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



 
DEPARTMENTS OF LABOR, HEALTH AND HUMAN SERVICES, EDUCATION, AND RELATED 
              AGENCIES APPROPRIATIONS FOR FISCAL YEAR 2005

                              ----------                              


                        THURSDAY, APRIL 1, 2004

                                       U.S. Senate,
           Subcommittee of the Committee on Appropriations,
                                                    Washington, DC.
    The subcommittee met at 9:30 a.m., in room SH-216, Hart 
Senate Office Building, Hon. Arlen Specter (chairman) 
presiding.
    Present: Senators Specter, Cochran, Stevens, and Harkin.

                DEPARTMENT OF HEALTH AND HUMAN SERVICES

                     National Institutes of Health

STATEMENT OF ELIAS A. ZERHOUNI, M.D., DIRECTOR
ACCOMPANIED BY:
        RAYNARD KINGTON, M.D., Ph.D., DEPUTY DIRECTOR, OFFICE OF THE 
            DIRECTOR
        WILLIAM R. BELDON, DEPUTY ASSISTANT SECRETARY FOR BUDGET
        DUANE ALEXANDER, M.D., DIRECTOR, NATIONAL INSTITUTE OF CHILD 
            HEALTH AND HUMAN DEVELOPMENT
        BARBARA ALVING, M.D., ACTING DIRECTOR, NATIONAL HEART, LUNG, 
            AND BLOOD INSTITUTE
        JAMES F. BATTEY, JR., M.D., Ph.D., NATIONAL INSTITUTE ON 
            DEAFNESS AND OTHER COMMUNICATION DISORDERS
        JEREMY M. BERG, DIRECTOR, NATIONAL INSTITUTE OF GENERAL MEDICAL 
            SCIENCES
        FRANCIS S. COLLINS, M.D., Ph.D., DIRECTOR, NATIONAL HUMAN 
            GENOME RESEARCH INSTITUTE
        ANTHONY S. FAUCI, M.D., DIRECTOR, NATIONAL INSTITUTE OF ALLERGY 
            AND INFECTIOUS DISEASES
        PATRICIA A. GRADY, Ph.D., DIRECTOR, NATIONAL INSTITUTE OF 
            NURSING RESEARCH
        RICHARD J. HODES, M.D., NATIONAL INSTITUTE OF AGING
        SHARON H. HRYNKOW, ACTING DIRECTOR, FOGARTY INTERNATIONAL 
            CENTER
        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
        STORY C. LANDIS, Ph.D., DIRECTOR, NATIONAL INSTITUTE OF 
            NEUROLOGICAL DISORDERS AND STROKE
        TING-KAI LI, M.D., DIRECTOR, NATIONAL INSTITUTE OF ALCOHOL 
            ABUSE AND ALCOHOLISM
        DONALD A.B. LINDBERG, M.D., DIRECTOR, NATIONAL LIBRARY OF 
            MEDICINE
        KENNETH OLDEN, Ph.D., S.C.D., L.H.D., DIRECTOR, NATIONAL 
            INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
        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
        PAUL A. SIEVING, M.D., Ph.D., DIRECTOR, NATIONAL EYE INSTITUTE
        ALLEN M. SPIEGEL, M.D., DIRECTOR, NATIONAL INSTITUTE OF 
            DIABETES AND DIGESTIVE AND KIDNEY DISEASES
        STEPHEN E. STRAUS, M.D., NATIONAL CENTER FOR COMPLEMENTARY AND 
            ALTERNATIVE MEDICINE
        LAWRENCE A. TABAK, D.D.S., Ph.D., NATIONAL INSTITUTE OF DENTAL 
            AND CRANIOFACIAL DISEASES
        JUDITH L. VAITUKAITIS, M.D., DIRECTOR, NATIONAL CENTER FOR 
            RESEARCH RESOURCES
        NORA D. VOLKOW, M.D., DIRECTOR, NATIONAL INSTITUTE ON DRUG 
            ABUSE
        ANDREW C. VON ESCHENBACH, M.D., DIRECTOR, NATIONAL CANCER 
            INSTITUTE
        JACK WHITESCARVER, Ph.D., DIRECTOR, OFFICE OF AIDS RESEARCH

               OPENING STATEMENT OF SENATOR ARLEN SPECTER

    Senator Specter. Good morning, ladies and gentlemen. The 
time is precisely 9:30, which is our starting time, and the 
Appropriations Subcommittee on Labor, Health, Human Services, 
and Education will now proceed.
    Today we will consider the appropriations process as it 
applies to the National Institutes of Health. And as I have 
stated on many occasions, I consider NIH the crown jewel of the 
Federal Government. It may be the only jewel of the Federal 
Government.
    But medical science and humanity is deeply indebted to the 
extraordinary work which has come out of medical research from 
the National Institutes of Health.
    The budget process is always complicated and a goal was 
established to double NIH funding, which we have more than met. 
When asked what would happen after doubling, as you know, my 
response was instantaneous and obvious, and it was tripling. It 
would be too hard to quadruple it before you triple it.
    When I took over the chairmanship of this subcommittee in 
January 1995, I took a look at the priorities and thought this 
was none higher, really at the top of the list. And Senator 
Harkin, the ranking member, agrees. We know around here if you 
want to get something done, you have to cross party lines. 
Sometimes it gets you into trouble if you have a primary 
election campaign. My opponent thinks I should not talk to 
Democrats. But Senator Harkin and I, when we have changed the 
gavel, it has been seamless and we have proceeded to give 
tremendous support to NIH.
    We have a very tight discretionary budget this year. It is 
up one-half of 1 percent, and that is very, very, very 
difficult. The administration has put in a figure of $729 
million over the $28.5 billion budget, and as I am sure you 
know, we offered an amendment to increase it by $1.3 billion 
and we were successful, 72 to 24.
    But there were some strenuous arguments raised by my 
colleagues in the Senate that NIH was getting too much funding 
compared to other important research Departments in the Federal 
Government. And when one of my colleagues made an impassioned 
plea, I agreed with him that the other Departments were not 
getting adequate funding. But that did not bear on not 
adequately funding NIH. And what it takes is the subcommittee 
chairmen to pick up those important research projects and take 
the lead and get them funded.
    We have a Federal budget of $2,400,000,000,000. Do you know 
how much money that is? Well, nobody else does either.
    They say if you took a room this size, it would be 
insufficient to stuff $10,000 bills into it.
    We can afford money for research. That is the best 
investment that we are making beyond any question. But it is a 
fight.
    NIH has its own problems which you know about, challenges 
on conflicts of interest, which we have addressed in a separate 
hearing and we will talk about today, the issues about 
compensation, an issue which I know is being addressed.
    NIH is being attacked on an ideological level. The November 
28, 2003 edition of Science had an editorial marked Don't Let 
Ideology Trump Science. An amendment was offered in the House 
of Representatives to strike four NIH grants because sex was 
mentioned in the title, peer-reviewed. One of them involved a 
question of spread of venereal disease at truck stops where 
truckers are highly vulnerable, long stops, fatigue, away from 
home, places frequented understandably by prostitutes, and NIH 
wanted to make a study. And that and three other of your 
projects were challenged because if you have sex in the title, 
it makes a good 30-second commercial, if you voted for it, to 
defeat you. The surprising thing was that in the House of 
Representatives the amendment almost passed: 212 to 210.
    Now, it just happens that the amendment was offered by the 
fellow who wants to take my seat on the U.S. Senate who has 
voted against every domestic spending bill, voted against Head 
Start, voted against Medicare reform, voted against the budget 
for Labor, Health and Human Services, voted against the budget 
for NIH. So in this town you have to be prepared to defend 
yourself against attacks. So if you have one or two, Dr. 
Zerhouni, do not think you are being discriminated against.
    It goes with the territory. I think it is within your pay 
grade to defend yourself, Dr. Zerhouni, and to prevail, and I 
think it is within my pay grade to prevail also. But it is a 
battle.
    So much for an opening statement. I read it just like Betty 
Lou wrote it for me.
    Super Senator Taylor. She is not just a regular Senator. 
She is a super Senator.
    Dr. Elias Adam Zerhouni began his tenure as the 15th 
Director of NIH on May 20, 2000. He had a very distinguished 
career prior to coming to NIH: executive vice dean of Johns 
Hopkins University School of Medicine, Chair of the Department 
of Radiology; Martin Donner Professor of Radiology; medical 
degree from the University of Algiers School of Medicine; and 
residency in diagnostic radiology at Johns Hopkins. Thank you 
for joining us, Dr. Zerhouni, and we look forward to your 
testimony.

                SUMMARY STATEMENT OF DR. ELIAS ZERHOUNI

    Dr. Zerhouni. Thank you, Mr. Chairman. It is our pleasure 
to be here with the 27 institute and center directors of NIH to 
present our budget, but also to express our thanks and 
appreciation for your strong leadership on behalf of research 
and medical research and NIH.

                INTRODUCTION OF NEW INSTITUTE DIRECTORS

    I would like to start by introducing three of our new 
directors, and I will ask them to stand up to be introduced to 
you, Mr. Chairman.
    Dr. Story Landis is now the Director of the National 
Institute of Neurological Diseases. She has been appointed in 
the past year and has done an outstanding job already working 
with all aspects of neurological disorders, including 
collaboration with patient groups in trying to find the best 
approaches to rising threats of neurological degenerative 
diseases.
    Dr. Nora Volkow is the new Director of the National 
Institute of Drug Abuse. She has joined us from the Brookhaven 
National Laboratory in Stony Brook University. She is a leader 
in imaging of drug addiction and has already changed the 
strategy of her institute in many appropriate ways.
    Dr. Jeremy Berg is the new Director of the National 
Institute of General Medical Sciences. Dr. Jeremy Berg joined 
us from Johns Hopkins where he was the Chair of the Basic 
Science Institute at Johns Hopkins and Chair of the Department 
of Biophysics.
    I also would like to mention two acting Directors, Dr. 
Barbara Alving, who is the acting Director of NHLBI, and Dr. 
Sharon Hrynkow, who is the acting Director of the Fogarty 
International Center.

                       BREAKTHROUGHS AND ADVANCES

    Mr. Chairman, members of the committee, it is my pleasure 
to actually summarize the written testimony that we submitted 
to you. What I would like to do is go right away and tell you 
how important your investment has been in terms of specific 
breakthroughs and advances between last year and this year.
    NIH developed a completely new Ebola vaccine that can 
protect the population in less than a month. This a real 
breakthrough in biodefense.
    Just 2 days ago, NIAID announced that a new SARS 
experimental vaccine has been successful in animal experiments 
and will enter human trials as soon as we can do so. This is 
less than a year after the SARS epidemics which we knew not the 
cause of and it took us several weeks to find the cause. A year 
later, we are ready to fight this disease if it reappears.
    We discovered in 2003 several genes, for the first time, 
associated with schizophrenia. This was ranked as the number 
two advanced scientific advance of 2003, following the 
discovery of dark matter in the universe.
    We identified just 3 weeks ago a new master switch gene 
relating to type 2 diabetes. This is a very important discovery 
that will help us in discovering how type 2 diabetes develops.
    We have changed the practice paradigm of long-term hormone 
replacement therapy for women because of the landmark studies 
of the Women's Health Initiative.
    Today on the cover of Nature magazine, we are announcing 
the completion of the rat genome, a very important advance. As 
you know, by 2005 we were hoping to only have the human genome 
available to us. We now have the mouse, the rat, and the human 
genome, and we will be able to do comparative analysis that 
will advance our understanding of biology and disease.

                    NIH ROADMAP FOR MEDICAL RESEARCH

    All throughout the past 2 years, we have also taken into 
account the need for new science strategies, and this is what 
we call the NIH roadmap for medical research. The roadmap is 
essentially our effort to find ways to accelerate basic 
research discoveries and speed the translation of those 
discoveries into clinical practice. It is a dedicated effort to 
explicitly address roadblocks that slow the pace of medical 
research in improving the health of the American people.
    The major driver for this approach is exemplified on this 
slide in front of you, and that is that we need to transform 
medical research in the 21st century. In the 20th century, we 
treated disease when symptoms appeared and normal function had 
been lost. Why was that? Because for the past 5,000 years and 
the 20th century included, we did not understand the molecular 
and cellular events that led to disease. So we had to wait 
until the disease was explicit. And this is very expensive in 
both financial and disability costs.
    The paradigm of the 21st century is that we will intervene 
before symptoms appear and preserve normal function for as long 
as possible because we do understand much better the genetic 
events that lead to disease.
    We have come up with very bold initiatives. We will 
integrate all clinical research networks that are under NIH 
throughout the country and link them to community physicians to 
form new communities of research that will translate much 
quicker, much more efficiently than we have in the past the 
benefits of our fundamental understanding of research.
    A good example is juvenile rheumatic diseases, a disease 
set that affects only 300,000 children in the country. To do 
good research and have enough understanding of what happens, we 
need to recruit patients across the Nation, and this will be 
facilitated by a project of the roadmap called National 
Clinical Research Networks with trained community physicians in 
every community linked to academic centers.
    We continue to invest across NIH in a combined and 
coordinated fashion to advance medical research as fast as we 
can. This year we are requesting $237 million for the roadmap.

                              STEWARDSHIP

    We have continued also to focus on management excellence 
and stewardship of our resources. Let me point out two very 
simple statistics. Our funding went up by 141 percent in the 
past 10 years, almost 2 and a half times, 2.4 times. Our FTE's, 
the number of people, at NIH needed to manage this portfolio 
has only increased by 16 percent. Why? Because we have 
aggressively used modern methods of management using 
information systems to prevent the need for us to increase our 
FTE numbers. Our Research Management and Support budget has 
gone from 4 percent of our budget to 3.5 percent of our budget. 
So we are doing what you are asking us to do and being very 
good stewards.
    As you said, we will have on May 6 a final meeting of the 
Advisory Committee to the Director to finalize the 
recommendations of the Blue Ribbon Panel for conflict of 
interest and will report back to you as soon as we have that.

                    FISCAL YEAR 2005 BUDGET REQUEST

    Mr. Chairman, we are requesting a budget of $28.607 billion 
which is $28.527 billion from this committee, and a 2.6 percent 
increase over 2004. We also have at our program level $47 
million for nuclear and radiological countermeasures which are 
housed in the Public Health Service emergency fund.

                           PREPARED STATEMENT

    We are pleased to be here and will answer any of your 
questions. Again, we would like to thank the bipartisan support 
of this committee over the years. Thank you, Mr. Chairman.
    [The statements follow:]

              Prepared Statement of Dr. Elias A. Zerhouni

    Good morning, Mr. Chairman and members of the Committee. Let me 
begin by expressing my deepest appreciation to the Congress, Secretary 
Thompson, President Bush, and the American people for their generous 
and bipartisan support of the NIH's efforts to help improve the health 
of all our citizens. I respect the extraordinary effort of this 
committee and, Mr. Chairman, your leadership as well. I thank you for 
it.
    The year 2004 marks a sea change for the NIH and its Roadmap for 
Medical Research. We are refining our basic and clinical research 
programs to ensure that new discoveries rapidly lead to new and 
improved diagnostics, treatments and prevention strategies that extend 
the length and improve the quality of human life.
    In my testimony today, I want to cover four areas: first, highlight 
several key research advances that took place in the last year which 
represent the critical contributions of NIH intramural researchers and 
grantees; second, give examples of how the NIH Roadmap effort will help 
shape our approach to patient-oriented research; third, offer examples 
of our stewardship; and fourth, present an overview of our budget. In 
the course of my testimony, I will mention emerging priorities and our 
plans for responding to the health challenges ahead.

                        BREAKTHROUGHS & ADVANCES

    Each year, the public investment in research yields critical 
scientific advances. The four I highlight here are just a sample of the 
many that represent the development of new and improved treatments, 
diagnostics, or prevention strategies that will affect the health of 
the entire nation.
    Few viruses are feared more than the Ebola, a deadly microbe that 
causes outbreaks in Africa and Asia and kills up to 90 percent of those 
it infects. Scientists at the NIH National Institute of Allergy and 
Infectious Diseases Vaccine Research Center developed a single dose, 
fast-acting, experimental Ebola vaccine that successfully protects 
monkeys after just one month, and human trials are now under way.
    This year NIH research further elucidated the role of widely used 
hormone replacement therapies. The NIH halted the estrogen alone study 
of the Women's Health Initiative on March 1, 2004 after 5.6 years of 
follow-up, due to increased risk of stroke. You will recall that NIH, 
in 2002, stopped the combination hormone trial arm of the Women's 
Health Initiative early due to an increased risk of invasive breast 
cancer, coronary heart disease, stroke, and pulmonary embolism in study 
participants on estrogen plus progestin compared to women taking 
placebo. It indicated that healthy postmenopausal women taking 
combination hormone therapy also suffered twice the rate of dementia as 
those taking a placebo. Together, the results of these clinical studies 
changed conventional dogma, and provided important new evidenced-based 
information to women who are deciding whether to begin or how long to 
continue menopausal hormone therapy. These trials clearly are having a 
major impact on the health of people we know and love--our wives, our 
sisters, our daughters and our mothers.
    The third advance was the discovery of genes associated with 
schizophrenia, which is a profoundly disabling disorder that affects 
one percent of the adult population. It is marked by hallucinations, 
delusions, social withdrawal, flattened emotions, and loss of social 
and personal care skills.
    Research like this on the genetics of mental illness was named the 
Number 2 scientific ``breakthrough of the year'' for 2003 by the 
prestigious peer-reviewed journal, Science. Most of this work was 
funded by NIH and included discoveries of candidate genes for 
schizophrenia, depression, anxiety and bipolar disorders. These 
discoveries bring us closer to developing new diagnostic tests, 
strategies for prevention, and targets for the treatment of 
schizophrenia and other mental disorders.
    The fourth advance came only three weeks ago, when NIH announced a 
major new discovery, the identification of a common variation of a 
pancreatic ``master switch'' gene that increases the risk of type 2 
diabetes by 30 percent. Type 2 diabetes now affects 17 million people 
in the United States, and is responsible for enormous health care 
costs. This gene discovery opens the door to the development of new and 
more effective methods of prevention and treatment.

                              NIH ROADMAP

    Let me now turn your attention to the NIH Roadmap for Medical 
Research. I want to tell you why the Roadmap is so important to the 
future of medical research and to innovations in improving people's 
health. I also want to give you some examples of how we at NIH expect 
the Roadmap to change the way we do research and the practice of 
medicine.
    One of the questions we face is how do we successfully do our part 
in the battle to contain health costs? We need to address the following 
issues: What are the roadblocks? What are the major challenges? How can 
we most effectively invest the funds that the American taxpayers 
entrust to us to fashion the fastest track to discovery as well as 
translate those discoveries to the patient's bedside or the doctor's 
office?
    In seeking answers to these questions, one thing becomes clear. The 
traditional paradigm of medical care--when practitioners waited for the 
disease to cause the patient the loss of some function--must be 
replaced by a paradigm where health professionals act before the 
individual loses any function. This has become even more critical since 
chronic diseases now consume about 75 percent of our fast-growing 
health care expenditures.
    Let me present four examples of how the NIH Roadmap will transform 
our approach to biomedical research in specific disease areas.
    The first example is schizophrenia, a disorder that--as I mentioned 
earlier--affects one percent of the U.S. population. The peak onset 
occurs between the ages of 18 and 25. Schizophrenia has the hallmarks 
of both a neurodevelopmental and a neurodegenerative disease. But after 
100 years of neuropathological study, we still lack knowledge of the 
precise cause of the disorder.
    Today, schizophrenia is the fifth leading cause of years lost due 
to disability among Americans from ages 15-44. Although we can treat 
the so-called ``positive'' symptoms, such as hallucinations and 
delusions, we do not yet have treatments for the ``negative'' symptoms, 
like withdrawal and cognitive deficits. And these are the largest 
source of disability.
    Less than 30 percent of people with this illness are currently 
employed. And people with schizophrenia represent one of the largest 
groups on atypical antipsychotics as the treatment of choice. In 2001, 
Medicaid paid for more than 50 percent of the total spending on 
atypical antipsychotics, amounting to $2.7 billion, a figure which has 
been growing at roughly 25 percent a year for the past 3 years.
    Today, we lack a diagnostic test or a strategy for preventing 
schizophrenia. This situation is similar to cardiovascular disease 30 
years ago in that we see schizophrenic patients only after their first 
``heart attack,'' that is, episode, and we do not have the equivalent 
of cholesterol as an identifiable risk factor.
    However, what we have done recently--and what holds great promise 
for those who are suffering--is identify 12 genes associated with risk. 
Our challenge now is to move from the discovery of those genes--most of 
which have no known function--to understand the role these genes play 
in the onset and progression of this brain disease--and do something 
about it.
    Our hope is to use these genes to identify what is abnormal in the 
brains of schizophrenics, identify it early and thus provide the 
psychiatric equivalent of serum cholesterol. To accomplish this, we 
must study the protein products of these genes by using molecular tools 
that can make their function transparent.
    It is precisely here that the NIH Roadmap will help accelerate the 
effort to study protein products through so-called molecular 
libraries--databases of information on small molecule compounds like 
aspirin and antihistamines. These libraries will let researchers screen 
hundreds of thousands of small molecules to yield these tools.
    For example, we know that a variation in the neuregulin gene is 
associated with an increased risk for schizophrenia. To understand how 
this gene confers risk, we need to find chemicals that mimic or inhibit 
the gene's function. This would give us a precise description of how 
alterations in the gene change the activity of brain cells. Molecular 
libraries will not only yield the tools to study the neuregulin gene 
but also provide a test for vulnerability to schizophrenia. With such 
tools and tests, doctors could approach risk for schizophrenia the way 
we currently approach risk for heart disease.
    A second example where the NIH Roadmap offers promise is in 
pediatric diseases, through the creation of clinical research networks.
    Uncommon disorders like the juvenile forms of rheumatic diseases, 
such as arthritis, lupus and dermatomyositis, affect 300,000 children 
in the United States. Not one of these diseases is common enough to be 
studied intensively at any one academic health center. Thus, many such 
centers as well as community-based pediatricians are needed to collect 
a sufficient group of patients who can participate in these studies to 
gather meaningful results.
    The development of clinical research networks that focus on chronic 
childhood diseases--like those already established for childhood 
cancers--and the potential to include community physicians trained in 
clinical research methodology in the research process will enable 
clinical trials to be more efficient and effective.
    Using the NIH Roadmap clinical research networks concept, this 
could occur without building a new, and often very expensive, 
infrastructure for every new trial. Including community-based 
pediatricians as full partners in the research will allow us to 
overcome some of the limitations of patient recruitment that we 
currently experience and enable more children to participate in these 
trials, and accelerate the development of new treatments.
    The third example is Alzheimer's Disease (AD). We have made 
considerable progress in understanding Alzheimer's Disease. Fifteen 
years ago, we knew none of the genes that cause AD and we had only a 
limited understanding of the biological pathways involved in the 
development of brain pathology. Ten years ago, we could not model the 
disease in animals. Five years ago, we were not funding any prevention 
trials and had no way of identifying persons at high risk for the 
disease. And, as recently as one year ago, we had no way of imaging 
AD's characteristic amyloid plaques in a living person.
    Today, we can do all of these things. And we are poised to make the 
discoveries that will transform our understanding of the basic and 
clinical aspects of AD and enable us to effectively prevent, diagnose, 
and treat it using several NIH Roadmap initiatives.
    Through basic research in Alzheimer's disease, we identified a 
number of brain pathways that are potential targets for preventive 
interventions. These range from dysfunction and death of specific 
neurons to loss of the connections between neurons. Roadmap efforts to 
improve imaging of small molecules will let us visualize the effects of 
treatments more rapidly and accurately, which could make effective AD 
clinical trials smaller, faster and more affordable.
    My fourth and final example is cardiovascular disease. One of the 
greatest public health success stories of the last half century is the 
dramatic reductions in mortality from cardiovascular diseases. Studies 
initiated by the NIH--the Framingham Heart Study and the Lipid Research 
Clinics Coronary Primary Prevention Trial--have been key to that 
success. They helped not only to identify risk factors that contribute 
to the development of cardiovascular diseases, but also to demonstrate 
the efficacy of therapeutic interventions to control them.
    Even so, cardiovascular disease remains an enormous health burden, 
accounting for 38 percent of all deaths in the United States in 2001. 
Progress in reducing that burden will require continued efforts to 
refine our understanding of risk factors, such as obesity and high 
cholesterol, and to identify and evaluate new prevention approaches. 
This means that large scale population-based studies will remain a 
critical component of our research effort.
    The NIH Roadmap will help fashion the interactive network and 
involvement of many community-based practitioners. For example, we can 
make better use of large-scale organizations set up for single studies, 
such as the recently completed Antihypertensive and Lipid-Lowering 
Treatment to Prevent Heart Attack Trial (ALLHAT). Instead of disbanding 
it, we can involve many or all of the investigators in other trials 
addressing not only cardiovascular disease but also other diseases. The 
National Electronic Clinical Trials and Research (NECTAR) initiative--a 
critical part of the Roadmap effort to re-engineer clinical research--
will enable data sharing and enhance comparison and aggregation of 
results from multiple trials by using standard definitions of outcomes 
and adverse events. In the future, patients will know directly from 
their own community doctors, who will be equipped with the new web-
based NECTAR, what medical research can do for them in terms of 
participation in studies, the best available therapies, and nearby 
advanced research centers.

                              STEWARDSHIP

    We realize that to advance the NIH scientific agenda, our 
management and administration must be effective, efficient and 
productive. By introducing new information technology and business 
systems and streamlining governance structures, we are placing 
continuous improvement of management and administrative functions at 
the forefront of our agency priorities. Let me highlight a few of our 
efforts.
    NIH is making rapid progress to modernize its business and 
financial systems. An agency-wide information technology system, known 
as the New Business System (NBS), is integrating such processes as 
acquisitions, travel, property, and financial management. This effort 
will reduce the cost and complexity of doing business, enhance the 
level of service, and improve management controls.
    NIH is also improving its peer review system, which is recognized 
as the cornerstone of NIH's success. The NIH Center for Scientific 
Review (CSR), the focal point of the NIH peer review system, reviews 
about 70 percent of the grant applications submitted to NIH. In fiscal 
year 2003, CSR received a record-breaking 66,000 grant applications.
    CSR is in the final stages of crafting new and more flexible review 
panels organized into 24 scientifically-related clusters. NIH is also 
incorporating new technologies into the review process through the 
electronic Research Administration (eRA). The goal is to implement an 
end-to-end electronic grants administration for NIH research award 
mechanisms that could reduce the waiting period from submission of an 
application to a grant award by more than two months--from 9 to 10 
months down to 7 months.
    Remarkably, because of improvements in productivity over the past 
ten years, NIH funding has grown 141 percent, while our FTEs have 
increased by only 16 percent.
    The NIH also realizes the need for a more efficient means of trans-
NIH coordination. To streamline decision making, we reduced the 
plethora of NIH administrative committees down to a trans-NIH Steering 
Committee and 5 working groups. Additionally, as we discussed when I 
met with the subcommittee in January, all our conflict of interest 
policies and procedures are under review both to ensure that they meet 
the highest standards and, most importantly, to preserve the public's 
trust in the NIH. I will soon receive the report of a Blue Ribbon Panel 
I created to advise NIH on what changes they think we should make. I 
will inform you about their conclusions, and mine, once they complete 
their work next month.

                                 BUDGET

    The discretionary fiscal year 2005 budget request for the NIH is 
$28,607 million ($28,527 million from this subcommittee and $80 million 
from the VA/HUD subcommittee), an increase of $729 million or 2.6 
percent over the fiscal year 2004 Enacted Level. In addition, $47.4 
million is included in the budget authority request of the Public 
Health and Social Services Emergency Fund (PHSSEF), for NIH research in 
radiological/nuclear countermeasures, and $150 million in mandatory 
funds was previously appropriated for the Special Type 1 Diabetes 
Initiative, bringing NIH's program level total to $28,805 million, or a 
2.7 percent increase. The budget increases funding for the NIH Roadmap 
(+$109 million), obesity research (+$40 million), which will thus grow 
by 10 percent from $400 million in 2004, and biodefense research (+$74 
million), an increase of 4.5 percent over fiscal year 2004.

                               CONCLUSION

    In conclusion, I want to reemphasize the NIH commitment to help 
improve the health of the American people. Although we have had great 
success in changing acute lethal diseases like AIDS and many cancers 
and childhood diseases into chronic manageable diseases, there are many 
challenges ahead. Life expectancy has increased and the diseases of 
aging and the aging population have become major priorities.
    With a shift from acute to chronic diseases, health disparities and 
pediatric diseases also present challenges, as do emerging and re-
emerging diseases, such as SARS. We are confident, as the committee has 
shown it is, that medical research will make a critical difference in 
the lives of all Americans.
    As the NIH director, I fully understand and embrace my role as the 
steward of our Nation's investment in medical discovery. And I remain 
vigilant to ensure that these precious resources--including over 
212,000 scientists working at 2,800 institutions in the United States 
and overseas and the 5,000 scientists at the NIH itself--are used 
wisely and efficiently and produce not only new knowledge but also 
tangible benefits that touch the lives of every individual who reaches 
out for our help.

                    BUILDINGS AND FACILITIES PROGRAM

    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's budget request for the Buildings and Facilities (B&F) 
Program for fiscal year 2005, a sum of $99,500,000.

                      ROLE IN THE RESEARCH MISSION

    State-of-the-science research and support facilities are a vital 
part of the research enterprise. The National Institutes of Health's 
(NIH) Buildings and Facilities (B&F) program designs, constructs, 
repairs and improves the agency's portfolio of laboratory, clinical, 
animal, administrative and support facilities at its six installations 
in three states. These facilities house researchers from the NIH 
Institutes' and Centers' (ICs) intramural basic, translational, and 
clinical research programs; the NIH leadership, and various programs 
that support agency operations. The fiscal year 2005 B&F budget request 
supports critically needed and timely investments to keep the agency's 
facilities and supporting physical infrastructure healthy, safe, 
secure, and research ready.
    The B&F budget request is the product of a comprehensive, corporate 
capital facilities planning process. This process begins with extensive 
consultation across the research community and the NIH's professional 
facilities staff. It works through the Facilities Working Group, an 
advisory committee to the NIH Steering Committee and the HHS Capital 
Investment Review Board. The budget request is the current year plan in 
a rolling five-year facilities plan. Through this process, the real and 
insistent program demand for more effective and efficient facilities 
designed to support current and emerging investigative techniques, 
technologies, and tools is integrated with, and balanced against, the 
need to repair, renovate, and improve the existing building stock to 
keep it in service and to optimize its utility.
    The fiscal year 2005 request provides the necessary funding support 
for the ongoing safety, renovation and repair, and related projects 
that are vital to proper stewardship of the entire portfolio. It 
provides funds to continue the functional integration of the clinical 
research components of the existing Building 10 with the new Mark O. 
Hatfield Clinical Research Center (CRC). Additionally, the request 
includes funds to: complete the design of the Animal Research Center 
(ARC) on the Bethesda campus; complete the creation of a security 
buffer around the Rocky Mountain Laboratories (RML), in Hamilton, MT; 
and to add another chiller to the NIH's Bethesda campus central utility 
system that is needed to meet current and anticipated cooling demands.
    The fiscal year 2005 B&F budget request is organized among five 
broad Program Activities: Construction, Essential Safety and Regulatory 
Compliance, Repairs and Improvements, Renovations, and Equipment/
Systems. The fiscal year 2005 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 facilities 
planning process and are the NIH's capital facility priorities for 
fiscal year 2005.

                    FISCAL YEAR 2005 BUDGET SUMMARY

    The fiscal year 2005 budget request for Buildings and Facilities is 
$99.5 million. The B&F request contains $16.5 million for Construction, 
including $5 million to complete the design of an Animal Research 
Center; $9.5 million to complete the creation of a security buffer 
around the Rocky Mountain Laboratories (RML) in Hamilton, MT; and $2 
million for concept development studies of projects proposed in the 
facilities plan.
    There is a total of $6 million for Essential Safety and Regulatory 
Compliance programs composed of $0.5 million for the phased removal of 
asbestos from NIH buildings; $2 million for the continuing upgrade of 
fire and life safety deficiencies of NIH buildings; $1 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 $2 million for 
the continued support of the rehabilitation of animal research 
facilities. In addition, the fiscal year 2005 request includes $59.2 
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. 
The request includes $10.8 million in Renovations to complete the 
Building 10 Transition Program. Finally, the request includes $7 
million in Equipment/Systems for the Chiller 27 project.
    My colleagues and I will be happy to respond to any questions you 
may have.

                                 ______
                                 
               Prepared Statement of Dr. Paul A. Sieving

    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's budget request for the National Eye Institute (NEI) for 
fiscal year 2005. This budget includes $671.6 million, an increase of 
$18.8 million over the fiscal year 2004 enacted level of $652.7 million 
comparable for transfers proposed in the President's request. As the 
Director of the NEI, it is my privilege to report on the 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.

                            RETINAL DISEASES

    Retinal diseases are a diverse set of sight-threatening conditions 
that include age-related macular degeneration, diabetic retinopathy, 
retinopathy of prematurity, retinitis pigmentosa, Usher's syndrome, 
ocular albinism, retinal detachment, uveitis (inflammation), and cancer 
(choroidal melanoma and retinoblastoma). One of the most tragic retinal 
diseases, retinopathy of prematurity (ROP), causes severe vision loss 
in premature, low-birthweight infants. ROP is characterized by 
excessive growth of abnormal blood vessels in the back of the eye that 
often hemorrhage and scar the retina. This year, results from an NEI-
funded clinical trial, called the Early Treatment of Retinopathy of 
Prematurity (ETROP), established that early treatment, based on newly 
developed diagnostic criteria, improves visual outcomes in infants at 
the greatest risk of developing ROP. The ETROP study also found that 
these new diagnostic criteria were helpful in select patient subgroups 
that may not ultimately develop ROP. For these infants, careful 
observation was found to be the best approach. Results from ETROP will 
greatly improve visual outcomes for children with ROP.
    Age-related macular degeneration (AMD) is a leading cause of 
blindness in patients over age 60 in the United States and is a major 
health problem in most other developed countries. More than 9 million 
Americans have some degree of AMD (Archives of Ophthalmology, In 
Press). Based on the results of an NEI-funded clinical trial, the Age-
Related Eye Diseases Study (AREDS), 1.3 million of these people would 
develop advanced AMD if no treatment were given to reduce their risk. 
If these people at risk for development of advanced AMD received the 
supplements (vitamins C, E, beta-carotene, and zinc) used in AREDS, 
more than 300,000 of them would avoid advanced AMD and any associated 
vision loss over the next five years. Delaying the advance of a disease 
in older-age populations is an essential strategy to reduce the burden 
and incidence of disease.
    Uveitis is an autoimmune inflammatory disease of the eye that 
accounts for up to 10 percent of blindness in the United States 
(Ophthalmology 2004; 111:491-500). In collaboration with researchers at 
the National Cancer Institute, NEI intramural scientists have reported 
promising results with the use of a monoclonal antibody (daclizumab) in 
the long term treatment of patients with uveitis. This new therapy 
seems to have many fewer side effects than existing immunosuppressive 
therapies, leading to an improved quality of life. Planning is underway 
to begin a Phase III study to evaluate the full potential of this 
therapy.

                            CORNEAL DISEASES

    The cornea is the transparent tissue at the front of the eye. 
Corneal disease and injuries are the leading cause of visits to eyecare 
clinicians, and are some of the most painful ocular disorders. In 
addition, approximately 25 percent of Americans have a refractive error 
known as myopia or nearsightedness that requires correction to achieve 
sharp vision; many others are far-sighted or have astigmatism.
    NEI intramural scientists found that serum albumin represents up to 
13 percent of the total water-soluble protein of the mouse cornea. 
Humans also have abundant serum albumin in the corneal stroma. Because 
the serum albumin accumulates in the corneal stroma by diffusion from 
the blood supply surrounding the cornea, it may provide an improved 
route of drug delivery to the cornea. Conjugating serum albumin to the 
drug of choice and injecting the conjugate into the blood stream will 
not only direct the drug within the cornea, but extend its half-life 
within this tissue. Future research will evaluate the usefulness of 
serum albumin as a drug carrier to treat corneal disorders.
    NEI intramural scientists recently identified an enzyme called CDK5 
that regulates corneal epithelial cell adhesion and migration. Using a 
model wound healing system, these researchers found that the rate of 
wound closure was significantly retarded in cells with too much CDK5 
and accelerated in cells in which the CDK5 was inactivated. 
Continuation of this line of research may provide the means to promote 
rapid healing of corneal tissues that have been damaged by disease or 
injury.

