforts are 
currently underway, led by NINDS, to craft the recommendations that 
emerged from the September 2002 conference into a formal research plan. 
NIH expects to finalize the plan and then submit a report to Congress 
in June 2003. This plan will help guide the development of NIH 
initiatives related to TSC and provide a framework that will allow the 
NIH Institutes and research and advocacy communities to coordinate 
their efforts to advance TSC research.

                             PAIN RESEARCH

    Question. Chronic pain affects anywhere from 35-110 million 
individuals per year, and is the most common reason consumers seek 
health care, accounting for 20-30 percent of doctor visits and 10 
percent of prescriptions sold.
    The NIH Pain Research Consortium has been in existence since 1996. 
Can you please provide this Committee with evidence of its activities 
over the past three years, and its planned activities for fiscal year 
2004?
    Answer. The NIH Pain Research Consortium was established in 1996 to 
enhance pain research and promote collaboration among researchers 
across the many NIH Institutes and Centers that have programs and 
activities addressing pain. Since its inception, the Consortium has 
been co-chaired by the Director of the National Institute of Dental and 
Craniofacial Research (NIDCR) and Director of the National Institute of 
Neurological Disorders and Stroke (NINDS), and most recently the 
Director of the National Institute of Nursing Research (NINR) has 
joined as the third co-chair. The working membership of the Consortium 
has been comprised of the key representatives of the Institutes, 
Centers (ICs) and Offices conducting and sponsoring pain research and 
programs at the NIH. It is designed to promote pain research and to 
increase awareness in the various NIH ICs in order to stimulate 
collaborative research initiatives, to coordinate both intramural and 
extramural research programs, to foster and maintain contact with 
research and patient communities, and to ensure that the results of 
NIH-supported pain research are widely communicated.
    In its first few years the Consortium:
  --Sponsored the symposium ``New Directions in Pain Research,'' which 
        brought together scientists within the mainstream of pain 
        research and exposed them to the work of investigators who do 
        not normally focus on pain. In this way, the symposium brought 
        new ideas, methodologies and techniques to pain researchers, 
        where novel approaches to understanding and treating pain are 
        greatly needed. Summary reports from the meeting appeared in 
        the journals Neuron and Science.
  --Sponsored the Symposium ``Gender and Pain,'' which covered subjects 
        such as the differing impact of the sex hormones testosterone 
        and estrogen on pain, brain imaging of nerve pathways involved 
        in the pain response, and efforts to identify genes that affect 
        pain sensitivity. This meeting received a great deal of media 
        attention, and thus information dissemination on the differing 
        responses to pain and current research.
  --Established a Pain Research Consortium website on the NIH web that 
        included information on the consortium's mission, its 
        membership, activities being coordinated both intramurally and 
        extramurally, conference proceeding and collaborative funding 
        announcements, among other things.
  --Developed a number of multi-institute supported Program 
        Announcements and Requests For Applications in the area of pain 
        research, that were also listed on the website.
  --Gave rise on the NIH campus to the formation of the Pain Interest 
        Group, which sponsors seminars, informal discussions and 
        communication via subscription to a list accessible to members 
        of the NIH community.
    In addition to these efforts, a number of institute-initiated 
efforts have been ongoing. Examples include:
  --In an effort to enhance the pain consult services within the NIH 
        Clinical Center, the highly successful Pain and Palliative Care 
        Service was established under the direction of a nationally 
        recognized pain clinician, Ann Berger, RN, MD.
  --Similarly, the NIDCR-directed Pain Research Clinic accounts for the 
        vast majority of translational pain research done intramurally 
        at NIH and has influenced the field of pain research through 
        training and the scientific productivity of its senior 
        investigators.
  --The NIH-FDA Analgesic Drug Development workshop attracted 250 
        registrants, resulted in a FDA Advisory Committee hearing in 
        July to develop new criteria for multi-dose studies and claims 
        structure for drugs indicated for Rheumatoid Arthritis and 
        Osteoarthritis, and has catalyzed the first revision of the 
        analgesic drug development process in nearly two decades.
  --The NIAMS-led Osteoarthritis Initiative resulted in greater than 
        $50 million in funding, with significant contributions from the 
        pharmaceutical industry, to develop improved clinical trials 
        methods, identification of biomarkers, and an innovative format 
        for future clinical trials for this disease.
    More recently, efforts are underway to capitalize and build upon 
these above activities and to reinvigorate the Consortium. Over the 
last six years, several changes of leadership in the NIDCR and the 
NINDS have resulted in a number of changes in individual co-chairs, 
and, as noted, NINR has joined as the third co-chair. Drs. Lawrence 
Tabak, Audrey Penn, and Patricia Grady, the current co-chairs of the 
Consortium, with the support of NIH Director, Dr. Elias Zerhouni, are 
facilitating the necessary efforts to see the Consortium reach its full 
potential to catalyze activities both intra- and extramurally in pain 
research.
    To this end, each Institute and Center Director, as well as the 
central NIH Office Directors, have been contacted and asked to reaffirm 
their commitment to the pain Consortium as members, and to update their 
liaisons to the Consortium. In addition, invitations to participate in 
the Consortium have been extended to NIH's sister agencies, including 
the Food and Drug Administration, and to pain researchers in the 
Department of Defense and the Veteran's Administration. An 
organizational meeting of the revitalized Consortium has been scheduled 
by the co-chairs to convene on June 10, 2003 to collectively frame the 
scope and activities of this group for the future, and update the 
scientific agenda for NIH pain research. Plans for the Consortium, 
which will address current IC activities as well as those for fiscal 
year 2004 and beyond, include catalyzing additional multi-institute 
supported research efforts within both the extramural and intramural 
programs, including more highly integrated, multi-institute sponsored 
PAs and RFAs in the area of pain research. The website for the 
Consortium will also be enhanced to make it an interactive source of 
more comprehensive information on pain and pain research for its 
various stakeholders, e.g., pain researchers; patients and patient 
advocate groups, professional associations, the public, and the media, 
among others.
    Question. According to pain advocacy groups, the NIH has difficulty 
in accurately accounting for its expenditures in pain and symptom 
management. Past estimates indicate that the NIH spends less than 2 
percent of its total budget on primary pain care research. The American 
Pain Foundation maintains that in a conversation with the NIH Office of 
Budget last summer, that office indicated that the NIH spent $124 
million on pain-related projects in fiscal year 2000, with an increase 
to $134.9 million in fiscal year 2001. However, other sources believe 
that those figures may exaggerate the actual expenditures because they 
included grant figures where pain was an underlying or secondary focus 
in the study.
    Can you prepare for this Committee an accurate accounting of the 
NIH's intramural and extramural activity in pain and symptom management 
research, to include detailed information and accounting on the 
projects that are primarily addressing pain issues from across the 
institutes and centers?
    Answer. Thirteen of the NIH organizations have reported support for 
pain-related research, as detailed in the following table and narrative 
descriptions:

          NATIONAL INSTITUTES OF HEALTH; FISCAL YEAR 2002 ACTUAL OBLIGATIONS; PAIN CONDITIONS, CHRONIC
                                            [In millions of dollars]
----------------------------------------------------------------------------------------------------------------
                                                                    Extramural      Intramural      Fiscal year
                        Participating ICs                            research        research          total
----------------------------------------------------------------------------------------------------------------
NCI.............................................................            10.6             0.4            11.0
NHLBI...........................................................            10.3  ..............            10.3
NIDCR...........................................................            21.4             5.1            26,5
NINDS...........................................................            47.7             1.4            49.1
NICHD...........................................................             4.8             1.1             5.9
NIA.............................................................             1.8             0.7             2.5
NIAMS...........................................................             6.6  ..............             6.6
NIMH............................................................             5.9  ..............             5.9
NIDA............................................................            22.6             0.4            23.0
NINR............................................................            10.9  ..............            10.9
NCRR............................................................            11.4  ..............            11.4
NCCAM...........................................................             9.0  ..............             9.0
OD..............................................................             1.9  ..............             1.9
                                                                 -----------------------------------------------
      NIH.......................................................           164.9             9.1           174.0
----------------------------------------------------------------------------------------------------------------

The National Cancer Institute (NCI)
    NCI supports clinical trials on secondary or indirect pain-related 
research where pain alleviation is a factor in determining patient 
quality of life during the patient's experimental treatment and care. 
Pain assessment/pain management research grants investigate how to 
overcome cultural barriers between providers and patients to better 
manage cancer related pain. These studies consider gender differences 
in the effectiveness of similar pain medications. NCI researchers are 
also developing new methods of pain measurement that are computerized 
for ease of patient use at the provider site or in the patient's home. 
Other complementary and alternative medicine pain relief research 
includes: hypnosis for postoperative breast surgery pain, massage for 
short-term relief from pain in advanced stage cancer patients, and 
acupuncture or acupressure for pain relief in advanced pancreatic 
cancer patients.
    Other NCI research examines the biological or molecular basis of 
pain. Researchers are studying cellular proteins that may be elevated 
in cancer cells to activate the pain response in humans or animal 
models. NCI has several ongoing studies on the reduction of therapy-
induced pain. These include studies on reversing opioid related 
constipation as well as determination of initial dosing rates to 
minimize the pain associated with use of photodynamic therapy for 
treatment of certain skin cancers. There are several phase II clinical 
trials underway on therapy induced pain in advanced stage cancers, 
including a study of radionuclides for metastatic prostate cancer 
tumors ablation, arsenic trioxide for pain relief of advanced prostate 
cancer, and radiation as a palliative care measure in advanced lung 
cancers. NCI is also funding pharmaceutical research on new delivery 
systems for natural delta-9-tertahydrocannabinol (THC) to alleviate the 
marked loss of appetite and weight in cancer and AIDS patients.
    Emerging evidence from several groups reveals that the capsaicin 
receptor (a biologic molecule involved in pain sensation) is modulated 
not only by compounds like capsaicin but also by signaling pathways 
such as protein kinase C. NCI is actively investigating the regulation 
of other (vanilloid) receptors by protein kinase C as well as the 
design of molecules that can manipulate the protein kinase C pathway to 
obtain useful therapeutic outcomes, such as modulation of pain.

The National Heart, Lung and Blood Institute (NHLBI)
    NHLBI supports research on the management of painful episodes 
associated with sickle cell disease (SCD). Its current portfolio 
includes a study to ascertain the impact of acute and chronic pain 
events on health care utilization among adults with SCD, as well as an 
examination of the relationship between sickle cell pain, mood, and 
stress in adolescent and adult patients. The NHLBI is also funding a 5-
year follow-up of adult patients who participated in a landmark 
clinical trial that established the usefulness of the drug hydroxyurea 
in preventing complications of SCD. The goal of the follow-up study is 
to assess the continuing effectiveness of hydroxyurea in decreasing 
rates of painful sickle cell episodes and improving quality of life.

The National Institute of Dental and Craniofacial Research (NIDCR)
    The history of pain research at NIH began over five decades ago 
when the NIDCR recognized many Americans' association of dentistry with 
pain. Since that time, NIDCR, in conjunction with other NIH Institutes, 
has built a comprehensive portfolio of pain research. Its scientists 
and grantees have made important contributions to define the basic 
neurocircuitry of pain, as well as translating this understanding into 
improved treatments that benefit millions of Americans.
    The NIDCR has established relevant research programs initiatives in 
both its intra- and extra-mural components. NIDCR scientists have long 
studied oral-facial pain, not only because of its importance in oral 
disease, but also because it provides an accessible model of pain 
elsewhere in the body. These investigations have greatly enriched our 
understanding of the basic mechanisms of pain perception and modulation 
and have helped delineate the complex pathways and multiple 
transmitters that convey pain signals. The NIDCR recognizes that a 
unique opportunity now exists, with the emergence of genomic, 
proteomic, and other powerful, information-generating technologies, to 
define in greater detail the genetic and molecular basis of pain. This 
basic research will serve as the pipeline for new strategies in pain 
management, allowing future clinicians to more selectively and 
efficiently control the pain process.
    NIDCR grantees are defining biological factors that might account 
for differences in pain perception. Novel imaging techniques that track 
the ``mu-opioid'' system, have revealed that people vary both in their 
capacity to produce mu-opioid receptors and in their ability to release 
the anti-pain chemicals themselves. Researchers found that at matched 
levels of pain intensity, men and women differ in the degree and 
direction of the mu-opioid response in distinct areas of the brain. 
Variability in the mu-opioid system appears to determine the emotional 
and sensory aspects of a painful experience may also help to explain 
why some people are more prone to chronic pain conditions or do not 
benefit from certain anti-pain medications. While the neurocircuitry 
involved in each of these processes is extraordinarily complex and 
inadequately understood, these initial imaging studies of pain 
perception offer an important starting point to further explore human 
perception and diversity.
    In preliminary animal studies, NIDCR scientists have demonstrated a 
treatment approach that selectively controls the chronic pain 
associated with tissue damage and recurrent inflammation. This 
discovery builds upon laboratory studies of the cell-surface protein 
vanilloid receptor I, known by the unrelated acronym TRPV1. Researchers 
have isolated a TRPV1-binding compound, which in animal studies 
selectively eliminates an entire class of pain-sensing neurons from the 
peripheral nervous system. This compound, known as resiniferatoxin 
(RTX), killed certain neurons, and blocked inflammatory pain, 
hyperalgesia, and thermal pain sensation. Importantly, the animals 
maintained their ability to sense pain and remained well coordinated, 
an indication that RTX did not affect proprioceptive nerves in the 
muscles and joints. These NIDCR researchers have yielded in just over a 
year of work a novel approach to pain management. This finding has 
important implications for the field of pain research, as well as the 
potential to impact American public heath. Additional studies are under 
way that will move RTX and related compounds into human clinical 
trials.

The National Institute of Neurological Disorders and Stroke (NINDS)
    NINDS supports a broad range of research focused on both 
understanding the causes and mechanisms of pain and on developing 
effective treatments for pain. Our portfolio includes research on the 
unique roles in processing and regulating pain that are played by 
different areas of the nervous system including: the peripheral nervous 
system, spinal cord, brainstem, and cerebral cortex. The portfolio also 
includes research aimed at gaining a better understanding of the 
different neurotransmitter systems involved in mediating pain. The 
NINDS supports research on a wide variety of pain conditions, 
including: neuropathic pain, visceral pain, pelvic pain, causalgia, 
painful peripheral neuropathies, cancer pain, back pain, muscle pain, 
migraine and other types of headache pain, post-surgical pain, and 
inflammatory pain. Research on the mechanisms of anesthesia and 
analgesia is another area funded by NINDS. The NINDS supports a number 
of clinical studies aimed at testing the effectiveness of different 
types of treatments (both drug and non-drug) for several pain 
conditions. For example, one clinical trial is comparing the 
effectiveness of either a drug or cognitive behavioral therapy for 
treatment of chronic tension-type headaches. Another clinical study is 
examining whether behavioral changes (e.g., changes in diet and 
exercise) can prevent the pain associated with peripheral neuropathy in 
individuals who have Impaired Glucose Tolerance, a condition of 
impaired glucose metabolism. Finally, the NINDS supports training 
programs at both the pre- and post-doctoral level with the goal of 
giving young scientists and physician-scientists a broad experience in 
the pharmacological, pathological, and molecular biological methods of 
pain research.

National Institute of Child Health and Human Development (NICHD)
    Chronic pain is a secondary condition in persons with disabilities. 
Currently funded research on the management of chronic pain explores 
the efficacy of innovative non-pharmacologic therapies, such as virtual 
reality analgesia in children with cerebral palsy and burns. Cognitive 
restructuring, relaxation training and hypnotic analgesia are pain-
management approaches being investigated in persons with cerebral 
palsy, multiple sclerosis, acquired amputation, and spinal cord injury. 
Research focused on the biomechanics of wheelchair propulsion may 
reduce shoulder pain and increase the mobility of wheelchair users.
    In the area of reproductive health, several investigators are 
studying pharmacologic treatments for the pelvic pain associated with 
vulvodynia, endometriosis, dysmenorrhea and hysterectomy. Other pain 
research examines the effects of epidural analgesia, used commonly to 
reduce pain in labor. There is evidence that suggests epidural 
analgesia may also prolong labor, influence the position of the fetus 
during labor and increase the likelihood of a high-risk cesarean 
delivery. Pre-term infants are subjected to many painful procedures in 
the NICU environment. The long-term neurodevelopmental effects of early 
exposure to pain and the effects of the sedatives and opioid analgesics 
used to reduce neonatal pain are the focus of other NICHD-supported 
research.

National Institute on Aging (NIA)
    It has been estimated that chronic pain affects approximately half 
of older adults living at home, and may cause significant disruption of 
physical, psychosocial, and cognitive function. Management of pain is 
also of particular concern in older surgical patients, Alzheimer's 
patients and other patients with diminished cognitive capacity, as well 
as in end-of-life care. NIA extramural studies include a study of pain 
management in hip fracture patients and the potential problem of 
overlooking pain symptoms in patients who experience delirium as well 
as an investigation of chronic low back pain and its effect on 
physical, psychosocial, and cognitive function in a group of adults 
over age 65. Another extramural study is examining the possible effects 
of a multidisciplinary palliative care consultation on pain management, 
dypsnea, and anxiety in a group of seriously ill, hospitalized older 
patients. A new study will research the effect that identifying pre-
visit concerns of older adult patients has on improved health status 
for the primary outcomes of pain and physical function. There is also a 
study to understand the major determinants of postoperative outcomes 
and improve functional recovery of elderly surgical patients, including 
the relationship between improved pain management and improved daily 
functioning.
    NIA has two intramural studies of pain. The first is a study of 
chronic musculoskeletal pain in hereditary disorders of connective 
tissue, such as Ehlers-Danlos syndrome and Stickler syndrome, that 
examines the efficacy of the use of the ``Mindfulness-Based Stress 
Reduction Program'' in the relief of chronic pain. The second is an 
epidemiologic study of the impact of pain and other symptoms of chronic 
diseases on the daily lives and functioning of older disabled women, 
which is specifically investigating whether musculoskeletal pain 
increases the risk for falls and other adverse health outcomes and if 
the risk can be reduced through the use of analgesic medications.

National Institute of Arthritis and Musculoskeletal and Skin Diseases 
        (NIAMS)
    The mandate of the NIAMS is broad and diverse, focusing on the 
whole array of diseases that affect the muscles, joints, bones, and 
skin. Many of these diseases are chronic, and are also accompanied by 
significant pain. The origin of pain and effective strategies for pain 
management are areas of research supported by the NIAMS. The NIAMS pain 
research portfolio includes a significant number of studies on 
fibromyalgia, a complex and chronic disorder that is characterized by 
widespread musculoskeletal pain, fatigue, and multiple tender points. 
``Tender points'' refers to tenderness that occurs in localized areas, 
particularly in the neck, spine, shoulders, and hips. The NIAMS 
supported studies related to fibromyalgia and pain include efforts to 
identify the central factors causing fibromyalgia; research on the 
changes that occur in the nervous and the hormonal systems in people 
with fibromyalgia; and a study that is using chronic low back pain as a 
model for fibromyalgia. Additional research topics include: exploring 
the roles of sex hormones, stress, and pain in fibromyalgia; work on 
the employment and health status of women with fibromyalgia; and 
adaptation to pain and stress in fibromyalgia. Other studies are 
focusing on rheumatoid arthritis and exploring the value of coping 
skills training for early rheumatoid arthritis as well as the roles of 
stress and adaptation to rheumatoid arthritis. Also, the NIAMS has 
teamed with the NIH Office of Research on Women's Health in funding a 
new Specialized Center of Research on gender differences in sensitivity 
to pain.

National Institute of Mental Health (NIMH)
    In keeping with the NIMH's mission, over one-half of the pain 
research NIMH supports is devoted to examining the relationship between 
pain and mood states. Examples of this work include studying the 
effects of anxiety on pain perception, and research evaluating 
depression as a consequence of pain. The NIMH portfolio also includes 
research on the basic neurophysiology of pain, including both central 
and peripheral nervous system mechanisms. NIMH also supports studies of 
the relevant receptors, neurons, neurotransmitters, and neuropeptides 
implicated in pain. NIMH-funded work also investigates the efficacy of 
psychosocial interventions in alleviating and preventing chronic pain. 
Thirty percent of the pain research funded by NIMH focuses specifically 
on children and elderly populations.

National Institute on Drug Abuse (NIDA)
    The National Institute on Drug Abuse (NIDA) has a comprehensive 
research portfolio that looks at all aspects of drug abuse and 
addiction and includes a significant pain and analgesia research 
program. NIDA's interest in this area stems from the fact that many 
analgesics also have abuse potential and research on drug abuse and 
addiction is relevant to pain issues. Thus, NIDA supports the 
development of treatments for chronic pain, including the use of 
opioids (e.g. morphine, oxymorphone, fentanyl, codeine) as well as 
finding alternatives to opioids. Innovative research funded by NIDA 
includes a device using transcutaneous electrical nerve stimulation 
(TENS) that was developed through NIDA's Small Business Innovation 
Research (SBIR) program. TENS stimulates certain nerves in the skin, 
and this activation inhibits pain. This device is now FDA approved and 
commercially available. NIDA also supports research on treating some 
severe forms of pain, such as cancer pain, using transplanted cells 
from the pituitary gland that produce opioids. Initial work in this 
area showed that implanting these cells into the spinal cord reduces 
pain in rats. Researchers are now looking at the use of this technique 
in monkeys. Another technology using ``targeted neurotoxins'' is being 
developed in animal models by several NIDA researchers. This technology 
is expected to reduce chronic pain by eliminating specific chronic pain 
fibers in the spinal cord. NIDCR has been examining specific targeted 
agents acting on ion channels in pain-sensing neurons that have shown 
potential as a clinical pain treatment. NIDA is partnering with NIDCR 
in completing toxicology studies on this agent and getting FDA approval 
for clinical trials in the treatment in cancer patients.

National Institute of Nursing Research (NINR)
    Nursing research focuses on ethnically and culturally sensitive 
interventions for pain prevention, assessment, management, and 
treatment. Emphases include end-of-life pain management and 
interventions that help people manage their own pain caused by chronic 
diseases, such as arthritis. NINR also focuses on the interaction of 
pain, the immune system, and illness at biological and cognitive 
levels. NINR supports research on non-pharmacologic interventions to 
reduce pain, including exercise, music and art therapy, and 
biofeedback, as well as the improving clinicians' ability to assess 
pain in those unable to express the level of pain they experience, 
including infants and cognitively impaired elderly.
    Research findings have set a new direction for pain research. For 
the first time, the influence of gender on pain relief was 
demonstrated. Study results showed that Kappa opioids, when used for 
acute pain, are more effective in women than men and have fewer side 
effects than stronger drugs, such as morphine. The role of hormones on 
the effectiveness of treatment is currently under study. NINR also 
conducts research on the importance of pain relief in improving the 
immune systems response to metastasis following surgery. In an animal 
model, researchers found that if morphine is provided before and after 
surgery, the immune system is less depressed, which suggests that pain 
relief improves resistance to the spread of cancer. Other research 
findings suggest that exercise helps fibromyalgia patients, who 
typically have both localized and widespread pain. Patients 
participating in muscle strengthening achieved the greatest benefit 
without significant exercise-induced flare-ups in pain.

National Center for Research Resources (NCRR)
    NCRR develops and supports critical research technologies and 
resources that underpin and advance health related research supported 
by the NIH and other research organizations. Research is carried out 
through support from the four NCRR divisions: Biomedical Technology, 
Clinical Research, Comparative Medicine, and Research Infrastructure. 
The Division of Biomedical Technology supports research resources that 
enable investigators to do basic research on the biochemistry and 
physiology of pain. NCRR's Division of Clinical Research supports 
General Clinical Research Centers where researchers are studying the 
clinical aspects of pain, including: drug testing and development, 
gender differences in pain, and pain associated with specific diseases. 
The Division of Comparative Medicine supports research on pain 
treatments in animal models, including a mouse model of analgesic 
regimens for surgery. Finally, the Division of Research Infrastructure 
supports studies on musculoskeletal pain and pain in children.

National Center for Complementary and Alternative Medicine (NCCAM)
    NCCAM supports an extramural pain research portfolio that involves 
extensive testing of complementary and alternative (CAM) therapies, 
such as acupuncture, chiropractic medicine, and yoga, to determine 
their efficacy in preventing and treating pain associated with a 
variety of conditions and diseases. For example, in a partnership with 
the National Institute of Arthritis and Musculoskeletal and Skin 
Diseases, NCCAM is supporting a large clinical trial to determine the 
efficacy of acupuncture in treating pain and functional limitations 
imposed by degenerative arthritis of the knee. At the Northwestern 
Health Sciences University, investigators are comparing chiropractic 
spinal manipulation, prescription medication, and self-care advice for 
neck pain, while at Harvard University investigators are evaluating the 
placebo effect and its role in treating repetitive strain injury. One 
of NCCAM's major research interests is to study how alternative 
therapies, primarily botanicals, interact with other medications. At 
the Fred Hutchinson Cancer Research Center researchers are studying how 
St. John's wort, a popular herb taken as an antidepressant, interacts 
with pain relieving opioids in the context of cancer pain therapy. In 
addition, NCCAM-supported researchers at the Johns Hopkins University 
Center for Complementary and Alternative Medicine are developing an 
animal model to study the reduction of cancer pain using herbal 
medicines that appear to contain anti-inflammatory properties. To help 
ensure a cadre of clinical investigators in the field of CAM research, 
including pain research, NCCAM has also awarded a grant to the Palmer 
Chiropractic University to develop a curriculum on research 
methodologies for chiropractors.

Office of the Director (OD)
    The Office of Research on Women's Health co-funded a total of $1.9 
million in pain research projects in the areas of: lower back pain, sex 
differences that influence pain, cellular mechanisms of neuropathic 
pain, pain management in temporomandibular disorders, and chronic pain 
conditions that predominantly affect women.

                              SCLERODERMA

    Question. There is significant vascular and autoimmune component to 
scleroderma, are there other institutes aside from the NIAMS at the NIH 
that you would recommend scleroderma researchers pursue to fund 
experiments aimed at finding a cure? For example, since the leading 
cause of death in scleroderma patients is through pulmonary 
hypertension and its effects on heart function, should grants on 
pulmonary hypertension that encompass issues unique to scleroderma 
patients be directed to the NHLBI instead of the NIAMS?
    Answer. Research on scleroderma is of interest to a number of NIH 
components. This is one of the strengths of the NIH--that we study 
diseases from a variety of perspectives. These efforts are 
complementary, not duplicative. To give an illustration, not an 
comprehensive list, in the case of scleroderma, the NIAMS is the lead 
Institute with interests in connective tissue and skin involvement. 
Other researchers interested in particular aspects of scleroderma 
include those supported by the National Heart, Lung, and Blood 
Institute (for example, work on pulmonary fibrosis, pulmonary 
hypertension, and vascular involvement), the National Institute of 
Diabetes and Digestive and Kidney Diseases (for example, work on the 
gastrointestinal tract and kidney function), the National Institute of 
Allergy and Infectious Diseases (for example, work on autoimmunity), 
and the NIH Office of Research on Women's Health (because scleroderma 
affects more women than men). As well, the National Center on Minority 
Health and Health Disparities also has an interest because of the 
increased incidence of scleroderma in Native Americans. This means that 
researchers interested in studying scleroderma should first consider 
what particular dimension they wish to pursue and contact the relevant 
Program Director within that Institute. The NIH web site includes links 
to the individual web sites of each Institute, so this is an effective 
way to identify the appropriate Program Director for the particular 
area of interest. I do want to underscore the close collaboration and 
collegial spirit that we have at the NIH--we team together to sponsor 
solicitations and to support research in targeted areas as well as 
jointly sponsor scientific meetings. All of this means that the NIH is 
able to bring a wealth of experience and complementary interests to a 
disease like scleroderma.
    Question. In your opinion is there sufficient infrastructure (i.e., 
enough scientists in the field) to support a significant increase in 
scleroderma funding? Aside from funding more grants specific to 
scleroderma research, how would the NIH propose increasing interest in 
the field?
    Answer. The issue of infrastructure is of significance to all 
scientific disciplines and diseases, and the NIH is actively working to 
address all of the dimensions of infrastructure. When we look 
specifically at scleroderma, I am pleased to tell you that this is an 
area that is the focus of a broad array of research efforts, and I want 
to cite highlights of several investments. First, the NIAMS made a 
significant commitment to boosting research on scleroderma when the 
Institute issued a special solicitation for research applications in 
fiscal year 2000. This successful solicitation resulted in the funding 
of ten new research grants totaling more than $2 million. These 
included both basic and clinical studies, and we were joined by the NIH 
Office of Research on Women's Health in co-funding two of the grants. 
The NIAMS also currently funds two Specialized Centers of Research in 
Scleroderma--one at the University of Texas Health Science Center and 
one at the University of Tennessee. Specialized Centers of Research 
(SCORs) increase the transfer of basic research findings into clinical 
practice by conducting basic and clinical studies under one roof. These 
SCORs focus only on scleroderma, and they serve as a national resource 
for researchers studying scleroderma. In addition,, the NIAMS 
established a national Scleroderma Family Registry and DNA Repository 
for scleroderma in June 2001 with the goal of identifying 
susceptibility genes. We believe these investments will provide 
critically important information on the causes of scleroderma and help 
us to develop improved treatments. In addition, through Dr. Zerhouni's 
Roadmap Initiative, infrastructure will be strengthened to facilitate 
clinical research across the spectrum of clinical diseases.
    With regard to increasing interest in the field, scleroderma is an 
autoimmune disease-a broad category of diseases in which the body's 
immune system attacks the body's own tissues as if they were foreign 
invaders, causing significant damage to target organs. The whole field 
of autoimmunity is currently exploding with activity and newly launched 
initiatives. Information that we learn from studying one autoimmune 
disease will provide valuable information for all autoimmune diseases. 
It is my opinion--and the goal of the NIAMS--that the significant, 
ongoing work on scleroderma as well as the broad interest in 
autoimmunity will be of great benefit for affected patients and their 
families and care givers.
    Question. There is strong scientific support for the NIH's 
``roadmap'' meetings with scientists from various disciplines to 
identify major cross-cutting biomedical challenges that the NIH could 
help address. How can representatives from the scleroderma community 
fit into one or several of these meetings to accelerate promising 
clinical opportunities and better enable new pathways to discovery for 
scleroderma and other illnesses?
    Answer. There is great excitement at the NIH as well as in the 
voluntary and professional communities about the newly launched NIH 
Roadmap Initiative and what it will mean to medical research. The NIH 
is committed to the participation of all of the voluntary and 
professional groups in this process. Opportunities range from serving 
as a member on one of the Working Groups that are just being formed, to 
providing comments through other venues such as public representatives 
serving on Institute National Advisory Councils or meetings of the NIH 
Director's Council of Public Representatives. As well, as the Roadmap 
Initiative moves forward, there will be opportunities to review draft 
recommendations from the many components of the Initiative as 
information is posted on the NIH Website and comments sought. I can 
assure you that NIH is seeking very broad input on this new Initiative, 
and will welcome the participation and thoughts of members of the 
scleroderma community as well as all of the other constituent 
communities.
    Question. Approximately what percentage of scleroderma-related 
grants or requests for funding did the NIH fund last year compared to 
the last five years?
    Answer. NIAMS is the lead Institute at NIH for funding research on 
scleroderma, and the Institute has undertaken several initiatives over 
the past 5 years to increase funding in this area. The total NIAMS 
spending for scleroderma research has grown from $4 million in fiscal 
year 1998 to over $10 million in fiscal year 2002-an increase of 155 
percent. NIH-wide, funding for scleroderma research has grown to a 
total of $15.1 million in fiscal year 2002.
    As mentioned previously, the NIAMS has recently increased efforts 
to expand the scleroderma portfolio including co-sponsoring a 
conference on ``Emerging Opportunities in Scleroderma Research,'' which 
led to the funding of a very successful special solicitation; support 
for two Specialized Centers of Research on scleroderma to enhance 
translational research; and support for the development of a national 
scleroderma family registry and DNA repository, with the overall 
objective of identifying genes that influence susceptibility to the 
disease.