                                CATARACT

    Cataract, an opacity of the lens of the eye, interferes with vision 
and is the leading cause of blindness in developing countries. In the 
United States, cataract is also a major public health problem. The 
economic burden of cataract will worsen significantly in coming decades 
as the American population ages.
    Age-related cataract formation is believed to result from the 
complex effects of aging on normal physiological processes. It has long 
been recognized that lens transparency is a function of a very high 
concentration of soluble proteins, the crystallins, within the 
specialized lens fiber cell. In the lens, a-crystallin has a dual 
function: it accumulates in fiber cells in high concentrations to 
produce the high refractive index needed for transparency, and it 
functions as a molecular chaperone to protect against clouding of the 
lens due to protein aggregation. For some time, scientists have 
attempted to understand how a-crystallin can continue to perform its 
chaperone functions over a range of stress conditions encountered by 
the lens during a lifetime. New data suggest that under low stress, a-
crystallin is maintained in a multi-subunit complex. Under conditions 
of high stress, a-crystallin breaks into smaller sub-units that can 
protect the clarity of the lens from protein aggregation. It has been 
hypothesized that this chaperone function decreases with age and leaves 
the lens more vulnerable to stressful conditions. Improving our 
understanding of this protective role of a-crystallin may one day lead 
to the means to prevent cataract.

                    GLAUCOMA AND OPTIC NEUROPATHIES

    Glaucoma is a group of eye disorders that share a distinct type of 
optic nerve damage, which can lead to blindness. Elevated intraocular 
pressure (IOP) is frequently, but not always, associated with glaucoma. 
Glaucoma is a major public health problem and is a leading cause of 
blindness in African Americans (Archives of Ophthalmology, In Press).
    A hallmark of glaucoma is the death of retinal ganglion cells (RGC) 
in the retina, which can lead to catastrophic vision loss. Previous NEI 
studies have found evidence that elevated IOP deprives RGCs of brain-
derived neurotrophic factor (BDNF), an endogenous protein that is 
crucial to RGC survival. Ocular injections of BDNF in rodent models of 
glaucoma have improved RGC survival. However, due to the relatively 
short half-life of this protein, the need for frequent ocular 
injections would not bode well in treating a chronic disease like 
glaucoma. To overcome this hurdle, NEI-supported researchers recently 
used gene therapy in rodent models of glaucoma to transfect RGCs with 
the gene that encodes BDNF, providing a lasting and direct supply of 
this essential protein. Ongoing NEI-supported laboratory work is 
evaluating whether gene therapy with BDNF provides long-term benefit 
and whether gene delivery with other neurotrophic agents, alone or in 
combination with BDNF, improves RGC survival.

              STRABISMUS, AMBLYOPIA AND VISUAL PROCESSING

    Developmental disorders such as strabismus (misalignment of the 
eyes) and amblyopia (commonly known as ``lazy eye'') are among the most 
common eye conditions that affect the vision of children. In addition, 
more than three million Americans suffer from visual processing 
disorders not correctable by glasses or contact lenses (Archives of 
Ophthalmology 1990; 108:286-290).
    Patching the stronger eye has been a mainstay of amblyopia therapy. 
Unfortunately, there is no specific patching regimen that is widely 
accepted for treating the disease. To address the clinical issue of the 
optimal number of patching hours for moderate amblyopia, an NEI-
supported clinical trial compared daily patching of two hours versus 
six hours for children with moderate amblyopia. Results from this 
clinical trial revealed that patching the unaffected eye of children 
with moderate amblyopia for only two hours daily is as effective as 
patching the eye for six hours. This finding should improve treatment 
compliance as patching can be a socially stigmatizing and uncomfortable 
practice for young children.

                       TECHNOLOGICAL INNOVATIONS

    The marriage of computer technology and medical science is creating 
advances in treating even the most intractable diseases. In one such 
union, specially designed computer chips implanted in the eye may one 
day make it possible to partially restore visual function to the blind. 
Ocular neuro-degenerative diseases such as retinitis pigmentosa (RP) 
and macular degeneration damage and destroy the light-sensitive 
photoreceptor cells in the retina. The microelectronic retinal 
prosthesis, a device developed by NEI-supported researchers, mimics the 
function of photoreceptor nerve cells by turning light into electric 
signals. In a recently published study, a 74 year-old patient blind 
with RP was able to see spots of light, detect motion, and recognize 
simple shapes. Although preliminary, these results are a promising 
first step in realizing a prosthetic device that can restore ambulatory 
vision to patients with retinal degenerative diseases, which are a 
major cause of vision loss in this country.

                          PROGRAM INITIATIVES

    The rapid progress in areas of gene discovery and bioinformatics 
has created the need for enhanced cooperation and coordination among 
groups that provide genetic diagnostic information to the clinician and 
patient, store and provide DNA specimens to researchers, and maintain 
data banks of genotype-phenotype information. Such groups are 
underrepresented in the area of human ocular disease. The purpose of 
this initiative is to explore the establishment of a national central 
registry and molecular database of securely coded information from a 
large number of people with ocular diseases caused by genetic 
mutations. Information will be provided through a network of 
cooperating groups who provide genetic and diagnostic services to 
patients and clinicians. Such a registry and database will be of great 
value in advancing research for these important diseases.
    Clinician scientists will play a major role in translating 
laboratory findings into safe and effective therapies. However, the 
vision research community has raised concerns about the future of 
clinician scientists. Declining clinical revenues are making it 
increasingly difficult for clinicians to find time away from the 
examination room to get the training they need. However, many of the 
investigational therapies now being contemplated will be translated by 
the next generation of clinician scientists. We need to make sure that 
current clinician scientists have a capable next generation to pass the 
torch to.
    In addition to its existing extramural training and career 
development grant programs, the NEI is working to increase the ranks of 
the clinician scientist through a new intramural clinician scientist 
training program at the NEI. The Clinician Scientist Development 
Program is designed for board eligible/certified clinicians who seek to 
develop an independent research program that integrates the field of 
vision research with the clinical study of patients with ocular disease 
or disorders.
    The NEI recently published its forward looking National Plan for 
Eye and Vision Research. The NEI's ongoing planning process involves 
the assessment of important areas of progress in eye and vision 
research and the development of new goals and objectives that address 
outstanding needs and opportunities for additional progress. The 
National Plan can be accessed through the NEI website at: http://
www.nei.nih.gov/strategicplanning.

                              NIH ROADMAP

    The NIH Roadmap provides a framework for the priorities the NIH as 
a whole must address in order to optimize its entire research 
portfolio. The NEI is committed to the initiatives of the Roadmap and 
is working to meet its goals. I would like to highlight NEI's 
involvement in two Roadmap Initiatives: ``Nanomedicine'' and ``Re-
Engineering the Clinical Research Enterprise.''
    The NEI and the National Human Genome Research Institute are 
heading an NIH committee charged with implementing the Nanomedicine 
Roadmap Initiative. Nanotechnology originated in the fields of 
engineering and physics and refers to the research and development of 
materials and devices at the atomic, molecular or macromolecular 
levels. Nanomedicine integrates nanotechnology with biomolecular 
processes. The long-term goal of the Nanomedicine Roadmap Initiative is 
the development of therapeutic nanotechnology interventions for medical 
diagnosis and the treatment of disease. To meet these goals we are 
establishing a process to solicit ideas and concepts germane to the 
development of Nanomedicine Development Centers.
    Nanomedicine Development Centers will be designed to achieve an 
understanding of biological systems at the nanomolecular level.
    Over the past decade NEI-supported laboratory research has given 
rise to an unprecedented number of promising, pre-clinical therapies 
for eye disease. NEI's continued success depends on building the 
clinical infrastructure for translational medicine. Consonant with the 
NIH Roadmap initiative ``Re-engineering the Clinical Research 
Enterprise'' the NEI is creating cooperative clinical research groups 
that will enhance and expand clinical trial infrastructure. Over the 
last year, the NEI implemented the Diabetic Retinopathy Clinical 
Research Network. More than 70 clinical centers with the capability to 
participate in the clinical trials network have been identified. This 
network joins the highly effective Pediatric Eye Disease Investigator 
Group as models for future clinical networks the NEI plans to build.
    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. 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 2005, a sum of 
$196,780,000, which represents an increase of $5,324,000 over the 
comparable fiscal year 2004 appropriation.

          A STRATEGIC APPROACH TO ELIMINATE HEALTH DISPARITIES

    Unprecedented scientific advances in biomedical research over the 
last several decades dramatically improved public health. However, 
racial and ethnic minorities and other populations that experience 
disparities in health status have not benefitted equally from our 
Nation's progress in scientific discovery.
    The NIH supports a comprehensive research program to better 
understand why a broad spectrum of diseases disproportionately impact 
racial and ethnic minorities and the urban and rural poor. No other 
scientific area so thoroughly transcends so many diverse areas of 
science and involves all of the NIH Institutes and Centers (ICs).
    The NCMHD plays a key role in framing the NIH health disparities 
research agenda by conducting and supporting basic, clinical, social 
sciences, and behavioral health disparities research; developing 
research infrastructure and training programs; reaching out to and 
disseminating health information to minority and other health disparity 
populations; stimulating scientific programs within the NIH ICs to 
uncover the causes of health disparities and eliminate their impact on 
society; and developing and updating the NIH Health Disparities 
Strategic Plan.
    This past year, the NCMHD, in collaboration with the NIH Director, 
every NIH IC, and the National Advisory Council on Minority Health and 
Health Disparities, completed the first comprehensive NIH Health 
Disparities Strategic Plan, based on scientific priorities and 
opportunities that will lead to new therapies and prevention strategies 
that will ultimately eliminate health disparities in America. This 
evolving plan will guide future NIH health disparities research 
efforts.

            INNOVATIVE EFFORTS TO COMBAT HEALTH DISPARITIES

    The NCMHD has accomplished much since its creation. Today, the 
NCMHD has 60 Health Disparities Centers of Excellence spread across the 
nation. These Centers of Excellence, now located in 23 states, the 
District of Columbia, and Puerto Rico, support health disparities 
research, research training, and community involvement to identify 
factors that contribute to health disparities and to develop and 
implement new diagnostic, treatment, and prevention strategies.
    The NCMHD addresses the national need to develop a diverse, strong, 
and a culturally competent scientific workforce by eliminating barriers 
that prevent racial and ethnic minority students and students from 
disadvantaged backgrounds from pursuing research careers. Currently, 
the NCMHD supports about 300 researchers from 38 states through its two 
Loan Repayment Programs, which help to level the playing field and make 
it possible for under represented individuals to enter the scientific, 
technological, and engineering workforce. These ``Health Disparities 
Ambassadors'' are key to creating the culturally competent health 
disparities and clinical research workforce of the future.
    The NCMHD has also created a one-of-a-kind Research Endowment 
Program. Unique at the NIH, this program addresses the national need to 
build research and training capacity in institutions that make 
significant investments in the education and training of minority and 
disadvantaged individuals. This program is making it possible for 13 
institutions located in 11 states and Puerto Rico to establish health 
disparities endowed chairs and programs, enhance student recruitment 
efforts, provide merit-based scholarships, recruit and retain faculty, 
develop innovative instruction delivery systems in minority and health 
disparities research areas, and access emerging technologies.
    The NCMHD Research Infrastructure in Minority Institutions Program, 
born out of a partnership between the National Center of Research 
Resources and the Office of Research on Minority Health, (the 
predecessor to the NCMHD) is making it possible for institutions to 
target research efforts on health disparities that exist in the 
Southwest Border States; in rural communities, such as the Appalachia 
Region, the Mississippi Delta, and the Frontier States; and in urban 
centers of the nation. Currently, 11 institutions in eight states 
benefit from this program.
    In addition to using its core programs, the NCMHD strategy to 
eliminate health disparities also includes leveraging NIH dollars and 
expertise by creating partnerships with the NIH ICs and other agencies 
within the Department of Health and Human Services to fund health 
disparities research, training, and outreach programs. Over the past 
two years alone, the NCMHD forged many new partnerships, supporting 
more than 400 research projects to combat health disparities in our 
nation.

                    CLOSING THE HEALTH DISPARITY GAP

    Racial and ethnic minorities and other health disparity populations 
experience a disproportionate burden of illness, disability, and 
premature death due to cancer, cardiovascular disease and stroke, 
diabetes, HIV/AIDS, infectious diseases, infant mortality, and other 
diseases. The Department of Health and Human Services, through its 
``Closing the Gap Initiative,'' designates these areas as major 
research priorities. NCMHD programs focus on these priorities and many 
others. The following initiatives represent a small sampling of the 
richness and diversity of NCMHD activities.

Cancer
    Cancer deaths vary by gender, race, and ethnicity. Certain racial 
and ethnic groups have lower survival rates than whites for most 
cancers. Colorectal cancer rates among Alaska Natives are higher than 
the national average and Asian Americans suffer disproportionately from 
stomach and liver cancers. African American men have the highest rates 
of colon, rectum, prostate, and lung cancers (Healthy People 2010).
    NCMHD Health Disparities Centers of Excellence in 12 states across 
the nation are bringing to bear their state-of-the-art research and 
outreach programs to eliminate the impact of cancer on diverse 
populations. These efforts take place in Alabama, Arizona, California, 
Colorado, Georgia, Maryland, Mississippi, New York, Pennsylvania, 
Tennessee, Texas, and Virginia. One example of this intense effort is 
the American Indian and Alaska Native Health Disparities Center in 
Colorado, which conducts cancer research to address the needs of Native 
American and Alaska Native populations.
    The NCMHD Research Infrastructure in Minority Institutions program, 
which focuses on building research capacity at minority serving 
institutions, also addresses cancer health disparities. The Charles R. 
Drew University is working to improve the detection and 
characterization of brain tumors, and researchers at San Francisco 
University are examining the impact of social support, spirituality, 
and depression on quality of life among breast cancer survivors from 
diverse populations.
    Forty-five Health Disparities Ambassadors supported by our Loan 
Repayment programs have also set their sights on combating cancer 
health disparities in 17 states including Alabama, California, 
Colorado, Georgia, Illinois, Kansas, Massachusetts, Maryland, Michigan, 
Minnesota, North Carolina, New York, Pennsylvania, Tennessee, Texas, 
Virginia, Wisconsin, and in the District of Columbia. Some of the 
exciting work taking place under this program includes a community-
based health promotion project to prevent cervical cancer in 
Vietnamese-American women; research studies on racial differences and 
barriers in obtaining breast, cervical, and colon cancer screening; and 
a population-based study that examines the variation in outcomes of 
colorectal cancer between African Americans and whites.
    Collaboration with the other NIH Institutes and Centers has allowed 
the NCMHD to extend the reach of its scientific expertise to tackle 
cancer health disparities in rural populations. For example, the 
Appalachia Cancer Network, cosponsored by the NCMHD and the National 
Cancer Institute, addresses cancer in rural and medically underserved 
Appalachian populations in West Virginia, Kentucky, Tennessee, 
Virginia, Ohio, Pennsylvania, Maryland, and New York. The goal of this 
network is to reduce cancer incidence and mortality and to prevent 
future increases; to increase cancer survival; and to stimulate greater 
coordination and participation among regional, state, and community 
cancer control networks throughout Appalachia.

Cardiovascular Disease & Stroke
    Cardiovascular disease takes a heavy toll on certain populations. 
Heart disease rates have been consistently higher in the African 
American population than in whites (Healthy People 2010). Data on 
stroke risk factors are sparse for most racial and ethnic populations, 
except for African Americans whose stroke deaths, when adjusted for 
age, are almost 80 percent higher than in whites (Healthy People 2010).
    Today, 13 NCMHD Health Disparities Centers of Excellence, located 
in nine states across the nation including California, Georgia, Hawaii, 
Maryland, Mississippi, North Carolina, New York, Pennsylvania, and 
Texas focus on eliminating disparities due to cardiovascular disease. 
Three Health Disparities Centers of Excellence in Georgia, Mississippi, 
and New York focus on stroke research. The NCMHD also supports 20 
Health Disparities Ambassadors spread across 11 states, including 
California, Florida, Illinois, Indiana, Massachusetts, Michigan, New 
Hampshire, New Jersey, New York, Ohio, and Texas, who have set their 
sights on eliminating health disparities due to cardiovascular disease.
    The NCMHD Health Disparities Center of Excellence at Jackson State 
University in Jackson, Mississippi is built on a partnership with the 
University of Mississippi Medical Center, the University of Pittsburgh, 
and the Jackson Medical Mall Foundation. This Center's research agenda 
focuses on cardiovascular disease, stroke, and cancer in the African 
American population in Mississippi.
    The NCMHD also partners with its fellow NIH ICs, in the battle 
against cardiovascular disease and stroke disparities. The NCMHD 
partners with the National Heart, Lung, and Blood Institute to support 
the Jackson Heart Study. This study evaluates the environmental and 
genetic factors contributing to the disproportionate incidence of 
cardiovascular disease in African American men and women living in 
Mississippi. To date, almost 5,000 participants have benefitted from 
the program by visiting the clinic, with an average of 25 participants 
per week.
    The NCMHD and the National Institute of Neurological Disorders and 
Stroke partner to support two Specialized Neuroscience Research 
Programs at the Morehouse School of Medicine and at the University of 
Texas at San Antonio. This funding allows institutions to develop 
state-of-the-art neuroscience research programs; strengthen 
collaborations and resource-sharing between minority medical and 
graduate schools, community-based organizations, and leading 
neuroscience laboratories; expand training opportunities for minority 
students to access and prepare for careers in neuroscience research; 
and build new stroke research capacity.

Diabetes
    Certain communities, including Hispanics, American Indians, African 
Americans, and certain Pacific Islanders and Asian populations, as well 
as economically disadvantaged and older people suffer 
disproportionately from diabetes (Healthy People 2010). Diabetes is the 
target of 27 Health Disparities Centers of Excellence in 17 states 
including Alabama, Arizona, California, Colorado, Georgia, Hawaii, 
Illinois, New York, North Carolina, North Dakota, Maryland, 
Mississippi, Oklahoma, Pennsylvania, South Carolina, Texas, and 
Wisconsin, as well as the District of Columbia. These programs include 
the University of Hawaii at Manoa, where efforts are underway to reduce 
and eliminate the major complications of diabetes in Pacific Islanders. 
The University of Pennsylvania is developing behavioral strategies for 
reducing obesity, a major factor contributing to diabetes in Latino and 
African American communities.
    The NCMHD has also deployed 15 Health Disparities Ambassadors to 10 
states, including Alabama, California, Florida, Georgia, Illinois, 
Massachusetts, New Hampshire, New York, Texas, and Virginia in the 
effort to eliminate diabetes-related health disparities. These 
individuals are conducting several important projects including 
reducing obesity in diabetic African American women in the state of 
Georgia and conducting educational interventions to prevent type 2 
diabetes in middle school children in Alabama. Under the NCMHD Research 
Endowment program, Xavier University of Louisiana is increasing the 
diabetes research capability of its College of Pharmacy, promoting 
health disparities research, and increasing the pool of well educated 
under represented minorities who pursue advanced education in 
biomedical and behavioral research.
    New NCMHD partnerships are also playing a significant role in 
eliminating diabetes health disparities. The NCMHD and the Indian 
Health Service recently formed a partnership to develop the Tribal 
Epidemiology Centers Program to address and eliminate health 
disparities, including diabetes disparities, experienced by American 
Indians and Alaska Natives. Recent NCMHD support enabled the creation 
of a new Northern Plains Tribal Epidemiology Center in Rapid City, 
South Dakota, continued funding for the other six existing EpiCenters, 
and the development of a summer training institute for Indian Health 
professionals. The funding will assist the EpiCenters to carry out 
their training program for local health staff, and expand their 
outreach activities to include a community-based research training 
program.

HIV/AIDS
    The disproportionate impact of HIV/AIDS on certain populations 
underscores the importance of sustained research and prevention 
efforts. In 2002, the AIDS diagnosis rate among African Americans was 
almost 11 times the rate among whites. African American women had a 23-
times greater diagnosis rate than white women. African American men had 
almost a nine-times greater rate of AIDS diagnosis than white men. 
(Centers for Disease Control and Prevention Division of HIV/AIDS 
Prevention 2003). In 2000, the AIDS incidence among Hispanics was 22.5 
per 100,000 population, more then three times the rate for whites 
(Centers for Disease Control and Prevention Division of HIV/AIDS 
Prevention 2002:1).
    In its fight against HIV/AIDS health disparities, the NCMHD 
partners with the Centers for Disease Control and Prevention to support 
the Racial and Ethnic Approaches to Community Health (REACH) Program. 
REACH serves African American, Asian American, Pacific Islander, 
Hispanic American, American Indian, and Alaskan Native populations at 
increased risk for HIV/AIDS, cardiovascular disease, breast and 
cervical cancer, diabetes and infant mortality. REACH develops, 
implements, and evaluates innovative community level intervention 
demonstrations that could be effective in eliminating health 
disparities by 2010.
    With the Agency for Healthcare Research and Quality, the NCMHD 
supports the EXCEED Program to examine the underlying causes and 
contributing factors for racial and ethnic disparities in health care 
and to identify and implement strategies for reducing and eliminating 
those disparities. Under this initiative, the Medical University of 
South Carolina is examining strategies to address HIV/AIDS disparities 
in health status between African Americans and whites, and the Baylor 
College of Medicine is assessing the extent to which problems in 
doctor-patient communication contribute to racial and ethnic 
disparities in health care use.

Infant Mortality
    In recent years, infant mortality rates in the United States have 
steadily declined; yet the rate of Sudden Infant Death Syndrome among 
African Americans is still twice that of whites. African American women 
continue to be three to four times more likely than white women to die 
of pregnancy-related complications. Hispanic women are less likely than 
whites to enter into early prenatal care. Fetal Alcohol Syndrome 
disproportionately impacts American Indian, Alaska Native, and African 
American babies. (Healthy People 2010).
    The NCMHD has Health Disparities Centers of Excellence in six 
states including Alabama, Florida, Georgia, Texas, Iowa, and Wisconsin 
that focus their efforts to improve the health of mothers and their 
infants. One of these, the ``Mexican-American Women's Health Project 
Center'' at the University of Texas, El Paso, partners with established 
Hispanic health disparities researchers at the University of Arizona. 
Their research efforts focus on modifying behaviors of Mexican-American 
women relating to alcohol use; maternal health and nutrition; smoking 
cessation; and the pursuit of recommended Pap and HPV screening tests. 
Another Center at the University of Northern Iowa focuses on maternal 
and child health disparities to address the special health needs of 
Iowa's minority groups, which include urban African Americans, members 
of the Meskwaki Indian Tribe, rural families, growing populations of 
Latino and East African immigrants, and refugees from Bosnia and the 
former Soviet Union.
    The NCMHD also supports six Health Disparities Ambassadors through 
its Loan Repayment Programs, who are focusing their attention on infant 
mortality health disparities. These efforts is take place in Florida, 
Maryland, Michigan, Missouri, North Carolina, and Pennsylvania. Ongoing 
efforts include evaluating the link between sexually transmitted 
diseases and infant mortality; determining leading health indicators 
for women and girls; and creating logic models for maternal, child, and 
family health programs.

                              RURAL HEALTH

    Another top priority of the NCMHD is improving rural health across 
the nation. In pursuit of this goal, the NCMHD established an 
innovative Health Disparities Center of Excellence partnership between 
Clemson University and Voorhees College, a Historically Black 
Institution in South Carolina. This partnership will build capacity for 
research, training, and outreach to address health disparities in rural 
Hispanic and African American communities in South Carolina. The 
Tuskegee University and the University of Alabama, Tuscaloosa Health 
Disparities Center of Excellence partnership, in conjunction with the 
University of Alabama Institute for Rural Health Research and community 
organizations, focuses on adult immunization, infant mortality, cancer, 
and diabetes.
    Over the past year, the NCMHD also created opportunities to include 
the expertise of other NIH ICs in addressing the needs of rural 
communities, forming 16 new rural health partnerships with the NCI, 
NHLBI, NIAAA, NIDA, NIEHS, NIMH, and the NINR. Examples of these new 
projects include the Appalachia Cancer Network; the Deep South Network 
for Cancer Control; the Rural Caregiver Telehealth Intervention Trial; 
and studies on the effects of alcohol and violence on rural women; 
coronary artery disease in Alaska Natives; migrant worker health and 
the environment; mental health treatment for rural Mexican Americans, 
African Americans, women, and the poor; cardiovascular health training 
and outreach in Latino communities; and substance abuse among Ojibwe 
children and youth.

                               CONCLUSION

    The diversity of the American population is one of the greatest 
assets of the nation. One of the greatest challenges facing the nation 
is reducing and eliminating the profound disparity in health status 
that exists for many of its populations. Without decisive action now, 
the health challenges of the 21st century will expand along with the 
increasing number of racial and ethnic minorities, inhabitants of rural 
areas, and low socioeconomic populations.
    The NCMHD will continue to combat health disparities through our 
flagship programs. We will explore new opportunities to support 
academic development for the health disparity researchers of tomorrow. 
We will seek to create innovative programs to serve as a bridge between 
NCMHD capacity building programs and an investigator's first 
independent research effort. Cognizant of the value of engaging 
communities in the elimination of health disparities, we will lead 
efforts to conduct effective community-based outreach and research to 
our numerous constituents. We will continue our legacy of creating and 
nurturing partnerships to further increase the reach of our activities 
to eliminate health disparities and we will encourage our fellow NIH 
ICs to join the core health disparities programs of the NCMHD. The NIH 
Roadmap Initiative should also provide opportunities for the NCMHD 
constituent populations and research community to participate in 
interdisciplinary research, clinical research, and technology.
    Our vision of the future is a collective one that is embodied in 
the NIH Health Disparities Strategic Plan. With leadership, commitment, 
and strong scientific partnerships the NIH can advance scientific 
discovery to ensure the health of all Americans. Working together, we 
can turn the vision of an America where all citizens have an equal 
opportunity to live long, healthy, and productive lives into reality.

                                 ______
                                 
            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 2005, a sum of $1,094,141,000, 
including support for AIDS research, which reflects a net decrease of 
$84,815,000 over the comparable fiscal year 2004 appropriation, due 
entirely to the phasing out of extramural construction projects for 
fiscal year 2005.
    It is a pleasure once again to have the opportunity to present the 
accomplishments of NCRR-supported investigators and the future 
directions for NCRR programs. As a component of the National Institutes 
of Health, NCRR enables all lines of health-related discovery by 
supporting the creation and development of critical research resources 
and technologies. Because significant discoveries can be made at a 
variety of levels--from molecules to patients, or even patient 
populations NCRR supports a wide range of research resources across 
several disciplines. These resources include state-of-the-art clinical 
research environments, such as the nationwide network of General 
Clinical Research Centers. The GCRCs facilitate clinical research and 
protect the safety of participants in research. Each year more than 
10,500 NIH-supported investigators conduct nearly 8,000 research 
projects at the GCRCs, predominantly through more than a half million 
outpatient research visits.
    NCRR also supports research resources that develop and enhance 
scientific access to advanced technologies, nonhuman models for the 
study of human diseases, and career development and training. Because 
of its trans-NIH focus, NCRR is well-positioned to facilitate research 
by promoting the sharing of research tools and technologies as well as 
providing the tools for research collaborations so that research teams 
may address more complex research problems.

                     TECHNOLOGY AND INSTRUMENTATION

    NCRR strives to ensure that neither the lack of research resources 
nor technology development becomes rate-limiting for research. Two 
Nobel Prize winners in 2003 can vouch for the importance of having 
ready access to NCRR-supported resources. Dr. Roderick MacKinnon of 
Rockefeller University, co-recipient of the Nobel Prize in Chemistry, 
was honored for his groundbreaking studies of the structures and 
functions of ion channels, which control the movement of electrically 
charged atoms across cell membranes. Ion channel malfunctions can 
trigger a host of human disorders, including irregular heart rhythms 
and seizure disorders. Dr. MacKinnon noted that his award-winning 
discoveries depended on having access to the scientific expertise and 
advanced research instrumentation available at NCRR-supported resources 
that specialize in mass spectrometry and crystallography of complex 
molecules.
    The challenge for NCRR is to keep pace with the biomedical 
community's changing needs for research tools and to ensure that 
tomorrow's research queries have tomorrow's critical instrumentation 
and technologies in hand. The research resources and tools needed for 
scientific investigations change dramatically over time as more complex 
research queries are posed and require new technologies. Many research 
tools now considered critical to understanding the cause of disease and 
protecting the health of Americans were unheard of just a few years 
ago. For instance, the Magnetic Resonance Imagers, or MRIs, now found 
in hospitals and medical centers across the country were rare and 
experimental less than 20 years ago. Dr. Paul Lauterbur of the 
University of Illinois, Urbana-Champaign, depended on NCRR for many of 
his investigations into magnetic resonance imaging. Dr. Lauterbur was 
co-recipient of the Nobel Prize in Physiology or Medicine for his 
studies that led to the development of MRI. From 1990 to 2000, Dr. 
Lauterbur headed an NCRR-funded magnetic resonance research center, 
which helped to facilitate the evolution of MRI into the invaluable 
diagnostic and clinical research tool that it is today.

                      CLINICAL RESEARCH RESOURCES

    Just as NCRR technology and instrumentation resources laid the 
foundation for critical discovery in the basic and applied sciences, 
NCRR also catalyzes clinical and patient-oriented research through the 
network of GCRCs. In addition, NCRR develops and supplies investigators 
with clinical-grade biomaterials, such as vectors for gene therapy and 
human pancreatic islets for transplantation into patients with type 1 
diabetes.
    Research on rare diseases is one area where the GCRCs are ideally 
positioned to catalyze clinical research. Rare disease research is 
challenging in part because few patients with a particular rare disease 
can be recruited from any one clinical center. The nationally 
distributed network of the GCRCs makes them well-suited for enabling 
multicenter studies of rare conditions. Therefore, NCRR has partnered 
with the NIH Office of Rare Diseases and other groups to launch a 
network of Rare Diseases Clinical Research Centers. The network 
provides researchers with access to sufficient numbers of affected 
patients for statistically meaningful studies. The network also 
facilitates collaborations among scientists from multiple disciplines 
and institutions.
    To ensure the safety of human subjects participating in clinical 
research projects, clinical investigators must adhere to Federal, state 
and local regulations, policies, and guidelines. Yet these necessary 
responsibilities place heavy demands on the time of already-busy 
clinician investigators. To address this issue, NCRR established a new 
GCRC staff position known as the Research Subject Advocate (RSA). The 
RSA assists GCRC investigators, nurses, and staff to underscore the 
safe and ethical conduct of clinical studies and represents the 
interests of research participants. NCRR plans to extend and strengthen 
the role of RSA in an approach that complements that undertaken by the 
host institution.

                           HEALTH DISPARITIES

    NCRR also supports clinical research studies on health disparities, 
or diseases that disproportionately affect racial and ethnic minority 
populations. NCRR has joined with the National Institute of Mental 
Health to establish three Comprehensive Centers on Health Disparities. 
These Centers will further develop the capacity of Research Centers in 
Minority Institutions' (RCMI) medical schools to conduct basic and 
clinical research in type 2 diabetes and cardiovascular disease, both 
of which disproportionately affect minority populations. The Centers 
will provide support to further develop the requisite research 
infrastructure, recruit magnet clinical investigators, recruit and 
develop promising junior faculty, and facilitate substantial 
collaboration between the RCMI grantee institutions and more research-
intensive universities. NCRR also supports a Stroke Prevention and 
Intervention Research Program that focuses on minorities, as well as a 
mentored clinical research career development program to provide 
clinical research training for doctoral and postdoctoral candidates in 
minority institutions.

                  BIOINFORMATICS AND COMPUTER NETWORKS

    Whether studying clinical manifestations of disease or the basic 
biology of cells and tissues, today's biomedical researchers generate 
vast data sets. This data deluge has increased scientific demand for 
access to scaleable computation and modern management tools. A related 
and equally important trend is the fact that biomedical research 
projects are becoming broader in scope. For example, neuroscientists 
now want to correlate brain images with events at cellular and 
molecular levels, including gene expression. These broad research 
projects require large multidisciplinary teams, gathered from 
scientists distributed across the country.
    To meet the challenges associated with these trends, NCRR supports 
the development of bioinformatics tools, including the software 
programs or algorithms that help scientists manage and analyze their 
data. NCRR also is instrumental in the creation of high-performance 
computer networks that link laboratories throughout the United States. 
A few years ago, NCRR joined with the National Science Foundation, 
Internet2, and investigators from several universities to establish the 
Biomedical Informatics Research Network (BIRN). The BIRN provides the 
tools for researchers to pool their data and to use federated databases 
so that they can oversee the integrity of their data, use 
bioinformatics tools for data mining, and visualize their data. In 
fiscal year 2004, NCRR began expanding the number of BIRN sites in 
order to establish a national infrastructure of bioinformatics tools 
and provide access to scaleable computing that, in turn, is linked to a 
nationally distributed network of modern imaging capabilities for 
studies of degenerative brain disorders.
    Other components of the BIRN network will link underserved 
institutions, such as doctoral degree-granting minority institutions 
and institutions in states that have received limited NIH research 
funding because they include very few research trained investigators, 
otherwise known as Institutional Development Award (IDeA) states. The 
networks will foster collaborative research and help investigators 
create a virtual critical mass of investigators. The BIRN also will 
foster collaborations across institutions located at remote sites. NCRR 
plans to establish a network for institutions with medical schools that 
are associated with NCRR's Research Centers in Minority Institutions 
(RCMI) Program. This electronic network will facilitate their 
participation in large clinical trials and other research studies and 
help define the factors contributing to health disparities among 
minority populations and ways to overcome those factors.
    In concert with other NIH components, NCRR participates in many NIH 
Roadmap initiatives for example, development of a National Electronic 
Clinical Trials and Research (NECTAR) network, which will form the 
backbone for all clinical research networks. An important component of 
NECTAR will be the standardization of patient data collection and 
storage procedures, which will facilitate data sharing by 
investigators. NCRR also supports other trans NIH Roadmap initiatives, 
including the National Centers for Biomedical Computing, Exploratory 
Centers for Interdisciplinary Research, and National Technology Centers 
for Networks and Pathways.

                               PROTEOMICS

    The availability of complete genomes for a variety of organisms 
provides an important first step in understanding many complicated 
biological questions, including the molecular basis for disease. The 
next step in this process will be to develop technologies to quantitate 
spatiotemporal differences in the levels of gene expression, assess 
post-translational modifications of proteins, and characterize protein-
protein interactions in both healthy and diseased cells.
    NCRR will support the development of the necessary technology and 
infrastructure to advance the science of proteomics. An advanced 
proteomics center will focus on multiple technologies, including 
techniques for protein purification, structural techniques, mass 
spectrometry, and DNA microarray instrumentation along with the 
necessary bioinformatics.

                               CONCLUSION

    I have today noted two important trends in biomedical research the 
rapid accumulation of data and the broadening scope of research 
studies. To these, I must add a third trend namely, the increasingly 
collaborative nature of biomedical science. Some of today's most 
pressing questions in biomedical science are so complex, so 
multifaceted, that they cannot be addressed by a single investigator or 
even a single research laboratory. In many cases, teams of scientists 
with diverse skills and backgrounds are needed to get the job done.
    It is my belief that this emphasis on interdisciplinary 
collaborations, as evidenced by the multiple NIH Roadmap initiatives 
related to this area, will bring about unprecedented gains in 
biomedical science, and ultimately lead to improved health of all U.S. 
citizens. Finally, as the research paradigm evolves toward greater 
complexity, the infrastructure required to support that research must 
evolve too.
    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 2005 President's budget request for the National 
Institute of Child Health and Human Development (NICHD). The fiscal 
year 2005 budget includes $1,280.9 million, an increase of $39.1 
million over the comparable fiscal year 2004 appropriation of $1,241.8 
million.
    The NIH Roadmap provides the schema to guide the NICHD in achieving 
its programmatic and research goals.
    Today I would like to share with you how the research supported by 
this committee is improving the lives of children, mothers, adults and 
families, and helping to reduce health disparities. The NICHD is 
participating in the trans-NIH obesity initiative identifying how 
primary care physicians can help children maintain a healthy weight.