                            VASCULAR DISEASE

    Question. There seems to be evidence that vascular diseases--
including stroke, high blood pressure, and diabetes--are associated 
with an increased risk of Alzheimer's disease. Some promising initial 
studies suggest that cholesterol-lowering drugs and changes in diet 
could reduce that risk. Are you conducting any research along these 
lines?
    Answer. A growing body of evidence suggests that some vascular 
conditions may be associated with an increased risk of cognitive 
impairment and/or Alzheimer's disease (AD), and such findings suggest 
that interventions to treat or prevent these conditions, particularly 
cholesterol-lowering drugs or dietary changes, could also be used to 
treat or prevent AD. For example, recent results from a biracial 
(African American and white) population-based community study in 
Chicago have suggested that dietary intake of vitamin E can decrease 
the risk of cognitive impairment and AD and that intake of dietary fats 
may increase or decrease risk of AD depending on the type of fat, while 
several epidemiological studies have suggested that individuals who 
take cholesterol-lowering drugs known as statins may have a reduced 
risk of cognitive impairment or AD.
    The NIA is currently conducting several clinical studies of 
cholesterol-lowering drugs and dietary modifications for AD treatment 
or prevention. For example, recent results from the Framingham Heart 
Study indicate that high blood levels of the amino acid homocysteine, a 
known risk factor for cardiovascular and cerebrovascular disease, may 
also be a risk factor for AD. The Alzheimer's Disease Cooperative Study 
(ADCS) will soon begin a clinical trial to determine whether lowering 
homocysteine using a combination of vitamins B6 and B12 and folic acid 
can modify progression of AD over a one-year period. Several other 
studies using various antioxidants to prevent or treat AD are ongoing. 
The NIA has also initiated a clinical trial through the ADCS to 
determine whether the cholesterol-lowering drug simvastatin can slow 
the progression of AD in people who have mild to moderate disease. 
Studies using another statin drug, lovastatin, are ongoing or planned.
    In addition, the NIA supports a number of basic studies elucidating 
the mechanisms of interventions that ameliorate both vascular and 
cognitive dysfunction. These include animal studies on the effects of 
cholesterol and cholesterol-lowering drugs on cognition. The Institute 
has provided support to several long-term cardiovascular health 
studies, including the Framingham Study, the Honolulu Heart Study, and 
the Cardiovascular Health Study, to explore links between vascular 
disease and cognitive impairment. We are also working with the National 
Heart, Lung, and Blood Institute to identify potential areas of 
collaboration in both epidemiologic studies and clinical trials.

                       DIABETES AND HYPERTENSION

    Question. Within the next 30 years, minorities will make up one-
fourth of the elderly population. (16 percent today) Some studies 
suggest that the two diseases that are most common in minority 
populations--namely diabetes and hypertension--are associated with an 
increased risk of Alzheimer's disease. Are you pursuing any research in 
this area?
    Answer. The NIA supports a number of epidemiological studies that 
are looking for risk and protective factors for AD, including diabetes 
and cardiovascular disease, in minority populations. For example, the 
Sacramento Area Latino Study on Aging (SALSA), a study of nearly 1,800 
community dwelling Latinos, primarily Mexican Americans aged 60 and 
above, has recently reported that risk of dementia was nearly 8 times 
higher in those individuals with both type 2 diabetes mellitus and 
stroke. In a community-based sample of African Americans in 
Indianapolis, the investigators found that use of antihypertensive 
medications was associated with preservation of cognitive function in 
older adults.
    The need to understand the driving factors behind persistent black-
white health disparities in cardiovascular disease, cerebrovascular 
disease, and overall longevity has led to the development of the HANDLS 
(Healthy Aging in Neighborhoods of Diversity across the Lifespan) 
study, a community-based research effort focusing on evaluating health 
disparities in socioeconomically diverse African-Americans and Whites 
in Baltimore. This multidisciplinary project will assess physical, 
genetic, demographic, psychosocial, and psychophysiological parameters 
over a 20-year period. It will also employ novel research tools to 
improve participation rates and retention. HANDLS researchers will 
investigate the longitudinal effects of socioeconomic status and race 
on the development of cerebrovascular disease and cardiovascular 
disease, as well as changes in psychophysiology, cognitive performance, 
strength and physical functioning, health services utilization, and 
nutrition, and their influences on one another and on the development 
of cardiovascular, cerebrovascular, and cognitive decline.

                          ALZHEIMER'S DISEASE

    Question. In your testimony you talk about the remarkable strides 
that have been made in understanding Alzheimer's disease. How quickly 
can we expect some of that new information to be put into the hands of 
physicians who are treating Alzheimer's patients? Along the same lines, 
do you feel that there are sufficient clinical researchers trained to 
translate all of this new knowledge into treatments and better patient 
care?
    Answer. NIA is currently conducting 18 clinical trials, seven of 
which are large-scale prevention trials. These trials are testing 
agents such as estrogen, anti-inflammatory drugs, and anti-oxidants for 
their effects on slowing progress of the disease, delaying AD's onset, 
or preventing the disease altogether. Other intervention trials are 
assessing the effects of various compounds on the behavioral symptoms 
(agitation, aggression, and sleep disorders) of people with AD. In 
addition, the NIA has a contract in place to facilitate testing of 
potential new therapeutic compounds in animals. This contract mechanism 
has now been in place for 8 years and has yielded several potentially 
promising compounds. So far, two of the drugs that have been tested, 
AIT-082 and phenserine, have entered human clinical trials.
    Although I cannot predict when potential treatments will be 
available to physicians treating AD patients, I am hopeful that the 
ability to support clinical trials directed at the multiple molecular 
targets identified by recent research advances will lead to positive 
results in the not-too-distant future.
    Expanding the numbers of AD-focused clinical researchers has long 
been a priority of the NIA. Opportunities for clinical research 
training exist throughout NIA's 29 AD Centers, as well as through the 
Alzheimer's Disease Cooperative Study. Many of our program project 
grants have also provided an avenue for training young physician-
scientists. An important aspect of each of these mechanisms is the 
exposure of basic scientists to clinical research; a number of these 
``clinically-trained'' basic scientists are now making important 
advances in the clinical arena. NIA has also initiated the Markey 
Training Program, which provides support for supervised research and 
study for clinically trained professionals who wish to redirect their 
careers toward research on Alzheimer's disease. In fiscal year 2002, 
six investigators received Markey Awards.
    Efforts are ongoing to find better ways to encourage and facilitate 
entry of clinicians into research careers (e.g., public/private 
collaborations, Beeson scholarships for training in geriatric 
research). Dr. Judy Salerno, NIA Deputy Director, has been leading a 
major effort, in collaboration with members of the National Advisory 
Council on Aging, to identify issues that affect the numbers of 
clinicians entering or remaining in research careers. Related to this 
effort, a symposium was held in November 2002 in Bethesda entitled 
``Finding Synergy: Advancing the Development of Physician-Investigators 
in Aging and Geriatrics'' at which experts in the field shared their 
views of what would be needed to increase the numbers of clinical 
researchers.

                        WOMEN'S HEART EDUCATION

    Question. I am concerned that heart disease remains the leading 
cause of death of women in the United States, yet many women do not 
realize this fact. I hear that you have been working with the fashion 
industry in your Women's Heart Health Campaign to increase women's 
knowledge about their No. 1 killer. Please tell the Committee about 
this initiative.
    Answer. The NHLBI launched a new campaign, The Heart Truth, last 
September to convey the message ``Heart disease is not just a man's 
disease--it's the No. 1 killer of women.'' The Institute unveiled the 
Red Dress Project as part of the campaign during Mercedes-Benz Fashion 
Week, February 7-14, 2003, in New York. Fashion Week is a twice-yearly 
event in which top fashion designers in the United States unveil their 
new garment lines for the following season. It garners attention from 
media in the United States and around the world, including editors from 
most daily newspapers, women's magazine editors/writers, and 
broadcasters such as Entertainment Tonight and local network 
affiliates. The Red Dress Project provides a platform to promote the 
messages of the campaign via the slogan ``heart disease doesn't care 
what you wear.'' Nineteen red dresses were contributed by leading 
fashion designers from either vintage or current collections and 
showcased throughout Fashion Week. A Red Dress Pin, specially designed 
for The Heart Truth campaign by a leading accessory designer, was 
introduced as the national symbol for women and heart disease.
    First Lady Laura Bush wore the Red Dress Pin during her visit to 
the Red Dress Project display in New York on Valentine's Day. She 
appeared on Good Morning America, Today, and The Early Show to promote 
awareness of women and heart disease. On February 21, in the Great Hall 
of the Hubert H. Humphrey Building, U.S. Department of Health and Human 
Services Secretary Tommy G. Thompson presented The Red Dress Project 
and designated the third Friday of February as Women's Heart Day. The 
Red Dress Project is the cover story of the May 2003 issue of 
Prevention magazine and has been featured in People magazine and 
Newsweek. A national tour of the Red Dress Project is also being 
developed, as well as plans to disseminate The Heart Truth messages and 
Red Dress Pin through channels that will reach a diverse population of 
women.

                                 PARITY

    Question. Dr. Insel, as you know there has been a lot of discussion 
during the last several years concerning the issue of mental health 
parity--that is, the requirement that health insurance coverage for 
mental disorders be provided on the same basis as that provided for 
coverage of so-called physical disorders. What is your view of that?
    Answer. As you know, the President has come out in support of 
parity coverage for mental disorders. Mental disorders are real and 
devastating illnesses. They account for a large proportion of the 
disability caused by all medical illnesses. Research supported by NIMH 
shows that the increase in cost to provide parity coverage for mental 
disorders can be limited, but not treating them would be very costly.

                       MEN AND DEPRESSION PROGRAM

    Question. I note that NIMH has recently launched--with the help of 
the Surgeon General of the United States--a major public campaign 
focused on men and depression. Can you tell me why you've done that?
    Answer. Depression is a treatable medical disorder that causes 
terrible suffering for its victims and is the cause of many of the 
Nation's 30,000 suicides each year. A major obstacle to getting people 
into treatment, however, is the stigma that accompanies admitting that 
you're depressed and that you need help--and this is especially true of 
men, including men who have suffered trauma. To help men recognize the 
signs of depression and to guide them toward more information and 
sources of assistance, the NIMH recently launched the ``Real Men/Real 
Depression'' public education campaign.
    Question. Isn't it true that far more women than men develop 
depression?
    Answer. Yes, more women than men are diagnosed with depression, but 
men do have depression and are less likely to seek treatment. One 
indication of the importance of this campaign is that four times as 
many men as women die by suicide. Figures from the Centers for Disease 
Control and Prevention and the 2000 census show that more than 70 
percent of all suicide victims are white males.
    Question. What do you hope to accomplish with this?
    Answer. The NIMH estimates that more than 6 million American men 
suffer from depression every year. We are trying to overcome the 
barriers that prevent these men from seeking help, and we are hoping to 
reduce the number of suicides in this country as a result of this 
effort. We already appear to be having success, based on the many 
thousands of e-mails and letters asking for help or more information 
that we have received to date--not only from depressed men, but from 
their friends, their family members, their co-workers, and others who 
care about them.

                             BUDGET REQUEST

    Question. For fiscal year 2004, the President is proposing $1.382 
billion for scientific and clinical research at NIMH. This is $41 
million over the fiscal year 2003 appropriation of $1.341 billion--a 3 
percent increase. This is barely enough to cover inflation and below 
expected increases in the cost of conducting clinical research. The 
Subcommittee is concerned that this funding request could prevent NIMH 
from sustaining the ongoing multi-year research grants that have been 
initiated over the past 2-3 years. What would be the impact of holding 
increases at NIMH to 3 percent this year? Would NIMH be able to 
continue ongoing, multi-year research programs such as the plan on mood 
disorders and bipolar disorder? Can you provide us with an estimate of 
the number of qualified grant proposals that you would expect to be 
unable to fund if NIMH's budget is held to a 3 percent increase in 
fiscal year 2004?
    Answer. Under the proposed 3 percent increase for NIMH's fiscal 
year 2004 budget, the Institute will honor its commitments to ongoing 
grants that have been funded over the past several years. The proposed 
budget provides funds to proceed on schedule in addressing the 
scientific priorities identified in The Strategic Plan for Mood 
Disorders Research. In fiscal year 2004, the NIMH estimates receiving a 
total of 2,535 applications for research project grants (RPGs). At the 
fiscal year 2004 President's Budget level, NIMH would fund an estimated 
636 of these applications while the remaining 1,899 RPGs would be 
unfunded. This is a success rate of 25 percent and is consistent with 
NIMH success rates over the last few years

                                RESEARCH

    Question. While steady funding increases have been achieved in the 
area of severe mental illness research, research on these illnesses 
remains underfunded, given the severe burden that these diseases 
present to the nation's public health. A 1996 independent study by the 
World Bank and World Health Organization (DALY: Disability Adjusted 
Life Years) found that four of the top ten causes of disability 
worldwide are severe mental illnesses: major depression, bipolar 
disorder, schizophrenia, and obsessive-compulsive disorder. But using 
the most recent estimates from NIH, research on mental illness lags far 
behind other diseases relative to public health costs, lost 
productivity, disability, etc.
    What efforts are underway at NIMH to focus greater attention and 
resources on promising research at the basic, clinical, and services 
levels on severe mental illness such as schizophrenia, bipolar disorder 
and major depression?
    Answer. NIMH maintains energetic communications, public liaison/
outreach, and public education programs, all of which are designed to 
draw attention to the opportunities and payoff of research on mental 
and behavioral disorders. The Institute's award-winning home page 
presents a wealth of information, (www.nimh.nih.gov) about mental 
disorders and recent progress in NIMH sponsored research. The page 
receives approximately 10 million hits per month from the public as 
well as members of the scientific and clinical communities. In April, 
NIMH launched a new mass media campaign, Real Men. Real Depression., 
which is focused on the leading cause of disability adjusted life years 
in the United States. The campaign features real men--that is, not 
actors--describing in everyday language what it felt like for them to 
be depressed. They talk about their confusion and concern for their 
ability to care for their families, about their jobs, about plans and 
hopes that are so easily shattered by depression. They talk about the 
difficulty of acknowledging that they were depressed and the struggle 
to force themselves to get help--help that is available largely because 
of NIMH-sponsored research.

                               TREATMENTS

    Question. In the last decade, many new treatments and services have 
been developed and proven for severe mental illnesses such as 
schizophrenia. Yet most individuals with these illnesses receive 
extremely poor treatment. What efforts are underway (or ongoing) to 
ensure that the improved treatment interventions being developed now 
will be effectively disseminated to providers and made available to the 
people who so desperately need these treatments?
    Answer. NIMH supports research on testing the best methods for 
dissemination of knowledge, whether in the form of evidence-based 
reports, algorithms, or guidelines. In addition to building a stronger 
base for understanding what are the best methods for sharing 
information, we also are engaged in research that seeks to determine 
how information is translated into sustained practice, or more simply 
put, how to get individuals, practitioners, and health care systems to 
adopt effective research-based practices. Examples of some of the 
grants we currently fund include studies that examine the use of 
depression guidelines in primary care settings, and the use of practice 
guidelines by physicians to improve care for hospitalized youth with 
aggression and impulsivity. Another project examines the use of the 
internet in educating families on care issues related to schizophrenia, 
while another applies technology for physicians' use with decision 
making in prescribing medications in community mental health clinics. 
Examples of program activities that occurred during 2002 include:
  --Two workshops on diffusion of evidence based practices in state 
        mental health systems
  --Workshop on special issues in disseminating research findings for 
        child and adolescent mental health
  --Initiation of new grants mechanisms that increase the capability of 
        providing centers to evaluate the delivery of their 
        interventions and improve their practices; and expedited 
        submission, review and funding of applications where evaluation 
        of changes being made in a delivery system requires time 
        sensitive research.
    Question. How is NIMH collaborating with SAMHSA and the Center for 
Mental Health Services (CMHS) on these efforts?
    Answer. The Science to Service Initiative that involves SAMHSA 
Centers and NIH institutes (NIMH, NIDA, and NIAAA) has as one of its 
goals the exchange of evidence-based practices that can be implemented 
by SAMHSA in natural settings, and then further researched by NIH as 
treatment and services questions arise from the practice field. NIMH is 
the principal source of support for mental health services research in 
the DHHS. In the past 22 months, we have been able to increase the 
number of services research applications by 45 percent. We are 
providing technical assistance to former SAMHSA grantees through 
workshops and individual consultations and working closely with CMHS 
staff members. Through co-sponsored activities we are working together 
to build the capacity of state mental health agencies and other 
``natural treatment settings'' to conduct research on the treatment 
they are providing, to evaluate its effectiveness and to examine 
factors that will increase readiness for adoption of research-based 
care.