                   ENCOURAGING HEALTHY BIRTH OUTCOMES

    Preeclampsia is a condition that affects five out of every hundred 
women who become pregnant. Preeclampsia can occur suddenly, and without 
warning, causing women to develop dangerously high blood pressure. In 
some cases, the condition may progress to eclampsia in which women 
experience potentially fatal seizures. Infants born to mothers with 
preeclampsia may be extremely small for their age or may be born 
prematurely, putting them at risk for a variety of other birth 
complications. Although a woman's high blood pressure and seizures can 
be treated, the only cure for preeclampsia is delivery of the baby. In 
a significant step toward treating preeclampsia, researchers have 
identified substances in the blood that have the potential to predict 
who will develop preeclampsia. This knowledge may help us treat women 
before preeclampsia becomes a serious problem, for them and their 
infant.
    We have also intensified our research in the area of stillbirth, a 
devastating occurrence that affects far too many families. Health care 
providers use the term stillbirth to describe the loss of a fetus after 
the 20th week of pregnancy. Stillbirth can occur before delivery or as 
a result of complications during labor and delivery. In at least half 
of all cases, researchers can find no cause for the pregnancy loss. We 
hope to change that. The NICHD has established the Stillbirth 
Collaborative Network, which consists of research centers in Texas, 
Utah, Rhode Island, and Georgia. In each center, a team of specialists, 
including obstetricians, nurses, statisticians, and even grief 
counselors will seek to understand the causes of stillbirth and 
eventually find ways to prevent these deaths.
    One way to increase the chances of a healthy pregnancy and healthy 
birth outcome is to avoid alcohol during pregnancy. Infants born to 
mothers who drink heavily during pregnancy are known to be at risk for 
mental retardation and birth defects. They are also at increased risk 
for Sudden Infant Death Syndrome (SIDS). NICHD researchers have now 
identified another reason that women should not consume alcohol during 
pregnancy: exposure to alcohol before birth affects the developing 
nervous system in the arms and legs.
    Recently, scientists in NICHD's Maternal-Fetal Medicine Units 
Network reported a breakthrough in reducing a major cause of infant 
mortality and the subsequent long term health problems associated with 
prematurity. The scientists, working collaboratively in 14 academic 
health centers across the United States, demonstrated that progesterone 
administered to women at risk for premature birth could significantly 
reduce the likelihood of early delivery. This was a very significant 
discovery and we were delighted that others recognized its importance. 
A few weeks ago, Parade magazine identified this discovery as one of 
the ten most significant health advances of the past year.

           NEW FRAGILE X CENTERS TO DEVELOP TREATMENT OPTIONS

    In 2003, the NICHD funded three new Fragile X research centers. 
Teams of researchers at each of the centers located in North Carolina, 
Texas, and Washington state are developing new ways to diagnose both 
the mild and severe forms of the condition, as well as new treatments. 
Fragile X syndrome is the most common genetically-inherited form of 
mental retardation currently known. It occurs in 1 out of every 2,000 
males and in 1 in 4,000 females. The syndrome is caused by a mutation 
in a specific gene, known as FMR1, on the X chromosome. In its fully-
mutated form, the FMR1 gene interferes with normal development, 
resulting in mental retardation. In a partially mutated form, the FMR1 
gene can cause fragile X syndrome in the children of a parent who is a 
carrier. Until recently, it was thought that carriers did not have any 
symptoms. Researchers have learned that some people with a form of 
fragile X have mild cognitive and emotional problems. In addition, some 
female carriers are likely to undergo premature menopause. In older 
male carriers, the fragile X is associated with a neurological 
degenerative syndrome. Identifying a means to predict which carriers 
will develop the symptoms could be a first step toward developing new 
treatments for these often overlooked symptoms. The Fragile X Research 
Centers are focusing their research on how the fragile X affects the 
developing brain and nervous system, how the disorder progresses 
throughout an individual's life span, and treatments that can improve 
the behavior and mental functioning of people with fragile X syndrome.

            IMPROVING TREATMENT FOR CRITICALLY ILL CHILDREN

    Critical care medicine for children is an emerging field where, in 
general, physicians continue to rely upon adult treatments that have 
not yet been tested for effectiveness in a young population. To change 
this situation, the NICHD will help establish a national pediatric 
critical care research network to develop and evaluate treatments for 
children with disabling conditions. The initiative will foster 
collaborations among scientists in many different fields and will 
support research such as the best approach to care for children with 
brain injury, the most effective way to transition a critically ill 
child from an acute care to a rehabilitation setting, and the care of 
critically ill children in the event of a bioterrorism attack.

             CUTTING OBESITY THROUGH RESEARCH AND PROGRAMS

    The increase in overweight and obesity among adults and children is 
a major public health concern. In fact, in a recent analysis of 
international data, NICHD researchers documented that U.S. teenagers 
were more overweight than youth in 14 other developed countries. Like 
many other health conditions that affect adults, the antecedents of 
adult obesity can be found in childhood. Young children who are 
overweight are likely to be overweight as adults. There is no single 
explanation for the increase in childhood overweight and there is no 
single solution. However, we know we must devise successful 
interventions that help children maintain a healthy weight. As part of 
the trans-NIH initiative, the NICHD will lead a major effort to 
determine whether a weight control program for children and youth led 
by primary care physicians as part of a comprehensive community-based 
effort can be successful. Currently, most weight management programs 
are administered through specialty clinics. However, there is strong 
evidence that an appropriate intervention by a physician can have a 
significant impact on personal behaviors such as tobacco use. Effective 
weight management programs in a primary care setting would be 
accessible to large numbers of children and would minimize the 
geographic, social, and economic barriers that commercial weight 
management programs can impose.
    We are also developing an exciting research-based program that 
helps to teach young children the fundamentals of good nutrition and 
physical activity as well as how to make sense of the messages that 
appear in the media. Three years ago, this committee provided funds to 
the NICHD and other health agencies to develop programs that encourage 
young people to engage in healthy behaviors. In response to this 
directive, the NICHD has developed ``Media Smart Youth,'' an after 
school program for children between nine and 13 years of age. The 
program focuses on good nutrition and physical activity. But it also 
provides skills to young children to interpret the messages about food 
and snacks they see on television, in magazines, and on the Internet. 
As part of their activity, the children who take part in Media Smart 
Youth develop messages about the importance of good nutrition and 
physical activity for their peers. The program has been tested with 
youth groups around the country. In fact, the children at P.S. 127 in 
the Bronx who took part in this program developed a message about 
physical activity for young people that appeared for 30 minutes on the 
Panasonic ``jumbotron'' screen in Times Square.

               HELPING YOUNG CHILDREN PREPARE FOR SCHOOL

    The preschool years are crucial for learning language, social 
skills, and developing the intellectual capabilities that set the stage 
for later success in school. Yet, comparatively little is known about 
how to help young children obtain the greatest benefit possible from 
the preschool experience. In December 2003, NICHD joined with two other 
HHS agencies and the Department of Education, and launched a five year 
research initiative to find the best ways to help preschoolers at risk 
for failure in school acquire the skills they need for school success. 
The initiative provided $7.4 million in funding for the first year. 
Eight projects were funded to test research-based approaches to 
preschool curricula, Internet based approaches to training preschool 
teachers, and the importance of parental involvement for preparing 
children to enter school. Funds requested for fiscal year 2005 will 
allow us to expand this effort by funding academic researchers and 
small businesses to develop and produce more effective measurements of 
outcomes from preschool interventions.

                SIDS RESEARCH SUPPORTS PROGRAM OUTREACH

    We have known for more than 10 years that placing infants on their 
backs to sleep reduces their risk of Sudden Infant Death Syndrome 
(SIDS). In fact, since the NICHD launched the Back to Sleep SIDS risk 
reduction campaign in 1994, the rate of SIDS in the United States has 
declined by more than 50 percent. The NICHD continues a vigorous 
research program to learn more about the causes and prevention of SIDS. 
For instance, a team of NICHD-funded researchers in Ohio recently 
discovered that infants who were placed to sleep on their backs were 
less likely to develop fevers, get stuffy noses or develop ear 
infection. Ear infections alone cost the health care system an 
estimated $5 billion a year. So this simple behavior of placing infants 
on their backs to sleep not only saves lives, it can save the health 
care system large sums money by reducing the use of antibiotics to 
treat ear infections. We also learned that infants who are normally 
placed to sleep on their backs are at greatly increased risk of SIDS 
when they are occasionally placed to sleep on their stomachs. New 
research on SIDS continues to shape our SIDS risk reduction outreach 
campaign. More recently, a major focus of the campaign has been 
reducing the risks of SIDS in African American communities.
    SIDS rates for African American babies have declined significantly 
since the NICHD initiated its Back to Sleep campaign ten years ago. 
Yet, the SIDS rate for African American infants is more than twice that 
of white infants. To address this health disparity, the NICHD joined 
forces with three national African American organizations in a unique 
collaboration to reduce the risks of SIDS in African American 
communities. The Alpha Kappa Alpha Sorority, the National Coalition of 
100 Black Women, and the Women in the NAACP, sponsored three regional 
summit meetings to raise SIDS awareness and train community leaders to 
be resources and spokespersons for SIDS risk reduction in their 
communities. The summit meetings were held in Tuskegee Alabama, Detroit 
Michigan, and Los Angeles California, and they helped build an 
infrastructure to involve faith-based, community, and service 
organizations in reducing the risks of SIDS and in promoting the health 
of infants. In Detroit, for instance, the summit ended with a ``SIDS 
Sunday,'' which was held at Hartford Memorial Baptist Church on the 
Sunday following that summit. Afterwards, other churches across the 
region held a ``SIDS Sunday,'' where pastors shared SIDS information 
from their pulpits, in their church bulletins, and with nurses and care 
givers in their childcare centers and nurseries. The successful 
collaboration of researchers, government officials, and the community 
will create a strong foundation for launching other interventions to 
eliminate health disparities.

         MOTHERS LEAVING WELFARE HAD NO EFFECT ON PRESCHOOLERS

    A study that received much of its funding from the NICHD 
demonstrated that when a mother leaves welfare to enter the labor 
force, it does not seem to have any negative effects on preschoolers or 
young adolescents. The study was undertaken in response to the Personal 
Responsibility and Work Opportunity Reconciliation Act of 1996, which 
mandated stricter welfare requirements for all welfare recipients. The 
researchers theorize that the positive and negative effects of going 
off welfare and getting a job may cancel each other out. For example, 
the increase in family income that comes with leaving welfare thought 
to relieve the stress on a family may make up for the decreased amount 
of time that mothers spend with their young children. In addition, 
mother's transition to work had a slightly positive effect on teens, 
reducing the teens' levels of anxiety. Conversely, teens whose mothers 
left the job market and went on welfare developed increased anxiety 
levels.

     MICROBICIDES THAT CAN PREVENT SEXUALLY TRANSMITTED INFECTIONS

    The NICHD is funding a number of projects to develop microbicidal 
compounds to prevent the spread of sexually transmitted infections and 
HIV. These compounds not only have the potential to prevent the spread 
of disease-causing bacteria and viruses, but may also be effective in 
preventing pregnancy. One project is a large scale test of the 
contraceptive effectiveness of Buffergel, a compound that kills the 
microorganisms that cause sexually transmitted diseases, and shows 
promise as a contraceptive. Another project is studying a microbicidal 
spermicide, C31G. The compound's effectiveness will be compared to that 
of a conventional spermicide preparation. Working with the National 
Institute of Allergy and Infectious Diseases, the NICHD has funded a 
new system to test the quality of potential microbicides to determine 
if they warrant further testing in human beings.

                   SAFER DRUGS FOR USE WITH CHILDREN

    In January 2002, President Bush signed into law the Best 
Pharmaceuticals for Children Act (BPCA). The law recognizes that drugs 
may have different effects in children than they do in adults, and 
seeks testing for drugs given to children. For roughly 75 percent of 
the drugs approved by the U.S. Food and Drug Administration (FDA) for 
adults, there is inadequate information available to ensure the safety 
and effectiveness of the drugs in children. Moreover, there is little 
or no data to guide physicians in prescribing dosages of these drugs 
for children. Working in close collaboration, the NICHD and the FDA, as 
directed by the BPCA, identified several high priority drugs to be 
tested. The NICHD is currently establishing partnerships with pediatric 
drug study networks in other NIH Institutes to expedite the study of 
other clinically important drugs.
    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 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.

                       NATIONAL CHILDREN'S STUDY

    In a few short years, The National Children's Study has evolved 
from a concept to an exciting research collaboration poised to answer 
critical questions about child development. The fiscal year 2005 budget 
request continues planning dollars for this important project, but does 
not reflect funding to launch the study itself, since it is still being 
developed. The National Children's Study plans to examine the effects 
of environmental influences on the health and development of more than 
100,000 children across the United States, following them from before 
birth until age 21. The NICHD serves as the lead agency on this 
ambitious project, working closely with the National Institute of 
Environmental Health Sciences, the Centers for Disease Control and 
Prevention, and the U.S. Environmental Protection Agency. The 
collaboration involves government agencies, the research community, 
industry, and community groups.

                   NIH ROADMAP AND CLINICAL RESEARCH

    To ensure that the necessary clinical research workforce is 
available to translate laboratory findings to improved treatments for 
patients, the NIH Roadmap is strengthening several stages in the career 
path for these researchers. One new program will provide clinical 
research experience and didactic training during medical and dental 
school. Another will train doctorate-level professionals in multi 
disciplinary collaborative clinical research settings that reflect the 
diversity of today's clinical research team. To attract community 
practitioners to clinical research, the NIH plans to create a cadre of 
National Clinical Research Associates, community practitioners trained 
in clinical research who will refer patients to large clinical trials 
to enhance patient recruitment and more rapidly test potential 
therapies. The NIH is also identifying ways to improve peer review of 
clinical research grant applications and to enhance promotion and 
tenure policies in academia for clinical researchers.

                                 ______
                                 
               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 2005, a sum 
of $1,876,196,000, which includes $150 million for the Special 
Appropriation for Research on Type 1 Diabetes through Sec. 330B of the 
Public Health Service Act. The NIDDK transfers some of these funds to 
other institutes of the NIH and to the Centers for Disease Control and 
Prevention (CDC). Adjusted for mandatory funds, this is an increase of 
$54,956,000 over the fiscal year 2004 enacted level of $1,821,240,000 
comparable for transfers proposed in the President's request.

                   HIGHLIGHTS OF PROGRAM ENHANCEMENTS

    I appreciate the opportunity to testify on behalf of the NIDDK's 
efforts to combat the wide range of debilitating, chronic health 
problems within our research mission, many of which are caused directly 
or indirectly by obesity. Last year, I reported the creation of an 
NIDDK Office of Obesity Research to intensify the fight against this 
major public health problem, which is harmful both in its own right and 
as a driver of type 2 diabetes, especially in minorities and the young. 
Obesity can also be a contributing factor to nonalcoholic fatty liver 
disease, gallstones, end-stage kidney disease, and urinary 
incontinence. According to the CDC, approximately 64 percent of adults 
and 15 percent of children and teens are considered either overweight 
or obese. Disturbingly, these rates reflect skyrocketing trends over 
the past two decades. To accelerate research to combat this epidemic, 
the NIH Director established the NIH Obesity Research Task Force in 
April 2003, with co-chairmanship by the Directors of the NIDDK and the 
National Heart, Lung, and Blood Institute (NHLBI). I am pleased to 
report that the Task Force has completed a draft Strategic Plan for NIH 
Obesity Research, with input from external scientific and lay experts. 
This Plan is posted on a newly established Web site that will alert 
investigators to NIH obesity research funding opportunities, and also 
inform the public about NIH efforts. Both the Plan and the Web site are 
dynamic, and will evolve with changes in science and public health 
needs. Acting alone, the NIH cannot halt or reverse obesity; however, 
by generating and disseminating new research knowledge, we can lend a 
vital scientific dimension to what must truly be a multifaceted 
national effort.
    The Strategic Plan will contribute to the prevention and treatment 
of obesity by bolstering research in three major avenues: (1) 
behavioral and environmental approaches to modify lifestyle; (2) 
pharmacologic, surgical, or other biological/medical approaches; and 
(3) ways to break the link between obesity and its associated health 
conditions, known as co-morbidities. Within the goals and strategies 
outlined in the Plan, the NIDDK will have a major role in three trans-
NIH initiatives.
    The first is an effort to combat pediatric obesity in site-specific 
ways--both in primary-care settings, and in other community settings, 
such as the home, day-care, pre-school, school, and other venues. 
Researchers will explore effective methods for the primary prevention 
of inappropriate weight gain among children and adolescents who are not 
overweight; secondary approaches to prevent further weight gain among 
those already overweight or obese; and tertiary efforts to prevent co-
morbidities. We will build on studies the NIDDK is already pursuing to 
evaluate the effects of so-called ``natural experiments'' in which 
States or localities are changing the food and lifestyle choices and 
cues that students encounter in school settings. We will also build on 
studies to determine the effects of modifying the home environment, 
such as the influence of T.V.-watching on obesity, eating behavior, and 
physical activity. Our children are precious, and we should do all we 
can to spare them the serious health problems that can attend a 
lifelong struggle with obesity.
    A second trans-NIH initiative will focus on the neurobiological 
basis of obesity, which includes the intricate brain-gut circuits that 
signal hunger and fullness, and thus are crucial to maintaining the 
body's energy balance between calories consumed as food and expended in 
physical activity. I previously reported on several hormones that 
mediate energy-related signals, such as leptin, adiponectin, and 
ghrelin. By exploiting these and other findings through innovative 
collaborations between biomedical and behavioral researchers, we will 
delineate the many pathways that modulate the control of eating 
behavior in humans.
    In a third trans-NIH initiative, the NIDDK will take the leadership 
role in creation of an Intramural Obesity Clinical Research Program to 
capitalize on the unique, collaborative infrastructure of the NIH 
Clinical Research Center. This Program will foster multidisciplinary 
approaches to obesity research in areas such as metabolism, 
endocrinology, nutrition, cardiovascular biology, liver and other 
digestive diseases, genetics, and the behavioral sciences. A ``magnet'' 
approach will draw upon the extensive expertise and resources of the 
NIH intramural program to frame state-of-the-art clinical investigative 
strategies and harness emerging technologies.
    In addition to these trans-NIH initiatives, the NIDDK will support 
a range of research, including ancillary studies to maximize the 
resources already invested in ongoing clinical trials. We will pursue 
challenging questions about obesity. What factors control where fat is 
deposited, and the relationship between its location and differences in 
metabolism, fat-cell regeneration, cell signaling, and associated co-
morbidities of obesity? What is the relationship between obesity and 
abnormal levels of circulating and stored lipids, which are a hallmark 
of metabolic problems? Can we identify biomarkers of change brought on 
by the obese state? What genetic abnormalities underlie the co-
morbidities of obesity? What steps can people take to achieve long-term 
maintenance of weight loss?
    As obesity is escalating in the United States, so is type 2 
diabetes. New estimates from the CDC place the number of people with 
diabetes at 18.2 million, and about 90-95 percent of them have this 
form of the disease. Disturbingly, about 5.2 million of those affected 
are unaware. Millions of adults also have a condition called ``pre-
diabetes,'' in which glucose levels are elevated, but not as high as in 
full-blown diabetes. Because clinical trials have demonstrated that 
lifestyle and medical interventions can significantly delay or prevent 
disease onset in those at high risk, it is critical to identify these 
individuals and underscore the preventive actions they can take. The 
NIDDK is taking vigorous steps to foster the generation of new 
laboratory tests to improve diabetes detection, as well as to promote 
the development of more cost-effective strategies to pinpoint those at 
risk who can benefit most from early intervention. We are also 
supporting studies to translate important advances from clinical trials 
in diabetes prevention and care into medical practice. For example, for 
a low-income Latino population, we are supporting a clinical trial to 
compare current translation efforts for type 2 diabetes prevention with 
a method that incorporates culturally-sensitive strategies. We are also 
studying an interactive video conferencing system to enable 
communication between health professionals at a large medical center 
and diabetes patients in a rural state, with limited access to health 
care providers. Interventions that are successful in these trials could 
pave the way to widespread use by communities throughout the country.
    Once considered an ``adult-onset'' disease, type 2 diabetes is 
being increasingly diagnosed in children and adolescents, especially in 
minority populations. We are launching a multi-center, school-based 
trial (STOPP-T2D) to find ways to prevent the development of risk 
factors for type 2 diabetes in middle-school children. The trial will 
include school-based programs targeting nutrition, physical activity, 
and behavior modification. Another multicenter trial (Treatment Options 
for Type 2 Diabetes in Adolescents and Youth TODAY) will seek the best 
treatment strategies.
    Diabetes can lead to serious complications, such as blindness, 
irreversible kidney failure, lower limb amputation, and heart disease. 
We have established an NIDDK Diabetes Complications Working Group, 
which is charged with seamless integration of these activities across 
the Institute. The NIDDK also recently convened an international group 
of clinical and basic researchers to brainstorm research approaches to 
the urologic complications of diabetes. Because complications can 
affect many organs, we collaborate with other components of NIH and the 
Department to benefit from their expertise. For example, studies have 
shown that the process of new blood vessel formation, called 
``angiogenesis''--traditionally studied in relation to cancer--is also 
critically important to vascular changes in diabetes, such as the 
dangerous proliferation of blood vessels in the eye that can lead to 
blindness. Angiogenesis will be the central theme of a new research 
collaboration involving multiple NIH institutes.
    In an aggressive research program on type 1 diabetes, we have 
established unique, innovative, and collaborative research groups, 
clinical trial networks, and consortia, with an overarching group to 
standardize and coordinate their efforts. We are also working to 
overcome barriers that currently prevent widespread clinical research 
on islet transplantation to restore normal insulin-producing capacity 
to patients. In collaboration with the National Institute of Allergy 
and Infectious Diseases (NIAID), we are establishing a national 
consortium to step up progress toward general clinical applicability of 
islet transplantation.
    To spur research in digestive diseases, the NIDDK recently 
established a new Liver Disease Branch within its Division of Digestive 
Diseases and Nutrition. With expert external input, this Branch is now 
spearheading the development of a Liver Disease Research Action Plan 
under the auspices of the Digestive Diseases Interagency Coordinating 
Committee. As requested by the Congress, the NIDDK is submitting a 
report on actions taken by the NIH and other HHS components in response 
to recommendations from a Consensus Conference on hepatitis C. In other 
research, broad approaches are providing insights into the inflammatory 
bowel diseases--Crohn's disease and ulcerative colitis. Fundamental 
studies are shedding light on the development of pathways that control 
gut motility; integration of pain, motility and behavioral neural 
circuits; and gut inflammation.
    For polycystic kidney disease (PKD), a research consortium has 
established the value of Magnetic Resonance Imaging for measuring 
kidney size. This advance portends dramatic improvements in assessing 
disease progression--a critical step in developing and evaluating new 
treatments. The HALT-PKD Network is testing a regimen designed to lower 
blood pressure and slow disease progression--the first of several 
clinical studies envisioned. A workshop on oxalosis and primary 
hyperoxaluria--an inherited cause of kidney stone disease--has 
identified future clinical research directions, which will apply 
emerging knowledge about underlying metabolic and genetic 
abnormalities. We have also launched or expanded initiatives on 
interstitial cystitis, urinary incontinence, and urinary tract 
infections, consistent with the scientific recommendations of the 
Strategic Plan of the Bladder Progress Review Group. A recently formed 
Interstitial Cystitis (IC) Epidemiology Task Force is guiding efforts 
in that area, as described in a requested report to the Congress.

                TRANSLATION RESEARCH AND ROADMAP EFFORTS

    Underpinning our disease-focused programs is an emphasis on 
``translation'' research, which benefits patients directly by bringing 
the fruits of laboratory discoveries into the arena of clinical 
research, and by propelling the positive results of clinical trials 
into medical practice. In one promising pilot effort to speed the 
development of therapies for type 1 diabetes, we are building on an 
innovative mechanism established by the NCI called ``Rapid Access to 
Intervention Development.'' We are also pursuing several translational 
efforts related to the NIH Roadmap for Biomedical Research. These 
include development of non-invasive methods for diagnosing and 
monitoring the progression of diabetes, kidney and digestive diseases; 
harnessing new technologies such as proteomics the study of proteins 
and their functions; as well as studying stem cells during human 
development and tissue repair. We are leading an NIH Roadmap initiative 
in ``New Pathways to Discovery'' by enhancing metabolomics--the study 
of networks within the cell, and constituents of the cell, such as 
carbohydrates, lipids, and amino acids. We are also playing a major 
role in Roadmap efforts to build ``Research Teams of the Future'' by 
spurring interdisciplinary research training. These efforts can benefit 
programs within the NIDDK mission by bridging scientific disciplines 
and catalyzing partnerships, such as collaborations between biomedical 
and behavioral researchers, which are so important to moving obesity 
research forward.
    Today, I have presented a cameo of our many and diverse research 
efforts and plans. Our research momentum has never been greater, and 
our commitment to improving health remains clear and strong.

                                 ______
                                 
              Prepared Statement of Dr. Sharon H. Hrynkow

    Mr. Chairman and Members of the Committee, I am pleased to present 
the President's Budget for the Fogarty International Center for fiscal 
year 2005, a sum of $67,182,000, which reflects an increase of 
$1,838,000 over the comparable fiscal year 2004 appropriation.
    I welcome this opportunity to relate Fogarty's progress over the 
past year and proposed plans for fiscal year 2005. Programs at Fogarty, 
developed with the support and guidance of the Administration and this 
Committee, reflect our nation's enduring commitment to achieve ``a 
healthy America, in a healthier world.'' These were the words of the 
late Congressman John E. Fogarty, Chairman of the House Appropriations 
Subcommittee from 1951 until 1967, and for whom the center is named. He 
championed research as the one truly global effort in which all nations 
can and will join as real partners.
    The health challenges facing the United States are many. Among the 
communicable diseases, AIDS and tuberculosis continue to challenge even 
the most sophisticated public health interventions. SARS emerged in 
Asia and washed upon our shores, as did West Nile Virus several years 
ago. And the emergence of avian flu in Asia and the United States is a 
compelling tale that is a harbinger of probable Asian flu pandemics yet 
to come. All told, the infectious threats cost our economy dearly. And 
as chronic disease such as cancer, cardiovascular disease, and mental 
health disorders increase year after year in the United States and 
world-wide, both treatment and prevention efforts must be applied. 
These challenges are shared with communities around the world.
    To address these challenges, Fogarty supports a broad range of 
research and training programs, each designed to tackle particular 
health problems shared by United States and foreign populations. Our 
particular focus is on improving the capacity of communities in poor 
settings to address health challenges. Accordingly, our emphasis has 
been on working with scientists and health professionals in low- and 
middle-income nations on shared health problems. Our programs identify 
research opportunities best addressed through international 
cooperation. Fogarty's efforts are multidisciplinary, embracing 
clinical, epidemiological, basic biomedical and social science 
research. They are multi-sectoral, closely coordinated with our sister 
institutes at NIH, the Centers for Disease Control and Prevention, and 
international organizations with health and development missions, 
including The World Bank and the World Health Organization. Moreover, 
the programs enhance foreign relations with governments and communities 
alike, and advance the historic humanitarian role of our nation. And 
importantly, our programs promote a global culture of science, founded 
on equal partnerships between scientists working across borders, in a 
culture of sharing of scientific information, peer review and sound 
management policies. Fogarty supports over twenty research and training 
programs in more than 100 countries, involving more than 5,000 
scientists in the United States and abroad.
    What follows is a selective summary of ongoing and planned Fogarty 
activities to support NIH international objectives and realize 
Congressman Fogarty's vision.

                         THE HIV/AIDS EMERGENCY

    HIV/AIDS has exacted a profound human toll in the United States and 
abroad, reversed gains in child survival in many nations, and 
threatened the economic stability of emerging markets by reducing the 
number of working men and women. Reducing the impact of HIV/AIDS in 
resource-poor countries, which bear the disproportionate burden of this 
disease, requires a strong national commitment on their part and 
international research cooperation to develop effective prevention and 
control strategies. The Fogarty AIDS International Training and 
Research Program (AITRP), now in its 16th year of operation, has been a 
major source of support for training a cadre of foreign medical 
scientists from developing countries needed to combat the global HIV/
AIDS pandemic. Working through U.S. universities, Fogarty has supported 
Masters level, Ph.D., and post-doctoral training for young scientists 
in countries most affected by the pandemic. These scientists are 
testing HIV/AIDS vaccines abroad, developing effective public health 
strategies to reduce transmission, and acquiring new knowledge for 
treatment for those already infected.
    Through the Fogarty AIDS Program, nearly 2,000 foreign researchers 
from over 100 countries have been trained in the United States, many at 
senior levels, and over 50,000 have trained in cutting-edge laboratory 
methodologies through workshops and courses conducted in those 
countries where HIV/AIDS is most devastating. This large international 
cadre of trained scientists has facilitated the implementation of new 
programs such as the Pediatric AIDS Foundation Call-To-Action, the 
President's initiative on prevention of maternal-to-infant transmission 
of HIV, and the President's Emergency Plan for AIDS Relief (PEPFAR). In 
addition, health scientists trained under the program have played vital 
roles in helping approximately 20 countries receive awards from the 
Global Fund for AIDS, TB and Malaria. As we work in partnership with 
colleagues around the world, the benefits of the Fogarty AIDS program 
accrue also in the United States. Interventions and strategies 
developed and tested abroad may have direct relevance to communities in 
the United States.
    Among research accomplishments in the past fiscal year, scientists 
at the University of North Carolina and the University of Malawi have 
identified a new and effective means to minimize postpartum 
transmission of HIV through implementation of an inexpensive two-drug 
antiretroviral regimen. This is of significance because low-income 
women in sub-Saharan Africa typically do not obtain medical attention 
during pregnancy and are usually uninformed of their HIV status until 
delivery. Effectively deployed, this intervention will mean that more 
newborn infants will have a chance to grow to be healthy adults, even 
where the lack of resources and other obstacles to extending medical 
care limit prenatal care and interventions.

                       CHANGING MICROBIAL THREATS

    HIV/AIDS is a cautionary example. The rapid emergence of new 
pathogens and re-emergence of infectious disease, believed to have been 
controlled or contained, presents a disturbing new chapter in the grim 
evolutionary battle between humans and microbes. This is the result of 
social and demographic trends, including increases in international 
travel and trading across borders, and changes in the genetic structure 
of microbes that increase virulence and transmission, and weaken the 
efficacy of existing drugs. Among major disease pathogens, malaria has 
resurged due to resistance of the parasite to available drugs and 
resistance of mosquitoes to insecticides. Malaria accounts for an 
estimated 2 million deaths per year with increasing mortality due to 
drug resistance and HIV-contaminated blood transfusions related to 
malaria-induced anemia.
    Building on the success of the AIDS training program, Fogarty 
launched in 1996 the International Training and Research in Emerging 
Infectious Diseases, a training program which builds expertise in 
microbiology, epidemiology, and laboratory methods as part of a broad 
effort to combat new and emerging diseases worldwide. Today, that 
program has been expanded to include other infectious diseases as the 
Global Infectious Disease Research Training Program, linking U.S. 
universities with counterparts around the world to advance research 
projects (through 27 Fogarty awards) and, importantly, to build the 
next generation of scientists able to combat emerging infections, such 
as SARS and West Nile Virus. Through this program, Fogarty is helping 
to address the infectious disease challenges of today while preparing 
for new pathogens yet to emerge tomorrow, as surely they will.
    A powerful new tool for malariologists and other infectious disease 
researchers concerns the use of sophisticated mathematics to predict 
the course of an epidemic. Such mathematics, sometimes termed models, 
can be used to chart the benefits of prevention and control measures. 
Most recently, mathematical models were used to project the course of 
the SARS epidemic in Asia, and to develop strategies to limit the 
spread of the disease. Several years ago, Fogarty established a unit at 
NIH concerned with the use of mathematical models for control and 
prevention of several diseases, including malaria. The elements of a 
malaria prevention program include reducing the population of 
mosquitoes, treatment of malaria patients, and use of personal 
protection such as bed nets to prevent mosquito bites. In addition, 
there is a major effort underway to develop a malaria vaccine. The 
Fogarty epidemiologists have used mathematical models to determine the 
best strategy to employ such a vaccine, when it becomes available, 
along with existing methods of malaria control and prevention. All this 
must be done within the various complex ecological settings in which 
malaria occurs. The use of such advanced mathematics in devising the 
most effective strategies in the study of infectious diseases will 
surely bring unexpected benefits to human kind. Importantly, through a 
network of in-house research experts and extramural scientists, Fogarty 
also employs mathematical models to assist biomedical research and 
public health policy-makers prepare for and respond to bioterrorism 
events. In coordination with DHHS, Fogarty has mobilized experts in 
epidemiology, terrorism-response and public health policy in the 
context of category A agents including plague, tularemia smallpox and 
anthrax.

               THE EMERGING EPIDEMICS OF CHRONIC DISEASE

    By the year 2020, chronic disease is expected to contribute 60 
percent of the global disease burden. The toll in the United States is 
already enormous: for example, obesity has more than doubled from 15 
percent during 1976-1980 to 31 percent in 1999-2000, and 65 percent of 
adults ages 20 to 74 were overweight to obese in 1999-2000. As 
populations age, and risk exposures shift due to environmental and 
dietary factors, non-communicable diseases are estimated to become a 
leading source of disability and premature death in developing nations 
as well. Tobacco-caused disease and death is a major concern in the 
United States and globally. In the United States, while picking up the 
habit of smoking is on the decline in most groups, in young girls it is 
on the rise (The World Bank). In low- and middle-income nations, as 
wealth increases in urban settings, smoking commencement in youth, and 
particularly in girls, is rising at alarming rates (The World Bank). To 
address this challenge, Fogarty launched in 2002 its International 
Tobacco and Health Research and Capacity Building Program. While in its 
early stages, our expectation is that research will lead to new 
interventions that will benefit U.S. communities as well as those 
around the world.
    There is a growing awareness of the burden on health inflicted by 
trauma and injury both in the United States and worldwide. The numbers 
are startling: more than 1.2 million people are killed in traffic 
accidents annually, and millions more are injured or disabled. Deaths 
from all types of injuries, including war and domestic violence, are 
projected to rise from 5.1 million in 1990 to 8.4 million in 2020, with 
road traffic injuries as a major cause for this increase, with millions 
more sustaining injury that results in life-long disability. In 
response to the growing epidemic of trauma, Fogarty is initiating a new 
research and training program. Among the features of the program will 
be training across the range of basic to applied sciences, the 
epidemiology of risk factors, acute care and survival, rehabilitation, 
and the long-term mental health consequences. Possible research areas 
will include development of low-cost synthetic blood products and 
diagnostic imaging tools, identification of behavioral intervention 
strategies, particularly in youth and other high-risk groups, and 
health services research to determine cost-effective measures for 
emergency care in low-income settings. The new knowledge from the 
program will benefit not only developing countries but, as low-cost and 
effective strategies are identified, communities in the United States.

     PREPARING THE NEXT GENERATION OF U.S. GLOBAL HEALTH LEADERSHI

    While Fogarty works to build capacity and train young scientists in 
the developing world, critical steps have been taken to ensure that 
U.S. investigators at a formative stage in their careers also have 
opportunities to engage in international research projects. The Center 
will enhance and expand two programs to bring the next generation of 
U.S. scientists more fully into the global culture of science. The 
first of these, the International Research Scientist Development Award 
(IRSDA) program, provides post-doctoral training for four years, two of 
which must be spent conducting research in a developing country. Nearly 
20 U.S. scientists are now being supported as IRSDA trainees. 
Addressing an earlier step in the career path, Fogarty has recently 
teamed with the Ellison Medical Foundation to create a second program, 
the new pre-doctoral clinical research training program for U.S. 
medical and public health students. Under this program, students will 
spend a year in a developing country conducting NIH-sponsored clinical 
research under the mentorship of an experienced foreign investigator 
and a collaborating research team. The first students to be selected 
will begin the program this summer.