                           SERVICES RESEARCH

    Question. Administration is returning agencies to their core 
mission, meaning that NIMH, rather than the Substance Abuse and Mental 
Health Services Administration, will be conducting services research on 
mental health issues.
    To what degree is NIMH prepared to assume greater responsibility 
with respect to services research?
    Answer. NIMH is the principal source of support for mental health 
services research in the DHHS. In the past 22 months, we have been able 
to increase the number of services research applications by 45 percent. 
We are providing technical assistance to former SAMHSA grantees through 
workshops and individual consultations and working closely with CMHS 
staff members. The Science to Service Initiative that involves SAMHSA 
Centers and NIH institutes (NIMH, NIDA, and NIAAA) has as one of its 
goals the exchange of evidence-based practices that can be implemented 
by SAMHSA in natural settings, and then further researched by NIH as 
treatment and services questions arise from the practice field.
    Question. People with mental illnesses often have conditions 
besides a mental health diagnosis. To reflect the real world in which 
mental health services are delivered, how will NIMH services research 
address people with multiple diagnosis?
    Answer. To insure rigor and maximize the possibly of detecting a 
treatment effect, randomized, controlled clinical trials--the 
traditional ``gold standard'' for medical research--have excluded 
anyone with a comorbid mental disorder, substance use disorder, general 
medical illness or other conditions ranging from pregnancy to active 
suicidality. Thus, the typical clinical trial for an antidepressant 
would be conducted with a relatively small, highly homogenous number of 
outpatients or, less frequently, inpatients, usually in an academic 
health center. The major outcome criterion would be a decrement on a 
behavioral rating scale such as the Hamilton Depression Scale.
    In real life, of course, the patient who typically appears in a 
psychiatrist's office is quite unlike the patient enrolled in the 
traditional clinical trial. Accordingly, while the NIMH will continue 
to fund the traditional form of clinical trial, the Institute's 
researchers also are adapting to the changing nature of treatments, 
patients, and the health care environment. In order to help clinicians 
provide optimal care to patients, research today also involves trials 
with larger sample sizes and with fewer exclusion criteria; trials are 
being conducted not only in academic clinics but also in more real 
world settings including managed care settings; and outcomes are 
assessed not only on the basis of symptom reduction but also on 
measures of functional rehabilitation, the end result that is of 
greatest interest to families and patients as well as employers and 
others who pay for treatment. This new type of trial--often called an 
``effectiveness'' trial--need not give up any of the traditional and 
indispensable emphasis on rigor. In trials of both pharmacotherapies 
and psychotherapies, the information sought should be geared toward 
helping clinical decision-making in real world settings and should 
demonstrate compelling types of functional outcomes. From a 
methodological perspective, new analytic techniques are being developed 
that allow clinical investigators and services researchers to move away 
from linear patterns and account for the complex interactions that 
occur in the real world.
    Question. Research at NIH focuses on randomized, clinical trials, 
despite the fact that many other proven research methods are more 
conducive to services research (such as multi-site research or analysis 
of nationally representative data sets such as the Census Bureau's 
Current Population Survey or the National Health Interview Survey). To 
what degree will NIMH utilize these other methods?
    Answer. NIMH supports a wide array of research designs and methods, 
not just randomized clinical trials. Researchers have the freedom to 
use the best techniques available to address the questions they are 
asking. This might involve using statistics to analyze large national 
data sets as in studies of risk factors for depression in children, or 
the use of interviews and qualitative techniques for research questions 
that require more context to understand. Other studies require control 
of variables to get at causation; thus randomized clinical trials are 
appropriate. Epidemiologic studies are also conducted in which surveys 
are the basic tools used. In summary, no one approach is used-the 
research question asked dictates the method to be used.

                             SCHIZOPHRENIA

    Question. Schizophrenia is the most devastating mental illness, 
affecting approximately 2.2 million American adults, or 1.1 percent of 
the population age 18 and older. Scientists still do not know the 
specific causes of schizophrenia; like many other medical illnesses 
such as cancer or diabetes, schizophrenia seems to be caused by a 
combination of problems including genetic vulnerability and 
environmental factors that occur during a person's development. While 
newer treatments for schizophrenia such as atypical anti-psychotic 
medications are proving effective, these treatments are largely 
palliative and help patients live with, rather than recover, from the 
illness.
    Given the enormous public health burden associated with 
schizophrenia and the demand for new treatments, what is NIMH doing to 
assure that the research base studying schizophrenia is strengthened 
and expanded?
    Answer. Recognizing that schizophrenia is among the most serious 
public health problems facing Americans, the NIMH has increased the 
proportion of it's budget devoted to this and other related 
neurodevelopmental disorders from 16 percent to 23 percent in the last 
five years. Reflecting the higher priority afforded this severe illness 
within NIMH, new initiatives have been launched that balance the need 
to focus on discovering the fundamental cause of the disease so a cure 
might be possible, with the need to improve treatments for patients who 
are suffering today.
    Efforts to understand the etiology of schizophrenia and other 
devastating mental illnesses are grounded in the neurosciences. For 
example, the NIMH Human Genetics Initiative is in the process of 
collecting biological materials on over 17,000 individuals to create a 
national scientific resource of DNA for broad use by investigators in 
the scientific community. Such samples help to identify risk genes 
associated with schizophrenia and shed light on the mechanisms 
malfunctioning in the brain. The Research Centers of Excellence (Silvio 
Conte Centers for the Neuroscience of Mental Disorders) have been 
established to develop and follow new leads generated by genetic and 
other basic studies in order to clarify abnormalities in brain 
functioning associated with major psychiatric illnesses. Over half of 
these Centers focus on schizophrenia, including two new centers (Mt 
Sinai, in New York City, and the University of North Carolina, Chapel 
Hill) that have been funded in the last fiscal year.

                           BIOPLOAR DISORDER

    Question. Bipolar disorder, or manic depression, is a serious brain 
disorder that causes extreme shifts in mood, energy and functioning. It 
affects 2.3 million adult Americans, or 1.2 percent of the population. 
Currently, there is no cure for bipolar disorder. While it can be a 
highly treatable and manageable illness, most of the approved 
treatments are indications associated with medications that were 
developed for other illnesses (anti-convulsants for epilepsy and anti-
depressants). In 1997, Congress requested NIMH to undertake a national 
research plan on bipolar disorder. This request resulted in the current 
research plan on mood disorders at NIMH. Can you please update the 
Subcommittee on the mood disorders research plan and what NIMH is 
learning about the causes and new treatments for bipolar disorder?
    Answer. NIMH completed the Strategic Plan for Mood Disorders last 
year and is now in the process of implementing the highest priority 
recommendations for new research on the nature, course, treatment, and 
prevention of these disorders. In addition, we are systematically 
monitoring and evaluating the ongoing research activities in each of 
the Divisions from neuroscience to services, to ensure movement toward 
our goals.
    In 1998 NIMH initiated funding of the STEP-BD program (Systematic 
Treatment Enhancement Program for Bipolar Disorder), a multisite study 
of bipolar disorder that is now following nearly 3,000 individuals 
receiving care for bipolar disorder in 18 centers across the United 
States. The budget for STEP-BD is approximately $25,000,000. This study 
is providing unique information on the course of bipolar disorder and 
on targets for treatment. We have learned, for example, that even under 
optimized treatment conditions about 5 percent of people with bipolar 
disorder will experience a relapse during the course of a year. 
Significantly, and counter to expectations, 80 percent of these 
relapses are depression, not mania, thus highlighting the need for safe 
and effective treatments for bipolar depression. Studies have been 
initiated to explore the value of rational strategies of combination 
treatment targeting bipolar depression. One of the benefits of large 
studies, such as STEP-BD is they provide training grounds and engender 
interest for new studies in bipolar illness. In fiscal year 2003 NIMH 
will be funding the first center specifically targeting interventions 
in bipolar illness in adolescents and adults-this new center is 
established at one of the primary sites of the STEP-BD study.
    With an increased awareness that bipolar disorder also affects 
children and adolescents, NIMH has recently funded two multisite trials 
to study the benefits of medications for youths with this disorder.
                                 ______
                                 
               Questions Submitted by Senator Tom Harkin

                              PARKINSON'S

    Question. Dr. Zerhouni, I appreciate that you have focused some of 
your attention on Parkinson's disease during your first year as 
director and that you and your staff have developed a ``matrix'' that 
outlines future NIH-funded research on Parkinson's. This matrix follows 
the release in 2000 of the NIH Parkinson's Disease Research Agenda. As 
you know, I have been concerned that funding for PD research during the 
past few years has increased at a rate below the overall percentage 
increase for NIH, despite the professional judgment estimates included 
in the Research Agenda. Please explain what the NIH is doing to fully 
implement the Research Agenda as well as the matrix.
    In addition, the President's proposed budget for fiscal year 2004 
includes $35 million for ``Roadmap Funding.'' The Budget describes its 
purpose ``as an additional effort to accelerate fundamental discovery 
and translation of that new knowledge into preventive and therapeutic 
strategies.'' Will you be focusing on any particular diseases when you 
implement the Roadmap, and will Parkinson's disease be one of the 
diseases you will choose?
    Answer. With regard to funding, NIH funding for Parkinson's disease 
research has been growing much more rapidly than the growth of the 
overall NIH budget, which of course has been very significant. During 
the first four years of the doubling effort--fiscal years 1999 through 
2002--actual NIH funding for Parkinson's disease research rose 
approximately 92 percent, while the overall NIH budget rose by a very 
generous 72 percent. To fully appreciate this increase, it is critical 
to recognize that in fiscal year 1998--the ``base'' year of the 
doubling--NIH had just increased its funding of Parkinson's disease 
research by 23 percent over fiscal year 1997, while the overall NIH 
budget increased only 7.2 percent in that time frame.
    More importantly, the NIH Parkinson's Disease Research Agenda and 
its updates encompass every research area critical to Parkinson's 
disease--genetics, environmental factors, cell death and survival, 
pharmacological treatments, deep brain stimulation, gene therapy, stem 
cell research, and the non-motor effects of Parkinson's--and the NIH is 
addressing every scientific aspect of that Agenda. This includes 
hundreds of research grants and contracts, at all levels of research, 
from basic through translational to clinical, including major clinical 
trials. We are following all plausible strategies to develop therapies, 
including drugs, surgery and cell transplantation. We have also held 
several scientific meetings since the original Agenda was developed to 
adjust to the changing scientific landscape, and to make sure that all 
scientific opportunities are pursued. This includes a ``summit'' of 
Parkinson's disease researchers that I convened in July 2002 to 
identify roadblocks that might be impeding progress. The Summit was 
very successful in identifying roadblocks, and NIH staff has drafted a 
matrix of short-to-long term, and low-to-high risk action items 
designed to target these issues. NIH is actively addressing these 
action items, both through enhanced support of individual Institute and 
Center efforts, and through improved coordination and collaboration 
with the research and voluntary Parkinson's communities.
    The Roadmap initiatives, being developed with input from a broad 
range of NIH staff and extramural scientific experts, are not disease 
or discipline specific, but rather take a cross-cutting approach to 
identify scientific challenges and roadblocks to progress. Driven by 
the enormous convergence in fundamental research approaches and 
technologies across diseases, organs and biological systems, the 
Roadmap will focus on facilitating and accelerating multi-disciplinary 
aspects of basic, translational, and clinical research. Roadmap 
initiatives will exploit new unprecedented opportunities and 
technologies that will accelerate progress in disease areas across the 
27 Institutes and Centers of the NIH. The exact nature of the progress 
will differ with each disease depending on our current knowledge of the 
disorder. Some diseases, which are in need of further basic research, 
will be aided by initiatives supporting portions of the Roadmap such as 
New Pathways to Discovery. Other diseases will benefit from Roadmap 
efforts aimed at optimal translation of discoveries into clinical 
reality, such as Clinical Trial Networks.

                      NATIONAL LIBRARY OF MEDICINE

    Question. The NLM and its Center for Biotechnology Information have 
made a major contribution to the fight against disease. To maximize 
this contribution, this committee has supported the design of a new 
facility. How is that going, and are you ready to initiate construction 
if funds are made available?
    Answer. The design of the National Center for Biotechnology 
Information is expected to be complete by August-September 2003 at 
which time the NIH, in consultation with the HHS Office of Facility 
Management and Policy, will develop a plan for scheduling and financing 
this project while considering other demands and priorities.

                                 ______
                                 
            Questions Submitted by Senator Pete V. Domenici

                        MENTAL ILLNESS RESEARCH

    Question. Dr. Zerhouni, can you please update the Subcommittee on 
efforts underway at NIH and NIMH to focus greater attention and 
resources on promising research at the basic, clinical, and services 
levels on severe mental illness such as schizophrenia, bipolar disorder 
and major depression to ensure that advances rapidly translate into 
better treatment for individuals living with these illnesses?
    Answer. At NIMH extensive efforts are underway to translate basic 
science findings (from genetics, structural and functional brain 
imaging, analysis of human post-mortem brain specimens, etc.) to an 
enhanced understanding of the causes (etiology and pathophysiology) of 
the major mental disorders. In the past few years significant progress 
has been made in identifying risk genes, refining disease phenotypes 
(characterizing more homogeneous subpopulations of patients), and 
implicating particular brain molecules, cells, circuits and structures 
as key players in these processes. The goal of these investigations is 
to develop more specific treatments and, ultimately, curative and 
preventive interventions. NIMH established a Clinical Neuroscience 
Research Branch in 1999 specifically to address these issues of 
translational science and, in the past several years, has significantly 
expanded its ``flagship'' translational program--The Silvio Conte 
Centers for the Neuroscience of Mental Disorders (currently 13 Centers 
are funded at an annual cost of $24 million).
    Carefully controlled, randomized, double-blind trials remain a 
cornerstone of clinical research sponsored by the NIMH. As 
practitioners are well aware, however, such studies cannot be the end 
of treatment research but a beginning. Clinical treatment research must 
adapt to the changing nature of treatments, patients, and the health 
care environment. Accordingly, NIMH has launched a series of clinical 
effectiveness trials that are characterized by large sample sizes and 
few exclusion criteria; to ensure the generalizability of findings, 
these trials occur not only in academic clinics but also in more real 
world settings including primary care settings. The approach also calls 
for aggressive dissemination of results. Four large-scale, multi-site 
clinical effectiveness trials include: (1) Systematic Treatment 
Enhancement Program for Bipolar Disorder (STEP-BD) to investigate 
strategies for managing bipolar disorder, (2) Clinical Antipsychotic 
Trials of Intervention Effectiveness (CATIE) to study the effectiveness 
of the new atypical antipsychotics in schizophrenia and Alzheimer's 
disease, (3) Sequenced Treatment Alternatives to Relieve Depression 
(STAR*D) to develop algorithms for managing especially difficult to 
treat depression, and (4) Treatment of Adolescents with Depression 
Study (TADS). In mid-fiscal year 2003, all of these trials are well on 
their way to attaining the targeted number of research participants. 
Through the network of research centers participating in these 
effectiveness trials, NIMH is creating an infrastructure for future 
clinical research involving direct comparisons of treatments and their 
benefits to different populations that can be conducted independently 
of pharmaceutical companies.
    Recognizing that much of the screening for mental illness and 
treatment is provided in other than specialty settings, NIMH continues 
to gain a better understanding of cost and financing associated with 
care in three different settings: juvenile justice system, school 
systems, and primary care. Use of non-traditional settings offer an 
opportunity to learn new ways of treating and managing co-existing 
addiction and mental illness problems through the use of non-specialty 
care providers working with the less numerous specialty providers. 
Research is also exploring preferences of individuals with mental 
disorders or combined disorders to seek treatment in general health 
care, or social services settings and determining if access to 
treatment in a preferred setting improves seeking treatment, staying in 
treatment, and adherence to treatment plans.

                         SCHIZOPHRENIA RESEARCH

    Question. Schizophrenia is the most devastating mental illness, 
affecting approximately 2.2 million American adults, or 1.1 percent of 
the population age 18 and older. Schizophrenia interferes with a 
person's ability to think clearly, make decisions, and relate to 
others. Scientists still do not know the specific causes of 
schizophrenia, but research has shown that the brains of people with 
schizophrenia are different, as a group, from the brains of people 
without the illness. While newer treatments for schizophrenia 
(including atypical anti-psychotic medications) are proving much more 
effective in treating both the positive and negative symptoms of 
schizophrenia, these treatments are largely palliative and help 
patients better live with, rather than recover from the illness.
    Given the enormous public health burden associated with 
schizophrenia and the need for new treatments, what is NIMH doing to 
ensure that schizophrenia research becomes a higher priority within the 
agency?
    Answer. Recognizing that schizophrenia is among the most serious 
public health problems facing Americans, the NIMH has increased the 
proportion of it's budget devoted to this and other related 
neurodevelopmental disorders from 16 percent to 23 percent in the last 
five years. Reflecting the higher priority afforded this severe illness 
within NIMH, new initiatives have been launched that balance the need 
to focus on discovering the fundamental cause of the disease so a cure 
might be possible, with the need to improve treatments for patients who 
are suffering today.
    Efforts to understand the etiology of schizophrenia and other 
devastating mental illnesses are grounded in the neurosciences. For 
example, the NIMH Human Genetics Initiative is in the process of 
collecting biological materials on over 17,000 individuals to create a 
national scientific resource of DNA for broad use by investigators in 
the scientific community. Such samples help to identify risk genes 
associated with schizophrenia and shed light on the mechanisms 
malfunctioning in the brain. The Research Centers of Excellence (Silvio 
Conte Centers for the Neuroscience of Mental Disorders) have been 
established to develop and follow new leads generated by genetic and 
other basic studies in order to clarify abnormalities in brain 
functioning associated with major psychiatric illnesses. Over half of 
these Centers focus on schizophrenia, including two new centers (Mt 
Sinai and University of North Carolina, Chapel Hill) that have been 
funded in the last fiscal year.
    Although the delusions and hallucinations of schizophrenia are 
often treated effectively by available medications, research indicates 
that impairments in cognition (memory, planning, abstract thinking) are 
most associated with disability in this illness. Unfortunately, 
available medicines do little to reverse this aspect of schizophrenia. 
To address this problem, NIMH has launched a Schizophrenia Treatment 
Development Initiative focused on both developing new drug treatments 
to remedy cognitive impairments. With the cooperation of the FDA, this 
initiative will develop standard measures and methods to test new drugs 
that target cognition in schizophrenia in order to provide the 
pharmaceutical industry with guidelines for drug registration and 
hence, enhanced incentives to invest in developing treatments for this 
aspect of schizophrenia. To jumpstart this effort, in fiscal year 2004 
NIMH will establish a new clinical trials network focused on 
collaborating with industry to identify and test new agents for 
cognition in schizophrenia.
    In addition to the large Clinical Antipsychotic Trials of 
Intervention Effectiveness (CATIE) project, which is designed to 
determine the long-term effects and usefulness of antipsychotic 
medications in a broad cross-section of persons with schizophrenia, 
NIMH is conducting a range of studies concerned with how to best use 
available treatments for schizophrenia. These include clinical trials 
of combination medication strategies. Recognizing that medication 
adherence is a crucial issue for many patients, active efforts to 
stimulate research on this problem have yielded a series of new studies 
designed to develop and test adherence-oriented intervention. Finally, 
rehabilitation-oriented studies are encouraged and supported to develop 
new approaches to enhancing patient skills and functioning.

        FOCUS & ACCOUNTABILITY ON SEVERE MENTAL ILLNESS AT NIMH

    Question. Dr. Insel, as you know, NIMH has been criticized in the 
past for failing to maintain an appropriate focus on severe mental 
illness in its portfolio. Over the years, concern has been expressed 
that basic scientific and clinical research on schizophrenia, bipolar 
disorder and other severe mental illnesses remain low priorities at 
NIMH. In order to challenge and rebut these criticisms, would you 
support a requirement for NIMH to provide an accounting of new and 
existing research grants broken down by specific illnesses?
    Answer. First, let me make clear that direct support for research 
of so-called ``serious mental disorders,'' such as schizophrenia, is a 
priority at NIMH. It is the lead Federal agency responsible for 
supporting research on mental and behavioral disorders. The goal of 
NIMH's portfolio of research on mental illness is to better understand, 
treat, prevent, and ultimately cure mental illness. This requires both 
direct and indirect approaches, which may not be apparent in accounting 
for spending by disease.
    Basic research, the relevance of which might not be immediately 
apparent, can produce knowledge critical for understanding mental 
illness. For example, studies of the brains of songbirds, brought the 
unexpected and startling news that adult brains can regenerate new 
nerve cells, a finding that completely changed scientists' thinking 
about the possibility for brain repair. Similarly, in October 2000, Dr. 
Eric Kandel, an NIMH grantee, won the Nobel Prize for Medicine based on 
his work with sea slugs, in recognition that this research had 
profoundly increased understanding of brain function and medication 
effects in humans. Both scientists have accelerated our understanding 
of brain processes important for mental illness.
    Over the years, Congress has expressed interest that NIMH take 
responsibility for many areas beyond mental illness including HIV/AIDs 
risk behaviors, violence, gambling, and many others. Nevertheless, NIMH 
has a strong and abiding commitment to a core focus on severe mental 
illnesses. Indeed, NIMH has launched four large-scale, public health 
oriented clinical trials in major disease conditions, including bipolar 
(manic depressive) illness; schizophrenia/Alzheimer disease; treatment-
resistant depression; and major depression in adolescents. These trials 
investigate ``real world'' effectiveness of mental health treatments, 
and because they are carried out in community settings they do not 
exclude people because they have a co-occurring substance abuse 
disorder or other problems B unlike typical short-term pharmaceutical 
trials. People with these disorders live in the community, and NIMH is 
committed to assuring that treatment interventions will work where the 
patient lives.
    NIMH is supporting many new activities with a focus on severe 
mental illnesses, and has increased the percentage of its overall 
research portfolio in this area. One major new initiative, for example, 
will look at the cognitive deficits associated with schizophrenia B the 
deficits that make it very difficult for people affected by the disease 
to be employed or otherwise function fully in society. This is an 
effort to develop new insights into the neurobiology of attention, 
working memory, and other fundamental cognitive processes in order to 
identify and test potential therapeutic agents targeting cognitive 
deficits in schizophrenia. As a part of this effort focused on 
schizophrenia, NIMH is establishing an expert Schizophrenia Cognition 
Measurement Development Group. Without measurement consensus, the Food 
and Drug Administration cannot recognize cognition as a valid treatment 
endpoint for industry-sponsored research and drug registration. Since 
cognitive impairment, rather than delusions and hallucinations, may be 
the major determinant of functional outcome in people with 
schizophrenia, this is an extremely important effort. NIMH also will 
support a Cognition Treatment Network to identify, evaluate, and 
acquire pharmacological agents to treat cognitive deficits in 
schizophrenia and related psychoses.
     In summary, the goal of NIMH's portfolio of research on mental 
illness is to better understand, treat, prevent, and ultimately cure 
mental illness. While the NIMH has significantly increased the 
percentage of its portfolio devoted specifically to studies related to 
severe and persistent mental illnesses, it continues to honor its 
mission and responsibility to support basic biomedical and behavioral 
research that will elucidate the underlying causes of these disorders. 
A strict focus on specific diseases would make this very difficult, if 
not impossible, and would certainly hamper scientific progress.

                                 ______
                                 
       Questions Submitted to the Social Security Administration

              Questions Submitted by Senator Arlen Specter

    Question. Commissioner, since 1997 the General Accounting Office 
(GAO) has included the Supplemental Security Income program in its list 
of programs that are at high risk for waste, fraud and mismanagement. 
Thanks to the Agency's dedicated effort, GAO's 2003 High Risk Update 
did not include the Supplemental Security Income program. However, as 
indicated by your Corrective Action Plan, additional steps can be taken 
to continue to strengthen program oversight and reduce the incidence of 
erroneous payments.
    What specific actions are supported in the fiscal year 2004 budget 
request to prevent the occurrence of erroneous payments in the SSI 
program and strengthen program oversight?
    Answer. The President's fiscal year 2004 budget includes 
appropriation language requiring the Social Security Administration 
(SSA) to spend no less than $1.446 billion of the Limitation on 
Administrative Expenses (LAE) for program integrity activities, 
including continuing disability reviews (CDR), non-disability 
redeterminations of eligibility in the Supplemental Security Income 
(SSI) program, and overpayment workloads. This language will ensure 
adequate resources for these three important and cost-effective 
workloads that reduce erroneous payments, within the overall SSA 
request of $8.53 billion. The fiscal year 2004 program integrity 
investment will return lifetime program savings of more than $10 
billion. The three key activities are:
  --Continuing Disability Reviews.--SSA conducts periodic reviews to 
        ensure that only those beneficiaries who are truly disabled 
        continue to receive benefits.
  --SSI Redeterminations.--Experience has shown that the most powerful 
        tool SSA has to detect and prevent improper payments in the SSI 
        program is to perform periodic reviews of the non-disability 
        factors of eligibility for SSI.
  --Overpayment Collections.--Prompt processing of the Agency's debt 
        collection workload is an important element of sound financial 
        management and program stewardship. Having sufficient 
        administrative resources will allow SSA to process substantial 
        overpayment workloads and move forward as quickly as possible 
        to implement new tools of prevention, detection and collection.
    SSA's substantial program integrity initiatives result in 
significant benefits to the Government in terms of detecting and 
collecting overpayments. Without these program integrity efforts, the 
Agency would pay out billions of trust fund and general fund dollars in 
erroneous payments. Experience has shown a $9-to-$1 return on for 
investments in CDRs and a $7-to-$1 return for investments in SSI 
redeterminations. Because these activities pay for themselves, many 
times over, resources to support them shouldn't compete with resources 
needed for service delivery; and the President's budget proposes 
funding them through adjustments to discretionary spending caps.
    The fiscal year 2004 budget also supports a number of initiatives 
to prevent and collect erroneous payments in the SSI program and 
strengthen program oversight, including piloting an automated monthly 
wage reporting system using voice recognition and touch-tone phone 
technology, testing electronic access to records of financial 
institutions, and implementing cross program recovery, credit bureau 
referrals, and Treasury Department administrative offset.
    SSA's fiscal year 2004 budget also contains a legislative proposal 
to apply the same requirements now in effect for reviewing title II 
initial disability allowances to title XVI adult disability allowances. 
Preeffectuation reviews have a high rate of return on investment, would 
strengthen the integrity of the SSI program and help assure the 
American people that their tax dollars are going only to individuals 
who are truly disabled under the law.
    Question. How will this budget request fully utilize all of the 
tools provided by Congress for preventing and collecting erroneous 
payments, in particular those authorized by the Foster Care 
Independence Act of 1999? Also, if erroneous payment prevention and 
collection authorities currently available are not being fully 
utilized, is it because of a lack of resources available to the SSA? If 
not, what is preventing SSA from fully utilizing these authorities and 
what steps are being taken to overcome those barriers to full 
implementation?
    Answer. SSA has a vigorous program for developing all debt 
prevention and collection tools authorized by Congress. The Agency's 
program encompasses the authorities granted by the Foster Care 
Independence Act (FCIA) of 1999, authorities given by other laws, and 
self-initiated projects. SSA's strategy for implementing all of the 
tools is to use its available resources first to develop those that 
yield the most savings or that can be easily integrated into the 
existing debt management framework.
    The authorities granted by FCIA are: access to financial 
institutions, credit bureau reporting, administrative offset, 
establishing overpayments on the records of representative payees of 
deceased beneficiaries, Federal salary offset, private collection 
agencies, and interest charging. Authorities granted by other laws 
include mandatory cross program recovery and administrative wage 
garnishment.

                            DEBT PREVENTION

    The top two reasons for SSI overpayment errors are unreported wages 
and unreported bank accounts with substantial assets. In the past, SSA 
has focused on the detection of errors in payments already made. 
Initiatives either planned or underway offer substantial promise as a 
means to preventing error.
  --Automated Monthly Wage Reporting Using Voice Recognition and Touch-
        Tone Phone Technology.--The Monthly Wage Reporting Pilot using 
        voice recognition and touch-tone phone technology is one of the 
        steps SSA is exploring to facilitate wage reporting and reduce 
        the incidence of erroneous overpayments in the SSI program. 
        Each year we detect approximately $500 million in overpayments 
        due to wages. Over half this amount is due to the failure to 
        report changes to SSA. SSI recipients are required to report 
        whenever there is a change in their income or the income of a 
        deemor (a spouse or parents of a child under the age of 18 
        living in the same household but not receiving SSI). Some 
        individuals report changes as required, but many do not. 
        Currently, few SSI recipients have access to the Internet. 
        Therefore, we are testing a new automated telephone reporting 
        system that could quickly process large numbers of wage 
        reports. We will ask approximately 4,000 people to use this new 
        system to report wages once a month for a 6-month period, May 
        through October 2003. We will then verify the wage amounts to 
        determine if they reported accurately. If this test is a 
        success, automated monthly wage reporting will be rolled out 
        nationwide.
  --Access to Financial Institutions.--SSA will test a process using 
        authority granted by FCIA to access the records of financial 
        institutions. Use of this tool during the initial claims 
        process will provide access to information on unreported income 
        or assets. Similarly, use of the tool during the SSI 
        redetermination process and periodically throughout the life of 
        a SSI recipient's entitlement will provide information 
        regarding a recipient's assets in relationship to limits 
        affecting eligibility. SSA is currently working to finalize the 
        rules for publication, which will enable SSA to proceed with a 
        proof of concept to test the capability of electronic access of 
        financial records later this year. If the proof of concept is 
        successful, SSA will develop plans for a phased rollout of the 
        new business process.

                            DEBT COLLECTION

    SSA is constantly striving to improve its debt management program. 
Since 1992, when the Agency implemented Tax Refund Offset (TRO) to 
collect delinquent title II overpayments, SSA has put in place eleven 
different improvements. These improvements include two major expansions 
to the TRO program, credit bureau reporting and administrative offset 
for delinquent title II overpayments and a streamlined remittance 
process that uses state-of-the-art equipment. In addition, SSA worked 
with Treasury's Financial Management Service to implement Benefit 
Payment Offset and the Federal Payment Levy Program, whereby Social 
Security benefits are offset or levied as collection toward delinquent 
tax and non-tax debts owed by beneficiaries to other Federal agencies.
  --Recent Initiatives.--In keeping with its developmental strategy, 
        SSA implemented mandatory cross program recovery in 2002 
        because of its promise of large debt collections. In fact cross 
        program recovery has enabled SSA to collect over $50 million in 
        SSI debt in less than one year. SSA also implemented credit 
        bureau reporting and administrative offset in 2002 because 
        those tools could be integrated easily into the existing debt 
        management system.
  --Current Initiative.--SSA also is developing administrative wage 
        garnishment (AWG), which was authorized by the Debt Collection 
        Improvement Act. We believe AWG has the potential to yield the 
        largest amount of collections of all the remaining tools. We 
        estimate this tool will yield $105 million in the first five 
        years of its use ($80 million in title II collections and $25 
        million in title XVI collections).
  --Future Initiatives.--When SSA completes its work on AWG, it will 
        move on to a pair of debt collection tools authorized by FCIA: 
        establishing overpayments on the records of representative 
        payees of deceased beneficiaries and Federal salary offset. 
        Although these two tools will yield direct collections from 
        payment sources such as tax refunds, other Federal payments and 
        Federal salaries, they will not approach the collection 
        potential of AWG, and that is why they will be developed after 
        garnishment.
    Implementation of interest charging and use of private collection 
agencies will follow the completion of Federal salary offset and the 
establishment of overpayments on the records of representative payees.