              ENHANCING OPPORTUNITIES FOR WOMEN IN SCIENCE

    NIH's goal to bolster the nation's intellectual capital includes 
attracting more women to careers in science, both to build a new 
generation of talented scientists and to ensure that research issues 
germane to women's health are addressed. Fogarty has extended this 
important goal to international programs. At an October 2003 colloquium 
on career path issues facing women in the life sciences, including 
women in the developing world, Fogarty and its co-sponsors, the NIH 
Office of Research on Women's Health and the National Institute of 
Environmental Health Sciences, invited perspectives on opportunities in 
advancing career issues for women in the life sciences from a community 
of scientists, administrators and science funding agencies. To follow 
up on the recommendations, Fogarty and its partners have agreed to: 
collect data on developing country women in science and their career 
paths; support workshops to develop skill sets for women scientists in 
the developing world that will better enable them to take on leadership 
roles within health research and/or policy settings; and develop and 
implement strategies to effectively use the Internet and other 
information technologies to support networking and mentorship.

             ADVANCING THE NIH ROADMAP: GLOBAL POSITIONING

    Fogarty supports programs linked to each of the three main Roadmap 
themes--New Pathways to Discovery, Research Teams of the Future, and 
Re-Engineering the Clinical Research Enterprise. In particular, to 
improve the clinical research enterprise, Fogarty supports two new 
programs aimed at training developing country professionals in 
clinical, operational and health services research. These programs 
represent a new approach to enhance clinical research, and pave the way 
for new partners, namely those in low- and middle-income nations, to 
work more closely on mental health, and on AIDS and TB with U.S. 
counterparts. In support of Roadmap themes of new approaches and new 
pathways to discovery, Fogarty is also supporting studies to identify 
the impact of environmental degradation on economic development and 
human health. These programs link social scientists, including 
mathematicians and economists, with clinicians and medical researchers 
to provide new insights and strategies to tackle urgent global health 
challenges.

                               CONCLUSION

    Mr. Chairman, global challenges require a global response. 
Collective action is not only an economically rational approach to 
global health research challenges, but a scientific and humanitarian 
imperative. With the continued support of this Committee, Fogarty will 
accelerate both research discoveries and applications through 
international cooperative action to the benefit of the United States 
and to global communities. ``A healthy America in a healthier world'' 
has never been as important as it is today. 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) of the National Institutes of Health 
(NIH). The fiscal year 2005 budget includes $297,647,000, an increase 
of $8,817,000 over the fiscal year 2004 enacted level of $288,830,000 
over the comparable fiscal year 2004 appropriation.
    The NIBIB's mission is to improve human health by leading the 
development and accelerating the application of biomedical 
technologies. The Institute is committed to integrating the physical 
and engineering sciences with the life sciences to advance basic 
research and health care. Our vision is to profoundly change healthcare 
by pushing the frontiers of technology to make the possible a reality.

                        PROGRESS TOWARDS SUCCESS

    Established by law in December 2000, the NIBIB has already 
demonstrated an impressive track record as a conscientious steward of 
public funds and has achieved significant milestones. In fiscal year 
2003 the NIBIB funded approximately 750 awards, including 300 new 
awards that received outstanding scores in a highly competitive peer 
review system. Consistent with our mission, approximately one-third of 
our new awards were for innovative, high-impact, though high-risk, 
exploratory studies. These studies addressed the feasibility of a novel 
avenue of investigation and/or breakthroughs in biomedical imaging and 
bioengineering within a specific area. The Institute has also been 
effective at reaching segments of the scientific community that 
traditionally have not been supported by the NIH, especially those from 
the engineering and quantitative sciences. Between the first and second 
years of our grant-making authority, proposals to the NIBIB from first-
time NIH applicants increased significantly. In fiscal year 2003, 
approximately 50 percent of respondents to requests for targeted 
applications identified themselves as first-time NIH applicants.
    The Institute has built a solid research infrastructure through the 
issuance of numerous basic and applied research solicitations in 
promising areas of scientific investigation. Responses to the 
Institute's targeted initiatives far exceeded even the most optimistic 
estimates based on prior NIH experience. Coupling this to the 
successful outreach to new applicants and to the science community, it 
is clear that NIBIB is filling an important need with regard to 
catalyzing interdisciplinary science and supporting engineering 
research aimed at translating scientific discoveries to practical 
applications.
    The NIBIB continues to foster successful linkages and 
collaborations with other NIH Institutes and Centers, Federal agencies, 
academic institutions, and private industry. We regard input from 
industry as critical for helping to identify research needs that will 
result in significant healthcare improvements as well as for 
translating technologies and research results to patient applications. 
As a first step in establishing collaboration with the biomedical 
industry, the NIBIB sponsored a workshop on ``Biomedical Industry 
Research and Training Opportunities'' in December 2003. Recommendations 
from this meeting will be considered in the planning and development of 
future NIBIB programs.

                ADVANCING TOMORROW'S TECHNOLOGIES TODAY

    Biomedical imaging and bioengineering are interdisciplinary fields 
requiring 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 treating disease, and improving 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, orthopedics, and cardiology.
    The quest for faster and more effective minimally invasive surgical 
interventions has resulted in the introduction of computer-assisted 
robotic technology, whereby the surgeon works with small tools through 
small incisions. However, current instrumentation prohibits the surgeon 
from actually feeling the forces exerted when manipulating tissue. This 
lack of sensory control can be particularly detrimental in surgery, 
where the forces applied to sutures are critical in creating knots that 
are strong enough to hold, but do not damage the tissue. To overcome 
this problem, NIBIB investigators are developing instruments with 
three-dimensional sensors designed to give the surgeon a feeling 
comparable to that of performing the task manually. This research has 
additional applications as well, including expert-assisted surgery in 
remote locations.
    Magnetic resonance imaging (MRI) has been used successfully for 
over 15 years to generate soft tissue images of the human body. 
However, a number of diagnostic MRI applications require further 
improvements in both imaging speed and spatial resolution. For example, 
accurate abdominal imaging generally requires a complete image obtained 
during a single ``breath-hold'' period, which can take up to 30 
seconds. Many patients, especially those with respiratory illnesses, 
cannot tolerate long breatholds. The NIBIB supports an active research 
program on optimizing MRI speed and spatial resolution. One new 
approach under study, called parallel imaging, collects MRI signals 
from a number of independent coil shaped antennas. The appropriate 
combination of these signals can provide an order of magnitude 
improvement in imaging speed or resolution. Enhancements such as this 
hold promise for greatly enhancing the non-invasive diagnosis and 
treatment of abdominal and neurological diseases.
    Functional magnetic resonance imaging (fMRI) is a relatively new 
technique that builds on the basic properties of MRI to measure quick 
and tiny blood flow related metabolic changes that take place in the 
active brain. Thus, fMRI studies are capable of providing not only an 
anatomical view of the brain, but a minute-to-minute recording of 
actual brain activity. This technology is now being used by NIBIB 
researchers to precisely map functional areas of the normal, diseased, 
and injured brain and to assess risks associated with surgery or other 
invasive treatments. Functional MRI can help physicians determine 
exactly which parts of the brain are responsible for specific crucial 
functions such as thought, speech, movement, and sensation. This 
information allows physicians to better plan surgeries and radiation 
therapies and to guide interventional strategies for a variety of brain 
disorders.
    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 and 
``highlight'' defined cellular targets, will allow this technique to be 
more broadly applied to biomolecules that are known indicators of a 
diseased state. For example, NIBIB researchers have developed nanometer 
sized fluorescent crystals, called quantum dots, that glow and can act 
as markers for specific cells when bound to certain targeting agents 
such as cancer cell antibodies. These agents can more precisely 
pinpoint the location of the sentinel lymph node in breast cancer 
patients. The sentinel node (SN) is the first node in the body to come 
into contact with cancer cells as they leave the breast and begin to 
spread to the rest of the body. Testing for metastatic cancer cells in 
the SN allows for accurate staging using information from a single 
lymph node, rather than 10 to 15 axillary nodes, and allows patients to 
avoid many of the complications and side effects associated with a 
traditional axillary lymph node dissection.
    Advances in bioinformatics have been identified as having great 
potential for positively impacting medical science and health care. 
NIBIB researchers are developing and evaluating several innovative 
technologies designed to help solve the information management problems 
faced by today's doctors. Concepts enveloped in this system include a 
medical record architecture designed for portability; a mechanism for 
linking laboratory findings with medical problems; and a real-time, 
context-sensitive visualization of the medical record. Taken together, 
these concepts form a comprehensive system for facilitating evidence-
based medicine in a real-world setting.

                NEW BIOMATERIALS FOR TISSUE ENGINEERING

    Tissue engineering holds the promise to repair and/or replace 
damaged organs using biologic materials. For success in this area, a 
number of scientific and bioengineering challenges must first be met. 
For example, we must learn to produce, manipulate, and deliver 
collections of cells not only as building blocks for tissues and organ 
systems, but as models for studying drug development. Toward this goal, 
NIBIB researchers have successfully transformed adult rat engineered 
tissue cells into cells that form cartilage and bone. The two cell 
types were integrated into separate layers, encapsulated in a gel-like 
biocompatible material, and shaped into the ball structure of a human 
jaw joint. Although more work is needed before this tissue-engineered 
joint can be used in humans, it holds great potential for treating 
patients with temporomandibular disorders, osteoarthritis, and 
rheumatoid arthritis. These procedures could also be further refined 
and adapted for developing artificial knee and hip joints.
    Coronary stents are small devices that serve as a scaffold to prop 
open the inside of an artery and provide vessel support. They are 
commonly made of stainless steel or nylon mesh and therefore remain as 
a permanent implant in a blood vessel. Although stents have 
revolutionized the treatment of coronary artery disease, limitations 
include an inflammatory reaction and the development of stent closure 
due to blood clots forming within the device, a process termed 
restenosis. To address this problem, NIBIB researchers have recently 
developed a mechanically strong, hemocompatible, and X-ray visible 
polymer as a noninflammatory fully-degradable coronary stent. While 
designed as a stent, work continues to refine the device to serve 
additionally as a drug-delivery vehicle. This may also have application 
as a drug-delivery mechanism for other diseases, such as cancer.

                          SENSORS FOR MEDICINE

    Biosensors are nanoscale or microscale devices that detect, 
monitor, and transmit information about a physiological change, or 
indicate the presence of various chemicals, gases, or biological 
materials. Laboratory diagnostics used in hematology, clinical 
chemistry, pathology, and microbiology already employ sensor 
technologies to perform simultaneous measurements for many substances 
in urine, blood, saliva, sweat, and interstitial fluids. The Institute 
has an active research program in sensor technologies and continues to 
expand this important area. For example, NIBIB researchers are 
engineering recombinant antibody fragments (recAbs) that will increase 
the sensitivity and specificity of a type of biosensor called a 
piezoimmunosensor. Piezoimmunosensors have been proposed for almost 20 
years; however, there has been no procedure for providing a sensing 
layer that is uniform, chemically stable during the measurement 
process, and contains high numbers of binding sites. By creating 
tightly packed monolayers of recAbs that will bind to the surface of 
the sensing unit, researchers are solving this problem while also 
preventing non-specific interactions with molecules, and thus improving 
specificity.
    Other researchers are focusing on the design and fabrication of 
miniaturized implantable responsive drug delivery devices that 
integrate a smart drug delivery system with a biosensor. These drug 
delivery systems are aimed at providing individualized therapies that 
monitor the patient's body chemistry and control drug flow as needed.

                              NIH ROADMAP

    To transform the Nation's medical research capabilities and to 
speed the movement of research discoveries from the bench to the 
bedside and into medical practice, the NIH has laid out a series of 
far-reaching initiatives known collectively as the NIH Roadmap for 
Medical Research. The NIH Roadmap focuses on the most compelling 
opportunities in three main areas: new pathways to discovery, research 
teams of the future, and re-engineering the clinical research 
enterprise.
    The NIBIB mission also strongly supports the NIH Roadmap 
initiative, since the Roadmap goal is to facilitate the development of 
innovative, novel and multidisciplinary science and technology that has 
the potential to further advances in health care. For example, the 
NIBIB is participating in an initiative that will facilitate the 
formation of collaborative research teams capable of generating novel 
probes for molecular and cellular imaging. The overall goal is to 
establish programs to create complete tool sets for the detection of 
single molecule events in living cells and to generate new strategies 
for dramatically increasing the imaging resolution of dynamic cellular 
processes.
    Other areas of immediate interest to and supported by the NIBIB 
include the development of nanomedicine technologies, new tools for the 
study of proteomics and metabolic pathways, data and techniques for 
computational biology, and advances in bioinformatics. The NIBIB also 
strongly supports the NIH Roadmap theme on research teams of the future 
through sponsoring multidisciplinary research and interdisciplinary 
training.

                    MULTIDISCIPLINARY RESEARCH TEAMS

    The value of collaboration among disciplines and organizations has 
long been recognized as important for developing novel approaches to 
problems in biology and medicine, and for effectively translating 
research results to patient applications. We are pleased to report that 
there have already been some successful ``NIBIB partnerships'' between 
biomedical engineers and imaging scientists that have had significant 
impacts on healthcare. For example, an ongoing Bioengineering Research 
Partnership team is using fMRI to integrate information on the 
suspected location of brain seizures with information about surrounding 
brain function in order to improve surgical outcome and reduce or 
eliminate seizures. In one early phase study, surgery employing fMRI 
strategies was used to almost eliminate seizures in a patient who had 
been suffering from as many as 100 seizures daily.
    In conclusion, the NIBIB is dedicated to promoting the development 
of emerging technologies and interdisciplinary collaborations that 
drive healthcare advances. I would be pleased to respond to any 
questions that the Committee 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 2005, a sum of $2,930,397,000 an increase of 5,000 
above the comparable fiscal year 2004 appropriation.
    The NIH represents the largest and most significant public 
investment in AIDS research in the world a comprehensive program of 
basic, clinical, and behavioral research on HIV infection and its 
associated opportunistic infections and malignancies. 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.

                           WORLDWIDE PANDEMIC

    AIDS is the deadliest epidemic of our time. More than 22 million 
people have already died of AIDS--3 million of them in 2003 alone--the 
largest number ever. HIV has already infected more than 60 million 
people around the world, and AIDS has surpassed tuberculosis and 
malaria as the leading infectious cause of death worldwide.\1\
---------------------------------------------------------------------------
    \1\ ``Report on the Global HIV/AIDS Epidemic: July 2002,'' (UNAIDS/
WHO, Geneva, Switzerland, 2002).
---------------------------------------------------------------------------
    The United Nations General Assembly's Declaration of Commitment on 
HIV/AIDS states ``. . . the global HIV/AIDS epidemic, through its 
devastating scale and impact, constitutes a global emergency and one of 
the most formidable challenges to human life and dignity, as well as to 
the effective enjoyment of human rights, which undermines social and 
economic development throughout the world and affects all levels of 
society national, community, family, and individual.'' \2\ According to 
a U.N. report, ``The epidemic has not only killed people; it has 
imposed a heavy burden on families, communities and economies. The 
misery and devastation already caused by HIV/AIDS is enormous, but it 
is likely that the future impact will be even greater . . . The HIV/
AIDS epidemic has erased decades of progress in combating mortality and 
has seriously compromised the living conditions of current and future 
generations. The disease has such a staggering impact because it 
weakens and kills many people in their young adulthood, the most 
productive years for income generation and family caregiving. It 
destroys families, eliminating a whole generation crucial for the 
survival of the younger and older persons in society.'' The report also 
highlights ``the long-term damage accruing to human capital, as 
children's education, nutrition and health suffer directly and 
indirectly as a consequence of HIV/AIDS. The effects of lowered 
investment in the human capital of the younger generation will affect 
economic performance for decades to come, well beyond the timeframe of 
most economic analysis.'' \3\ Another dimension to the epidemic in 
Africa was cited in the New York Times: ``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.'' \4\
---------------------------------------------------------------------------
    \2\ ``The Impact of AIDS'' (Department of Economic and Social 
Affairs, United Nations, 2003).
    \3\ Ibid.
    \4\ A. de Waal, ``What AIDS Means in a Famine,'' New York Times, 
11/19/02.
---------------------------------------------------------------------------
    A recent CIA report estimated that by 2010, 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.\5\ 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.'' \6\ Dramatic 
increases in HIV infection also are occurring in Eastern Europe, 
Central Asia, Latin America, and the Caribbean.
---------------------------------------------------------------------------
    \5\ ``Intelligence Community Assessment: The Next Wave of HIV/AIDS: 
Nigeria, Ethiopia, Russia, India, and China.'' (CIA, 2002).
    \6\ ``The Future of AIDS,'' Foreign Affairs, November/December 
2002.
---------------------------------------------------------------------------
                           THE U.S. EPIDEMIC

    According to CDC, the decline in death rates observed in the late 
1990s, due largely to expanded use of new antiretroviral therapies 
(ART) that prevent progression of HIV infection to AIDS, has now 
leveled off; and AIDS incidence increased 2 percent in 2002 (over 
2001). This means that the overall epidemic is continuing to expand.\7\ 
\8\ \9\ 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. HIV infection rates are continuing to climb 
among women, racial and ethnic minorities, young homosexual men, 
individuals with addictive disorders, and people over 50 years of 
age.\10\ The appearance of multi-drug resistant strains of HIV presents 
an additional serious public health concern.\11\ \12\ \13\ \14\ \15\ 
According to CDC reports, approximately one quarter of the HIV-infected 
population in the United States also is infected with hepatitis C virus 
(HCV). HIV/HCV co-infection is found in 50 to 90 percent of injecting 
drug users (IDUs). HCV progresses more rapidly to liver damage in HIV-
infected persons and may also impact the course and management of HIV 
infection, as HIV may change the natural history and treatment of 
HCV.\16\ This expanding and evolving U.S. epidemic presents new and 
complex scientific challenges.
---------------------------------------------------------------------------
    \7\ CDC Year-End HIV/AIDS Surveillance Report for 2002 (CDC, 2003).
    \8\ ``Centers for Disease Control and Prevention HIV Prevention 
Strategic Plan Through 2005,'' (CDC, 2001).
    \9\ ``HIV/AIDS Update--A Glance at the HIV Epidemic,'' (CDC, 2001).
    \10\ ``U.S. HIV and AIDS Cases Reported Through June 2000,'' CDC 
HIV/AIDS Surveillance Report, Vol. 12 (2002).
    \11\ N. Loder, Nature 407, 120 (2000).
    \12\ H. Salomon et al., AIDS 14, 17 (2000).
    \13\ Y.K. Chow et al., Nature 361, 650 (1993).
    \14\ M. Waldholz, ``Drug Resistant HIV Becomes More Widespread,'' 
Wall Street Journal, 2/5/99.
    \15\ ``World Health Report on Infectious Diseases: Overcoming 
Antimicrobial Resistance,'' (WHO, Geneva, 2000).
    \16\ ``Frequently Asked Questions and Answers About Coinfection 
with HIV and Hepatitis C Virus'' (CDC, 2002).
---------------------------------------------------------------------------
              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 planning process also serves to monitor and assess scientific 
progress on an annual basis.
    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.

                    VACCINES AND PREVENTION RESEARCH

    Vaccine research remains a critical priority. 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, approximately 14 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. The development of vaccine candidates also requires 
sufficient quantities of non-human primates for preclinical testing.
    In addition to vaccines, our biomedical prevention research 
priorities include the development 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.

                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 that 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.

                         INTERNATIONAL RESEARCH

    NIH bears a unique responsibility to address the urgency of the 
global AIDS epidemic. To meet that need, 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.

                                SUMMARY

    The human and economic toll of the AIDS pandemic is profound, 
demanding a unique response that is complex, comprehensive, multi-
disciplinary, and global. The NIH role in this response is fundamental 
and unprecedented. The nation's investment in AIDS research is reaping 
even greater dividends, as AIDS-related research is unraveling the 
mysteries surrounding many other infectious, malignant, neurologic, 
autoimmune, and metabolic diseases. The authorities of the OAR allow 
NIH to pursue a united research front against the global AIDS epidemic. 
We are deeply grateful for the continued support the Administration and 
this Committee have provided to our efforts.

                                 ______
                                 
              Prepared Statement of Dr. Francis S. Collins

    Mr. Chairman, I am pleased to present the President's budget 
request for the National Human Genome Research Institute for fiscal 
year 2005, a sum of $492,670,000, which reflects an increase of 
$13,842,000 over the fiscal year 2004 Final Conference appropriation.
    Following the completion of the Human Genome Project last year, the 
National Human Genome Research Institute (NHGRI) of the National 
Institutes of Health announced an ambitious plan for applying genomics 
to human health benefits. A Vision for the Future of Genomics Research, 
the outcome of almost two years of intense discussions with over 600 
scientists and members of the public, has three major areas of focus: 
Genomics to Biology, Genomics to Health, and Genomics to Society. 
Several ambitious projects are already underway to help achieve this 
vision including the International Haplotype (HapMap) Project, the 
Encyclopedia of DNA Elements (ENCODE), the NIH Roadmap initiative on 
Molecular Libraries, and a new Ethical, Legal and Social Implications 
(ELSI) Center initiative. As we enter the genomic era, the continued 
support of biomedical research in this area is more vital than ever.

                       ONGOING NHGRI INITIATIVES

International HapMap Project
    To study genetic variation more effectively across the human 
genome, the NHGRI and a team of partners has launched the International 
HapMap Project. The goal of the project is to determine the common 
patterns of DNA sequence variation in the human genome, and to make 
this information freely available in the public domain. This 
international consortium is developing a map of these patterns across 
the genome by determining the genotypes of one million or more sequence 
variants in DNA samples from populations with ancestry from Africa, 
Asia, and Europe. When complete, the HapMap will enable the discovery 
of sequence variants that affect common disease, the development of 
diagnostic tools, and the ability to choose targets for therapeutic 
intervention. Detailed information about the HapMap project was 
published in a landmark article in Nature, and updated details can be 
found on the web at www.hapmap.org.

Comparative Genomics to Understand the Human Genome
    One of the most powerful approaches for unlocking the secrets of 
the human genome is comparative genomics. While the completed sequence 
of the human genome represents a milestone of historic proportions, a 
daunting challenge that still lies ahead is to interpret its biological 
meaning and function. Recently sequenced genomes of the mouse, rat, and 
a wide variety of other organisms--from yeast to chimpanzees--prove 
that the genomes of other species are amongst the most powerful tools 
in advancing understanding of the human genome. The current NHGRI-
supported, large-scale sequencing centers have built a prodigious 
capacity for, and expertise in, sequencing entire genomes. The combined 
capacity of these centers is expected to yield the equivalent of about 
20 additional draft vertebrate genomes in just the next three years. 
These additional species sequences will provide exciting new insights 
into the function of the human genome, and will assist genome 
scientists in translating the basic findings of the Human Genome 
Project into tangible applications, including the diagnosis, 
prevention, and treatment of disease.

ENCODE--ENCyclopedia Of DNA Elements
    To understand the meaning of the human instruction book, the 
genome, the identities and precise locations of all functional elements 
must be determined. Thus, the NHGRI has launched the ENCyclopedia Of 
DNA Elements (ENCODE) project to identify these elements 
comprehensively. The ENCODE project seeks to characterize the tools 
needed for exploring genomic sequence, improve those tools when 
necessary, and define a clear path for the determination of all of the 
functional elements in the entire human genome. On October 9, 2003, the 
NHGRI announced the first ENCODE grants in a three-year, $36 million 
project (www.genome.gov). ENCODE begins as a pilot effort to evaluate 
methods for the exhaustive identification and verification of 
functional sequence elements in a carefully selected 30 million base 
pairs, or about one percent, of human genomic DNA. This will require 
access to information, resources, ideas, expertise, and technology 
beyond the capabilities of any single group. Therefore, a consortium of 
investigators with diverse backgrounds and expertise will work 
cooperatively to carry out this project to: (1) evaluate rigorously the 
relative merits of a varied set of computational and experimental 
techniques, technologies, and strategies for identifying the functional 
elements in human genomic sequence, and (2) test the capabilities of 
such methods to scale up efficiently to allow, ultimately, analysis of 
all the functional elements encoded in the entire human genome 
sequence.

Centers Of Excellence In Genomic Science (CEGS)
    The NHGRI Centers Of Excellence In Genomic Science (CEGS) program 
has been in place for four years. This program is a centerpiece of the 
Institute's effort to stimulate new interdisciplinary approaches to 
genomic research and technology development. A total of about 10 CEGS 
grants are ultimately expected to be funded. These will generally be 
five-year awards of up to $3 million per year. Seven awards have been 
made to date; each involves multiple investigators and disciplines, and 
several cut across departments and institutions. A grantee meeting in 
October 2003 stimulated new collaborations and identified ways to share 
CEGS grant data and resources with the larger research community.

Clinical Research Activities in the NHGRI Intramural Program
    Research efforts of NHGRI Division of Intramural Research (DIR) 
investigators are aimed at deciphering the genetic contributions to 
common disorders, to provide a better understanding of diseases such as 
cancer, diabetes, and heart disease, as well as to a number of less 
common but equally debilitating afflictions. DIR investigators have 
been at the forefront of scientific innovation, developing a variety of 
research approaches that accelerate the understanding of the molecular 
basis of disease. These include the development of DNA microarray 
technologies for large-scale molecular analyses, innovative computer 
software to study fundamental biological problems, animal models 
critical to the study of human inherited disorders, and the clinical 
testing of new therapeutic approaches for genetic disease. Three 
examples of gene discoveries within the past year include the gene 
responsible for Hutchinson-Gilford progeria syndrome, the disease 
causative gene for Charcot-Marie-Tooth disease type 2D, and a gene 
variant that contributes to the risk of type 2 diabetes. These and 
other advances should ultimately lead to improved diagnostic, 
prevention, and treatment strategies having a direct impact on human 
health.

                            NEW INITIATIVES

    The NHGRI is very enthusiastic about the initiatives included in 
the NIH Roadmap and is deeply involved in implementation plans for 
several of the projects embodied in the ``New Pathways to Discovery'' 
theme.

Molecular Libraries
    As part of its Vision for the Future of Genomics Research, and in 
partnership with many other NIH Institutes as part of NIH's new Roadmap 
for Medical Research, the NHGRI is taking a lead role in providing 
access to high throughput screens for small organic molecules to public 
sector researchers. These small molecules can be used as chemical 
probes to study cellular pathways in great depth and will broadly 
enable public and private biomedical research into basic biology and 
accelerate the validation of new therapeutic targets, and thus the 
discovery of new drugs. For this effort to provide maximal benefits, 
the library of small molecules must contain a sufficient number of 
compounds. To build such a library, a network of six national centers 
will establish a common collection of 500,000 or more chemically 
diverse small molecules, of both known and unknown activities. 
Investigators who develop assays suitable for high throughput screening 
will apply for access to these centers. After peer review, suitable 
assays will be run through a screen of 500,000 or more compounds, and 
the positives subjected to a first pass of chemical optimization to 
generate useful compounds. We anticipate that this new resource will 
catalyze a genuine paradigm shift, because it will give academic 
investigators a new and powerful research tool not previously at their 
disposal.

$1,000 Genome Sequence
    Current sequencing costs are too high to collect the quantity and 
quality of soome sequences optimal for research and clinical 
applications. Completely sequencing the genomes of many individuals 
would greatly advance understanding of the role of DNA sequence 
variation in human health, but using DNA sequence information for care 
of individuals is not possible at current costs. Thus, NHGRI has 
launched an aggressive program to develop technologies to lower the 
cost of DNA sequencing dramatically. The goal for the first five years 
of this program is to develop the capability to produce a high quality 
draft sequence for a large, complex (e.g., mammalian) genome for 
$100,000. The goal of the second phase, which is estimated to take ten 
years, is producing a genome sequence for $1,000. Once achieved, a 
$1,000 genome analysis would be of great use to correlate DNA 
information with health outcomes. This includes determining genes in 
each individual that predispose that individual to specific diseases, 
and assessing which drugs are likely to elicit adverse reactions in 
each individual, so that drugs can be used more effectively and with 
fewer side effects.

Centers for Excellence in ELSI Research
    The NHGRI Ethical Legal and Social Implications (ELSI) research 
program recently released a Request for Applications inviting proposals 
for the development of Centers of Excellence in ELSI Research (CEER). 
The CEER program is designed to support the development of groups that 
will pursue research questions best approached through intensive and 
extended collaboration among investigators from multiple disciplines, 
using diverse methodologies. CEER investigators are encouraged to 
consider new ways to explore these questions, design innovative and 
efficient research projects, propose and disseminate health or social 
policy options based on Center research, and, when feasible, facilitate 
policy development pertinent to a specific issue. Center applicants are 
particularly encouraged to identify cutting edge research topics and 
approaches that may lead to high payoff solutions to important ELSI 
problems.

Intramural Social and Behavioral Research Branch
    The NHGRI has formed a new Social and Behavioral Genetics Research 
Branch within its intramural research program. The main focus of the 
Branch is to conduct research on the social and behavioral aspects of 
translating genomic discoveries into improved health. The Branch will 
also: (1) study innovative ways of applying genetic discoveries to 
promote health and well-being; (2) apply social, behavioral, and 
communication theories to understand how to communicate genetic risk 
effectively; (3) develop and refine evidence-based methods of 
communicating genetic risk to individuals, families, communities, and 
populations; (4) seek to understand how social factors influence 
genetic discoveries and research; and (5) investigate the ethical and 
public policy implications of genetic research and the use of genetics 
in clinical practice.

                   OTHER AREAS OF INTEREST FOR NHGRI

Genetic Discrimination
    The NHGRI remains concerned about the risk of genetic 
discrimination and supports the President's call for federal 
legislation. Many Americans are worried that insurers and employers may 
use genetic information to deny, limit, or cancel their health 
insurance or to discriminate against them in the workplace. A total of 
41 States have enacted legislation on discrimination in health 
insurance and 31 have enacted legislation on workplace genetic 
discrimination. However, only comprehensive federal legislation can 
guarantee everyone in the United States protection from genetic 
discrimination. Last October, the full U.S. Senate voted unanimously 
(95-0) in favor of the ``Genetic Information Nondiscrimination Act of 
2003'' (S. 1053), which would address this problem. It is hoped that 
the House will soon take similar steps.

Intellectual Property Rights in Genetics and Genomics Research
    NHGRI has long worked on issues of intellectual property related to 
genetic and genomic data. The NHGRI ELSI program plans soon to issue a 
new initiative to encourage studies of the role of intellectual 
property rights in genetics and genomics research, as well as the 
impact of exclusivity on progress in these fields. The initiative will 
support legal, economic, political science, and statistical analyses 
and empirical investigations of theories and practices of rights 
holders, stakeholders, and researchers in genetics and genomics 
research and development, with the specific goal of helping build the 
research base necessary to inform the rational development of future 
policy options regarding intellectual property in genetics, and 
genomics.
    The NHGRI, with several other NIH Institutes, has recently provided 
funds for a National Academy of Sciences' study, ``Intellectual 
Property in Genomic and Protein Research and Innovation.'' This 18-
month study, involving experts from law, public policy and genomics, 
will address such important questions as: What is the impact of 
intellectual property and licensing on genetic and proteomic research? 
What policy options should be considered in this area? How have other 
regions of the world addressed these issues? It is hoped that this 
study will provide insights on how to address the thorny issues 
surrounding the interface of intellectual property, biomedical 
research, and patient care.

Direct-to-Consumer Marketing of Genetic Tests
    Marketing of products or services that promise to provide consumers 
with genetic insights into personal health has proliferated 
dramatically in recent years. NHGRI's intramural Division of Bioethics 
has systematically studied this issue. So far, researchers have found 
that many direct-to-consumer (DTC) advertisements exaggerate the 
scientific basis of claims made and/or fail to communicate effectively 
the current limitations of the specific genetic knowledge discussed. In 
particular, the Internet has provided a powerful medium for the 
construction of ``informational'' resources through which DNA analysis 
is often linked to a claim to individualize consumer profiles for 
specific products available through the website. Additionally, the 
first example of a multi-media DTC advertising campaign for a genetic 
test, the BRCA1/2 test, was piloted in two metropolitan areas in the 
last year. The NHGRI recently held a workshop to assess DTC marketing 
of genetic tests, and considered the scope of the practice and possible 
policy options. The NHGRI will work with the Secretary's Advisory 
Committee on Genetics Health and Society on this issue.

Trans-NIH Obesity Initiative
    The NHGRI Deputy Director represents the Institute on the trans-NIH 
obesity working group. We believe that this initiative is vitally 
important, and that the genomic tools produced by the Human Genome 
Project can be of considerable utility in discerning the role of genes 
and environment in causing obesity, and in predicting which obese 
individuals will develop which diseases.

                               CONCLUSION

    With the completion of the human genome sequence, we have fully 
entered the genomic era. The NHGRI has now spearheaded many specific 
and innovative initiatives to understand how genetics affects human 
health, the ultimate motivation for the Human Genome Project. The most 
interesting and important applications of genomics lie not behind us, 
but ahead of us. Continued investment by the Congress in genetic/
genomic research is vital to our efforts to enhance the health of all.