                     FULL UTILIZATION OF FCIA TOOLS

    Debt management represents one of the many different areas 
requiring resources. In fact, SSA has a multitude of initiatives 
spanning all aspects of its business process. The Agency must 
prioritize projects and choose the order in which they are developed.
    SSA has a process for determining the priority of initiatives. This 
process is manifested in SSA's Information Technology plan, where 
projects are assessed based on their return on investment and other 
critical factors. Based on this rigorous examination of projects, SSA 
is focusing first on monthly wage reporting, access to financial 
information and administrative wage garnishment.
    Question. The ``Justification of Estimates for Appropriations 
Committees'' for the fiscal year 2004 budget request for Social 
Security Administration (SSA) states that: ``The Ticket to Work Program 
is up and running in 33 States and the District of Columbia and will be 
expanded to all States and U.S. territories in 2003.''
    Specifically, how much funding is available within the fiscal year 
2004 request for the Limitation for Administrative Expenses account to 
support implementation of the Ticket to Work program and what 
activities are supported?
    Answer. SSA's fiscal year 2004 LAE account includes $39 million to 
fund the following activities in support of the Ticket to Work program:
  --Benefits Planning and Assistance Cooperative Agreements ($23 
        million).--Benefits planning, assistance and outreach (BPAO) 
        cooperative agreements are intended to ensure that these 
        community based services are available in every state, the 
        District of Columbia and every U.S. territory. The law 
        authorizes $23 million to be appropriated each year through 
        2004 for this purpose, and SSA's fiscal year 2004 budget 
        includes funding in this amount (including costs of related 
        training and technical assistance).
  --Protection and Advocacy Grants ($7 million).--The 1999 Ticket to 
        Work Legislation authorizes $7 million to be appropriated each 
        year through 2004 for Protection and Advocacy (P&A) grants. 
        These grants will be used to provide advice to beneficiaries 
        and to provide an avenue for resolving disputes. Consistent 
        with the $7 million authorization, we plan to spend $7 million 
        (including costs of support services such as training and 
        technical assistance) for P&A in fiscal year 2004.
  --Program Manager Contract ($9 million).--The Program Manager 
        contract was awarded to Maximus Inc. in fiscal year 2000 at a 
        total cost of $56 million covering the period September 29, 
        2000 through September 30, 2005. Maximus is a private Virginia 
        based organization that will help SSA manage the over-all 
        Ticket to Work program. Phase IV of the contract is funded in 
        fiscal year 2004 at $9.4 million.
    In addition SSA's administrative budget supports other Return to 
Work activities such as:
  --The Ticket to Work and Work Incentives Advisory Panel advises the 
        Commissioner of SSA, the President, and Congress on issues 
        related to work incentives for people with disabilities.
  --Other administrative costs include quality assurance contracts, 
        notices, miscellaneous printing costs such as public education 
        materials and reference guides, postage, training, travel, and 
        systems enhancements.
  --Nationwide training and outreach efforts to build employment 
        support expertise in SSA's field offices. SSA also is looking 
        at its current incentives as they pertain to young people with 
        disabilities who are making the transition from school to work 
        and to disabled individuals with more challenging 
        rehabilitation issues.
    Question. How much funding from other sources support the program 
within the fiscal year 2004 budget request?
    Answer. SSA's fiscal year 2004 budget includes program funding to 
cover outcome and milestone payments made to Employment Networks (EN) 
under the Ticket to Work program. Milestone payments are provided to 
ENs based on a beneficiary's successful achievement of prescribed work 
activity. Outcome payments are made once an individual's benefit 
payments cease due to work activity and earnings. For fiscal year 2004, 
we have budgeted $25 million in each program--Social Security (OASDI) 
and Supplemental Security Income--to cover Ticket payments. In 
addition, SSA provides reimbursement payments to State Vocational 
Rehabilitation (VR) agencies, which elect to be paid under this system 
and not as ENs, when they are successful in rehabilitating disability 
beneficiaries. The budget includes an estimated $73 million to cover 
OASDI VR reimbursement payments and $75 million to cover SSI 
reimbursement payments in fiscal year 2004.
    In addition, SSA's fiscal year 2004 section 1110 research budget 
request, funded through the SSI appropriation, includes $5.2 million 
for evaluation of the Ticket to Work and Self-Sufficiency Program. This 
project will identify the most promising components of the Ticket to 
Work initiative, the most efficient incentive structure for the 
program, the refinements necessary to improve Ticket outcomes, and the 
individuals most likely to benefit from the program. It also will 
examine the adequacy of incentives in delivering services under the 
program for hard-to-serve beneficiaries.
    SSA's fiscal year 2004 budget for research and demonstration 
projects also funds several other projects that support the return-to-
work initiative and the Ticket to Work program's goal of transitioning 
disabled individuals into the workforce, including the Youth Transition 
Process Demonstration, the Early Intervention Demonstration, and 
evaluation of the Disability Program Navigator project with the 
Department of Labor.
    Question. Now that the SSA has roughly one year of experience with 
Social Security and SSI disability recipients receiving Tickets for VR 
services, what trends are evident in terms of the choices consumers are 
making whether to utilize their ticket, the characteristics of 
participating individuals, the organizational characteristics of 
selected Employment Networks (including VR agencies), the way in which 
such Employment Networks are paid and the employment outcomes for 
participating individuals?
    Answer. Our early information reveals that a fairly diverse group 
of beneficiaries have made the decision to assign Tickets to providers 
and to begin employment. So far, the profile of beneficiaries who have 
assigned Tickets closely tracks the profile of Ticket-eligible 
beneficiaries with regard to type of benefit, sex, type of disability 
and time on the rolls. One interesting trend we will be watching is 
that younger beneficiaries, those under age 40, are assigning Tickets 
at a much higher rate than older beneficiaries are.
    With respect to providers, approximately 85 percent of individuals 
participating in the Ticket program have assigned their Tickets to the 
State VR agencies; of these, about 60 percent are new clients to VR. VR 
agencies have elected to receive payment under the traditional cost 
reimbursement program for 95 percent of these beneficiaries. ENs with 
Tickets assigned to them include traditional employment service 
providers in the public and private sectors, and such non-traditional 
providers as employers, colleges, employment agencies and job placement 
services, hospitals, faith-based organizations and Department of Labor 
One-Stop centers.
    As of May 8, 2003, about 4 million Tickets have been mailed, and 
more than 16,000 have been assigned to ENs or VR agencies. Although we 
have information regarding payments to providers, it is still too early 
to draw broad conclusions regarding the employment outcomes of 
beneficiaries participating in the Ticket program. We will be 
evaluating the Ticket program to identify its most promising 
components, refinements needed to improve Ticket outcomes, and the 
individuals most likely to benefit from the program, as well as to 
assess the program's cost effectiveness. Nevertheless, many Ticket 
participants are now working, and we are pleased to learn the success 
stories from individuals whose receipt of the Ticket has provided them 
the opportunity to return to productive employment.
    By the end of this year, the Ticket-to-Work program will be 
available in all 50 States. I truly believe that we're entering a new 
era for people with disabilities--an era of new attitudes, new 
possibilities, and new hopes. Many people want to work, and this 
program helps them do that:
  --Arizonian, Bob Q., used his Ticket, set up an appointment with an 
        employment network, and is now working as a marketing designer 
        for the real estate industry.
  --Didi A. credits the Ticket-to-Work program for helping to provide 
        the motivation that brought her to Arizona Bridge to 
        Independent Living (ABIL). Using her Ticket, she met with a job 
        counselor who prepared her for work. Last September, Didi 
        accepted a position with the Arizona State Government.
  --Vera L. has the longest recorded employment of the Ticket Program, 
        more than a year. Vera works 40 hours a week as a personal 
        assistant and has already received a raise.
    Question. Through what means has SSA informed eligible 
beneficiaries and recipients, employers, service providers and other 
stakeholders about the Ticket program?
    Answer. We've informed beneficiaries and recipients, employers, 
service providers and other stakeholders about the Ticket program 
through:
  --The initial Ticket mailings, which we will complete in 2004;
  --Media events to kick-off the Ticket program in several States in 
        the first two rounds of Ticket roll-out. I joined former 
        Senator Roth in Wilmington, Delaware to highlight presenting 
        ``The First Tickets in the First State'' to individuals in 
        Delaware. I also hosted Ticket media events with Senator Ted 
        Kennedy in Boston, MA and Representative J.D. Hayworth in 
        Phoenix, AZ., and with Virginia State officials in Arlington, 
        VA;
  --Partnering with the Office of Personnel Management (OPM) to promote 
        the Ticket program throughout the Federal government;
  --Partnering with the Department of Labor's Office of Disability 
        Employment Policy to utilize its Employer Assistance Referral 
        Network and create a subunit named Ticket to Hire (TTH), which 
        specializes in matching employers with job-ready candidates 
        from the Ticket program;
  --Partnering with private organizations to promote the program to a 
        diverse mix of employer groups;
  --Recruitment fairs to educate service providers about the Ticket 
        program and encourage them to become ENs;
  --Significant outreach to service providers and others by MAXIMUS, 
        our contracted program manager;
  --Our Internet website, which educates and provides resources to 
        Ticket to Work stakeholders;
  --National and regional representation, by specialized Ticket to Work 
        staff, at hundreds of conferences and forums that promote the 
        hiring of people with disabilities; and
  --SSA's extensive informational materials provided in print and other 
        formats. SSA's Red Book on Work Incentives and a number of 
        other materials are used extensively in the field to inform and 
        train beneficiaries, advocates, service providers and others.
    We are working on further enhancements to our outreach and public 
information efforts. Plans include written and video presentation of 
Ticket success stories, a new training effort to assist present and 
potential ENs with information on potential funding sources and 
analysis of emerging data on the Ticket program to target our 
informational efforts.
    Question. How much funding within the fiscal year 2004 Budget 
supports training, technical assistance and outreach to these different 
groups?
    Answer. SSA's fiscal year 2004 administrative budget includes $39 
million for BPAO cooperative agreements, P&A grants, and continuation 
of the Program Manager contract. A large portion of that amount is used 
to provide training, outreach and public information.
    Question. How has SSA provided support to individuals in making 
well-informed, work-related decisions, as well as in ensuring that 
their legal rights are protected under new program authorities?
    Answer. SSA has a multi-faceted approach to help beneficiaries with 
disabilities obtain accurate and timely information and support 
regarding return to work. The approach centers around continued 
education and training for all direct service employees, the 
establishment of partnerships with other agencies and organizations, 
improved workload management and control systems, and the establishment 
of a corps of full-time Area Work Incentives Coordinators (AWIC). The 
AWIC will specialize in employment support workloads and services, and 
serve as the Agency's ombudsman and focal point of contact for 
advocates.
    Two grant programs authorized by the Ticket to Work and Work 
Incentives Improvement Act of 1999 provide support to individuals 
regarding their participation in the Ticket program.

           BENEFITS, PLANNING, ASSISTANCE AND OUTREACH (BPAO)

    SSA awarded 116 cooperative agreements to a variety of community-
based organizations for BPAO projects. The goal of the BPAO program is 
to enable SSA's beneficiaries with disabilities to make well-informed, 
work-related decisions.
    BPAO projects cover every State, Territory, and the District of 
Columbia. Collectively they employ over 400 Benefits Specialists who 
explain the complex interrelationship of SSA's benefits, those of other 
Federal agencies and an individual's local programs. They assess the 
potential impact of employment on a beneficiary's Federal and State 
benefits eligibility and overall financial well being. Benefits 
Specialists then develop a comprehensive framework of possible options 
and projected results for each as part of the career development 
process. Benefits assistance involves effective management of benefits 
as well as problem-solving support as needed. It includes analysis, 
reassessment, education, advisement and monitoring. Almost 50,000 
beneficiaries have received direct services under the program to date.
    Outreach activities by the BPAO projects are ongoing efforts to 
inform beneficiaries, their families, service providers and other 
stakeholders about the work incentives available. By enhancing 
awareness and understanding of the supports to be had, the Benefits 
Specialists alleviate the fear and uncertainty of beneficiaries 
considering work. The BPAO program has become an important step on the 
road to economic self-sufficiency for persons with disabilities.
    SSA contracted with 3 universities to provide ongoing technical 
assistance and training to BPAO projects so they may effectively and 
responsibly serve clientele. Benefits Specialists must pass an 
intensive 7-day orientation class and successfully complete a field 
assignment before providing services under the program. In addition, 
they attend refresher and follow-up courses throughout the award 
period. This training is necessary to ensure dissemination of accurate 
and timely information to our beneficiaries. SSA has provided an arena 
in which persons with disabilities can confidently ask questions of a 
trained professional who is not a federal employee.

                  PROTECTION AND ADVOCACY (P&A) GRANTS

    The Ticket to Work and Work Incentives Improvement Act of 1999 also 
granted the Commissioner authority to make payments to P&A systems for 
the purpose of providing services to beneficiaries with disabilities. 
Those services include providing information and advice about obtaining 
vocational rehabilitation and employment services as well as providing 
advocacy or other services that a beneficiary with a disability may 
need to secure or regain gainful employment. Under this new program, 
P&A grantees ensure that beneficiaries' legal rights are protected.
    SSA awarded a total of 57 grants to each of the States as well as 
the District of Columbia, Puerto Rico, the United States Virgin 
Islands, Guam, American Samoa, the Commonwealth of the Northern Mariana 
Islands, and one for the Native American community.
    In 2002 alone, more than 10,000 beneficiaries with disabilities 
received P&A services free of charge which ranged from information and 
referral to legal representation. The P&As gave over two thousand 
outreach presentations during this period. Through conferences, 
seminars, publications, websites, and public service announcements on 
television and radio, the projects made people aware of viable 
approaches to overcoming employment barriers. Examples of the 
assistance provided under this program include:
  --Fighting discrimination by employers against persons with 
        disabilities;
  --Obtaining reasonable accommodations in the workplace;
  --Mediating disputes involving job coaches and individual plans for 
        employment;
  --Resolving transportation issues related to work;
  --Acquiring tuition assistance and accommodations at educational 
        institutions;
  --Locating the best Employment Network for a beneficiary's specific 
        circumstances;
  --Working to improve Employment Networks' grievance procedures;
  --Educating beneficiaries regarding the employment supports and 
        incentives available; and
  --Educating the local community regarding the legal rights of 
        individuals with disabilities.