                                 ______
                                 
               Prepared Statement of Dr. Richard J. Hodes

    Mr. Chairman and Members of the Committee: The NIA is requesting an 
fiscal year 2005 budget of $1,055,666,000, an increase of $31,068,000 
or 3 percent over the comparable fiscal year 2004 appropriation.
    Thank you for this opportunity to participate in today's hearing. I 
am Dr. Richard Hodes, Director of the NIA, and I am pleased to be here 
today to tell you about our progress making and communicating 
scientific discoveries that will improve the health and well-being of 
older Americans.
    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: Studies confirm 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.
    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. Over half of Americans over age 
50 have osteoporosis or low bone mass. Cardiovascular disease, cancer, 
and diabetes remain common among older Americans. And as many as 4.5 
million Americans suffer from Alzheimer's disease (AD), the most common 
cause of dementia among older persons.
    The mission of the National Institute on Aging is to improve the 
health and well-being of older Americans through research. In support 
of this mission, the Institute conducts and supports an extensive 
program of research on all aspects of aging, from the basic cellular 
and molecular changes that occur as we age, to the prevention and 
treatment of common age-related conditions, to the behavioral and 
social aspects of growing older, including the demographic and economic 
implications of an aging society. In addition, the NIA is the lead 
federal agency on Alzheimer's disease research; our activities in that 
area encompass prevention, detection, clinical trials, and caregiver 
issues. Finally, our education and outreach programs provide vital 
information to older people across the United States on a wide variety 
of topics, including living with chronic conditions such as arthritis 
or diabetes, caring for a loved one with Alzheimer's disease, and 
maintaining optimal health through exercise.
    The NIA works to rapidly translate research findings into practical 
interventions and information that will benefit older Americans. This 
may involve enhancing our methods of communicating important research 
findings to physicians or the public; creating opportunities for 
patients to benefit from groundbreaking research through participation 
in clinical trials; or even recognizing the potential of a very basic 
finding in a mouse, a worm, or a molecule to eventually have a powerful 
impact on the public health.
    For example, recent findings in C. elegans, a tiny worm that is 
frequently used for genetic studies, are providing important insights 
about fat regulation and storage that may lead to improved 
understanding of overweight and obesity in humans. NIH-supported 
researchers used RNA interference (RNAi), a technique in which genes 
are inactivated one at a time to determine their function, to screen 
the worm's genome and found some 417 genes involved with fat regulation 
and storage. Many of the genes they found have human counterparts, a 
number of which had not been previously implicated in the regulation of 
fat storage. Overweight and obesity are widespread in the United States 
and are associated with an array of health problems, including heart 
disease, stroke, osteoarthritis, adult-onset diabetes, and certain 
types of cancer; the genes identified in C. elegans may ultimately 
suggest new targets for treating human obesity and its associated 
diseases.
    Another recent basic discovery, this one in mice, may have profound 
implications on the field of reproductive biology. Since the 1950s, 
scientists have believed that women are born with all the oocytes 
(eggs) they will ever have, and that these eggs die off as a woman 
ages, with fertility diminishing and, at menopause, disappearing as a 
result. However, NIH-supported researchers recently found that oocyte-
containing follicles continue to develop in the ovaries of adult mice. 
If this finding is confirmed--and extended to humans--it could lead not 
only to new treatments for premature ovarian failure (which affects 
some 250,000 American women under age 40, according to the National 
Institute of Child Health and Human Development), but also to 
interventions to delay menopause and extend fertility.
    NIA-supported investigators in all fifty states are conducting 
research that is changing the way we prevent, diagnose, and treat the 
diseases of aging. NIA also supports networks of centers that focus on 
specific topics, including demography and the basic biology of aging. 
There are currently 29 NIA-supported Alzheimer's Disease Centers 
(ADCs), at which investigators are working to translate research 
advances into improved care and diagnosis for AD patients while 
focusing on the program's long-term goal--finding ways to treat and 
possibly prevent AD. Many ADCs have satellite facilities that offer 
diagnostic and treatment services and collect research data in 
underserved, rural, and minority communities. Another type of Center, 
the Edward R. Roybal Centers for Research on Applied Gerontology, 
translates behavioral and social research findings into practical 
outcomes for older adults. Each of the six Roybal Centers addresses one 
or more central themes (e.g., cognitive influences on physician/patient 
interaction affecting medical compliance; safe driving behavior; social 
role adjustment upon retirement).
    The NIA also supports a variety of clinical trials, frequently in 
collaboration with one or more NIH Institutes or other organizations. 
For example, NIA is currently supporting 25 AD clinical trials, seven 
of which are large-scale prevention studies. These trials are testing 
agents such as 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 to AD, NIA supports clinical trials for a number of other 
conditions, including cardiovascular disease, Parkinson's disease, and 
certain types of cancer.
    A major clinical trial in which NIA-supported researchers took part 
is the Diabetes Prevention Program, a multi-institutional study that 
was initiated by the National Institute on Diabetes and Digestive and 
Kidney Diseases and was designed to identify interventions that could 
prevent or delay the development of type 2 diabetes. The researchers 
found that people who are at high risk for diabetes can sharply reduce 
their risk by adopting a low-fat diet and 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 the study participants to 
determine long-term effectiveness of these interventions.
    The NIA also has a number of ongoing or planned special initiatives 
on diverse research topics. These include:
    Health Disparities.--The NIA's Healthy Aging in Neighborhoods of 
Diversity Across the Lifespan (HANDLS) project is a community-based 
study of health disparities among different racial, ethnic, and 
socioeconomic groups in Baltimore. The purpose of HANDLS is to 
disentangle the effects of race and socioeconomic status on risk 
factors for morbidity and mortality, incidence and progression of pre-
clinical disease, development and persistence of health disparities, 
longitudinal health status, and health risks. The pilot phase of the 
study was completed in December 2001, and the full-scope study is now 
being planned for implementation in 2004-2005. Unique to the HANDLS 
study is the use of two fully-equipped mobile research laboratories 
that enable investigators to collect data directly in the neighborhoods 
under study, establishing links with the community and increasing both 
the interest of potential participants and the retention rate.
    Neuroimaging.--The NIA is developing an Alzheimer's Disease 
Neuroimaging Initiative, a longitudinal, prospective, natural history 
study of normal aging, mild cognitive impairment, and early AD to 
evaluate neuroimaging techniques such as magnetic resonance imaging 
(MRI) and positron emission tomography (PET). The study objectives are 
to:
  --Identify the best markers for early diagnosis of AD
  --Identify markers for following disease progression and monitoring 
        treatment response
  --Develop surrogate endpoints for clinical trials
  --Decrease time and expense of drug development
  --Establish methods for the collection, processing, and distribution 
        of neuroimaging data in conjunction with other biological, 
        clinical, and neuropsychological data
    The initiative is planned as a partnership among the NIA/NIH, 
academic investigators, the pharmaceutical and imaging equipment 
industries, the Food and Drug Administration, the Centers for Medicare 
and Medicaid Services, and the NIH Foundation, with participation from 
the Alzheimer's Association and the Institute for the Study of Aging. 
The clinical, imaging, and biological data and samples will be made 
available, with appropriate safeguards to ensure participant privacy, 
to scientific investigators in the academic and industrial research 
communities.
    Testosterone replacement in men.--Levels of circulating 
testosterone decline as men age, and this decline may be related to 
decrements in physical and cognitive functioning--for example, recent 
research suggests that older men with lower levels of free, or unbound, 
testosterone circulating in their bloodstreams could be at increased 
risk of developing Alzheimer's disease (AD). Increasingly, middle-aged 
and older men are turning to testosterone replacement therapy (TRT) to 
forestall these symptoms: In 2002, over 800,000 men received some form 
of testosterone replacement. However, as with the use of hormone 
replacement therapy among women prior to the release of the Women's 
Health Initiative results demonstrating serious HRT-related risks, men 
are using TRT in the absence of clear scientific data supporting its 
use. A multi-disciplinary panel, led by the Institute of Medicine and 
supported by the NIA and the National Cancer Institute, recently 
evaluated the pros and cons of conducting clinical trials of 
testosterone replacement therapy in older men to answer many of the 
lingering questions about the effects of this hormone in the aging 
body. The NIA is considering the IOM recommendations very carefully and 
will act on the recommendations to begin clinical trials to determine 
the efficacy of testosterone in treating symptomatic older men with low 
testosterone levels.
    Genetics.--The NIA has established a new AD Genetics Initiative, a 
program to accelerate the pace of AD genetics research by creating a 
large repository of DNA and cell lines from families with multiple AD 
cases. The goal of this initiative is to develop strategies for 
identifying the remaining late-onset AD (LOAD) risk factor genes, 
associated environmental factors, and the interactions of genes and the 
environment. The NIA's AD Genetics Initiative will intensify sample 
collection and encourage data sharing by providing access to the 
repository to qualified investigators. To date, several well-integrated 
components of the Genetics Initiative have been launched. Mechanisms to 
efficiently identify and share large numbers of samples for AD genetic 
analysis have been developed through the recently-enlarged National 
Cell Repository for AD (NCRAD), and eighteen of the NIA's Alzheimer's 
Disease Centers have received supplemental funding to recruit new 
family members participation. Uniform standards for sample collection 
have also been developed. As of late January, over 200 families have 
been evaluated and enrolled, and over 800 blood samples have been 
logged at NCRAD. A clinical task force has been established which is 
helping to determine the correct phenotypic data to be included with 
the biological samples. A major goal is the long-term follow-up of 
individuals participating in the study.
    In order to publicize the initiative, the NIA Office of 
Communications and Public Liaison, together with its Alzheimer's 
Disease Education and Referral Center, Columbia University, and NCRAD, 
partnered with the Alzheimer's Association to conduct focus groups and 
develop publicity materials to help recruiting efforts. These publicity 
materials, including a workbook, CD ROM, fact sheet, and brochure were 
distributed at the a recent meeting of the ADCs and will now be sent to 
ADCs and Alzheimer's Association chapters to help recruiting efforts.
    Longevity.--The NIA has formed a Longevity Consortium to help 
identify and understand genetic and other factors that predispose to 
human longevity or protect against multiple age-related conditions, a 
major goal in aging research. The Consortium is an innovative system 
for expeditious generation, review, and funding of new projects as 
opportunities arise, and includes epidemiologists, geneticists, 
population biologists, statisticians, and others with an interest in 
the genetic and molecular basis for longevity. Participants can draw on 
the study populations of 15 of the largest human aging studies, 
including the Cardiovascular Health Study, the Women's Health 
Initiative, Health ABC, the Study of Osteoporotic Fractures, the 
Rotterdam Study, the Honolulu Heart Study, and the New England 
Centenarian Study. Altogether, Consortium researchers will have access 
to data on some 200,000 study subjects.
    Demography.--As the percentage of Americans over age 65 increases, 
profound societal changes will likely occur. NIA-supported researchers 
are exploring the changing demographic, social, and economic 
characteristics of the older population. Research embraces topics such 
as: trends in the age-structure of populations; changes in levels of 
disease and disability; economic costs of disability; cost-
effectiveness of interventions; migration and geographic concentrations 
of the elderly; decision-making about retirement; pensions and savings; 
the relationship between health and economic status; and health 
disparities by gender and race. The results of this research often have 
important implications for public policy. Such research often involves 
large datasets that are frequently co-sponsored by NIA and other 
government agencies in the United States and overseas. These include:
  --Health and Retirement Study, a biennial survey of more than 22,000 
        Americans over age 50, which provides data for researchers, 
        policy analysts, and program planners who are making major 
        policy decisions that affect retirement, health insurance, 
        saving and economic well-being.
  --National Long-Term Care Study, which explores trends in the 
        prevalence of self-rated old age disability and physical, 
        cognitive, and sensory limitations.
  --Longitudinal Study of Aging, a long-term study in which the NIA 
        participates with the National Center for Health Statistics.
  --Panel Study of Income Dynamics, begun in 1968 and conducted by the 
        National Science Foundation, is a nationally representative 
        longitudinal study that collects information on U.S. 
        households. Notably, the PSID contains information on 
        approximately 5,000 heads of households and spouses who are 
        baby boomers (born 1945-1964)--a cohort not yet represented in 
        the Health and Retirement Study (HRS). Continued data from the 
        PSID will shed light on individual household saving behavior of 
        the baby boom generation and its neighboring age cohorts.
    Health Communication.--Communication of research-based health 
information is another key activity of the NIA, and the Institute uses 
both traditional and innovative means to disseminate information. In 
2003, the Pew Internet and American Life survey found that 22 percent 
of Americans age 65 or older have access to the Internet, and that 58 
percent of these ``wired seniors'' had used the Internet to look for 
information about a specific disease. However, NIA-supported research 
has demonstrated that with age come changes in cognition (such as 
working memory, perceptual speed, text comprehension) and vision 
(including loss of ability to detect fine details, less light reaching 
the retina, and loss of contrast sensitivity) that could hinder the 
older person's ability to use the Internet easily and effectively. To 
respond to the unique needs of Internet users over 60, the NIH launched 
NIHSeniorHealth.gov on October 23, 2003. Developed by the NIA and the 
National Library of Medicine, and featuring content developed in 
collaboration with several other NIH Institutes, this web site is easy 
for older adults to read, understand, remember, and navigate. For 
example, the site features large print and short, easy-to-read segments 
of information repeated in a variety of formats--such as open-captioned 
videos and short quizzes--to increase the likelihood it will be 
remembered. Consistent page layout and prompts help users move from one 
place to another on the site without feeling lost or overwhelmed. The 
site also has a ``talking'' function, which allows users the option of 
reading the text or listening to it as it is read to them.
    The risk of many diseases increases with age, so the site focuses 
on health topics or specific diseases that are of particular interest 
to older people, including Alzheimer's disease, Alzheimer's disease 
caregiving, arthritis, balance problems, breast cancer, colorectal 
cancer, exercise for older adults, hearing loss, lung cancer, and 
prostate cancer. Upcoming and planned topics include complementary and 
alternative medicine, diabetes, falls, shingles, vision changes, and 
others. Each topic provides general background information, quizzes, 
frequently asked questions (FAQs), open-captioned video clips, 
transcripts for the videos, and photos and illustrations with captions. 
From its launch in October 2003 through late January, 
NIHSeniorHealth.gov has received over a million page views and been 
visited by nearly 118,000 unique visitors.
    The NIA also maintains a large selection of lay-language Age Pages, 
which cover an array of topics relevant to older people and include 
information on a number of diseases and conditions, suggestions for 
coping with these conditions, and information on other resources. Most 
of the Age Pages have been translated into Spanish.
    At a March 2002 hearing of this Committee entitled ``Bench to 
Bedside,'' Chairman Regula recommended that NIA and the Administration 
on Aging (AoA) work together to disseminate research-based consumer 
education to the thousands of seniors who participate in the Meals-on-
Wheels program across the Nation. In response, NIA staff, with the 
participation of AoA, have conducted focus groups of program managers 
from the Meals on Wheels Association of America (MOWAA) to determine 
the types of information of greatest interest to MOW's clients, as well 
as the best ways to deliver such information (e.g., meal tray liners 
printed with key health messages, articles for MOWAA newsletters, or 
specially crafted Age Pages.) Based on focus group feedback, NIA is 
currently revising Age Pages on diabetes, alcohol, and depression; 
these materials will be tested at the upcoming MOWAA meeting in 
September 2004, and we anticipate that distribution to MOWAA clients 
will begin shortly thereafter.
    The Alzheimer's Disease Education and Referral (ADEAR) Center has 
been compiling and disseminating information about AD for health 
professionals, persons with AD and their families, and the public since 
1990. NIA is also working to translate research findings into action 
through its highly successful campaign to encourage older people to 
exercise. In the last four years, NIA has distributed over 611,000 
copies of its exercise guide and 93,000 copies of its companion video 
to the public. A Spanish-language version of the guide was published in 
January 2002, and over 33,500 copies have been distributed to date. The 
NIA's efforts to promote exercise and strength training are conducted 
in support of the President's ``HealthierUS'' and the Department of 
Health and Human Services' ``Steps to a HealthierUS'' initiatives.

                                 ______
                                 
           Prepared Statement of Dr. Andrew C. von Eschenbach

                            BUDGET STATEMENT

    The fiscal year fiscal year 2005 budget includes $4,870,025,000, an 
increase of $134,052,000 over the fiscal year 2004 enacted level of 
$4,735,973,000 comparable for transfers proposed in the President's 
request.

                          2015 CHALLENGE GOAL

    The Nation's unwavering support of cancer research has enabled the 
National Cancer Institute (NCI) and our many partners throughout the 
cancer research community to make enormous strides over the past three 
decades. Our understanding of cancer as a disease process, and the 
associated opportunities to prevent, detect early and successfully 
treat it has improved dramatically. However, even in the face of this 
progress, the magnitude of the cancer burden means that the disease 
still affects nearly every family in America. This year, approximately 
1.4 million of our citizens will face a cancer diagnosis, and over 
560,000 of our citizens--about 1,540 each day--will die from their 
disease. Furthermore, the fact that cancer occurs primarily in 
individuals over the age of 50 means that more of our citizens will 
suffer the terrible burden of this disease in the next 10-20 years due 
to the aging and changing demographics of our population.
    Fortunately, the convergence of science and advanced technologies 
is changing our perceptions of what is possible. In fact, we are 
entering a period in biomedical research where progress in cancer 
research can be exponential--an inflection point. Last year I informed 
this committee that ``our nation's investment in basic research has 
fueled the engine of discovery, which is rapidly illuminating the 
cumulative genetic changes and associated molecular mechanisms that 
ultimately produce cancer.'' As I said then and I reiterate now ``for 
the first time, we have within our grasp the ability to design target-
specific interventions to preempt this process.'' Based on the current 
astounding pace of progress in cancer research and the transformational 
effects of advanced biomedical technologies, I am even more fervent in 
my belief that we can achieve this vision.
    To capitalize on this inflection point, I have set forth an 
ambitious challenge goal for the NCI, and for the entire cancer 
research and care community: to eliminate suffering and death from 
cancer by 2015. This ``stretch goal'' is intended to unify and focus 
our thinking, strategies, and actions in new ways that will optimize 
the use of our resources and accelerate progress against cancer. This 
challenge also presents new opportunities for the NCI to provide 
leadership for our Nation's effort to conquer cancer, especially in the 
development of the new synergies and partnerships needed to achieve 
this bold vision.
    Recent progress across nearly all of biomedical research has set 
the stage for unimagined progress in biomedicine early in the 21st 
century. Thanks to research, we now understand that cancer is a disease 
process--where normal cells are transformed into cancer cells through a 
series of defined steps that begin with a simple change in the genetic 
material. If left unchecked, these transformed cells can progress and 
spread to cause the suffering and death that we recognize as the 
horrific burden of cancer. Thankfully, our growing understanding of 
this process has revealed multiple opportunities to intervene. These 
new intervention strategies include preventing initiation of the 
process; detecting it early when it is most amenable to elimination; 
and arresting the process to stop the spread (metastasis), which is the 
primary reason that patients suffer unduly and die from their disease. 
In short, we are rapidly learning how to ``preempt'' the cancer disease 
process. We believe in the next few years that new intervention 
strategies will allow us to prevent and/or eliminate many cancers--and 
ultimately transform cancer into chronic, manageable diseases that 
patients live with--not die from.
    Scientific advances and major discoveries from areas such as 
genomics, nanotechnology, proteomics, immunology, and bioinformatics 
allow us to envision a not too distant future when a patient's genetic, 
lifestyle, and environmental risk for cancer can be combined with 
effective prevention and early intervention strategies especially for 
those at high risk. Serum genomic and proteomic patterns, and advanced 
imaging technologies, will be employed to detect cancers at the 
earliest stages. Precise molecular diagnosis and patient-specific 
prognostic profiling will allow physicians to predict response to 
specific interventions and provide a rational basis for tailoring 
therapies. The result will be more efficacious and less toxic, targeted 
agents delivered to patients. Achieving these outcomes will result in 
the preemption of a great deal of cancer. I believe that this is no 
longer a dream but an achievable reality.
    To achieve the 2015 challenge we must take the steps necessary to 
accelerate the pace of progress across the entire cancer research 
continuum. The basic research which is aimed at discovering the 
pathways that lead to cancer represents the beginning of a continuum 
that proceeds through development of new agents and technologies and 
ultimately to the delivery of these new interventions to patients. 
Using our ever increasing knowledge of the molecular defects in cancer 
cells and the biomarkers that define the cancer process will enable the 
development of the new targeted interventions we need to prevent, 
detect, and treat cancer.
    To achieve this acceleration the NCI has identified six ``mission-
critical'' research areas that we believe will offer significant 
potential for near term progress against cancer. These include: 
harnessing the power of the newly emerging science of molecular 
epidemiology to better identify risk populations; developing an 
integrative understanding of cancer (systems) biology to discover key 
biomarkers and targets; facilitating the development of ``strategic'' 
cancer interventions for targeted prevention, early detection, and 
treatment; creating a national integrated clinical trials system to 
more effectively test these interventions; overcoming health 
disparities to deliver these advances to those in greatest need; and 
developing a bioinformatics network to connect the cancer research 
community and optimize the collection, analysis, and use of the 
enormous amount of data and knowledge that must be managed and shared.

               CANCER BIOMEDICAL INFORMATICS GRID (CABIG)

    In this past year's Appropriations Committee Report, NCI was 
requested to explore ways in which information could be better shared 
among researchers and cancer care deliverers. In early 2004, the NCI 
responded by launching an unprecedented program to connect cancer 
researchers through an advanced technology platform called the Cancer 
Biomedical Informatics Grid (caBIG). This pilot initiative has the 
potential to transform the pace of cancer research by providing the 
tools needed to share information and data. caBIG will be developed by 
connecting 50 of our NCI-designated cancer centers through an NCI-
developed open source system which will in effect become the ``World 
Wide Web'' of cancer research. This platform which integrates with the 
NIH Roadmap informatics initiative will link individual cancer 
researchers and research institutions across the nation, and around the 
world, in an open source, federated network that will enable 
researchers to share tools, standards, data, computing applications, 
and technologies. This unprecedented bioinformatics system will 
facilitate the collection, storing, searching, analysis, 
classification, management, and archiving and retrieval of research 
data. caBIG will improve the quality of data, provide unimagined access 
to heretofore limited databases, increase the pace of cancer research 
and enhance the effectiveness of our investments in cancer research. 
caBIG has the capability to virtualize cancer research.
    caBIG leverages the unique resources and capabilities of NCI's 
cancer centers to meet the needs of the broad cancer research and care 
communities. The cancer centers, along with NCI's platforms for 
translational research, the Specialized Programs of Research Excellence 
(SPORES), are our partners in this strategic effort to ensure that the 
fruits of fundamental scientific research can be rapidly captured for 
the benefit of cancer patients. This is an example of how the future 
can be transformed if we can successfully integrate advanced 
technologies across the discovery, development, and delivery research 
continuum. In this instance the whole will be a great deal more than 
the sum of the parts.

           NATIONAL ADVANCED BIOMEDICAL TECHNOLOGY INITIATIVE

    In developing strategies to optimize progress in NCI's high 
priority research areas, it became clear that we must proactively 
identify, develop, and deploy advanced biomedical technologies, such as 
bioinformatics, across the entire cancer research continuum. This 
concept represents a critical new element of our overall strategy to 
achieve the 2015 challenge goal; however, there is clearly a gap 
between our current level of capabilities in advanced technologies and 
what is needed. I believe that we now have the opportunity to address 
this gap through the creation of an unprecedented national advanced 
biomedical technology initiative that will be transformational for 
cancer and other diseases.
    Achieving our challenge goal will require that we fully integrate 
advanced ``enabling'' technologies with the cancer research and care 
enterprise. Advanced technologies represent those new tools and 
approaches that enable new approaches to the challenging problems of 
detecting, controlling, and preventing cancer. Advanced technologies 
allow cancer researchers to generate, collect, and analyze vast amounts 
of data, and to pursue innovative approaches that could not be 
accomplished without these sophisticated tools. As illustrated by our 
efforts in bioinformatics, the NCI is providing leadership in the 
development and integration of advanced technologies and we are also 
building the cross-disciplinary teams needed to implement these new 
strategies.
    Providing advanced technology platforms to scientists working in 
cancer research is one of our highest priorities at the NCI; and to 
that end, we have undertaken a cancer-enterprise wide planning effort 
to develop a national advanced technology initiative for cancer. In 
planning for this initiative, the NCI has identified (in addition to 
bioinformatics) multiple areas of advanced technology development that 
will be crucial in building this national resource. Examples of cross-
cutting capabilities, which will support the range of strategic 
research priorities that we have identified as pivotal areas for 
progress, include: advanced imaging; biomarkers and proteomics; 
nanotechnology; and development capabilities such as scale-up for new 
cancer therapies and prototyping for new diagnostics devices.
    We have made significant progress in cancer diagnosis and treatment 
based on static imaging of the body's organs provided by x-ray, CT, 
PET, and MRI. The new generation of advanced imaging technologies will 
target specific molecules and cells. We will be able monitor cellular 
processes to assess the effectiveness of experimental treatments and to 
define cancer cells at their earliest stages. Nanotechnology will 
provide opportunities to develop biosensors that have the capability of 
detecting changes in cells at the earliest stages of cancer and 
``report'' back on them. This breakthrough technology will also 
facilitate the design of new technologies to probe cell functions, 
measure cellular events with unimagined precision, and specifically 
deliver molecular entities to attack cancer. The combination of 
advanced imaging and nanotechnology offers the promise of realizing 
these advances to achieve the exponential progress that is possible at 
the current inflection point.
    The post-genomics era in cancer research has produced vast amounts 
of information aout the genetic basis of cancer, but perhaps of more 
importance, we are learning that the functioning of normal and tumor 
cells is controlled by the proteins that are transcribed from these 
abnormal genomes. These proteins, along with genes and other indicators 
of the processes and pathways that distinguish cancer, are called 
biomarkers. Through the use of advanced technologies NCI is developing 
innovative strategies to discover and validate biomarkers for use in 
clinical applications. Biomarkers, along with advanced imaging, 
nanotechnology, and other advanced technology platforms, will comprise 
an unprecedented National Advanced Biomedical Technology Initiative for 
Cancer (NABTIc).
    This initiative is a major element of our strategy to achieve NCI's 
challenge goal to eliminate suffering and death due to cancer by 2015. 
The NABTIc would leverage and align the capabilities and resources in 
advanced technology development across the nation--and gain strength 
from all sectors. Through a network of technology ``nodes'' it would 
capitalize on capabilities in our cancer centers and SPORES and 
optimize the deployment of NCI's existing strengths in advanced 
technologies that currently exist at our Frederick campus. This 
initiative is currently being refined and further developed with the 
aid of our advisors and partners in the extramural community, and a 
plan to purse this concept is under development.

                         STRATEGIC PARTNERSHIPS

    Finally, to implement many elements of our strategic plan, we will 
partner broadly With all of the sectors that comprise the cancer 
community, including other federal agencies and private industry. The 
NCI is an active partner with many federal agencies, including the 
Department of Defense, the Veterans Administration, the Centers for 
Disease Control and Prevention, the Agency on Healthcare Research and 
Quality, and the Centers for Medicare and Medicaid Services. One 
partnership that is critically important to optimizing the pace at 
which laboratory discoveries progress to become new interventions for 
cancer is our alliance the Food and Drug Administration (FDA). Early 
last year we created the NCI/FDA Interagency Oncology Task Force to 
leverage the expertise of both agencies for the expressed purpose of 
streamlining and accelerating the development of preventive, 
diagnostic, and therapeutic interventions for cancer. Considerable 
progress has already been made in the areas of joint training and 
fellowships, developing markers of clinical benefit, improvement in the 
overall process of oncology drug development, and creation of a common 
bioinformatics platform (caBIG) to improve the organization and 
reporting of data from oncology clinical trials. These partnerships are 
critical. Each agency, along with the other sectors involved in the 
development, commercialization, and delivery of the new inventions we 
desperately need to preempt cancer, is a valued partner who can unite 
with us to facilitate and speed the overall process.
    Last year, I closed by telling members of this committee that we 
stand at a pivotal crossroads--a defining moment in this nation's 
effort to prevent and cure cancer. Over the past 12 months we charted 
the future course forward--through the creation and implementation of 
innovative strategies--and have undertaken initiatives that will allow 
us to move rapidly toward a day when cancer will become a chronic 
disease. What was once a vision is becoming reality through the 
combined efforts of researchers and leaders from all sectors, patients 
and their families--and so many others. I believe that together we will 
realize the economic and human benefits of eliminating the suffering 
and death due to cancer, and in this quest, inform our efforts to 
transform our overall health care system.

                                 ______
                                 
               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 2005 budget of $4,425,507,000 includes an 
increase of $122,467,000 over the fiscal year 2004 enacted level of 
$4,303,040,000, comparable for transfers proposed in the President's 
request.
    NIAID conducts and supports research studies to understand, treat, 
and prevent infectious diseases such as HIV/AIDS and other sexually 
transmitted infections, influenza, tuberculosis, malaria, and illness 
from potential agents of bioterrorism. In addition, the Institute 
supports research on transplantation and immune-related illnesses, 
including autoimmune disorders, asthma and allergies. For 56 years, 
NIAID-sponsored research has led to new therapies, vaccines, diagnostic 
tests, and other technologies that have improved the health of millions 
of people worldwide. Historically, NIAID has accomplished its mission 
with a strong commitment to basic and targeted research in immunology, 
microbiology, and infectious disease, disciplines that are related and 
complementary. The new initiatives of the NIH Roadmap, and the 
information, reagents and infrastructure they will produce, will 
further promote the efficient and effective movement of NIAID 
discoveries from the laboratory bench to the bedsides of patients.

       THE NIAID RESEARCH RESPONSE TO THE THREAT OF BIOTERRORISM

    The use of deadly pathogens such as smallpox or anthrax as agents 
of bioterrorism is a serious threat to the citizens of our nation and 
the world, and biodefense research to mitigate this threat is a key 
focus of NIAID research. Since the anthrax attacks of 2001, NIAID has 
significantly strengthened, accelerated, and expanded our biodefense 
research program. NIAID-supported biodefense research includes: (a) 
basic studies of the structure, ecology, and disease-causing mechanisms 
of microbes that could be used by bioterrorists; (b) the response of 
the immune system to these pathogens, and; (c) the translation of this 
knowledge into safe and effective countermeasures--treatments, 
diagnostics, and vaccines. To achieve our biodefense research goals, 
NIAID works closely with partners in academia, industry, and other 
private and public-sector agencies. Research on potential agents of 
bioterror promises to enhance not only our preparedness for 
bioterrorism, but also for naturally occurring endemic and emerging 
infectious diseases.
    Progress in biodefense research has been swift and substantial. 
More than 50 major NIAID initiatives involving intramural, academic and 
industrial partners have been undertaken. As part of this effort, the 
Institute has greatly increased biodefense research capacity. For 
example, NIAID recently funded eight Regional Centers of Excellence for 
Biodefense and Emerging Infectious Diseases Research. This nationwide 
network of multidisciplinary academic centers will conduct wide-ranging 
research on infectious diseases and the development of diagnostics, 
therapeutics and vaccines. In addition, NIAID is supporting the 
construction of two National Biocontainment Laboratories (NBLs) and 
nine Regional Biocontainment Laboratories (RBLs). These high-level 
biosafety facilities promise to speed the development of effective 
therapies, vaccines and diagnostics for diseases caused by agents of 
bioterror as well as for naturally occurring emerging diseases such as 
SARS and avian influenza.
    In addition, NIAID has developed and expanded contracts to screen 
new drugs; develop new animal models and establish a reagent and 
specimen repository. NIAID also has made a significant investment in 
determining the genetic sequences of the genomes of a range of 
pathogens, which has helped to illuminate the workings of all classes 
of microorganisms. NIAID-supported researchers and their international 
colleagues have sequenced genomes representative of all bacteria 
considered bioterror threats (including multiple strains of the anthrax 
bacterium), as well as at least one strain of every potential viral and 
protozoan bioterror pathogen. NIAID also is funding research to better 
understand the body's own protective mechanisms. A new NIAID program, 
the Cooperative Centers for Translational Research on Human Immunology 
and Biodefense, will conduct research to better understand the human 
immune response to potential agents of bioterror, with the objective of 
developing new bioterror countermeasures. Another large-scale program 
is funding sophisticated studies of the human innate system, comprised 
of the cells that are the ``first responders'' to infection. Boosting 
innate immunity holds great promise for developing fast-acting 
countermeasures to mitigate the effects of bioterror pathogens or 
toxins.
    The ultimate goal of all NIAID biodefense research is the 
development of medical countermeasures. NIAID-supported scientists have 
identified: (a) antivirals that may play a role in treating smallpox or 
the complications of smallpox vaccination; (b) several approaches to 
blocking the toxins of the anthrax bacterium; as well as (c) 
antibiotics, antivirals and antitoxins against other major bioterror 
threats. New and improved vaccines against smallpox, anthrax and other 
potential agents also are being developed, with the objective of adding 
them to the Strategic National Stockpile (SNS). For example, NIAID has 
sponsored the development of a next-generation anthrax vaccine known as 
rPA, with the goal of adding 75 million doses to the SNS to protect 
U.S. citizens. Clinical trials of rPA are ongoing; results to date 
build on similar findings in animal studies and suggest that the 
vaccine is safe and capable of evoking a robust immune response. 
Researchers also will test whether the currently recommended course of 
antibiotic therapy for individuals exposed to anthrax spores can be 
reduced by vaccinating exposed subjects with rPA.
    NIAID-supported researchers also are testing several new smallpox 
vaccines that may prove at least as effective as the current smallpox 
vaccine, but with fewer side effects. One of these, modified vaccinia 
Ankara (MVA), is based on a strain of the vaccinia virus that 
replicates less robustly than the traditional Dryvax vaccinia virus, 
and is known to cause fewer side effects than the latter. Human trials 
of MVA vaccines are underway at NIH and elsewhere. Encouragingly, 
recent studies by NIAID intramural scientists and their colleagues have 
shown that MVA protects monkeys and mice from smallpox-like viruses. 
NIH also has launched the first human trial of a vaccine designed to 
prevent infection with Ebola virus. The trial vaccine, a type called a 
DNA vaccine, is similar to other investigational vaccines that hold 
promise for controlling such diseases as AIDS, influenza, malaria and 
hepatitis.

                           HIV/AIDS RESEARCH

    Most recent estimates on the scope of the HIV/AIDS pandemic are 
profoundly sobering. Approximately 40 million people worldwide are 
living with HIV/AIDS. In 2003 alone, 5 million people worldwide were 
newly infected with HIV--about 14,000 each day, more than 95 percent of 
whom live in low and middle income countries. In 2003, 3 million people 
worldwide with HIV/AIDS died. In the United States, nearly one million 
people are living with HIV/AIDS, and by the end of 2002, more than 
500,000 people with HIV/AIDS had died. As shocking as these numbers 
are, they do not begin to adequately reflect the physical and emotional 
devastation to individuals, families, and communities coping with HIV/
AIDS, nor do they capture the huge deleterious impact of HIV/AIDS on 
the economies and security of nations, and indeed entire regions. Even 
as the burden of HIV/AIDS continues to grow, recent developments 
provide some measure of optimism. For example four new antiretroviral 
drugs were licensed in 2003 by the U.S. Food and Drug Administration 
(FDA), each of which built on NIAID-sponsored research and/or has been 
tested in NIAID clinical trials networks. Many other ``next-
generation'' anti-HIV drugs are in clinical trials.
    A vaccine that prevents HIV infection--or at least slows the 
progression of disease--is a critical NIAID priority. Vaccine 
developers face formidable obstacles, including the genetic diversity 
of the virus and the lack of a clear understanding of the immune 
responses that might protect against HIV infection. Nonetheless, NIAID 
and our academic, industrial, international and philanthropic partners 
have made significant progress. Numerous HIV vaccine candidates are in 
various stages of preclinical and clinical development. The new 
Partnership for AIDS Vaccine Evaluation (PAVE) promises to optimize 
these efforts. PAVE is a coordinated HIV vaccine research effort that 
includes the three government agencies most involved in this activity--
NIH, the Centers for Disease Control and Prevention (CDC), and the 
Department of Defense. These agencies will work together to ensure that 
research protocols, standards, and measures are developed in a 
coordinated and harmonized manner so that outcomes can be compared 
across trials in the most cost effective and scientifically efficient 
manner. International non-government organizations (NGOs) and companies 
also have expressed interest in joining the partnership. Concurrently, 
novel approaches to HIV prevention are being studied and validated, 
including topically applied microbicides that individuals could use to 
protect themselves from HIV and other sexually transmitted pathogens. 
As discussed in the new NIAID Strategic Plan for Topical Microbicides, 
more than 50 candidate agents have shown laboratory activity against 
HIV and other STDs, and several of these agents have demonstrated 
safety and efficacy in animal models. In small human studies, several 
products have proven safe; later this year, NIAID's HIV Prevention 
Trials Network (HPTN), in conjunction with the National Institute of 
Child Health and Human Development, will launch a large international 
study to test two promising products in more than 3,000 women at high 
risk of acquiring HIV in the United States, five African countries, and 
India.

      RESEARCH ON OTHER EMERGING AND EMERGING INFECTIOUS DISEASES

    Infectious diseases have always afflicted humanity, and they will 
continue to confront us as long as man and microbes co-exist. 
Unfortunately, the viruses, bacteria, and parasites that cause 
infectious diseases do not remain static, but continually and 
dramatically change over time as new pathogens (such as HIV and the 
SARS coronavirus) emerge and as familiar ones (such as influenza virus 
and West Nile virus) re-emerge with new properties or in unfamiliar 
settings.
    West Nile virus (WNV) first appeared in the western hemisphere in 
1999, and by 2003 had spread to 45 states in the United States. NIAID 
has moved quickly to address this threat with basic research on the 
virus and its maintenance in nature, the development of vaccines and 
treatments, and the provision of reagents and other resources to the 
research community. NIAID also is supporting the development of three 
types of vaccines, as well as the screening and testing of WNV 
therapies. For example, the NIAID-sponsored Collaborative Antiviral 
Study Group is assessing the safety and efficacy of WNV immunoglobulins 
in patients with, or at high risk of serious brain diseases caused by 
WNV.
    Severe acute respiratory syndrome (SARS) is a new infectious 
disease first identified in humans in early 2003. The prompt 
recognition that SARS is caused by a new type of coronavirus, and the 
rapid progress in SARS research reflect the dedication of and 
collaboration by the world's medical researchers and public health 
experts, including NIAID-sponsored scientists in the United States and 
abroad. NIAID supports research to understand the epidemiology and 
biology of the SARS virus and how it spreads, and to develop SARS 
countermeasures. Several approaches to SARS countermeasures are being 
pursued by the NIAID Laboratory of Infectious Diseases, the NIAID 
Vaccine Research Center, and by our contractors and grantees. For 
example, NIAID is participating in a project to screen up to 100,000 
antiviral drugs and other compounds for activity against the SARS 
virus, and will test the most promising in animal models and human 
clinical trials. A number of compounds have shown promise in the test 
tube, including alpha interferon, a drug already approved by the FDA 
for the treatment of hepatitis B and C infections.
    NIAID scientists and grantees are pursuing several parallel 
approaches in the search for a SARS vaccine. Once these experimental 
vaccines are ready, NIAID plans to test them in human clinical trials 
in our network of Vaccine and Treatment Evaluation Units. New research 
suggests that a SARS vaccine is within reach: NIAID intramural 
scientists have demonstrated that the mouse immune system develops 
antibodies capable of single-handedly neutralizing the SARS virus. This 
discovery affirms that researchers developing vaccines that trigger 
antibodies to the SARS virus are heading in the right direction. These 
findings also indicate that drug researchers can use laboratory mice as 
a model to evaluate whether a drug blocks the SARS virus. Both findings 
could help lessen the time it takes to develop an effective vaccine or 
antiviral drugs for SARS.
    Influenza is a classic example of a re-emerging disease; it is not 
a new disease, but it continually changes. Because the replication 
machinery of the influenza virus is error prone, as the virus 
multiplies it can mutate to a slightly different form; this is referred 
to an ``antigenic drift.'' Such viruses might require a slight 
modification of the yearly influenza vaccine to accommodate these 
changes. In addition, non-human influenza viruses such as avian 
influenza, can emerge that may be able to jump species into domestic 
poultry, farm animals such as pigs, and humans. This type of 
significant change in the antigenic makeup of the virus is referred to 
as ``antigenic shift.'' Deadly pandemics associated with antigenic 
shifts are known to have occurred in 1918, 1957, and 1968. The pandemic 
that occurred in 1918-1919 after an antigenic shift killed 20-40 
million people worldwide, including more than half a million in the 
United States. This recent history explains the current high level of 
concern about the appearance of new forms of virulent H5N1 avian 
influenza viruses in Asia that can adapt themselves by mutation to 
infect humans as has been the case already in dozens of individuals in 
Viet Nam and Thailand. Of even greater concern is the possibility that 
this avian virus can combine or reassort its genes with a human 
influenza virus and acquire the capability of readily spreading from 
person to person resulting in a new pandemic. Given the poor condition 
of public health systems in many underdeveloped regions and the speed 
of modern air travel, the consequences of such an event, should it 
result in an influenza pandemic, would be severe.
    To address this threat, NIAID supports a broad program to develop 
more effective approaches to controlling influenza virus infections. 
Research includes programs to understand the pathogenesis, 
transmissibility, evolution, epidemiology, and the immune response to 
influenza viruses, as well as to develop new diagnostics, antiviral 
drugs and vaccines. NIAID currently supports several research projects 
to develop vaccines that could be manufactured more rapidly, are more 
broadly cross-protective, and are more effective than current influenza 
vaccines. The use of reverse genetics--a tool developed by NIAID 
grantees--holds the promise for more rapid generation of vaccine 
candidates that match the anticipated strain expected to circulate 
during the influenza season. Reverse genetics also can be used to turn 
highly pathogenic influenza viruses into vaccine candidates more 
suitable for vaccine manufacturing by removing or modifying certain 
virulence genes; laboratories around the world are using the technique 
to prepare vaccine candidates against the H5N1 viruses emerging in 
Asia. NIAID also is funding the development of new influenza vaccine 
technologies. Recently, NIAID supported a Phase II clinical trial of a 
new influenza vaccine produced in a cell culture system as an 
alternative to manufacturing the vaccine in eggs. Because NIAID has had 
remarkable success in the past with groundbreaking vaccine research--
including advances that led to hepatitis B, Haemophilus influenzae b, 
pneumoccocal pneumonia, and acellular pertussis vaccines--we are 
confident that one of the approaches that we are pursuing also will 
lead to a useful, ``next-generation'' influenza vaccine that can 
readily be adapted to emerging influenza strains.

                  RESEARCH ON IMMUNE-MEDIATED DISEASES

    Immune-mediated diseases such as autoimmune diseases, allergic 
diseases, and asthma are important health challenges in the United 
States and abroad. Autoimmune diseases 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, and the leading cause among children. 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, 
which has led to the development of many useful therapies. 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. NIAID-sponsored researchers are 
now developing novel ways of selectively blocking inappropriate or 
destructive immune responses, while leaving protective immune responses 
intact, an area of research known as tolerance induction. In the Immune 
Tolerance Network, a consortium of basic and clinical scientists, 
promising studies are underway using tolerance induction to treat 
autoimmune diseases, such as rheumatoid arthritis, type 1 diabetes, and 
multiple sclerosis; asthma and allergic diseases; and the rejection of 
transplanted organs, tissues, and cells. So-called ``tolerogenic'' 
therapies would replace current lifelong non-specific immunosuppressive 
regimens (and their often debilitating side-effects) with short-term 
specific regimens that hold the promise of being curative.
    Other important research is being conducted by the recently 
expanded Autoimmunity Centers of Excellence. The nine centers that make 
up this program conduct basic research and clinical trials on new 
immune-based therapies for diseases that collectively afflict between 
14 and 22 million Americans. The Institute and our collaborators also 
have significantly bolstered the study of primary immunodeficiency 
diseases--disorders caused by inherited flaws in the immune system that 
increase susceptibility to infections--with funding of the Primary 
Immunodeficiency Research Consortium (PIRC), a coalition of the world's 
most prominent researchers in the field of primary immunodeficiency 
diseases.
    Another important NIAID research focus is the development of new 
interventions to reduce the burden of asthma, a significant and growing 
public health problem in the United States and many nations worldwide. 
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. To develop interventions to 
prevent the onset of asthma, more information is needed on the events 
that induce asthma. NIAID's Inner-City Asthma Consortium (ICAC) will 
soon launch a large study to define and analyze immunological and 
environmental influences upon the development of childhood asthma in a 
cohort of urban children followed from birth.

                               CONCLUSION

    With a strong research base, talented investigators in the United 
States and abroad, and the availability of powerful new research tools, 
NIAID anticipates that our basic and applied research programs will 
provide the countermeasures to improve our defenses against those who 
would attempt to harm us with bioterrorism, will develop new tools in 
the fights against HIV/AIDS and other infectious diseases, and will 
improve therapies and management of immune-mediated diseases.

                                 ______
                                 
                Prepared Statement of Dr. Nora D. Volkow

    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 2005 budget includes $1.019 billion, an increase 
of $28.273 million over fiscal year 2004 conference level of $990.787 
million comparable for transfers proposed in the President's request.

                      NIDA: 30 YEARS OF DISCOVERY

    As the National Institute on Drug Abuse (NIDA) prepares to 
celebrate its 30th anniversary this year, I am honored to have this 
opportunity to tell you about some of our remarkable scientific 
accomplishments and how these advances are setting the course for a 
better future. A tomorrow that will bring us even better prevention 
interventions to deter the initial use of drugs by those at risk before 
they become one of the more than 180 million people around the world 
who currently abuse illegal drugs. A future that will also bring us 
better treatment interventions to help those who have already become 
addicted, and who may suffer from some of the myriad consequences of 
drug abuse including HIV/AIDS and comorbid mental illnesses. Research 
supported by NIDA, the world's largest supporter of research on the 
health aspects of drug abuse and addiction, may even bring us 
innovative and improved ways to deal with other major health epidemics 
impacting our society, such as chronic pain and obesity.

        ADDICTION AND OBESITY: COMMON NEUROBIOLOGICAL MECHANISMS

    Obesity and addiction are serious National health problems that may 
have much in common. Both addiction and some forms of obesity represent 
problems resulting from excessive behaviors and lack of impulse 
control. Knowledge derived from addiction research shows that the brain 
circuits involved in compulsive eating and impulse regulation are part 
of the same brain systems involved in addiction, with the 
neurotransmitter dopamine playing a prominent role. (See Figure 1.) A 
better understanding of the role of the dopamine and other systems in 
the motivation for and salience of food may lead us to the development 
of better medications and behavioral interventions for obesity, as well 
as addiction. In addition, medications being developed for obesity may 
also help to reduce drug use. Because of the commonalities between 
these disorders, we are able to share knowledge of brain and behavior 
and combine efforts across institutes to forge new insights and 
approaches that may result in improved health for all. NIDA is pleased 
to be a key participant in a trans-NIH initiative that is looking at 
all aspects of this chronic health problem, from its neurobiological 
underpinnings to helping people establish healthy behaviors.

             THE INTEGRATION OF BRAIN, BEHAVIOR AND HEALTH

    Understanding the connections between brain, behavior, and health 
will be critical to improving the health of ALL Americans. Science is 
at a point where all the elements of the human brain (genes, proteins, 
circuits) and its development can now be mapped out.
    We did it with the Human Genome and I am confident we can do it 
with the brain. We are already beginning to unravel how various genes, 
proteins, brain circuits and pathways interact with each other and the 
environment to affect all aspects of human behavior. This overarching 
approach is necessary if we are to make progress in improving the 
quality of life for individuals who suffer from complex disorders, such 
as drug addiction, which can start at a young age and continue across 
the lifespan. Now that advances in medical sciences have increased the 
lifespan of humans, a major challenge becomes to improve the quality of 
life of individuals, which hinges on our ability to understand the 
neurobiological underpinnings of human behavior and the impact and 
malleability the environment can have on it. This pertains not only to 
problems such as addiction, but other health problems such as obesity, 
adherence to medical regimens and with establishing and maintaining 
healthy life styles.

           ADOLESCENCE, THE DEVELOPING BRAIN, AND PREVENTION

    Collaborating with other Institutes to map out structural and 
functional aspects of the brain and how it changes throughout 
development will help us better understand human behavior, and how we 
can modify it to improve and extend human life. In particular, 
understanding the developing adolescent brain will be useful in drug 
abuse prevention efforts. Research indicates that exposure to drugs of 
abuse in adolescence, when many changes are occurring in the brain, may 
be a period of significantly increased vulnerability to drugs' effects. 
Fortunately, advances in science and NIH-funded studies have now 
brought us to a point where our researchers can use new animal models, 
new brain imaging technology and other neurobehavioral assessment tools 
to probe the development of brain and behavior interactions. These new 
directions in adolescent research will help to inform us on important 
aspects of cognition, decision-making, emotional regulation, and risk 
perception during adolescence, and will help us determine how these 
play a role in the use and consequences of illicit drugs. Armed with 
new knowledge about how adolescents make decisions, NIDA will be poised 
to design interventions that can reduce drug experimentation and 
addiction. We are making progress in this regard through our National 
Prevention Research Initiative and through our science education 
activities like ``NIDA Goes Back to School Campaign'' where science-
based materials were disseminated to teachers and students all across 
America.

                   EXCELLENT NEWS: DRUG USE DECLINES

    Some of the best news to a NIDA Director came in December 2003 when 
we released the latest data on teen drug use trends. NIDA's long-
standing Monitoring the Future Survey showed an approximately 11 
percent decline in illicit drug use over the last 2 years by students 
in the eighth, tenth, and twelfth grades combined. (See Figure 2.) The 
use of MDMA or Ecstasy decreased by almost fifty percent for the three 
grades combined in that same time period Also encouraging was the fact 
that tobacco use among this population was the lowest in the 28 year 
history of the survey.

          NEWS FOR CONCERN: PRESCRIPTION DRUG ABUSE CONTINUES

    There was also some disturbing news last year about youth drug use, 
showing very high rates of abuse of prescription pain killers (e.g., 
Vicodin and OxyContin). Remarkably, 1 in 10 twelfth graders reported 
abusing Vicodin last year, making it the second most widely abused 
illicit substance after marijuana in this population. Hospitals are 
also seeing more patients coming to emergency rooms for prescription 
drug abuse. According to data from SAMHSA, between 1994 and 2001 the 
number of emergency room mentions for hydrocodone and oxycodone 
increased 131 percent and 352 percent respectively. When used as 
prescribed, medications like Vicodin can be very effective, but when 
used improperly they can have very serious adverse health consequences 
including death from overdose. More research is needed to prevent, 
educate, and treat prescription drug abuse. Developing new medications 
that have no abuse or diversion potential is a high priority for NIDA.
    Researchers are making progress in this area. Just last year, 
researchers developed a compound to selectively affect a cannabinoid 
receptor that is involved in regulating pain. Unlike many other 
receptors, this one is not found in the brain. When the compound 
(AM1241) was given to animals, they were less sensitive to several 
forms of painful stimulation. Not only does this research open up a new 
arena for pain medication development, but it also sets the stage for 
developing new medications that are less likely to be abused. Also, 
NIDA's investment in the development of buprenorphine/naloxone for 
treating opioid addiction, for example, provides an alternative 
medication for pain that has less diversion potential than that of 
other opiate analgesics, and exemplifies how science can help alleviate 
our Nation's problems.

 RESEARCH ON THE CONSEQUENCES OF MARIJUANA, AND THE DEVELOPMENT OF NEW 
                              MEDICATIONS

    Research continues to shed new light on the deleterious 
consequences of marijuana, the most abused illegal drug in the United 
States. Early exposure to marijuana, for example, has been found to 
increase the likelihood of a lifetime of subsequent drug problems. A 
recent study, published in the Journal of the American Medical 
Association of over 300 fraternal and identical twin pairs, who 
differed on whether or not they used marijuana before the age of 17, 
found that those who had used marijuana early had elevated rates of 
other drug use and drug problems later on, compared to their twin who 
did not use marijuana before age 17. This study re-emphasizes the 
importance of primary prevention by showing us that early drug 
initiation is associated with increased risk of later drug problems, 
and it provides more evidence for why preventing marijuana 
experimentation during adolescence could have a big impact in 
preventing addiction.
    We are also finding that a lifetime of heavy cannabis use can 
result in an overall dissatisfaction with oneself and with life for 
most users. Last year, researchers published data on the impact of 
long-term cannabis use on life achievement such as educational 
attainment and income. Significantly fewer of the heavy cannabis users 
completed college and more had household incomes of less than $30,000 
compared to individuals who used marijuana minimally.
    It is clear, more research is needed to curtail use of this drug. 
Although the number of marijuana treatment admissions has increased 
from 92,414 in 1992 to 255,394 in 2001, there are relatively few 
treatments that have been shown to be effective specifically for 
marijuana addiction. NIDA is encouraging researchers, as well as the 
pharmaceutical industry, to become more active in finding new 
medications for marijuana and for other drugs of abuse. With the fairly 
recent discovery of an endogenous cannabinoid system with specific 
receptors and endogenous ligands, the likelihood of finding new targets 
for medications development is increased. One form of a cannabinoid 
receptor antagonist (CB1-receptor) has already been developed by 
several pharmaceutical companies and is undergoing clinical 
investigation for the treatment of alcoholism and nicotine addition, as 
well as obesity. Moreover, preliminary data in humans has shown that it 
can block the effects of marijuana.

    ACCELERATING RESEARCH DISCOVERIES BENCH TO BEDSIDE: BEDSIDE TO 
              COMMUNITY NIH ROADMAP AND OTHER INITIATIVES

    For science to be useful in preventing and treating addiction this 
knowledge has to reach the communities. This is an area where NIDA 
continues to excel. Over the past few years, NIDA has established and 
strengthened strong collaborative relationships with a number of 
government agencies, including the Substance Abuse and Mental Health 
Services Administration (SAMHSA) to build national infrastructures that 
can facilitate the flow of research into community practice. NIDA's 
National Drug Abuse Treatment Clinical Trials Network (CTN), which now 
serves 27 states plus the District of Columbia and Puerto Rico, and the 
more newly established National Criminal Justice Drug Abuse Treatment 
Study (CJ-DATS) exemplify NIDA's commitment to bringing science out of 
the laboratory and to the community. These initiatives parallel and 
complement those proposed as part of the NIH Roadmap, including the 
promotion of interdisciplincary research and the development of 
improved infrastructures for clinical research, which aim to accelerate 
the advancement of research discoveries from the bench to the bedside 
and to the community.

GETTING THE MEDICAL COMMUNITY MORE INVOLVED IN SCREENING AND ADDRESSING 
               HIV/AIDS AND OTHER DRUG ABUSE CONSEQUENCES

    Because drug abuse begins in youth and most pediatricians and 
family physicians typically do not ask questions about drug use, NIDA 
has launched a Primary Care Outreach Initiative to educate 
pediatricians and other primary care physicians about the importance of 
early detection and treatment. The medical community is also being 
reminded of the need to recognize substance abuse and addiction as 
disorders that will affect the course of other diseases, including 
mental illness, cancer, cardiovascular and pulmonary diseases, trauma 
and infectious diseases. Injection drug use has directly and indirectly 
accounted for more than one-third (36 percent) of AIDS cases in the 
United States. Data show that drug abuse treatment can reduce 
activities related to drug use that increase the risk of getting or 
transmitting HIV. Also the fact that the health and social consequences 
of drug abuse, including HIV/AIDS, disproportionately affect racial and 
ethnic minority populations; for example almost half of HIV/AIDS cases 
occur in African Americans even though they constitute only 11 percent 
of the population according to the latest Census data, which highlights 
the urgency to conduct research that can benefit all populations. (See 
Figure 3.)
    Using our established networks (CTN and CJ-DATS), NIDA is 
strengthening its commitment to attend to associated health problems 
like HIV/AIDS, hepatitis and co-morbidity that often accompany 
substance use. The CTN, for example has a number of treatment protocols 
underway that address HIV/AIDS and hepatitis. Also, because data 
suggest that the prevalence of HIV and other infectious diseases is 
high among drug users in the criminal justice system, with HIV 
seropositivity rates estimated to be 8-10 times higher than in the 
general population, NIDA is encouraging more research to prevent and 
treat the spread of HIV/AIDS and other diseases among individuals in 
the criminal justice system with substance abuse related problems.

                               CONCLUSION

    Our Nation's investment in drug abuse research is showing 
reductions in drug abuse rates and its deleterious consequences at the 
individual, family, and community level. A continued commitment to 
medical research, and to working with other agencies and sectors, will 
lead to new advances, technologies and innovations that will result in 
a healthier population.



                Prepared Statement of Dr. Jeremy M. Berg

    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 2005 
budget includes a sum of approximately $1,960 million which reflects an 
increase of $55 million over the fiscal year 2004 enacted level of 
$1,905 million.

                CROSS-CUTTING AND CUTTING-EDGE RESEARCH

    Both before joining NIGMS as its new director last November and 
since then, I have been tremendously impressed by the Institute's 
leadership in supporting basic biomedical research--that is, scientific 
studies into the most fundamental biological processes that govern 
human health. The kinds of research that we fund are both cross-cutting 
and cutting-edge. NIGMS-supported studies have shed light on everything 
from the three-dimensional structures of individual proteins--life's 
building blocks--to the complex interactions between molecules inside 
cells. More importantly, by uncovering the previously hidden workings 
of this cellular machinery, not only do we gain a better understanding 
of the very basis of human health, but we also gain valuable clues to 
fixing this machinery when it goes awry. Those clues are essential in 
helping scientists develop better methods to diagnose, treat, and even 
prevent a wide range of human diseases.
    NIGMS has a successful track record of supporting the nation's 
brightest minds in basic biomedical science. Perhaps the highest 
recognition of that success can be seen in the number of Nobel Prizes 
that NIGMS grantees have won over the past four decades: a remarkable 
55 to date. This past year was no exception. Roderick MacKinnon, M.D., 
a biophysicist at the Rockefeller University and a long-time NIGMS 
grantee, won the 2003 Nobel Prize in chemistry for discovering the 
structure and function of membrane ion channels--the ``gatekeepers'' 
that control what essential molecules move in and out of cells. 
MacKinnon's breakthrough provides direct visualization of the basis for 
the electric circuits that are responsible for the functioning of our 
brains and the beating of our hearts. The detailed structural 
information is revealing how local anesthetics work and why some drugs 
have life-threatening cardiac side effects. The work of literally 
thousands of other researchers has been redirected in response to his 
discoveries.
    NIGMS' impressive return on investment in basic biomedical research 
is also evidenced by the many other prestigious awards honoring our 
grantees. In 2003, Rockefeller researcher C. David Allis, Ph.D., won 
the third annual Wiley Prize in the Biomedical Sciences for his work on 
chromatin, the complex of DNA with proteins that packages genetic 
information inside each cell nucleus. The structure of chromatin is 
largely responsible for why one cell is a nerve cell while another cell 
is a muscle cell, even though they contain exactly the same DNA 
sequence. Allis' studies of the chemical modifications that regulate 
chromatin hold promise for learning how to control genes that suppress 
and inhibit the growth of tumors in cancer. The previous year, two 
other NIGMS grantees--Andrew Z. Fire, Ph.D., of the Stanford University 
School of Medicine, and Craig C. Mello, Ph.D., of the University of 
Massachusetts Medical School--were among the winners of the second 
annual Wiley Prize for their groundbreaking discovery of gene silencing 
by a mechanism called RNA interference. The phenomenon of RNA 
interference is the subject of upcoming meetings at both the National 
Academy of Sciences and NIH because of its potential impact for both 
basic research and for entirely novel approaches to preventing and 
treating disease.
    Even greater advances in biomedical science are possible in the 
years to come. Through forward-thinking programs designed to foster 
innovative research and train the next generation of pioneering 
scientists, NIGMS is playing a leading role in the NIH Roadmap for 
Medical Research--the exciting new vision of the future recently 
launched by NIH director Elias Zerhouni, M.D. I would like to share 
with you some of the key strategies we have developed to help realize 
this important vision.

                  BLAZING A TRAIL FOR THE NIH ROADMAP

    Throughout its history, NIGMS has helped push back the frontiers of 
medical knowledge primarily by funding the most promising research 
grant applications submitted by both new and established scientists. 
This so-called investigator-initiated research--supported through the 
NIH's R01 grant mechanism continues to be the most important instrument 
NIGMS has to promote experimentally based, hypothesis-driven research--
the heart of our nation's scientific mission.
    In recent years, NIGMS launched a number of larger, targeted 
initiatives to address both significant opportunities and critical gaps 
in biomedical research today. In many ways, programs such as NIGMS' 
Protein Structure Initiative (PSI), its large-scale collaborative 
``glue grants,'' and its new Center for Bioinformatics and 
Computational Biology have blazed a trail for the NIH Roadmap. Today, 
NIGMS is well positioned to participate with other NIH institutes in 
transforming the nation's biomedical research capabilities and 
accelerating the translation of scientific discoveries from the bench 
to the bedside.
    Structural biology is part of the Roadmap's New Pathways to 
Discovery theme, and NIGMS is playing a key role in this area. One 
major activity is the PSI, an ambitious 10-year project launched in 
2000. The aim of the PSI is to solve the three-dimensional structures 
of thousands of proteins experimentally and ultimately produce 
computer-based tools for modeling the 3-D structure of any protein from 
its genetic spelling, or sequence. Knowing the structures of proteins 
helps scientists understand how these molecules function in health and 
disease and aids in the development of new medicines.
    Results from the nine pilot centers set up in the first phase of 
the PSI are promising, demonstrating that automated protein production 
``factories'' are feasible and are yielding high-resolution data that 
is already being used by scientists around the world. This year, NIGMS 
plans to ramp up the PSI in its second phase, with the funding of 
large-scale centers that will dramatically reduce the time and cost of 
solving protein structures, as well as specialized centers that will 
tackle challenging problems such as membrane proteins and protein 
complexes.
    NIGMS is also contributing substantially to Roadmap-related 
initiatives through its support of research aimed at unraveling the 
complexities of living systems. In 2003, the Institute awarded its 
fifth glue grant, bringing together a diverse team of scientists to 
assemble a complete picture of lipids--fats and oils--inside cells, and 
the role they play in heart disease, arthritis, and other major 
illnesses. Other ongoing glue grants awarded since the program started 
in 2000 include projects aimed at understanding cellular signaling and 
communication, cell movement, and inflammation and the way the body 
responds to injury.
    Last year, NIGMS also added two new Centers of Excellence in 
Complex Biomedical Systems Research. At these centers, 
interdisciplinary teams of researchers from both the biological and 
physical sciences will focus on the emerging field of ``systems 
biology,'' which seeks to find hidden patterns of biological 
interactions at all levels, from individual proteins to entire 
organisms. The new centers join two others launched the previous year 
with NIGMS funding.

           COMPUTER-BASED SOLUTIONS TO BIOMEDICAL CHALLENGES

    Harnessing the power of computers to solve complex problems in 
biology is another major theme in both the NIH Roadmap and NIGMS' 
research mission. In 2003, the Institute's recently created Center for 
Bioinformatics and Computational Biology welcomed its first director, 
Eric Jakobsson, Ph.D., a leading researcher in the field from the 
University of Illinois at Urbana-Champaign. Dr. Jakobsson has been 
instrumental in launching one of the first Roadmap initiatives, a 
program to fund the creation of NIH National Centers for Biomedical 
Computing. The centers will bring together computer scientists, 
biomedical researchers, and experts from the experimental, clinical, 
and behavioral sciences to tackle such challenges as developing 
computer simulations that will accurately model the complex inner 
workings of the human brain and other vital systems.
    One of the most exciting prospects for computational biology is the 
promise of turning the vast amounts of data generated by the Human 
Genome Project into promising new medical treatments that are tailored 
to the individual. As Allen D. Roses, M.D., senior vice-president of 
genetics research at GlaxoSmithKline, recently observed, ``The vast 
majority of drugs--more than 90 percent--only work in 30 to 50 percent 
of the people.'' NIGMS is addressing this critical issue through the 
Pharmacogenetics Research Network, a nationwide collaboration of 
scientists from academia, government, and industry that the Institute 
spearheaded in 2000, with additional funding from five other NIH 
institutes. The network has already produced a key computer-based 
resource that scientists are now actively using: the Pharmacogenetics 
and Pharmacogenomics Knowledge Base (PharmGKB). With this and other 
tools at their disposal, scientists will be able to study the effect of 
genes on people's responses to a wide variety of medicines including 
antidepressants, chemotherapy, drugs for asthma and heart disease, and 
many others. The ultimate goal of pharmacogenetics research is to help 
tailor medicines to people's unique genetic make-ups, thus making 
medicines safer and more effective for everyone.
    Computational biology is also at the heart of another NIGMS 
initiative: the Models of Infectious Disease Agent Study (MIDAS). An 
integral component of the overall NIH biodefense plan, MIDAS is a 
network of scientists who will produce user-friendly computational 
models for policymakers, public health workers, and other researchers 
to assist them in making better-informed decisions about emerging 
infectious diseases. The first centers funded through the MIDAS 
initiative will launch this year and are expected to contribute 
significantly to our ability to prevent, detect, and respond to new 
infectious diseases, either natural or human-made.
    Other NIH Roadmap-related initiatives include NIGMS' program to 
establish high-quality chemical libraries that provide scientists with 
powerful tools for discovering potential new drugs, and a portfolio of 
grants designed to stimulate the development of new molecular imaging 
technologies that can be harnessed to visualize the actions of 
individual molecules over time in living cells. The effort to create, 
distribute, and apply these tools will be tremendously enhanced by 
initiatives that are part of the Roadmap.

              TEAM SCIENCE AND INTERDISCIPLINARY TRAINING

    The increasingly complex nature of biomedical research today 
demands new approaches to carrying out the scientific enterprise. NIGMS 
has been at the forefront of addressing this issue, especially in its 
support for ``team science''--interdisciplinary research that seeks to 
combine the skills and expertise of scientists from diverse fields and 
backgrounds. And now as part of another major theme in the NIH 
Roadmap--Research Teams of the Future--NIGMS is bringing its own 
experience to the table to help build successful synergies in large-
scale research collaborations, and to help prepare the next generation 
of biomedical scientists trained in multiple disciplines.
    For example, NIGMS has led the way in supporting cross-disciplinary 
research and training through its Medical Scientist Training Program--
which leads to the combined M.D.-Ph.D. degree and produces 
investigators who can bridge the gap between basic and clinical 
research. Other NIGMS programs support training in the cellular, 
biochemical, and molecular sciences; systems and integrative biology; 
the pharmacological sciences; genetics; molecular biophysics; 
biotechnology; the chemistry-biology interface; and bioinformatics and 
computational biology.
    Many NIGMS research and training programs combine both the 
biological sciences--cellular and molecular biology, genetics--and the 
quantitative sciences--physics, chemistry, engineering, mathematics. 
Indeed, bringing together these two scientific cultures is essential if 
we are to continue to make important advances in biomedical research in 
the 21st century. That growing realization has spurred a flurry of 
activity in recent years. For example, NIGMS joined forces with the 
National Science Foundation in 2002 to launch an initiative to 
encourage the use of mathematical tools and approaches to study 
biology. NIGMS is also partnering with the NIH Office of Science 
Education on a program to transform undergraduate biology education by 
incorporating examples and perspectives from the quantitative sciences 
into biology courses. This program responds to the National Research 
Council's Bio2010 report.
    NIGMS also has a long-standing commitment to increasing the number 
of underrepresented minorities engaged in biomedical research. Through 
our Division of Minority Opportunities in Research, NIGMS takes a 
leading role at NIH to encourage and prepare minority students to 
pursue training for scientific careers and to enhance the science 
curricula and faculty research capabilities at institutions with 
substantial minority enrollments. Both these programs and the efforts 
to train and recruit more scientists from the physical sciences into 
biomedical research are essential if we are going to have the 
biomedical workforce necessary to solve the challenging problems that 
lead to human disease and drive up the costs of providing health care.

                BALANCING LARGE- AND SMALL-SCALE SCIENCE

    As promising and worthwhile as these major initiatives are, we must 
not lose sight of NIGMS' mainstay over the past four decades: 
investigator-initiated research. By encouraging the best and brightest 
basic scientists to pursue new directions in their fields, NIGMS has 
made tremendous contributions to advancing biomedical science. It is 
often a single investigator, supported by a single grant, who discovers 
something that turns out to be the tip of a very important iceberg. And 
we must continue to support these creative minds in order to sow the 
seeds for tomorrow's advances.
    At the same time, we must recognize the need to invest 
strategically in targeted, larger-scale research to meet the critical 
needs of ensuring the nation's health and well-being, its technological 
competence and competitiveness, and its security. In short, we need to 
balance small- and large-scale science in a way that both catalyzes and 
capitalizes on innovation. With our experience in managing thousands of 
individual research grants every year along with a growing number of 
multi-institutional, multidisciplinary research efforts, NIGMS can 
strike that balance while leaving open the door to future directions 
that are still beyond our powers of prediction.
    Thank you, Mr. Chairman. I would be pleased to answer any questions 
that you may have.

                                 ______
                                 
               Prepared Statement of Dr. Story C. Landis

    Mr. Chairman and Members of the Committee, I am Story Landis, 
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 2005. The fiscal year 2005 budget includes 
$1,546,623,000, an increase of $44.9 million over the fiscal year 2004 
enacted level of $1,500,693,000 comparable for transfers proposed in 
the President's request.
    The mission of the NINDS is to reduce the burden of neurological 
disorders by finding ways to prevent or to treat these diseases. When I 
began as Director about six months ago, one of my first priorities was 
to meet with voluntary groups representing patients and their families. 
So far, I have met with more than 40 groups, and this remarkable 
experience has educated me about the extraordinary range of diseases 
within the NINDS mission, the power of their impact, and the urgency of 
finding ways to prevent or treat these disorders. These discussions 
also reinforce the importance of increasing public-private 
partnerships, which is a goal of our Institute, as well as a major 
focus of the NIH Roadmap process.
    My own research has focused on fundamental questions about how the 
nervous system develops how genes help wire up connections in the 
brain, how cells choose to become a particular type, and whether there 
is any ``plasticity'' in this process. Issues such as these, long 
central to basic neuroscience research, are now at the crux of efforts 
to devise treatments for neurological diseases. I am encouraged by the 
prevention and treatment strategies emerging from the investment in 
basic research drugs to home in on the molecules that cause disease, 
stem cells to repair the damaged nervous system, natural neurotrophic 
factors to promote survival and growth of brain cells, ``vaccines'' to 
prevent stroke, implantable stimulation devices to compensate for brain 
circuits unbalanced by disease, therapies to turn off, repair or 
replace defective genes, neural prostheses to read control signals 
directly from the brain, and behavioral and drug interventions to 
encourage the ``plasticity'' of the brain and spinal cord to compensate 
for damage. The NINDS must continue to support basic research. We must 
also re-energize our efforts to translate opportunities into practical 
therapies. Today I will highlight a few of the ways we are working to 
bring people and resources together to accomplish that.

                               STEM CELLS

    Neural stem cell biology is one area in which basic science and 
clinical promise are so closely intertwined that it is easy to forget 
the origins of our understanding of neural stem cells in very basic 
research. The generation of new neurons in the adult brain was 
discovered when a basic scientist sought to understand how male 
canaries learn a new song each spring. This year, NINDS researchers 
have contributed to advances in identifying and isolating adult neural 
stem cells, in understanding the signals that control embryonic and 
adult neural stem cells, and in developing stem cell therapies in 
animal models that show promise for Parkinson's disease, demyelinating 
diseases, such as Canavan, Krabbe, or Tay-Sachs, and many other 
disorders. The NINDS has helped foster research on embryonic and adult 
stem cells through several initiatives, including training programs in 
the use of approved human embryonic stem cells, grant supplements to 
compare these to cells from other sources, and scientific workshops. An 
NINDS intramural researcher also leads a new NIH facility that is 
characterizing the approved human embryonic stem cell lines. For the 
coming year, an initiative targeting collaborative research in stem 
cell biology, designed to bring together teams of experts from several 
areas of stem cell biology, is a high priority.

                      GENES AND THE NERVOUS SYSTEM

    Genetics is another neuroscience research area that has made 
astonishing progress. Overall, researchers have identified more than 
200 genes that can cause neurological disorders. Gene findings in the 
past year are relevant to diseases such as Parkinson's disease, 
Charcot-Marie-Tooth disorder, and cerebral cavernous malformations, 
which can predispose people to strokes. Discoveries such as these lead 
to improved diagnosis, development of animal models, and the first 
clues to what underlies disease processes and how to stop them.
    Several NINDS efforts bring people and resources together in 
genetics. Some are simple, but important, such as programs to promote 
sharing of transgenic mice that are essential models of human diseases. 
Others are more ambitious, such as the Gene Expression Nervous System 
Atlas (GENSAT) project, which will map the activity of thousands of 
genes in the brain and provide genetically engineered mouse strains 
that allow scientists to study how these genes contribute to health and 
disease. Microarray screening centers make another new technology and 
the data arising from it widely available. Microarrays allow scientists 
to simultaneously monitor the activity of virtually all genes, with 
wide potential applications to basic and clinical neuroscience; for 
example, recent studies show micrarrays may predict which patients will 
respond to approved drugs for multiple sclerosis. The NINDS Human 
Genetics Resource Center, established this year, makes DNA samples, 
immortalized cell lines, and accompanying clinical and pedigree data 
available to all qualified researchers. The repository currently 
contains samples related to stroke, epilepsy, Parkinson's disease, and 
motor neuron diseases, including amyotrophic lateral sclerosis (ALS) 
and spinal muscular atrophy (SMA).

                         TRANSLATIONAL RESEARCH

    ``Translational research'' encompasses the many steps that are 
needed to move from basic research insights to a therapy that is ready 
for human testing in clinical trials, and the NINDS has a long history 
of programs in this arena. For example, over three decades, the Neural 
Prosthesis program has supported research on electronic and mechanical 
devices that help compensate for abilities lost through disease or 
injury, including pioneering research on direct brain control of 
prostheses, which has recently become a focus of such forward thinking 
agencies as the Defense Advanced Research Projects Agency (DARPA). The 
NINDS has responded to increasing opportunities by developing a 
comprehensive translational research program that fosters cooperative 
efforts, provides peer review criteria tailored to the needs of 
translational research, and utilizes milestone driven funding, which is 
common in industry. In fiscal year 2003, the Institute funded the first 
projects in this program, focused on gene and stem cell therapies for 
Parkinson's disease, neuroprotectants for stroke and trauma, treatments 
for brain tumor, and drugs for epilepsy, ALS and Huntington's disease.