                           OTHER INITIATIVES

    In addition to these programs, SSA plans to create a new position, 
the Area Work Incentives Coordinator, to provide technical information 
and assistance to beneficiaries and outside groups and coordinate work 
incentive-related activities within the field offices of the Area they 
represent.
    At the same time, we plan to provide a customized training 
curriculum to accommodate training needs specific to each employee's 
role in administering employment support programs. For example, 
continuing education on Ticket to Work and related issues of concern to 
our beneficiaries will allow our public affairs personnel, using their 
communications skills and community outreach opportunities, to become 
effective ambassadors for these programs. In addition, our enhanced 
training will ensure that field and 800-Number personnel will maintain 
expertise on work incentives and employment support programs to be 
responsive to inquiries and process actions as appropriate.
    SSA is enhancing systems and establishing procedural changes that 
will assist field personnel in processing actions efficiently and 
accurately and will provide information to beneficiaries with 
disabilities who are working or want to work. SSA is also building 
these systems to improve workload management control and to provide 
more management information about beneficiaries with disabilities who 
are able to return to the workforce. It is important that there be a 
pool of experts with technical expertise in the complicated issues that 
can arise with a disability recipient who is pursuing and taking 
advantage of employment opportunities. But it is equally important that 
we continue to change the organizational culture to make return-to-work 
an integral part of the entire Agency's mission.
    In addition to providing designated experts, we plan to leverage 
our resources by heightening the awareness of employment support 
programs internally and externally and broadening the knowledge of our 
entire Operations workforce.
    Question. How has SSA collaborated with other federal agencies and 
partners to increase the work opportunities of individuals receiving 
Social Security and SSI disability payments and what resources are 
included within the fiscal year 2004 budget request to carry out such 
activities?
    Answer. SSA is collaborating with others in the following research 
and demonstration projects to increase the work opportunities of 
individuals receiving Social Security and SSI disability payments. 
Amounts budgeted for these activities and evaluations in fiscal year 
2004 total about $20 million.
  --Youth Transition Process Demonstration.--SSA will support State 
        projects to test and deliver needed services to young Social 
        Security and SSI beneficiaries with disabilities to assist them 
        in achieving independence.
  --Disability Research Institute.--One of the goals of this 
        cooperative agreement with the University of Illinois at 
        Urbana-Champaign is to provide research findings in critical 
        disability policy areas, such as return to work strategies.
  --State Partnership Initiative (SPI).--States have been testing 
        innovative approaches to coordinating vocational planning and 
        support, employer and employee coaching, financial planning, 
        health and long-term care, and other necessary supports for 
        disability beneficiaries. SSA will be evaluating the 
        effectiveness of these approaches.
  --Disability Program Navigator.--SSA has partnered with the 
        Department of Labor (DOL) to support Benefit Navigators at DOL 
        One-Stop Career Centers to provide beneficiaries with 
        information on the Ticket to Work program and other SSA work 
        incentives and well as assistance with related programs that 
        may affect their ability to enter and retain employment 
        (Medicare and Medicaid, housing, etc.).
    SSA also is collaborating with the U.S. Department of Labor (DOL) 
to sponsor the Ticket to Hire program. This free nationwide referral 
service is designed to assist employers in locating and hiring 
qualified job candidates with disabilities from the Ticket to Work 
program. Ticket to Hire connects employers to ENs or State VR agencies 
from SSA's Ticket to Work program with job ready candidates. Ticket to 
Hire provides the employer with a referral list of ENs in their 
community. The employer can then contact these organizations to find 
qualified candidate(s) who are participants in the Ticket to Work 
program.
    Ticket to Hire is a specialized unit of Project EARN (Employer 
Assistance Referral Network), which is also sponsored by DOL and SSA. 
If the Ticket to Hire staff is unable to locate organizations with 
qualified candidates in their database, the vacancy information is 
shared with EARN. EARN staff then searches a database that includes 
additional organizations that are employment service providers and may 
not be participating in the Ticket to Work program.
    Question. The fiscal year 2004 budget request proposes obligations 
of $2 million for Medicare Savings Program Outreach to continue 
outreach efforts to all new eligible individuals, as well as to a 
portion of those previously notified. Specifically, what outreach 
efforts will be undertaken to newly- and previously-eligible 
individuals? What portion of those previously eligible will be notified 
in fiscal year 2004 and subsequent years?
    Answer. SSA intends to send Medicare Savings Programs outreach 
letters annually to all new beneficiaries who meet the statutory income 
test and are not already receiving help with their share of Medicare 
expenses. SSA will mail outreach letters to two groups of Medicare 
beneficiaries who were on the roles before the previous letter 
selection:
  --Beneficiaries who had too much income for this help before but now 
        meet the statutory income test (e.g., as a couple there was too 
        much income, but the new widow's income now meets the statutory 
        test); and
  --One-fifth of people who received outreach letters before who 
        continue to meet the statutory income test and are not already 
        receiving help with their share of Medicare expenses.
    SSA will continue to share electronic files of selected potentially 
eligible beneficiaries of the Medicare Savings Programs with their 
servicing Medicaid State agencies.
    SSA plans to continue the letter and file-sharing activities 
described above for new and previous eligibles annually. These 
activities will ensure that every potentially eligible beneficiary 
receives an outreach reminder letter at least once every five years and 
States will receive appropriate information each year.
    Question. How has the GAO evaluation of outreach efforts guided 
development of your proposed fiscal year 2004 activities?
    Answer. GAO has not yet shared evaluation data or results with SSA. 
SSA looks forward to receiving the GAO evaluation as a potential source 
of information that could be used to improve this process.
    Question. Earlier this year, the General Accounting Office (GAO) 
added Social Security's disability programs to its list of High-Risk 
programs. Your fiscal year 2004 budget request supports making 
substantial progress towards national implementation of an electronic 
disability process--AeDib--by the end of fiscal year 2004 as a means to 
improving the timeliness of and efficiency associated with disability 
decisions.
    How much funding is included in the request to support the AeDib? 
GAO has stated (GAO-03-225, page 132) that the agency has had ``mixed 
success in past technology investments.'' How has the agency's previous 
experience with major technology investments helped guide the design 
and implementation strategy for this new initiative?
    Answer. The Agency will begin national implementation of the 
Accelerated Electronic Disability System (AeDib) on January 1, 2004. 
Over an 18-month period the system will be installed in every State 
Disability Determination Services (DDS) center in the country. We 
estimate an initial IT investment of about $150 million during the 
budget period for AeDib planning, development and implementation. In 
addition, significant SSA staff effort will be devoted to project as 
well as related non-IT support costs.
    A previous effort to automate the disability process at SSA was 
called the Reengineered Disability System (RDS). In 1999 Booz Allen 
Hamilton assessed RDS and made recommendations to the Agency concerning 
the use of technology to improve future disability processing. AeDib is 
based on those recommendations.
    Many technological lessons were learned from RDS. For example, 
while RDS was designed to create one processing system for all of the 
State DDSs, AeDib will not replace the current DDS case processing 
systems. Instead, each State is upgrading and enhancing its systems in 
order to accommodate the Electronic Folder.
    SSA is building applications that allow the public to file for 
disability over the Internet. SSA also is creating a fully automated 
Office of Hearings and Appeals Case Processing and Management System. 
This system will automate the hearing process from initial receipt 
through final disposition.
    In order to evaluate our progress every step of the way and to 
continue to meet the goals of the project, each project associated with 
AeDib has been or will be rolled out in phases. This process allows SSA 
to gain the experience it needs in order to continue to meet the 
customer's needs.
    To effectively enhance the capabilities of the Electronic Folder 
and to provide the infrastructure needed for other initiatives, SSA has 
completed an initial upgrade to its telecommunications infrastructure. 
SSA also is maximizing the use of Commercial Off-the-Shelf products.
    To document and ensure that we target our development work by 
determining specific areas with the highest paybacks, Booz Allen 
Hamilton has completed a Cost Benefit Analysis for AeDib.
    Question. What actions are planned to ensure that all components, 
including state disability determination services, have sufficiently 
trained staff, available technical and program support and adequate 
resources to implement this initiative and how much is provided within 
this budget request for these activities?
    Answer. AeDib will provide the infrastructure to support paperless 
and electronic processing of disability claims from initial contact 
through the hearing decision. To ensure success and ease implementation 
activities, AeDib has been broken into several interrelated projects.
    First, the American public will have the ability to complete 
disability claims over the Internet. We have already successfully 
implemented the adult version of the Social Security disability 
application and medical form. Prior to national implementation, members 
from the public came to SSA headquarters to test the disability form. 
Between now and January 2004, we will be adding additional forms to the 
Internet.
    What the Internet provides for the public, the Electronic 
Disability Collect System (EDCS) provides to field offices. EDCS is 
used to electronically collect medical information previously obtained 
on paper forms for initial adult and children cases. Regional trainers 
from across the nation came to SSA headquarters to receive ``Train the 
Trainer'' instruction on EDCS. As of February 2003, every field office 
received EDCS training. Between now and January 2004, additional 
functionality including hearings and continuing disability reviews will 
be added to the program.
    The next (and most complicated) project is the Electronic Folder. A 
prototype of the Electronic Folder was completed in October 2002, and 
pilots are scheduled to run from July 2003 through December 2003. One 
of the major activities that SSA needed to accomplish to allow the 
State Disability Determination Services (DDS) to interface with the new 
Electronic Folder was to provide them with new computer hardware. We 
accomplished this in September 2002. We provided the hardware training 
to the DDSs. We are now in the process of upgrading the software. 
Implementation of the Electronic Folder, combined with EDCS, will 
significantly change the business process and reduce case processing 
times.
    The last project is to create an automated system known as the 
Office of Hearings and Appeals Case Processing and Management System 
(CPMS). Currently OHA has very limited automation. This project will 
automate the process from initial receipt through the final decision, 
which will improve case processing and contribute to productivity 
improvements. We are working closely with our user groups to build a 
successful CPMS prototype.
    Our training strategy also is multifaceted. SSA has conducted AeDib 
training for regional trainers at SSA headquarters. At SSA 
headquarters, technical staff has been undergoing extensive training to 
learn how to use and integrate new technologies.
    In order to ensure a successful implementation of the Electronic 
Folder, SSA will provide onsite technical training and support to the 
various components. The goal is to ensure that the architecture is 
operating smoothly and that SSA/DDS staffs supporting the system are 
provided with expert training. SSA, working with the DDSs, will also 
provide hands-on business training to all Federal and State components 
working with the new Electronic Folder.
    Our fiscal year 2004 budget includes approximately 300 workyears in 
order to support these implementation initiatives and meet our goals.
    Question. What steps have been taken to secure the privacy of 
electronic information collected?
    Answer. Several steps are being taken to secure the privacy of 
electronic information for the AeDIB process as well as for other 
projects SSA is undertaking. Specifically for AeDIB:
  --Developers are following the SSA Systems Development Life Cycle, 
        which includes ongoing security review (access controls, 
        separation of duties, integrity, audit trail etc.), on an 
        iterative basis.
  --We are currently piloting a secure transport mechanism for 
        disability data.
  --A systems manager responsible for the overall project has been 
        named and is drafting a security plan for the project.
  --We are in process of awarding a contract for a security risk 
        assessment monitored by the project officer, system manager and 
        security staff.
  --We have implemented ongoing monitoring of Electronic Medical 
        Evidence and Security status meetings by Chief Security Officer 
        staff.
    Question. What additional steps are being considered to improve the 
accuracy, timeliness and cost-efficiency of the disability 
determination process and what is the timeline for their 
implementation?
    Answer. AeDib is one of the key steps SSA is taking to improve the 
disability process. AeDib rollout will begin in January 2004 and 
continue for 18 months. While processing time is expected to improve 
slightly in 2004, this initiative is expected to substantially reduce 
processing time over the long term.
  --AeDib will provide us with tools to move work seamlessly from place 
        to place, increasing access to agency medical and technical 
        expertise, maximizing agency resources, and supporting quality 
        adjudication. The first piece of AeDib is the electronic intake 
        system Electronic Disability Collect System (EDCS) which began 
        in October 2002. By automating data collection, the accuracy of 
        the information will be enhanced and more complete information 
        will be passed to the Disability Determination Services (DDS) 
        and later to the Office of Hearings and Appeals.
  --We will be conducting assessments throughout start-up and rollout 
        of the new system and process. Additionally, we will be 
        conducting a post implementation review that will help 
        determine impacts, efficiencies and quality results based on 
        AeDib.
  --SSA also is working with the medical community to leverage their 
        electronic processes in coordination with our AeDib medical 
        evidence activities. Our goal is to increase the electronic 
        exchange of medical evidence to maximize efficiencies in 
        alignment with Health Insurance Portability and Accountability 
        Act (HIPAA) regulations. On May 8, I met with representatives 
        from some of the nation's largest medical professional 
        associations to discuss SSA's medical evidence needs, the 
        process for obtaining evidence, the new HIPAA compliant 
        authorization form, and our vision of a future electronic 
        business process.
    SSA has been engaged in a number of efforts to redesign and improve 
the disability determination process by testing several initiatives 
over the past several years. Based on our review of their results, we 
have decided to:
  --Encourage early and frequent contacts with claimants during the 
        development process;
  --Eliminate the claimant conference at the end of the process; and
  --Temporarily extend the ``elimination of reconsideration step'' 
        feature in the Prototype States that are currently doing this, 
        while SSA develops an alternative approach.
    The amount of time the SSA appeals process takes also has been a 
major concern. SSA has made the following near-term changes to the 
hearing process, based on analysis of the Hearings Process Improvements 
(HPI) initiative:
  --Include ALJs in early case screening to more quickly identify cases 
        for dismissal and possible on-the-record decisions;
  --End the requirement that cases be certified as ``ready to hear'', 
        removing a step in the process;
  --Allow ALJs to issue fully favorable decisions from the bench 
        immediately after a hearing; and
  --Expand the use of technology in the Office of Hearings and Appeals, 
        including video teleconferencing, speech recognition and 
        digital recording of hearings.
    SSA also is assessing its policies and procedures to enable 
simplification of data collections and case documentation. We have 
revised and consolidated data collection forms to ensure consistency 
and accurate data propagation. For example, we are combining 3 forms 
into a single public-use document as part of the appeals process.
    SSA currently reviews at least 50 percent of all title II initial 
disability allowances made by State agencies on behalf of SSA. The 
fiscal year 2004 President's budget includes a proposal to apply the 
same requirement for adult disability allowances in the SSI program. 
That is, when fully phased in, 50 percent of initial SSI disability 
allowances would be reviewed, applying consistency across both 
disability programs.
    We expect to make recommendations soon regarding additional steps 
we can take to improve the disability process.
    Question. Commissioner, you have stated that the Hearings Process 
Improvements (HPI) initiative, which was implemented in 2000, has not 
worked and that SSA has implemented additional changes to the process, 
based on your assessment of HPI.
    What lessons has SSA learned from the failure of HPI and how were 
they used to develop and implement the latest changes?
    Answer. What we learned during the course of HPI has yielded 
insights valuable to the further refinement of our hearings processes. 
We have not yet implemented our contemplated mid-term and long-term 
process changes. Therefore, these responses chiefly address changes we 
have made in the short-term.
    We learned that the HPI processes included unnecessary case 
handoffs. In our latest changes, we sought to eliminate these handoffs. 
For instance, we observed that attorney and paralegal certification of 
cases as ``ready to hear'' before sending those cases to Administrative 
Law Judges (ALJs) for prehearing review was a step of limited value. We 
have eliminated that step. Though we had initially thought that 
rotating functional assignments among support staff would improve 
overall hearing office performance, we discovered that rotation 
actually undermined the strengths of our staff. Consequently, we 
discontinued rotations and created a new position, the Case Intake 
Assistant, with duties that incorporated the previously rotated 
functions.
    HPI taught us the importance of a strong management team in the 
hearing offices. We are striving to strengthen the management structure 
in the field. HPI also taught us the importance of prompt 
implementation of systems support needed to support new initiatives. We 
are proceeding as expeditiously as possible with the development and 
implementation of new technology and applications to support the Office 
of Hearings and Appeals' (OHA) business processes.
    Question. Given that implementation of reforms is very costly in 
terms of additional delay for individuals involved in the process, lost 
production time, and staff anxiety, what steps were taken to involve 
all stakeholders in the latest reform and what resources are included 
in the fiscal year 2004 request for staff training and support of 
implementation?
    Answer. We haven't undertaken a major reform of the hearing process 
since HPI. However, we recognize there are significant hearing backlogs 
and we need to make every effort to move toward reducing those 
backlogs. For this reason, with the proposed transfer of Medicare 
hearings to the Department of Health and Human Services in fiscal year 
2004, this budget redirects 478 workyears previously used to process 
Medicare hearings to processing SSA disability hearings and appeals 
instead. This will enable SSA to process 46,000 more SSA hearings in 
fiscal year 2004 than in fiscal year 2003 and improve service by 
reducing the hearings processing time.
    We have focused on processing the work with incremental initiatives 
that could be effectuated in the short term with little delay for 
individuals involved in the process and minimal, if any, loss of 
production time. We believe the nature of these changes, our candid 
discussions with all of the unions representing our employees, and the 
initiatives' incremental implementation over the past year have helped 
to minimize any potentially adverse impact on employee morale and 
productivity. And, despite additional investments in training, savings 
from initiatives will increase the overall production rate for SSA 
hearings from fiscal year 2003 to fiscal year 2004.
    The budget continues to support base levels of ongoing and new 
staff training for OHA staff, plus significant training for 
technological enhancements to the business process in fiscal year 2003 
and fiscal year 2004, including training related to implementation of 
AeDIB. Most of the cost of staff training is the workyear cost, along 
with related non-payroll expenses for instructors and travel. For 
fiscal year 2004, we estimate about 250 workyears for OHA training, 
including about 100 workyears related to AeDIB.
    Question. How will the latest reforms improve timeliness, accuracy 
and efficiency of decision making? What other changes have been 
implemented to help improve productivity and increase the likelihood of 
getting the right decision at the earliest possible time?
    Answer. We are preparing cases for hearing more quickly and in 
greater numbers with the aid of contract file assemblers, who furnish 
clerical support for file preparation. As previously noted, we also 
have eliminated rotational assignments for case technicians. These 
actions free case technicians to concentrate their attention on more 
complex case preparation tasks.
    We have asked our most highly trained employees, ALJs, to join 
other professional hearing office employees in early screening and 
reviewing cases most likely to warrant on-the-record decisions. ALJ 
participation in this process facilitates review of a higher percentage 
of such cases, thus increasing the number of cases that can be decided 
early, without the necessity of a hearing.
    We have implemented a new decision writing program for fully 
favorable decisions that is easy for ALJs and decision writers to use 
and fully documents the legal basis for fully favorable decisions. 
Providing the new program as a tool for their use, we have asked ALJs 
to use their personal computers to draft any fully favorable decisions 
they reach as a result of early screening, as well as any decisions 
that they announce orally at a hearing. This eliminates case handoffs 
to the decision writers and frees the decision writers to concentrate 
on more complex cases.
    We are providing speech recognition software to ALJs and decision 
writers to facilitate decision drafting. The introduction of this 
software will eliminate the need for transcription of dictated 
decisions by case technicians, shortening case processing time and 
freeing the case technicians for case preparation duties.
    Question. The GAO Report ``Social Security Disability: Efforts to 
Improve Claims Process Have Fallen Short and Further Action is Needed'' 
(GAO-02-826T) found that in fiscal year 2000, about 40 percent of the 
applicants whose cases were denied at the initial level appealed this 
decision and about two-thirds of those who appealed were awarded 
benefits. What resources and activities are supported in the fiscal 
year 2004 budget request to specifically address this issue and reduce 
the likelihood that initial decisions are changed upon appeal?
    Answer. Our goal is to make the right decision on disability claims 
as early in the process as possible. We should note, however, that a 
different decision during the appeals process does not necessarily mean 
that the initial decision was wrong when it was issued. Unfortunately, 
currently many months may elapse between the initial determination and 
the various steps of the appeals process and, during that time, the 
claimant's medical condition may have worsened. And, we allow a 
claimant to provide additional information at any time during the 
process. So a person who may not have met the criteria for disability 
assistance at the first step may meet those criteria by the time a 
hearing can be held. This kind of situation shows the importance of 
reducing the delays and backlogs that currently make the appeals 
process take so long. (We also are working on finding ways to ensure 
that complete information is provided at the initial determination step 
so that the decision-maker can consider all factors that may affect the 
decision.) For this reason, I have made eliminating backlogs a primary 
focus.
    As I indicated in my testimony at the March 4, 2003 House 
appropriations hearing before the Subcommittee, the President's budget 
request for fiscal year 2004 demonstrates our commitment to continuing 
efforts to improve service, efficiency and program integrity in the 
disability program. Issues regarding the appeals process and reducing 
the likelihood that initial decisions are changed upon appeal are 
longstanding concerns in the disability program. We expect to make 
recommendations that address those issues in the coming months, and 
expect to propose changes that are cost-neutral in terms of the overall 
impact on SSA's budget.
    In order to effectively address the systemic issues in the 
disability process, we need to get the existing disability workloads 
under control. Based on the work that has been done on our Service 
Delivery Assessment, it is clear that eliminating backlogs and 
processing special workloads are prerequisites for providing good 
service to the public. Although approximately 40 percent of disability 
claims are approved within three and a half months of initial 
application, for applicants who exercise all administrative appeal 
rights provided under current law and current processes, an average of 
1,153 days is required for a final Agency decision. Based on our 
analysis, almost 50 percent of this time in the process results from 
the backlog of cases.
    We are taking a number of actions in the near term to reduce 
processing times and increase efficiency. The fiscal year 2004 budget 
request supports those actions. As indicated above, we are engaged in 
review of strategies to further improve the disability program and 
expect to make recommendations soon.
    Question. The fiscal year 2004 President's Budget proposes to 
transfer responsibility for Medicare hearings from SSA to the 
Department of Health and Human Services (HHS).
    What are the actual expenditures and associated workload processed 
in fiscal years 2000, 2001 and 2002, as well as those estimated in 
fiscal year 2003?
    Answer. The chart below provides actual expenditures and associated 
workloads for Medicare hearings for fiscal years 2000, 2001 and 2002 as 
well as those estimated for fiscal year 2003 in the fiscal year 2004 
President's budget. The estimates for fiscal year 2003 assume an 
increase in receipts related to the Medicare, Medicaid and SCHIP 
Benefits Improvement and Protection Act of 2000 (BIPA) and 
implementation of a streamlined process for handling Medicare appeals. 
Neither of these has occurred.