              DRUG DEVELOPMENT FOR NEUROLOGICAL DISORDERS

    New and expanding efforts to develop drugs complement the broad 
translational program. The NINDS has awarded a contract for a high 
throughput screening (HTS) facility, and solicited proposals for the 
development of disease-related screening tests. HTS uses robotics to 
rapidly test large numbers of chemicals to find lead compounds for drug 
development and use as research tools. Ongoing screening efforts focus 
on ataxia telangiectasia, ALS, and Parkinson's disease. Several NIH 
institutes are working together to develop chemical libraries focused 
on the brain, and the NIH Roadmap ``Molecular Libraries'' component 
will directly facilitate screening efforts such as these.
    Another NINDS drug development effort is a longstanding public-
private partnership. Since 1975, the NINDS Anticonvulsant Screening 
Project has worked with more than 140 companies and 230 academic 
institutions to test more than 20,000 compounds for anti-convulsant 
properties, including several drugs now in clinical use. Guided by the 
epilepsy benchmarks planning process, the Institute is expanding this 
program with increased focus on preventing the development of epilepsy 
and on treatment-resistant epilepsy. The NIH Roadmap ``Structural 
Biology'' goals to improve our understanding of membrane proteins, such 
as ion channels that are implicated in some types of epilepsy and 
neurotransmitter receptors that are often the targets for drugs, will 
have an important impact on future efforts to develop drugs for this 
and many other neurological disorders.
    Some drugs developed for epilepsy have shown promise for other 
diseases, such as chronic pain. To take advantage of that kind of 
crossover, observed in many areas of medicine, the NINDS worked closely 
with academia and voluntary disease organizations to develop a 
consortium of 26 laboratories to screen a set of 1,040 known drugs, 
mostly approved by the U.S. Food and Drug Administration (FDA) for 
other uses, for potential use against neurodegenerative diseases. The 
Consortium is sharing data on 29 laboratory screening tests based on 
molecules, cells in culture, or simple organisms. Several promising 
drugs have moved to further testing in animals, and a few may move soon 
to clinical trials.

         PROGRAM TO ACCELERATE THERAPEUTIC DEVELOPMENT FOR SMA

    Valproic acid is one example of a drug, now used for the treatment 
of epilepsy, that in the past year has shown promise in cell culture 
for a different disease, spinal muscular atrophy (SMA). SMA is the most 
common single gene cause of infant mortality. In recent years, 
scientists have discovered the gene defects that cause SMA, developed 
animal models that mimic essential aspects of the human disease, and 
devised plausible strategies for developing therapies. Because of the 
impact of SMA and the state of the science, the NINDS chose this 
disease as the focus of an innovative approach, initiated in fiscal 
year 2003, to expedite the development of therapies. The performance-
based contract mechanism accelerates all steps from recognition of a 
research need, through solicitation and review, to funding of targeted 
research subprojects, with guidance by an expert steering committee 
that takes a very active role in driving the process. If successful, 
this approach might be applied to other diseases.

                MUSCULAR DYSTROPHY AND CENTERS PROGRAMS

    The muscular dystrophies are another group of inherited disorders 
that are a high priority for NIH. Researchers, beginning more than a 
decade ago, have identified defects in several genes that can cause the 
various kinds of muscular dystrophy. These findings have brought 
improved understanding of what causes these diseases, better animal 
models to develop therapies, and some practical benefits for example, a 
new diagnostic test for Duchenne muscular dystrophy will eliminate the 
need for painful muscle biopsy in many children, and help identify 
female carriers of the disease before they pass it on to their sons. 
Therapies to slow or stop muscular dystrophies have been elusive, but 
there have been encouraging results recently in animals using drugs, 
stem cells, and gene therapy approaches. To expedite progress against 
the muscular dystrophies, the NIH has funded three Senator Paul D. 
Wellstone Muscular Dystrophy Cooperative Research Centers, with the 
expectation that up to three more will be funded competitively in 
fiscal year 2005. The NIH is also working together with the broadly 
representative interagency Muscular Dystrophy Coordinating Committee 
(MDCC) on developing a muscular dystrophy research and education plan 
for NIH.
    The NINDS, often working with other components of NIH, has several 
centers programs, such as the Morris K. Udall Parkinson's Disease 
Centers of Excellence, the Specialized Programs of Translational 
Research in Acute Stroke (SPOTRIAS), the Studies to Advance Autism 
Research and Treatment (STAART), and the Specialized Neuroscience 
Research Program (SNRP), which encourages minority scientists and 
addresses health disparities in neurological disorders. Other centers 
focus on disorders such as brain tumor, spinal cord injury, and head 
trauma.

                            CLINICAL TRIALS

    The NINDS continues to set standards of quality and innovation in 
clinical trials that evaluate whether potential treatments or 
preventive measures are safe and effective. One recent example, the 
Neuroprotection Exploratory Trials in PD (NET-PD), was launched in 
April 2003 to evaluate drug therapies that might slow the progression 
of Parkinson's disease. The project rigorously selected candidate drugs 
from a broad array of potential compounds identified by working with 
clinicians and researchers throughout academia and industry. The 42 
clinical sites have recruited individuals with early, untreated 
Parkinson's, and early phase trials of four drugs will be completed in 
early 2005. In the coming year, the NINDS clinical trials program is 
also working to train researchers to conduct clinical trials and to 
develop a broad clinical trials network that will encompass the greater 
community of neurologists. Clinical trials for neurological disorders 
is another area in which the cross-cutting NIH Roadmap efforts for 
``Re-engineering the Clinical Research Enterprise'' are likely to have 
a major impact.

                          INTRAMURAL PROGRAMS

    Before becoming the director of NINDS, I led the Institute's 
intramural program on the NIH campus in Bethesda, MD, which is one of 
the largest basic and clinical neuroscience programs in the world. In 
addition to recruiting superb individual scientists in fields such as 
ion channels, genetic diseases of the nervous system, brain tumors, and 
stroke, a central focus of the program has been to bring researchers 
together from disparate fields of science. To this end, the Porter 
Neuroscience Research Center, opening its first phase in 2004, brings 
together scientists from eight institutes to ``put the brain back 
together'' by overcoming artificial disciplinary boundaries within and 
across institutes and by setting the standard for collaborative 
research in neuroscience.

                       FUTURE COOPERATIVE EFFORTS

    I have mentioned a few areas in which the NIH Roadmap efforts will 
facilitate our efforts against neurological diseases, but the same can 
be said of virtually every major effort within the Roadmap. Driven by 
the science, several NIH components that have a major focus on the 
brain are also increasingly working together to form a ``blueprint for 
the brain,'' in which cooperative efforts across Institutes can 
expedite progress. These Institutes already cooperate extensively in 
areas such as training of researchers, genetics, autism, muscular 
dystrophy, health disparities, brain tumors, stroke, and pediatric 
neuroimaging, to name a few examples. I hope to report to you in the 
future about progress in forming other cooperative ventures aimed at 
our common goal of finding better ways to prevent or to treat all 
disorders that affect the brain and other parts of the nervous system.
    Thank you, and I would be pleased to answer questions.

                                 ______
                                 
              Prepared Statement of Dr. Stephen E. Straus

    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's fiscal year 2005 budget request for the National Center 
for Complementary and Alternative Medicine. The fiscal year 2005 budget 
includes $121.1 million, an increase of $4.2 million over the 
comparable fiscal year 2004 appropriation of $116.9 million.

                              INTRODUCTION

    Five years ago, recognizing the increasing public health 
opportunities of complementary and alternative medicine (CAM) and the 
challenges to research in this area, Congress elevated the NIH Office 
of Alternative Medicine to the National Center for Complementary and 
Alternative Medicine (NCCAM). Several months later, as NCCAM's first 
Director, I articulated a set of priorities for the Center that 
emphasized growth in the portfolio of rigorous research project grants, 
enhanced investments in research training and careers awards to build 
an effective CAM research collective, creation of an intramural 
research program (IRP), and commitment of stable funding for research 
centers. As we embark on planning our second 5 years of work, I am 
pleased to report that NCCAM has achieved these and many other critical 
objectives.
    NCCAM's success to date is evident in some of its vital statistics:
  --Under the President's proposed fiscal year 2005 budget, NCCAM's 
        investment in research project grants will have increased from 
        approximately $10 million in 1999 to almost $76 million, while 
        funding for research training and career awards will have 
        increased from under $1 million in 1999 to approximately $8.8 
        million.
  --In collaboration with other NIH Institutes and Centers (ICs), NCCAM 
        has launched nine multi-center Phase III clinical trials of 
        popular CAM interventions for chronic illnesses that affect so 
        many Americans, including osteoarthritis, dementia, cancer, and 
        coronary artery disease.
  --NCCAM established an intramural research program in 2001, which 
        studies CAM approaches to diseases of aging, including 
        arthritis, depression, muscle wasting, cancer, pain, and 
        diabetes.
  --Based on a comprehensive external review, NCCAM refined its 
        research centers program to support rigorous investigations at 
        both traditionally research-intensive and CAM institutions. In 
        2003, NCCAM made its first round of revised center awards in 
        three categories: Centers of Excellence for Research on 
        Complementary and Alternative Medicine, Developmental Centers 
        for Research on Complementary and Alternative Medicine, and 
        Planning Grants for International Centers for Research on 
        Complementary and Alternative Medicine. NCCAM's Centers program 
        will foster capacity in CAM research, catalyze more effective 
        and essential partnerships between CAM institutions and 
        research-intensive universities, and facilitate the integration 
        of effective CAM therapies with conventional medical 
        approaches.
    Already, the nearly 800 projects that NCCAM has supported since 
1999 have yelded over 700 scientific publications, including some that 
were published in the most prestigious journals--Journal of the 
American Medical Association, New England Journal of Medicine, and 
Proceedings of the National Academy of Sciences. Complementing these 
research and research training activities are extensive efforts to 
communicate research results and other critical information about CAM 
to the public and practitioners. NCCAM's award-winning Web site is 
visited over 1.5 million times each year for its 90 fact sheets, 
consumer alerts, news releases, and announcements of new research 
initiatives. In a partnership with the National Library of Medicine, 
NCCAM helped create a CAM subset on the reference database PubMed that 
now hosts nearly 400,000 reports about CAM studies, which are available 
to anyone with Internet access. In the aggregate, the investments made 
in NCCAM's first 5 years are already informing the health care 
decisions Americans make at home and in consultation with their 
practitioners.
    In its first 5 successful years, NCCAM has become fully integrated 
within the NIH, developing a research agenda that is responsive to its 
mission, fiscally accountable, and supportive of rigorous CAM research. 
NCCAM's research priorities today encompass six thematic areas in which 
CAM can have a public health impact: obesity, botanicals, brain-body 
interactions, acupuncture, neurodegenerative diseases, and HIV/AIDS. 
The next section highlights some of the advances and activities in 
three of these priority areas.

                    ADDRESSING THE OBESITY EPIDEMIC

    An alarming 65 percent of American adults,\1\ 16 percent of 
adolescents, and 10 percent of American children are now overweight.\2\ 
Obesity results from complex interactions among human biology, 
behavior, and the environment and, therefore, requires a 
multidisciplinary approach to prevent and treat it. NCCAM is 
contributing to the trans-NIH strategy to address this epidemic by 
supporting studies of the safety and efficacy of popular, but 
unsubstantiated, dietary approaches to obesity and its many 
complications. One of the most popular approaches today is the diet 
plan championed by the late Dr. Robert Atkins, which emphasizes a low-
carbohydrate, high-fat, high-protein regimen.
---------------------------------------------------------------------------
    \1\ Journal of the American Medical Association, 288 (14): 1723-
1727, Flegal et al, ``Prevalence and trends in obesity among U.S. 
adults, 1999-2000''
    \2\ Journal of the American Medical Association, 288 (14): 1728-
1732, Ogden et al, ``Prevalence and trends in overweight among U.S. 
children and adolescents, 1999-2000''
---------------------------------------------------------------------------
    In fiscal year 2003, NCCAM-sponsored researchers reported in the 
New England Journal of Medicine on a ground breaking 1-year, multi-
center trial about the effects of the Atkins diet on weight loss and 
risk factors for cardiovascular disease. At 6 months, those on the low-
carbohydrate diet had lost more weight and had reduced levels of blood 
lipids more than those on the conventional diet. At the end of 1 year, 
however, the differences between the two groups of dieters lessened, 
leading investigators to call for larger and longer-term studies. NCCAM 
is working with its NIH partners to support a larger and more 
definitive study.
    In its intramural program, NCCAM researchers are testing whether 
the dietary supplement glucosamine, used by over 4 percent of older 
Americans for degenerative arthritis, causes resistance to insulin, a 
condition that predisposes one to diabetes--a disease linked to 
obesity. Other IRP studies are evaluating carnitine, a nutrient 
essential for the normal metabolism of fats, to see whether it can 
reduce abdominal fat content, stimulate weight loss, and improve 
glucose utilization.
    In fiscal year 2005, as part of the overall trans-NIH focus on 
obesity, NCCAM will cosponsor two major initiatives in obesity 
research, Neurobehavioral Basis of Obesity and Prevention and Treatment 
of Pediatric Obesity in Primary Care Settings. The first seeks to 
bridge the gap between understanding the molecular and genetic 
regulation of food intake and behavioral influences on obesity. The 
pediatric initiative will evaluate preventive and therapeutic 
strategies for obesity that could be recommended for children and 
adolescents in primary care settings, such as a physician's office, 
primary care clinic, or HMO.

      EXAMINING THE SAFETY AND EFFECTIVENESS OF BOTANICAL PRODUCTS

    Approximately 14 percent of Americans use herbal supplements to 
prevent disease, maintain wellness, or treat illness or pain.\3\ Many 
of these people also take prescription drugs. NCCAM-supported research 
is identifying herbal products that interact with drugs and the 
underlying biochemical mechanisms of these interactions. For example, 
studies have shown how St. John's wort and PC SPES (a botanical mixture 
that had been used to treat advanced prostate cancer) induce the 
activity of a key liver enzyme that is responsible for the metabolism 
of some 80 percent of all drugs. This finding shows how herbal 
supplements have the potential to either enhance a drug's toxicity or 
reduce a drug's effectiveness when a patient takes both dietary 
supplements and prescription medication.
---------------------------------------------------------------------------
    \3\ Journal of the American Medical Association, 287 (3); 337-344; 
Kaufman et al., ``Recent patterns of medication use in the ambulatory 
adult population of the United States: the Slone survey.''
---------------------------------------------------------------------------
    Each year in the United States, an estimated 70,000 people are 
diagnosed with head and neck cancers, which are typically resistant to 
multi-drug chemotherapy. In fiscal year 2003, NCCAM-sponsored 
researchers examined extracts from the root of Scutellaria baicalensis, 
a Chinese herb, for activity against head and neck cancers. The new 
study is promising because it shows that the herbal extracts strongly 
inhibit the growth of human head and neck cancer cells in vitro as well 
as in mice with tumors composed of human cells. Future studies will 
determine the herb's effects on regulating the cell replication cycle 
and whether it can be translated into a safe and effective intervention 
for head and neck cancer patients.
    While some research studies confirmed the promise of certain 
botanicals, others have found herbs that do not deliver on their 
claims. One example is guggulipid, a botanical extracted from the resin 
of the mukul myrrh tree, that is marketed in the United States as a 
dietary supplement to help control blood cholesterol levels and 
maintain a ``healthy heart.'' In an 8-week placebo-controlled study 
involving over 100 subjects, NCCAM-funded scientists found that neither 
the standard or even higher doses of guggulipid significantly lowered 
the levels of the key low-density lipoprotein (LDL) form of cholesterol 
in people with high blood cholesterol. This study highlights the need 
to study popular botanicals that the public is using so that 
individuals can make informed decisions regarding their own care.
    In fiscal year 2005, NCCAM will co-sponsor three important 
initiatives on the use of botanicals as dietary supplements. Through a 
newly refined Botanical Research Centers Program being mounted with the 
NIH Office of Dietary Supplements and the National Institute of 
Environmental Health Sciences, NCCAM will support interdisciplinary 
studies of botanicals to generate evidence regarding their safety and 
potential public health benefits. NCCAM also plans to establish a Phase 
I Resource Center (PRC) to define the pharmacology and optimal dosing 
of botanical products and functional foods. Finally, in fiscal year 
2005, NCCAM plans to initiate in vitro, animal, and preliminary 
clinical studies of Silybum marianum (milk thistle) and its derivative 
silymarin as a treatment for chronic hepatitis and cirrhosis of the 
liver, conditions that affect millions of Americans for whom, to date, 
there is no effective treatment.
    Through these programs, NCCAM thoughtfully is investing in programs 
of basic research to discover natural products and food supplements 
that could open new avenues for prevention and treatment of conditions 
that affect the health, well being, productivity, and quality of life 
of millions of Americans.

                 INVESTIGATING BRAIN-BODY INTERACTIONS

    NCCAM scientists are exploring ancient practices such as 
meditation, Tai Chi, hypnosis, and yoga to understand their abilities 
to harness the healing effects of the mind on the body. For example, 
NCCAM grantees are conducting pilot studies of yoga as a behavioral 
intervention for the management of chronic obstructive lung disease, 
insomnia, and chronic low back pain, as well as investigating whether 
one's spirituality and religiosity have a significant influence on 
immune system functioning.
    In 2003, NCCAM-funded researchers reported that a traditional 
Chinese meditative exercise regimen, Tai Chi, could enhance physical 
performance and immune responses in older people. As people age, 
immunity to the virus that causes chicken pox wanes until the infection 
can reactivate from its dormant state in nerves and develop into the 
painful condition shingles. The study concluded that older adults who 
participated in a form of Tai Chi for 15 weeks experienced 
statistically significant increases both in ellular immune responses to 
the virus and in physical performance. This is the first scientific 
study to show that a CAM approach is responsible both for improvements 
in physical function and in virus-specific immunity and provides the 
basis for a larger study of Tai Chi currently being supported by NIH.
    To further stimulate research in the field of brain-body 
interactions, NCCAM is a cosponsor of several NIH research initiatives. 
The first effort, entitled Mind-Body Interactions and Health: 
Exploratory/Developmental Research Program, will foster program 
development at institutions that have high potential for advancing 
mind-body and health research. The second initiative, Research on Mind-
Body Interactions and Health, will support interdisciplinary 
collaborations and innovations to understanding the underlying 
processes of mind-body interactions and health and translating basic 
knowledge into interventions and clinical practices.

                            LOOKING FORWARD

    Five years ago, the discipline of rigorous CAM research was in its 
infancy. Absent precedents for the field, NCCAM's initial efforts led 
to supporting an array of studies spanning numerous CAM practices and 
health conditions. In these first years, NCCAM found that to better 
ensure that its funds yield compelling results, it needed to encourage 
studies on mechanisms of action of CAM approaches, well-developed Phase 
I and II clinical trials as a foundation for future definitive studies, 
and collaborations between CAM and research-intensive institutions. In 
the coming years, the Center will refine its research priorities even 
more, to emphasize those areas and conditions for which CAM can have 
the greatest health impact. To this end, in 2004, NCCAM began a formal 
process to seek input from its many stakeholders, including the 
scientific community, health professionals, and the public to further 
target its research, training, and communication goals and to craft a 
long-term plan to guide the way toward its tenth anniversary.
    Complementing this strategic planning process are the trans-NIH 
Roadmap for Medical Research activities in which NCCAM leadership has a 
significant role. Core themes of the Roadmap resonate strongly with 
NCCAM because they promise to provide NCCAM grantees access to more 
sensitive technologies, richer environments for learning and conducting 
interdisciplinary research, and a re-engineered platform for clinical 
trials, all in ways that small institutes and centers could never 
achieve on their own.
    In the coming months and years, I look forward to sharing with 
members of the Committee, the scientific community, practitioners, and 
the public our second strategic plan and the results of the research 
and training investments that we have made. Thank you for your interest 
in NCCAM's progress and plans. I would be pleased to answer any of your 
questions.

                                 ______
                                 
                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 2005 budget is $650,027,000, 
an increase of $18,964,000 over the comparable fiscal year 2004 
appropriation.

                              INTRODUCTION

    Most complex diseases arise from the interplay between biology, 
environment and behavior. It is the NIEHS' mission to understand this 
interplay as it translates into increased disease risk. Thanks to the 
rare confluence of technology breakthroughs in analysis of genes and 
proteins and their recent application to the environmental health 
sciences, gene-environment interactions can now be investigated with 
more rigor and specificity. Our new opportunities within the framework 
of the NIH Roadmap also offer promise for a more rapid understanding 
and translation of this knowledge into improved public health. I will 
outline several of the NIEHS' most important efforts.

                         GENES AND ENVIRONMENT

    There are two principal avenues for exploration of the complex 
interplay between genes and environment. One is to look at the 
variations of genes themselves, and the other is to examine how genes 
respond to environmental stressors. In the case of the first approach, 
NIEHS is conducting the Environmental Genome Project (EGP) an effort to 
resequence 544 ``environmentally responsive'' genes--genes which are 
thought to be involved in an individual's susceptibility to 
environmental exposures--and to identify alleles or genetic variants 
associated with these genes. The key objective of the EGP is to 
discover and characterize these alleles or genetic variants, called 
polymorphisms, and to define their roles in the pathways by which 
environmental agents exert their effects on human health and disease.
    Last April, the EGP completed the first phase, publishing a catalog 
of variation in over 200 genes responsible for detoxifying 
environmental compounds such as pesticides, as well as metabolizing 
natural biological components such as hormones. Over 17,000 single 
nucleotide polymorphisms (SNPs) were identified, with more than 1,000 
in coding sequences. This information is already being used to make 
significant scientific discoveries. For example, it was found that 
people suffering from benzene-induced leukemia lack a certain SNP in 
the gene responsible for utilizing a vitamin B, folate, that healthy 
people have. Thus, the ability to metabolize folate might relate to the 
relative risk of developing leukemia among benzene workers.
    To aid in the functional characterization of SNPs in both coding 
and regulatory sequences of specific genes, NIEHS initiated the Mouse 
Genetic Variation Mapping Initiative. The mouse is the most widely used 
mammalian model system for the study of human health and disease for 
several reasons, including the fact that the genomes of mice and other 
mammals are highly conserved. Most human genes have counterparts in the 
mouse genome; thus, cloning of a gene in one species often leads to 
cloning of the corresponding gene in the other. The mouse also offers 
well developed toxicological and pathology databases and molecular 
genetic techniques for construction of gene knockout strains. Data 
generated using rodent models have been used widely in preparation of 
environmental regulatory policy and by the pharmaceutical industry.
    One of the greatest challenges for comparative toxicogenomics is 
the integration of the vast amount of genomic information being 
generated for a variety of model organisms. At present, there are 
several disparate but complementary databases on genomic sequences. 
Most of these databases provide data on gene and genome sequences for 
individual animal species. These databases do not provide a means to 
link the genome data to specific environmental chemicals or to 
toxicological and biological endpoints. They also do not enable 
researchers to compare information about potentially similar genes and 
biological responses across multiple species.
    Integrating the large number of disparate data sets is the goal of 
the Comparative Toxicogenomics Database (CTD). The CTD was developed 
through a collaboration of five NIEHS-funded Marine and Freshwater 
Biomedical Sciences Centers. The goal of the CTD is to develop a 
comparative database that links sequence information for genes that are 
relevant to toxicology to information about gene expression, toxicology 
and biological processes. The primary focus of the CTD is on marine and 
aquatic organisms as model systems for human diseases. The initial 
focus is also on genes that have been identified through the NIEHS' EGP 
as important for toxicology in these model systems. However, the 
database will eventually merge all gene sequence information generated 
on all vertebrates and invertebrates, including aquatic organisms, 
worms, flies, rodents, and people. The CTD provides information about 
gene curation and annotation (gene synonyms, sets and functions) and 
links between gene sequence and toxicity data published in the 
scientific literature. These aspects of the database represent an 
important advancement for comparative toxicogenomics. Understanding 
these mechanisms will allow more informed assessment of human risk by 
extrapolating toxicity data from animal models to people and will 
provide a mechanism by which members of the research community can 
share their data and promote fruitful avenues for future toxicological 
research.
    At present, the CTD is the only fully curated, publicly available 
database of its kind in the world. However, it serves as a prototype 
database and data resource for more comprehensive efforts ongoing at 
the NIEHS. The centerpiece for these discoveries is the NIEHS' National 
Center for Toxicogenomics (NCT), which uses a multidisciplinary 
approach to identify genes and proteins affected by specific 
environmental exposures. When a person is exposed to a chemical, 
physical, or biological agent, cells in the body may respond by 
switching on some genes and switching off others, potentially changing 
the proteins that are produced by the cells. The on/off pattern of 
various genes is different for each specific exposure, creating a 
characteristic pattern or ``signature,'' which scientists hope will be 
useful in classifying chemicals by their effects on various cellular 
processes. By constructing and populating a database of chemical 
effects on biological systems, the NCT is assisting the field of 
environmental health research to evolve into an information science in 
which gene and protein expression datasets are compiled and made 
readily available to the scientific community. By building on the data 
infrastructure being developed through the CTD and other databases, 
NIEHS scientists are developing the sequence-driven and context-
documents Chemical Effects in Biological Systems (CEBS) knowledge base. 
CEBS is planned as a public toxicogenomics knowledge base that combines 
and integrates scientific data from a multitude of public domain data 
sources. These data sources include studies of genetic polymorphisms, 
gene expression and proteomics, metabolism and toxicology. Once 
sufficient high quality data have been accumulated and assimilated, it 
will become possible to characterize an unknown environmental exposure 
by comparing its gene and/or protein expression profile to compendia of 
expression profiles in the database. Ultimately, the NCT will develop 
the capacity to use gene expression signatures and other data to 
facilitate characterization of toxicants and their biological effects. 
Through the predictive capabilities expected from toxicogenomics, 
adverse toxicity in clinical trials will be reduced and the efficiency 
of bringing new therapeutics to the public will be increased; adverse 
effects from long-term use or from combinations of therapeutic agents 
will be better understood and reduced. The final payoff for investing 
in CTD and CEBS will be more rational environmental health policy and 
an improved understanding of gene-environment contributions to the 
major causes of human death and disease.

                        OBESITY AND ENVIRONMENT

    Environment and behavior intersect in fundamental ways, 
intersecting with our biology but also with each other. In no area of 
public health is this more apparent than with the problem of obesity. 
There is a growing body of literature that illustrates the negative 
physical and mental health effects of unregulated and poor urban, 
rural, and suburban development and planning. These studies have 
documented increased rates of obesity, diabetes, depression, anxiety, 
and heart disease in these poorly developed areas. For example, in 
sprawling communities, higher dependence on motor vehicles has resulted 
in polluting the atmosphere with ground-level ozone and particulate 
matter, contributing to human health problems such as lung and 
cardiovascular disease. People most affected by air pollution include 
older adults with pre-existing diseases; children, especially those 
with asthma; persons with inadequate health care; and even healthy 
individuals who work and exercise outdoors. Lack of safe sidewalks in 
growing urban areas has resulted in a reduction in the number of 
children walking or biking to schools. Today, only 10 percent of 
children walk or bicycle to school--a 40 percent reduction over the 
last 20 years (according to researchers in Urban Land). Research 
suggests that inadequate urban planning, such as a lack of bike paths 
and sidewalks, results in a more sedentary lifestyle of children, 
which, in turn, may be a factor in the growing rates of childhood 
obesity. All of these examples demonstrate how the physical or built 
environment influences choices that ultimately affect health.
    The NIEHS is designing a program as part of the trans-NIH obesity 
initiative which is designed to examine how the built environment 
affects obesity and the effectiveness of changes in community planning, 
design, and development in reducing the extent of obesity and 
associated comorbidities. These intervention research projects will 
develop tools to characterize and measure individual and population-
level indicators of healthful communities--and of residents' lifestyles 
and behaviors--that prevent or reduce obesity. We hope that not only 
will studies of interaction between parameters of the built environment 
and individual lifestyle choices and behaviors help delineate factors 
that can prevent or reduce obesity, but also that this work will point 
the way towards new, cost-effective intervention strategies that 
promote healthful environments and behaviors.
    In a related initiative, NIEHS is partnering with the Robert Wood 
Johnson Foundation to support a program called Active Living by Design, 
which will provide support to 25 communities across the country to 
implement active living programs, policies, and communication 
strategies to improve community development and promote more healthy 
lifestyles. The NIEHS is providing an evaluation component to the 
program to determine the efficacy of various policies and promotions in 
reducing obesity.
    It is critical to delineate the role and impact of community 
design, planning, and development on individual and population health 
by understanding the contribution of urban/rural planning (i.e., land 
use decisions), housing structure, transportation issues, and the 
availability of public and green spaces as determinants of mental 
health, physical activity, nutrition, and access to healthy foods. In 
turn, modifying such parameters may reduce the prevalence of obesity in 
adults and children. This research effort will require integrated, 
interdisciplinary research teams, including biomedical scientists, 
behavioral scientists, social scientists, clinicians, epidemiologists, 
urban planners, developers, and architects, as well as active 
participation of community members. It is expected that such research 
will result in a greater understanding of the health benefits of living 
in communities that promote healthful environments and behaviors and 
may also impact policy for land use and public health.

            TOXICOLOGICAL EVALUATION OF NANOSCALE MATERIALS

    Nanoscale materials are a broadly defined set of substances where 
at least one critical dimension is less than 100 nm. Ultrafine 
particulate matter, e.g. the very smallest particles of soot from such 
sources as diesel exhaust, is a well-known example of ambient 
nanoparticles; however, this initiative will initially focus on 
manufactured nanomaterials of current or projected commercial 
importance. Nanoscale materials can in theory be engineered from nearly 
any chemical substance; semiconductor nanocrystals, organic dendrimers, 
and carbon fullerenes and carbon nanotubes are a few of the many 
examples. Nanoscale materials are already appearing in commerce as 
industrial and consumer products and as novel drug delivery 
formulations. Commercial applications and resultant opportunities for 
human exposure may differ substantially for nanoscale vs. ``bulk'' 
materials.
    Currently there is very little research focus on the toxicology of 
manufactured nanomaterials. Studies from the ultrafine particle 
inhalation toxicology literature hint at the complexity of the topic 
and suggest that nanoparticle size can impact toxicity equally if not 
more so than chemical composition. There are indications in the 
literature that manufactured nanomaterials may distribute in the body 
in unpredictable ways and that certain nanoparticles have been observed 
to preferentially accumulate in particular organelles. Surface 
properties can be changed by coating nanoparticles with different 
materials, but surface chemistry also is influenced by the size of the 
particle. This interaction of surface area and particle composition in 
eliciting biological responses adds an extra dimension of complexity in 
evaluating potential adverse events that may result from exposure to 
these materials.
    The National Toxicology Program (NTP) is developing a broad-based 
research program to address potential human health hazards associated 
with the manufacture and use of nanoscale materials. The intent of the 
NTP/NIEHS research program is to evaluate the toxicological properties 
of major nanomaterials classes which represent a cross-section of 
composition, size, surface coatings, and physico-chemical properties, 
and use these as model systems to investigate fundamental questions 
concerning if and how nanomaterials can interact with biological 
systems. Some of these fundamental questions include: What are the 
appropriate methods for detection and quantification of nanoscale 
particles in tissues? How are nanoparticles absorbed, distributed in 
the body and taken up by cells? Are there novel toxicological 
interactions?
    Discussion and review of efforts in this area has highlighted the 
need for studies of nanoscale materials that not only apply existing 
toxicology testing methodologies, but also explore the development of 
appropriate novel toxicological methods to adequately assess potential 
human health effects. The NIEHS is looking ahead to be able to 
supplement our critically inadequate knowledge of this rapidly emerging 
technology.

                                 ______
                                 
               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 2005, a sum of $1,421 million, which 
reflects an increase of $39 million over the comparable fiscal year 
2004 appropriation.
    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 describe some of our efforts, in collaboration 
with trans-NIH initiatives, to bring new treatments from the laboratory 
to the clinical research arena and ultimately to widespread practice in 
the community.

                        BURDEN OF MENTAL ILLNESS

    The National Institute of Mental Health faces an enormous 
challenge: to reduce the burden of mental and behavioral disorders 
through research on mind, brain, and behavior. Mental disorders are 
real illnesses that can be diagnosed and in many cases, treated 
effectively. The need is vast: 450 million people worldwide suffer from 
a mental disorder. Mental illnesses account for four of the top six 
causes of disability among 15-44 year olds in the Western world. By 
2020, psychiatric and neurological conditions will have likely 
increased their share of the total global burden by almost half, from 
10.5 percent to 15 percent.
    In addition to morbidity, mental illnesses are a substantial source 
of mortality. Of the 30,000 Americans who die by suicide each year, 90 
percent have a mental illness. Deaths from suicide outnumber deaths 
from homicide (18,000) as well as deaths from AIDS and most forms of 
cancer. Suicide is high among several ethnic minority groups, though 
remains highest in older white males. Between 1952 and 1992, the 
incidence of suicide among adolescents and young adults nearly tripled; 
currently it is the third leading cause of death in adolescents.
    In addition to the emotional costs, the economic costs of mental 
illness are staggering. According to the recent report from the 
President's New Freedom Commission on Mental Health, the cost in the 
United States from both direct (treatment-related) and indirect 
(productivity loss) expenses may exceed $150 billion per year with 
rapid annual increases, especially in the drug treatment area. Adding 
to that, more than three million people are receiving disability 
benefits due to mental disorders. They constitute nearly 28 percent of 
disabled workers in the Social Security Disability Insurance Program, 
and more than 35 percent of people with disabilities receiving 
Supplemental Security Income. Together they accounted for an estimated 
$25 billion dollars in cash benefits in 2001.

                           SCIENCE TO SERVICE

    For many mental disorders, there is some form of treatment, but 
there is no cure. The report from the President's New Freedom 
Commission on Mental Health describes the need for transforming the 
delivery of evidence-based treatment and services to communities where 
they can directly benefit people with mental illness. To achieve this 
goal, NIMH recognizes the need for the research enterprise to partner 
with other organizations such as the Substance Abuse and Mental Health 
Services Administration (SAMHSA), state governments, and advocacy 
groups. In one such example, NIMH and SAMHSA recently funded nine one-
year grants to state mental health agencies to support planning 
activities toward the implementation of evidence-based practices. 
Proposed science to service research activities include devising 
evidence-based group-focused activities for specific ages (child, 
adult); managing medication for those with schizophrenia; and providing 
cognitive behavioral therapy for people with depression. Each grant is 
expected to result in future research and service development 
initiatives. Translating scientific breakthroughs into far-ranging 
clinical care, we believe, is an urgent and achievable task.

                          PROGRESS IN GENETICS

    In addition to applying what we already know, we must continue the 
scientific efforts required to develop better treatments to bring us 
closer to our ultimate goals of curing or preventing severe mental 
health disorders. To attain these ambitious goals, we will need a much 
larger variety of medications and behavioral therapies than are 
currently available--treatments that can be tailored to work for all 
those who need them, not just a small subset. As an initial first step, 
we must discover how genes and the environment interact to produce the 
biological variations that can signal vulnerability to disease. This 
year has been remarkable in its wealth of discoveries of genes as well 
as gene-environment interactions. In depression, for example, NIH-
sponsored researchers found that a variation in the gene that regulates 
serotonin transmission can make a person more vulnerable to depression 
when faced with stressful life experiences. Those without the gene 
variation had no such vulnerability, and appeared to be resilient even 
in the face of many life stresses. Those with the gene variation were 
not depressed until and unless they faced major life stressors. This 
suggests that some of the environmental contributors to illness may 
only be detected by first identifying variations in genetic risk. 
Future research could help us apply this information to identify those 
most at risk, and develop treatments that either target genes or the 
environment, or both. It also suggests a new model with which to test 
genetic vulnerability and environmental stresses in other major 
diseases, such as schizophrenia, anxiety disorders, or eating 
disorders.
    This year we have also seen exceptional progress in research on 
schizophrenia. Several genes have been found which appear to 
significantly contribute to the development of schizophrenia, providing 
at least a partial blueprint for the genetic risk architecture of the 
disease. While we still need to learn more about how they work, this 
group of genes should bring us closer to diagnostic tests for early 
detection, new targets for treatment, and even new strategies for 
prevention. In other studies, genes have been found which are thought 
to play a role in obsessive-compulsive disorder, panic disorder, and 
autism. NIMH researchers have also identified genes involved in memory 
and information processing, both of which are impaired in schizophrenia 
and various other disorders. These studies were among those named 
collectively as the number two scientific ``breakthrough of the year'' 
by the prestigious journal Science in December. Most of the studies 
listed were conducted by intramural or NIMH-funded investigators. 
Studies this year have also provided new insight into the neural 
circuitry of anxiety and fear processing, suggesting new targets for 
drug development to treat anxiety, post-traumatic stress disorder, and 
various phobia disorders.