----------------------------------------------------------------------------------------------------------------
                                                                        Actual fiscal year             Estimate
                      Medicare hearings                      --------------------------------------- fiscal year
                                                                  2000         2001         2002         2003
----------------------------------------------------------------------------------------------------------------
Receipts....................................................       77,872       77,726       71,576      122,147
Processed...................................................       88,084       69,663       77,388      105,000
Pending.....................................................       35,904       43,517       37,705       54,852
Expenditure (dollars in millions)...........................          $79          $74          $78          $79
----------------------------------------------------------------------------------------------------------------

    Question. What planning and transition activities are being 
undertaken with HHS/CMS to ensure that a timely and smooth transition 
occurs, if legislation is enacted that transfers the Medicare appeals 
function effective October 1, 2003 as proposed in the President's 
budget?
    Answer. While we have agreed with HHS/Centers for Medicare and 
Medicaid Services (CMS) in principle to transfer responsibility for the 
Medicare hearings function effective October 1, 2003, we are still 
working out the details of the workload transfer. In January 2002, I 
established an executive level position on my staff to work directly 
with the CMS Administrator and his staff to provide technical 
assistance in the design of a hearing process and service delivery plan 
tailored to the unique needs and opportunities of Medicare appeals. SSA 
and HHS/CMS have had an ongoing dialogue since that time. These 
discussions focus on issues such as transfer of cases, sharing of 
resources (e.g., video teleconferencing), and systems support. A 
Memorandum of Agreement that will reflect these decisions is being 
prepared.
    Beginning with fiscal year 2004, consistent with the 
Administration's plan to transfer the Medicare hearings function to the 
Department of Health and Human Services, SSA's annual budget request 
does not include the resources that would be needed to process Medicare 
hearings. The President's budget now includes the Medicare hearings 
function and related funding under the Department of Health and Human 
Services, which is accountable by law for management and administration 
of the Medicare program.
    Question. What amount of budget authority is required in fiscal 
year 2004 to process fully this workload, if legislation is not enacted 
consistent with the President's budget?
    Answer. Funds to process Medicare hearings are budgeted in HHS/CMS 
for fiscal year 2004. Consistent with our assumption that HHS/CMS will 
assume responsibility for the Medicare hearings function beginning 
October 1, 2003, SSA has not included any resources in its fiscal year 
2004 budget request to process this workload.
    Question. In January 2001, the General Accounting Office identified 
strategic human capital management as a governmentwide high-risk area.
    What steps are you taking to acquire, develop, and retain an 
appropriate mix of agency staffing/talent, particularly in light of the 
Agency's impending retirement wave? What is the agency's plan for 
creating an organizational culture that promotes high performance and 
accountability and empowering and including employees in setting and 
accomplishing programmatic goals? How does the fiscal year 2004 budget 
support these activities?
    Answer. SSA is taking a number of steps to acquire, develop, and 
retain an appropriate mix of agency staff.
    SSA started retirement wave analysis and planning over five years 
ago. This analysis was the impetus for our Future Workforce Transition 
Plan (FWTP), which positions us well to transition to the workforce of 
the future. The FWTP contains milestones regarding recruitment, 
retention, employee development and a satisfying work environment. It 
is aligned with our mission, goals and objectives and is integrated in 
budget, strategic and performance plans. Selected highlights of our 
activities include:
    To acquire staff, SSA:
  --Created a national recruitment coordinator position with 
        responsibility for developing and implementing recruitment 
        initiatives SSA-wide;
  --Uses recruitment and retention incentives, including above minimum 
        starting salaries, recruitment bonuses, relocation bonuses and 
        retention allowances;
  --Uses delegated expedited methods to reduce the time it takes to 
        fill jobs, and continues to work with the Office of Personnel 
        Management to find ways to accelerate the staffing process;
  --Is piloting a competency-based hiring process;
  --Fills vacancies as early as possible in the fiscal year, subject to 
        budget and hiring authority; and
  --Rehires experienced annuitants in times of critical need.
    To develop and retain staff, SSA:
  --Incorporates organizational values into entry level training and 
        new hire orientation;
  --Offers extensive technical and leadership training via Interactive 
        Video and the Intranet. Personal development courses are also 
        available online and can be taken at home.
  --Is restructuring curricula around identified competencies to ensure 
        that employees have the knowledge and skills to respond to 
        emerging needs;
  --Has a variety of career paths for employee advancement;
  --Offers career counseling services;
  --Offers national Leadership Development Programs designed to build 
        identified leadership competencies for GS-9 through GS-14 
        employees, as well as a Senior Executive Service (SES) Career 
        Development Program designed to develop executive leadership in 
        the Agency's succession planning efforts. SSA's organizational 
        components also have a variety of development programs at 
        various grade levels nationwide; and
  --Offers SES development opportunities outside of the formal 
        programs.
    SSA is creating an organizational culture that promotes high 
performance and accountability and empowering and including employees 
in setting and accomplishing programmatic goals. SSA's revised SES 
performance management system is linked to strategic goals and 
distinguishes between high and low performance. A revised system for 
non-bargaining unit GS-15s will be implemented October 1, 2003. An 
executive level workgroup is currently developing alternative 
performance systems models for all other employees, taking into account 
the connection with the awards and promotion systems. Plans for all 
other employees will take effect with the signing of a new labor 
contract with AFGE in fiscal year 2004.
    Also, SSA sets programmatic goals through our strategic planning 
process. This process considers our responsibilities to the public we 
serve and environmental factors such as demographics, health and 
disability trends, technological advances and workforce trends. Our 
employees are key to success in accomplishing these programmatic goals. 
They are actively encouraged to offer suggestions through our newly 
automated suggestion program. They are invited to participate on 
workgroups or provide input as we develop and test new processes.
    Additionally, in early fiscal year 2003 I held a series of 11 
candid, interactive meetings with all supervisors, managers and 
executives in the Baltimore/Washington headquarters area, discussing 
leadership principles, management philosophy and the Agency's four 
major performance areas. During the summer of fiscal year 2003, I plan 
to discuss this same set of critical topics with the full management 
cadre in each of the 10 regional office cities and from field offices 
in commuting distance of those cities.
    The fiscal year 2004 budget supports these activities with a 
consistent level of baseline funding to accomplish many of the 
activities cited. Consistent with actual spending in fiscal year 2002, 
the fiscal year 2004 budget also includes approximately $4 million in 
project-specific funding for the following initiatives:
  --Interactive Video Teletraining
  --Leadership Development Programs: Senior Executive Service, Advanced 
        Leadership Program, Leadership Development Program, and 
        Presidential Management Intern Program;
  --Leadership Seminars
  --Performance Management Training
    SSA's budget also provides funding for participation in LEGIS 
Fellows Programs, OPM Management Development Programs and Federal 
Executive Institute programs. Funding to maintain the recruitment 
marketing program developed in fiscal year 2002 and to advance the 
competency-based recruitment initiative also is included in the budget.
    Question. The Congress appropriated additional funds from fiscal 
year 1996 through fiscal year 2002 to ensure that the Agency would 
carry out a 7-year plan to become current in processing CDRs. The 
fiscal year 2004 request includes dedicated funding of $1.4 billion, 
for among other things to process continuing disability reviews.
    Is the Agency on schedule to remain current with processing CDRs in 
fiscal year 2003?
    Answer. In fiscal year 2003, SSA is focusing on keeping up with 
claims workloads so that the number of disability claims pending does 
not grow. Consequently, we will not be able to process all CDRs 
necessary to remain current. We began this year under a continuing 
resolution and operated for four months at last year's level. In 
addition, we are absorbing an across-the-board rescission of .65 
percent and a higher-than-budgeted pay raise. Nevertheless, we will 
continue to assess our ability to process more CDRs in fiscal year 2003 
than reflected in the fiscal year 2004 President's budget, while 
keeping up with claims receipts, and will increase the number of CDRs 
processed to the extent that we are able.
    Question. What lessons did SSA learn during this 7-year period 
about efficiently using these funds to stay current with its CDR 
obligations?
    Answer. If SSA is adequately funded for CDRs we can stay current 
with this workload. However, we also have learned that we need to work 
closely with the States and balance the resources applied to CDRs with 
those for processing initial claims. We have been unable to keep up 
with incoming disability claims receipts since fiscal year 1997. This 
situation was compounded by a recent surge in initial receipts. As a 
result, DDSs entered fiscal year 2003 with the highest initial pending 
level in DDS history. Currently, it is difficult to ensure adequate 
funding for stewardship activities when they compete for the same 
discretionary dollars. Specifically, we face two significant competing 
demands: (1) the need to pay disabled claims as quickly and 
proficiently as possible; and (2) the need to serve as stewards of the 
public trust and perform CDRs to protect program integrity in our trust 
fund and general fund programs.
    The discretionary funding cap adjustments for CDRs authorized by 
Congress for fiscal years 1996 through 2002 were crucial to realizing 
currency for both the title II and title XVI disability review programs 
at the close of fiscal year 2002. The discretionary spending cap 
adjustment for CDRs and other integrity workloads that the President is 
recommending in the fiscal year 2004 budget would ensure adequate 
funding for the future to maintain currency with CDRs and process other 
cost-effective program integrity work thereby, enabling SSA to meet 
both its stewardship responsibilities and overall service demands.
    The Agency would not have achieved currency at the close of fiscal 
year 2002, nor will it be able to remain current in the future, without 
the CDR profiling/mailer process. SSA uses highly skilled statistical 
support from contractors in performing the statistical analyses that 
determine who can be sent a CDR mailer, what action to take (automated 
decision logic) when a CDR mailer is returned, and many of the 
automated functions of both CDR mailer and full medical processing. SSA 
has a wealth of data at its disposal resulting from hundreds of 
thousands of CDR decisions. Over the past several years the 
contractors' products have enabled SSA to perform mailer, rather than 
full medical reviews, for several hundred thousand additional CDRs than 
was possible in the first few years of the 7-year plan.
    The CDR mailer process involves little public burden (it is 
estimated to take approximately 15 minutes to read the instructions and 
complete the form), and it is also cost-effective. Agency budget 
documentation indicates that the unit cost of a CDR mailer in fiscal 
year 2001 was $27, while the unit cost of a full medical review was 
$689. In fiscal year 2001, the CDR mailer accounted for over 50 percent 
(about 895,000 of 1,731,000) of reviews reported to Congress. In fiscal 
year 2001 alone, even if the Agency had the workforce capacity, an 
additional 895,000 full medical reviews would have cost an additional 
$592 million when compared to processing the same number of CDR mailer 
deferral actions. (The Agency did not have the workforce capacity that 
would have allowed us to accomplish these medical reviews had there 
been funding available.)
    Since its inception, integrity sampling has been a key element in 
assuring that the process is a legitimate alternative to a full medical 
review. The CDR mailer process undergoes continuous, rigorous studies 
and audits, including yearly audits by PricewaterhouseCoopers as agent 
for SSA's Office of the Inspector General.
    Question. What is SSA's plan for remaining current this year and in 
the future for processing CDRs?
    Answer. As previously indicated, in fiscal year 2003 SSA is 
focusing on keeping up with claims workloads and therefore will not be 
able to remain current with CDRs this year. SSA plans to include 
sufficient resources in its budget requests to maintain currency with 
CDR workloads. In support of that goal, the fiscal year 2004 
President's budget includes earmarked funding of $1.446 billion for SSA 
program integrity workloads, including CDRs, and a proposal to treat 
this funding outside the discretionary spending caps.
    Question. Please provide the subcommittee with a breakdown of the 
administrative costs associated with legislative proposals included in 
the fiscal year 2004 budget. Are these costs fully covered within the 
fiscal year 2004 budget request for LAE?
    Answer. The President's fiscal year 2004 budget for SSA includes 
eight legislative proposals, only one of which would have significant 
administrative costs for SSA. That is the proposal for implementation 
of pre-effectuation reviews (PER) of SSI adult disability allowances, 
similar to the reviews now in place for Social Security disability 
program allowances. SSA's fiscal year 2004 LAE request includes $10 
million to implement SSI PER. Generally, SSA's administrative budget 
requests to Congress are based on current law. We have made an 
exception to the general practice in this case, due to the likelihood 
of enactment of SSI PER, based on the progress of this proposal in the 
107th Congress and now in the 108th. Implementation of SSI PER will 
yield substantial program savings.
    The other SSA legislative proposals are as follows:
  --Improved reporting of pension income from non-covered employment--
        The Administration is working to determine the best way to 
        obtain noncovered pension information systematically from State 
        and local government employers, for enforcement of the Windfall 
        Elimination Provision (WEP) and Government Pension Offset (GPO) 
        provision of the law. The details of the proposal are still 
        being developed.
  --Close the loophole that allows exemption of spouses from the GPO 
        based on one day in covered employment.
  --Trust fund compensation for Military Service Wage Credits--This 
        proposal makes the trust funds whole for FICA tax equivalents 
        that remain unpaid by the Department of Defense for 2000 and 
        2001, including appropriate interest, together with adjustments 
        for prior years. There is no administrative impact.
  --SSI Program proposals:
    --Exclude from determination of individual income all interest and 
            dividend income earned on countable liquid resources and 
            revise the infrequent and irregular income exclusion.
    --Remove the restriction on payment of benefits to children who are 
            born or who become blind or disabled after military parents 
            are stationed overseas.
    --Treat all cash military compensation as earned income.
    --Count nonrecurring income only for the month it is received 
            during the transition to retrospective monthly accounting 
            during the first three months of eligibility.

                          SUBCOMMITTEE RECESS

    Senator Specter. Thank you all very much. The subcommittee 
will stand in recess to reconvene at 9:30 a.m., Wednesday, 
April 9, in room SD-138. At that time we will hear testimony 
from the Honorable Elaine L. Chao, Secretary, Department of 
Labor.
    [Whereupon, at 11:10 a.m., Tuesday, April 8, the 
subcommittee was recessed, to reconvene at 9:30 a.m., 
Wednesday, April 9.]
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