                   SCHIZOPHRENIA TREATMENT INITIATIVE

    While the news on schizophrenia has been exciting, we recognize 
that the road from gene discovery to prevention and treatment is 
neither simple nor rapid. To accelerate this process, we created a new 
initiative on schizophrenia research. A primary component is a new 
intramural interdisciplinary team, ranging from molecular to clinical 
scientists, who will lead a broad effort to understand how different 
gene variations alter neural networks and disrupt brain activity, 
leading to cognitive impairment and psychosis. The team will work to 
identify the role of these vulnerability genes, including their 
individual contributions to risk, severity of the disease, and drug 
response.
    A second component of the initiative is a program that targets 
cognitive problems for people with schizophrenia. Cognitive deficits, 
such as trouble with memory, attention, and executive function 
(capacity to make judgments and control impulses) are major 
determinants and predictors of long-term disability in schizophrenia. 
They remain a significant barrier to a productive life for people with 
the disease, yet the medications currently available provide no relief 
for cognitive problems. There has been a lack of scientific consensus 
on which cognitive impairments should be targeted and which tools are 
best for measuring them. As a result, the FDA has not been able to 
recognize cognition in schizophrenia as a valid treatment endpoint for 
drug registration. To address these issues, NIMH launched the 
Measurement and Treatment Research to Improve Cognition in 
Schizophrenia (MATRICS) program. It brings together representatives 
from academia, industry, and regulatory agencies to develop a 
comprehensive assessment tool to measure cognitive functioning in 
people with schizophrenia. The second phase is to develop and test 
novel compounds designed to enhance cognition.

                                ROADMAP

    For most of our recent genetic discoveries, we lack the molecular 
tools needed to link the genes to new treatments. The search for new 
molecular tools for schizophrenia and other mental disorders will be 
aided greatly by one of the NIH Roadmap initiatives that will establish 
a repository of diverse organic chemicals. Organic chemicals, commonly 
referred to as ``small molecules,'' have proven to be extremely 
important to researchers exploring the functions of the cell at the 
molecular level. In fact, most medicines, from aspirin to 
antihistamines, are small molecule compounds. This new ``molecular 
library'' will offer researchers access to hundreds of thousands of 
small organic molecules that can be used as chemical probes to study 
cellular pathways. These compounds will help validate new targets for 
drug therapy more rapidly, and will enable other researchers to move 
them into the drug-development pipeline.

                                 AUTISM

    NIMH plays a major role in a broad-based NIH effort to create a 
network of autism research centers focusing on the biomedical and 
behavioral aspects of the disease. Five institutes at NIH are 
coordinating their research efforts in an initiative called the Studies 
to Advance Autism Research and Treatment (STAART) Centers program. This 
year, the institutes awarded grants to support six new autism research 
centers, in addition to the two that were funded last year. NIH expects 
to spend $65 million over five years for the eight centers.
    NIMH is the lead agency for the Interagency Autism Coordinating 
Committee (IACC), a group charged with coordinating research and other 
efforts on autism within the Department of Health and Human Services 
(HHS). NIMH took the lead in organizing the ``Autism Summit Conference: 
Developing a National Agenda,'' a joint effort of the HHS and the 
Department of Education, held in November 2003. About 650 people 
attended the meeting to address three major areas of emphasis: 
biomedical research, implementing early screening and diagnosis, and 
improving the accessibility and coordination of services. A key focus 
of the meeting was the introduction of a 10-year national research 
agenda, developed by an IACC-appointed expert panel. The research 
agenda identified roadblocks hindering progress in understanding 
autism's causes and developing treatment, and provided goals and 
strategies for the next 10 years to overcome these challenges. These 
research efforts will be carried out through the centers of excellence 
within the STAART network.

                       PRACTICAL CLINICAL TRIALS

    To improve human health, scientific discoveries must be translated 
into practical applications. Such discoveries typically begin at ``the 
bench'' with basic research where scientists study the mechanisms and 
pathogenesis of a disease at a molecular or cellular level--then 
progress to the clinical level, or the patient's ``bedside.'' Equally 
important is the translation from bedside to practice. Moving new drugs 
and therapies more quickly and smoothly out of the research environment 
and into the hands of clinicians is a key feature of the NIH Roadmap. 
To achieve this, NIH will promote the creation of better integrated 
networks of academic centers that work jointly on clinical trials and 
which include community-based physicians who care for large groups of 
patients. Implementing this vision will require new ways of organizing 
the methods in which clinical research information is recorded, 
defining new standards for clinical research protocols, and creating 
new models of cooperation between NIH and patient advocacy alliances.
    For its part, NIMH is finishing up four large-scale, longitudinal 
research studies to compare therapeutic approaches for serious mental 
illnesses, including schizophrenia, Alzheimer's disease, major 
depression, and bipolar disorder. These are different than most 
clinical trials, which are usually of short duration and limited to 
assessment of clinical symptoms. The NIMH studies are testing the 
various treatment options currently available for these disorders in 
diverse community populations, recruiting people from a variety of 
``real world'' practice settings, and expanding outcome measures to 
include functional status and economic costs. The clinical populations 
currently enrolled in these NIMH treatment trials are among the largest 
and best characterized populations with bipolar disorder, 
schizophrenia, and depression ever studied through clinical trials in 
mental health. These trials will answer urgent questions about the 
treatment of adolescents with depression, the use of atypical anti-
psychotics in people with schizophrenia and Alzheimer's, and the 
optimal long-term medication for bipolar patients. When the studies are 
over within the next two years, we hope to be able to continue 
utilizing this valuable clinical infrastructure--made up of staff, 
investigators, federal and state agencies, industry, patients, and 
patient advocacy groups--to answer other critical public health 
questions in diverse populations.

                            PRIORITY-SETTING

    Over the past five years, we have witnessed unparalleled advances 
in the basic sciences relevant to mental health. Genomics, imaging, and 
many areas of neurobiology are beginning to reveal a new understanding 
of normal and abnormal behavior. Against this backdrop of scientific 
progress, we continue to face extraordinary challenges for our patients 
with mental disorders. Science now yields opportunities that promise to 
deliver for each of these challenges. To realize this promise, we must 
define areas of high priority. To assist us, workgroups of our National 
Advisory Mental Health Council are reviewing the NIMH portfolio 
initially in two key research areas: clinical trials and basic science. 
Both workgroups plan to deliver reports by May 2004 and both will 
define priority areas using the criteria of relevance, traction, and 
innovation. Both workgroups have done an impressive job in reviewing 
the hundreds of relevant grants in the portfolio. We look forward to 
their recommendations, as well as to those of our Outreach Partners in 
every state, the mental health advocacy community, and the public. We 
rely on these groups to help us meet our ultimate goal of relieving the 
profound misery suffered daily by patients and families affected by 
mental disorders.

                                 ______
                                 

               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 2005, a sum of $359,645,000, which reflects an increase of 
$32,556,000 over the comparable fiscal year 2004 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 the OD in greater 
detail.

                              NIH ROADMAP

    As part of the NIH Roadmap for Medical Research, the NIH has 
launched initiatives in fiscal year 2004 critical to addressing the 
roadblocks to the acceleration of science conduct and transfer to the 
public. These initiatives promise to yield far-reaching dividends in 
medical knowledge and improved health for the public. Under the theme 
of New Pathways to Discovery, initiatives are aimed at quantifying and 
cataloging complex biological systems and in developing a better ``tool 
box'' for today's researchers, for research teams of the future, and 
for re-engineering the clinical research enterprise. Examples of 
initiatives include the creation of an accessible public library 
database for chemically diverse small molecules, centers that will 
create new tools to describe the dynamics of protein interactions, 
development of novel technologies to study cellular metabolites, 
creation of national software engineering system that can facilitate 
the ability of scientists to tap into supercomputing networks and share 
and analyze complex data, and the early conceptual development of 
nanomedicine. The NIH Roadmap initiatives also have taken steps to 
prepare Research Teams of the Future, the second theme, by encouraging 
scientists and research institutions, including the NIH, to test 
alternative models for conducting research that take advantage of the 
scientific advances and complexities. A major focus has been placed on 
planning and research workforce training for the conduct of 
interdisciplinary research, that research that spawns new disciplines 
of science. In addition, a new award--the NIH Director's Pioneer 
Award--will support a select group of investigators who have the 
potential for ground-breading discoveries. Ultimately findings from the 
laboratory must reach the public, and the initiatives under the third 
them--Re-engineering the Clinical Research Enterprise--are geared to 
address the roadblocks to the conduct of clinical research and its 
translation to patients. These initiatives include the exploration of 
the ability to create and enhance interoperability among clinical trial 
networks, the testing the feasibility of establishing a National 
Clinical Research Associations program where community-based clinicians 
are trained to participate in studies and play a role in augmenting the 
transfer of research to their patients, and the assessment of patient-
reported chronic disease outcomes. Critical work continues in the area 
of research policy analysis and coordination with an emphasis on 
harmonization and standardization of policies and requirements 
pertaining to clinical research. In addition, extension and expansions 
of clinical research training programs extramurally and intramurally 
have been initiated.

                      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 2005 budget request for OAR is 
$61,435,000.

                THE OFFICE OF RESEARCH ON WOMEN'S HEALTH

    The Office of Research on Women's Health (ORWH), the focal point 
for women's health research for the Office of the Director, 
strengthens, enhances and supports research related to diseases, 
disorders, and conditions that affect women, and sex/gender studies on 
differences/similarities between men and women; ensures that women are 
appropriately represented in biomedical and biobehavioral research 
studies supported by the NIH; and, develops opportunities for the 
advancement of women in biomedical careers and investigators in women's 
health research. The report, An Agenda for Research on Women's Health 
for the 21st Century, provides a framework for the ORWH to collaborate 
with the scientific and advocacy communities to address gaps in 
knowledge about women's health and sex and gender factors in health and 
disease. The fiscal year 2005 budget request of $41,577,000 includes an 
increase of $626,000 over the fiscal year 2004 appropriation.
    Research priorities for women's health emphasize the importance of 
interdisciplinary research with collaboration and integration of 
knowledge from multiple areas of scientific expertise; lifespan issues 
and the continuum from intrauterine life into elderly years; health 
disparities/differences and diversity among different populations or 
subpopulations of women; and, sex/gender differences in health and 
disease and therapeutic interventions at genetic, molecular, cellular, 
and functional levels. Areas of research interest for 2005 include: 
pathogenesis of diseases including prevalence/validation of sex 
differences in diagnosis/treatment of disorders/diseases; clinical 
trial methodology; mental health studies; new agents for management of 
menopausal symptoms; treatments/interventions for diseases that show 
enhanced clinical features in women; and other specific areas such as 
CFS, and benign gynecologic disorders including uterine fibroids. 
Special emphasis areas for women's health research include genetics/
pharmacogenomics, and the genetic, molecular and cellular bases for 
action of pharmacologic agents known to have differential effects in 
females; and, prevention and treatment, from basic biological factors 
to effects of risk behaviors or interventions. There is expansion of 
new research in the ORWH specialized centers of interdisciplinary 
research in women's health and sex and gender factors, and the unique 
ORWH interdisciplinary career development program in women's health 
research that fosters the mentored development of junior faculty and 
assists them in bridging advanced training towards a goal of 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 
ORWH continues to partner with Institutes and Centers to ensure 
compliance with NIH policies for the inclusion of women and minorities 
in clinical research, and that analyses by sex/gender are addressed by 
investigators funded by the NIH.

         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 2005 OD budget includes $26,321,000 for OBSSR, an 
increase of $415,000 over the fiscal year 2004 appropriation.
    Many exciting scientific developments are occurring at the 
intersection of behavioral and social science research and biomedical 
research. It has become apparent that increasingly, scientific advances 
are being made at the interfaces of traditional disciplines, and that 
approaches to science are becoming more integrative. OBSSR has begun 
development of a program to provide interdisciplinary training to 
postdoctoral fellows in NIH intramural laboratories. This program would 
provide a mechanism hereby an individual with a PhD in a behavioral or 
social science discipline might acquire interdisciplinary training that 
included biomedical research. Alternatively, someone trained in a more 
traditional biomedical field would receive postdoctoral training that 
included a behavioral or social science component. In addition to the 
benefits to be realized by the individual trainees, this program would 
also show NIH leading, by example, our Roadmap efforts to build 
interdisciplinary Research Teams of the Future.
    OBSSR is also developing an initiative to advance discovery of 
scientific knowledge about eHealth technologies for health behavior 
change and chronic disease management. Consumers, patients, and 
providers are increasingly using eHealth applications, particularly the 
Internet, to seek health information for themselves or family and 
friends, communicate with others who have a similar disease or illness, 
and to communicate with their health care providers. These technologies 
offer people the ability to obtain health information at relatively low 
cost, including those with limited or no access to health care 
professionals or services, and historically underserved populations. 
While the use of eHealth interventions is becoming widespread, these 
techniques have yet to receive much rigorous evaluation. This 
initiative's goal is to bring together components of NIH, the Robert 
Wood Johnson Foundation and other public agencies and private 
foundations in a ``meeting of the minds'' about the state of eHealth 
evaluation research for health behavior change and chronic disease 
management, future directions in the field, and the role of NIH and 
others in developing a research agenda for this area.
    Behavioral and social factors contribute significantly to racial 
and ethnic health disparities. Consequently, OBSSR is committed to 
developing better knowledge of specific pathways to health disparities 
and to finding solutions. In February 2003, OBSSR published in the 
American Journal of Public Health a set of papers presenting scientific 
evidence of the effects of racial/ethnic bias on health and identifying 
areas for future research to further explicate the relationship. The 
papers were the product of an OBSSR meeting of approximately 100 
leading scientists held in April 2002. Currently, OBSSR is convening 
discussions among ICs regarding the role of social and behavioral 
science in their health disparities research activities and avenues for 
coordinated initiatives.
    An effective way to ensure that results of behavioral and social 
science improve our society's health involves incorporating these in 
clinical practice. In order to start this process at an early stage in 
the training of the next generation of physicians, OBSSR funded the IOM 
to determine how to improve medical education. The results of this 
study [April 2004] will inform a training initiative that OBSSR with 
several ICs will launch this year.

                    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 2005, the Office of Dietary Supplements (ODS) within 
ODP requests a budget of $26,218,000, an increase of $414,000 over the 
fiscal year 2004 appropriation. In fiscal year 2004, ODS published its 
5-year Strategic Plan for 2004-2009, a major component of which is to 
significantly expand efforts to address the role of dietary supplements 
in reducing the risk for chronic diseases. 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.
    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 2004 based upon this review, which will 
serve as the basis for planning further NIH research on omega-3 fatty 
acids. Congressional language in recent 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 U.S. 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. ODS collaborates with USDA to develop an 
analytically-based database of dietary supplement ingredients. ODS 
collaborates with other federal agencies to develop an approach to 
assessment of the health effects of bioactive factors in foods and 
dietary supplements. In its continuing efforts to inform the public 
about the benefits and risks of dietary supplements, ODS collaborates 
with USDA on the International Bibliographic Information on Dietary 
Supplements (IBIDS) database, which now includes 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 
1999-2002. 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.
    Another component of ODP, the Office of Rare Diseases (ORD) was 
formally established through the Rare Diseases Act of 2002, Public Law 
107-280. The purpose of this Act is to increase the national investment 
in the development of diagnostics and treatments for approximately 25 
million patients with more than 6,000 rare diseases. A rare disease is 
defined as one where fewer than 200,000 persons are affected in the 
United States. The fiscal year 2005 budget request for ORD is 
$15,787,600, an increase of $253,000 above the fiscal year 2004 
appropriation.
    Through its Extramural Research Program, the ORD supports a Rare 
Diseases Clinical Research Network with NIH Institutes and Centers 
(ICs). The major goals for the network include the systematic 
collection of clinical information to develop biomarkers and new 
approaches to diagnosis, treatment, and prevention of rare diseases, 
and to promote training of new clinical research investigators in rare 
diseases. ORD funded seven Rare Diseases Clinical Research Consortia 
and one Data and Technology Resources Coordinating Center. The 
consortia focus on urea cycle disorders, inborn errors of metabolism, 
rare neurological channelopathies, idiopathic bone marrow failure 
states and cytopenias, vasculitides, and defects in steroidogenesis. 
The patient support organizations are closely integrated into the 
consortia and the network.
    The ORD Intramural Research Program promotes training in the areas 
of clinical and basic research into rare diseases and in biochemical 
genetics, fosters protocol-based initiatives into rare diseases not 
currently investigated in the intramural program, assists in the 
investigation of select, unique disorders of unknown etiology, provides 
overall research support for diagnostics and therapeutics of rare 
disorders, and supports five Bench-to-Bedside grants.
    In its Scientific Conferences Program, in fiscal year 2004, the ORD 
will cosponsor more than 70 scientific conferences on rare diseases. 
The 460 conferences sponsored to date since 1995 have been shown to be 
excellent venues to establish a research agenda for specific rare 
diseases, take advantage of scientific opportunities, or eliminate 
barriers to dvancing research.
    To provide more comprehensive 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/or rare disorders. In its third year of 
operation, the information center broadened its language base to 
include Spanish in addition to English.
    In fiscal year 2004, ORD plans to establish a Trans-NIH Rare 
Diseases Working Group to encourage collaborative research activities, 
provide opportunities for input as new rare diseases research programs 
unfold, and gather information about the rare disease research programs 
supported by the ICs and Offices for mandated annual and biennial 
reports.

                    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 2005 Budget request 
for OSE is $3,899,000.

                 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 2005 Budget request for OLRS is $7,250,000.
    Thank you for giving me the opportunity to present this statement; 
I will be pleased to answer questions.

                                 ______
                                 

              Prepared Statement of Dr. Patricia A. Grady

    Mr. Chairman and Members of the Committee: The fiscal year 2005 
budget includes $139.198 million, an increase of $4.497 million over 
the comparable fiscal year 2004 appropriation level.
    I am pleased to be here today to discuss the activities of the 
National Institute of Nursing Research (NINR). NINR supports research 
that converges well with NIH's top priorities and activities. Our 
research emphases are also reflected in the NIH Roadmap, the strategy 
to accelerate scientific discoveries and take new approaches to make 
them more rapidly available to patients. NINR's scientific community is 
excited about the opportunities within the current and future NIH 
Roadmap initiatives. NINR is already supporting important 
interdisciplinary research training and interdisciplinary research, 
including community-based research. NINR's scientific community has 
been alerted to the procedural changes that need to take place in order 
to capitalize on the NIH Roadmap initiatives; their enthusiasm predicts 
a high level of support for the Roadmap.
    From its inception, NINR has emphasized interdisciplinary research 
teamwork and clinical and translational research, which are prominently 
featured in the Roadmap agenda. Our studies address national health 
problems head on. We have moved from an acute to a chronic disease 
focus, with emphasis on older people, who are living longer with 
illness and want the highest quality of life possible. We promote 
ethnically and culturally sensitive research and are aggressively 
pursuing research on health disparities, devoting about 20 percent of 
our budget to this area of science.
control of high blood pressure in young inner-city african-american men
    A good example of a program of research that improves health care 
disparities in a vulnerable African-American population is located a 
short distance from here--East Baltimore. The number of people with 
hypertension nationally is 40 percent higher for African-Americans than 
for Caucasians, and there is more severe disease impact among African-
Americans that can include heart enlargement and kidney dysfunction. 
The Johns Hopkins School of Nursing conducted this unique hypertension 
study, targeting a high-risk population of hypertensive young African-
American men between 21 and 54 years of age who are generally 
considered underserved by the healthcare system. At the study's start, 
only 17 percent had control of their blood pressure, but after three 
years, 44 percent of the men receiving the intensive form of a 
carefully designed community-based intervention attained control of 
their blood pressure. In some cases, the study represented the first 
time the study participants experienced formal healthcare. Of special 
significance is that 90 percent of the young men were retained in the 
study for the entire three-year period. A key to this success was the 
culturally appropriate, multidisciplinary research team approach that 
involved nurse practitioners, community health workers, and physicians. 
Among the lessons learned from this research is the need to modify 
healthcare for vulnerable populations like this one in Baltimore--
health care that involves home visits that offer educational and 
behavioral counseling to supplement visits to the clinics, and 
addresses factors beyond the disease itself, such as reducing substance 
abuse and obesity.

 HEALTH OF MINORITY, INNER CITY NEWBORNS IMPROVED BY NURSE HOME VISITS

    Another example of a health disparity is infant mortality, with 
rates for African-Americans twice those of Caucasians. Researchers 
tested a carefully designed intervention tailored to the risks of the 
populations studied to help close this health disparity gap. Findings 
after one year of the project indicate that the health outcomes of both 
mother and infant were improved, and costly health care was avoided. 
The intervention involved focusing on low-income, pregnant African-
American and Mexican-American mothers from the inner city, who received 
a program of planned prenatal care and post-natal monitoring with 
teaching and counseling at each encounter. Home visits made by a team 
of trained community residents and led by a nurse were an important 
feature, and the mothers received monthly phone calls for a year after 
their babies were delivered. The effects of the program varied by race 
and ethnicity. For African-Americans, findings indicated that mothers 
had more realistic expectations of their parenting role and were able 
to document the immunization of their infants. Their infants' mental 
development scores were higher than the control group. Mexican-American 
mothers showed improved skills in dealing with everyday life and in 
playing with their infants. This research and previous studies indicate 
that home visits by a nurse-health advocate team are among the most 
successful interventions in improving maternal and infant health--even 
for-inner city, low-income minority families. The key is to implement 
culturally sensitive interventions that are intensive and adequately 
staffed and funded.

              WOMEN'S EARLY WARNING SIGNS OF HEART ATTACK

    Although heart disease is the number one cause of death in both 
genders, far less is known by physicians and by women themselves about 
how women experience the disease. Research focusing on women's symptoms 
prior to heart attack found that women have different early warnings of 
heart attach than men have. Of note is that most clinicians consider 
chest pain as the most significant symptom for both sexes. Yet in this 
study the most prevalent symptom was reported to be unusual fatigue (70 
percent), followed by sleep disturbance (48 percent), and shortness of 
breath (42 percent). Fewer than a third of the women reported chest 
pain or discomfort. Even during the heart attack, 43 percent did not 
experience chest pain. Clearly, women's symptoms appear to be different 
from men's. This underscores the importance of women and clinicians, 
both, recognizing early warning signs of impending heart attack in 
women, so that they can prevent it or ease its effects.

              CHOLERA REDUCED BY LOW TECH WATER FILTRATION

    A growing global problem faced by developing nations is the 
availability of healthy drinking water, a most basic need for life and 
health. Cholera is carried by untreated surface water and kills 
thousands of people around the world by causing severe vomiting and 
diarrhea. The World Health Organization reports that the number of 
countries with cholera is increasing. In our own hemisphere, cholera 
incidence is now increasing in 16 Latin American nations. Researchers 
in Bangladesh have found a simple preventive technique that works and 
may be transferable to other countries. Inexpensive and widely 
available cotton sari cloth, when folded four to eight times, creates a 
filter small enough to remove most plankton, where cholera bacteria 
often live. In 65 villages with 133,000 inhabitants, the number of 
cholera cases was almost cut in half when people filtered their water 
with the sari cloth. Cultural barriers were not an issue, and about 90 
percent of the rural study participants followed the filtering 
procedure. When cholera did occur, those villagers had drunk unfiltered 
water at villages not participating in the study. The sari filtering 
technique could work just as well using other types of inexpensive 
cloth filters if replicated in countries where cholera is widespread.

                    THE NINR ROLE IN THE NIH ROADMAP

    Last year, NINR developed what we call Research Themes for the 
Future, which represent NINR priorities over the next five plus years. 
These themes blend well with the NIH Roadmap overall, especially in two 
areas--Interdisciplinary Research Teams of the Future, and Re-
engineering the Clinical Research Enterprise. In the first area, NINR 
has considerable experience carrying out interdisciplinary team 
research projects. In fiscal year 2003, more than half of NINR 
investigator publications appeared in non-nursing journals. This 
underscores the promise of future successful interdisciplinary research 
and practice collaborations. It also indicates that many other 
disciplines value nursing research findings. In the area of improving 
the clinical research enterprise, most of NINR's research is clinical 
in nature and can bring research questions to the laboratory from the 
clinical researcher's perspective. Investigators also translate 
research findings into the clinical practice of healthcare providers 
and develop partnerships with communities to speed new scientific 
knowledge into mainstream health regimens. Late last year, NINR 
supported a national conference to promote research-intensive 
environments in clinical settings, including academic medical centers 
and those that are nontraditional as far as research is concerned, such 
as nursing homes and community-level health enterprises. The goal was 
to create partnerships between academic researchers and potential 
investigators in these settings to develop resources and ease barriers 
to innovative research.
    To make the Roadmap a reality for nurse researchers, since the 
Roadmap will not be business as usual, but business as usual plus, NINR 
recently convened an implementation meeting with interdisciplinary 
experts from across the country. The meeting addressed ways to 
intersect NINR's themes and priorities with those of the Roadmap, as 
well as suggestions for new Roadmap directions that reflect the 
expertise of nursing research. Since NINR has always stressed 
interdisciplinary research, we look forward to increased participation 
in the Roadmap.

                              INITIATIVES

    Looking ahead to our fiscal year 2005 initiatives, reduction of 
obesity, a major public health issue, is certainly on the NINR agenda. 
Pediatric and adolescent obesity is particularly disturbing in and of 
itself, because it forewarns of future poor health. We plan to target 
minority populations at risk for obesity and children who are 
underserved--for example, those in rural areas. Research will address 
biological, behavioral and social science factors leading to or 
perpetuating obesity.
    Our genetics initiative is novel for NINR, since it involves 
incorporating behavioral, biological and molecular science into nursing 
research. Our focus will be on the interactions between genes, 
environment and behavior, including health promotion behavior. We will 
also assess the results of genetic education and counseling, and the 
effects of genetic testing on health, including lifestyle changes and 
the reduction of risks for disease.
    Increased attention is required to build the knowledge base for 
effective end of life care. NINR is the lead Institute at NIH for end-
of-life research. The research agenda we have identified for better 
healthcare management at this final stage of people's lives includes 
improved methodology, instruments, communication, and interventions 
that helped making choices. Previously published NINR-funded research 
findings on symptom management are already being integrated into 
standards of care. Further study is taking place to develop new 
behavioral approaches to improve the lives of patients and their 
caregivers and to devise new techniques to improve management of pain.
    Self-management has become the most basic way people can improve 
their lives when they are living with long-lasting, incurable chronic 
illness. Successful self-management interventions tested in mainstream 
populations, such as how to improve coping skills and how to maintain 
and improve cognitive functioning, will be tested in populations with 
special needs: the unemployed, homeless, very old, impoverished, 
disabled, or geographically isolated.
    Another initiative involves symptom management. Traditionally, 
clinical practice treats symptoms one symptom at a time. Yet symptoms 
rarely occur alone they occur in clusters. NINR plans to support 
research that will identify and describe groups of symptoms in HIV/AIDS 
and cancer patients by determining these clusters' effects on the 
patient, and developing interventions to manage the multiple symptoms. 
In addition to assisting how one symptom impacts the others in a 
cluster, we will consider the effects of age, treatment, gender, and 
type and stage of disease.
    NINR will expand on past and current research initiatives that 
focus on minority and underserved women's health, such as health 
disparities and reduction of low birth weight among minority women. The 
new initiative will focus on other aspects of women's health outside of 
reproduction, which in the past was frequently the central focus of 
women's health research by investigators of many disciplines.

              INCREASING THE NUMBER OF NURSE INVESTIGATORS

    The well documented and current shortage of nurses was preceded by 
a significant shortage of nurse researchers. The shortage of nurse 
researchers also means fewer nursing faculty to train future nurses and 
to conduct research that provides the scientific base for healthcare 
practice. In confronting this issue, NINR continues to collaborate with 
universities nationwide to rapidly develop baccalaureate-to-doctoral 
fast-track programs. This is in response to one of the recommendations 
of the National Research Council four years ago, which urged 
preparation of more nurse researchers more quickly. NINR revised the 
predoctoral training mechanism to enable nurses to enroll in the many 
fast-track doctoral programs in nursing which accept baccalaureate-to-
doctoral students. NINR has been responsive to the National Research 
Council's recommendation, and the nursing community has also responded 
by rapidly developing these baccalaureate-to-doctoral programs all over 
the nation.
    NINR supports Developmental and Core Centers to stimulate research 
and research training opportunities. Creating partnerships and 
leveraging funds is a hallmark of those Centers. We also initiated 17 
Nursing Partnership Centers to Reduce Health Disparities, in 
collaboration with the National Center on Minority Health and Health 
Disparities. These Centers partner eight research-intensive 
universities with nine minority-serving institutions. As a result of 
this program, we expect health disparities research to expand and the 
number of minority nurse investigators to increase.
    NINR will continue to offer career development awards, and we will 
make a special effort to train minority investigators through mentored 
research scientist awards and research supplemental awards. NINR's 
small but growing intramural research program is initiating a graduate 
partnership program with universities across the country this year and 
continues to support postdoctoral training opportunities on the NIH 
campus.
    In closing, the upcoming year contains new opportunities to 
configure scientific research in new ways. NINR and the nursing 
research community look forward to participation in the NIH Roadmap 
initiative and in other research that directly impacts the improvement 
of people's health.
    Thank you, Mr. Chairman. I will be pleased to answer any questions 
the Committee might have.

                                 ______
                                 
                Prepared Statement of Dr. Barbara Alving

    I am pleased to present testimony before this Committee on behalf 
of the National Heart, Lung, and Blood Institute (NHLBI).
    The NHLBI leads a national program directed at alleviating the 
burdens of diseases of the heart, blood vessels, lungs, and blood. The 
Institute also is responsible for research on the clinical uses of 
blood and its products and the management of blood resources. For more 
than a decade, the National Center on Sleep Disorders Research has been 
part of the NHLBI and, since fiscal year 1998, the NIH Women's Health 
Initiative has been administered by the Institute. Our diseases and the 
burdens associated with them touch the lives of all Americans.

                 BASIC AND CLINICAL RESEARCH APPROACHES

    The ultimate goal of the NHLBI is to improve the public health 
through discovery of effective methods to prevent and treat disease. 
Progress toward this goal depends on the existence of a coordinated 
program that focuses on clinical investigation as the culmination of 
basic research to unravel the fundamental processes that govern health 
and disease. The Institute has fostered and sustained a longstanding 
commitment to laboratory investigations of relevance to its mandate. 
Moreover, in recent years it has allocated a significant share of the 
generous budget increases provided to it to aggressive pursuit of 
promising, cutting-edge opportunities in such disciplines as genomics, 
proteomics, and nanotechnology. Advances in these areas promise to 
enable, among other things, more specific approaches to health 
promotion based on detailed assessment of individual characteristics 
rather than on general observations about what does or does not foster 
good health. Our optimism about the probable yield of these new 
endeavors cannot be overstated.
    However, the health-related outcomes of these basic science 
endeavors depend greatly on the extent to which laboratory discoveries 
are translated into approaches applicable to ``real-life'' health 
problems. And that, in turn, depends on clinical research. Being a 
disease-oriented agency, the NHLBI has for many years placed strong 
emphasis on developing and maintaining a robust clinical research 
portfolio. Particularly with regard to clinical trials, the Institute 
has worked to design efficient, less costly research approaches to 
evaluating therapeutic and preventive strategies. As part of this 
effort, the NHLBI has developed and refined the ``clinical research 
network'' concept and successfully applied it to evaluate new 
therapeutic approaches to conditions such as pediatric cardiovascular 
disease, asthma, acute respiratory distress syndrome, and Cooley's 
anemia. The networks provide an infrastructure that enables rapid and 
cost-effective testing of new therapies as they come to light.

                   THE NIH ROADMAP--CLINICAL RESEARCH

    It naturally follows that the NHLBI is an enthusiastic participant 
in the NIH Roadmap initiative titled Re-Engineering the Clinical 
Research Enterprise: Feasibility of Integrating and Expanding Clinical 
Research Networks. This new solicitation seeks to identify ways in 
which clinical research networks can collaborate to conduct clinical 
trials and other multicenter clinical research studies more efficiently 
than the current system allows. We at the NHLBI believe that 
application of lessons learned from this Roadmap initiative will better 
position the Institute to accelerate the pace of research and to reduce 
barriers that prevent research advances from becoming incorporated into 
clinical practice.

                     POSTMENOPAUSAL HORMONE THERAPY

    Major unexpected findings from the NIH Women's Health Initiative 
(WHI) illustrate the critical importance of the randomized, controlled 
clinical trial in determining the risks and benefits of preventive 
strategies. The study, which assessed the role of estrogen therapy, 
with or without added progestin, in preventing major causes of death 
and disability among postmenopausal women, was predicated on strongly 
suggestive evidence from basic research, observational studies, and 
smaller clinical trials that often measured so-called surrogate end 
points (e.g., changes in heart disease risk factors or subclinical 
manifestations), rather than events such as heart attacks or deaths 
from coronary disease. Indeed, at the outset of the WHI, much doubt 
existed regarding the feasibility and ethics of conducting the trial, 
because ``everybody'' already ``knew'' that hormone therapy helped 
women remain youthful and ``feminine forever,'' by not only relieving 
troublesome menopausal symptoms but also improving general health. Much 
to the surprise of researchers, practicing physicians, and women 
themselves, the trial of estrogen plus progestin last year was halted 
when it found increased risks of heart attack, stroke, invasive breast 
cancer, and blood clots among women assigned to take hormones. And 
quite recently, the estrogen-alone part of the study was discontinued 
because the hormone did not appear to have the hoped-for beneficial 
effect on heart disease (or, on the other hand, the feared unfavorable 
effect on breast cancer), but it did increase risk of stroke. These 
findings have major public health significance: the conclusion is that 
postmenopausal hormones, once ranking among the most-prescribed 
preparations in the United States, should generally be used only for 
short-term alleviation of menopausal symptoms.

                  LUNG-VOLUME-REDUCTION SURGERY (LVRS)

    Another trial of great practical importance was a rigorous 
assessment of LVRS, a procedure that was first used to treat emphysema 
during the 1950s. Although some patients seemed to benefit from this 
radical and invasive procedure, high mortality and morbidity 
discouraged its widespread use until the early 1990s, when some 
surgeons began performing LVRS again and insurance reimbursement became 
one of several issues demanding resolution. The National Emphysema 
Treatment Trial (NETT) clarified the short-and long-term risks and 
benefits of LVRS and identified the characteristics of patients who may 
be most likely to benefit from LVRS, as well as those who are at 
greater risk of death and complications from the procedure. The NETT 
reflects a unique relationship in which the NIH funded and administered 
the study and the Centers for Medicare and Medicaid Services (CMS), 
which sought evidence regarding the advisability of providing Medicare 
reimbursement for LVRS, supported participants' care costs. 
Additionally, the Agency for Healthcare Research and Quality 
contributed support for analysis of the cost-effectiveness of LVRS. The 
study results have provided a scientific basis for reassessment of 
Medicare coverage for LVRS.

             TRIALS OF HYPERTENSION CONTROL AND PREVENTION

    Last year, we reported results from the ALLHAT (Antihypertensive 
and Lipid-Lowering Treatment to Prevent Heart Attack Trial), which 
found persuasive evidence that traditional diuretics should be the 
initial treatment of choice for lowering high blood pressure. This is a 
study that only the NIH would likely have undertaken, as the comparison 
drugs--a calcium channel blocker and an ACE (angiotensin-converting 
enzyme) inhibitor--were already established as blood-pressure-lowering 
agents; it further illustrates the unique role played by the NIH in 
addressing issues of public health importance. Of additional interest 
is the observation that blood pressure control rates among ALLHAT 
participants increased from 25 percent at the beginning of the ALLHAT 
to 66 percent after five years of followup. These gains were achieved 
in a variety of clinical practice settings and in subgroups of people 
known to experience difficulty with blood-pressure control, such as 
blacks, the elderly, and diabetic patients. These results offer 
encouragement that blood pressure control is obtainable, and they 
challenge us to pursue this goal vigorously.
    The ALLHAT findings, in combination with evidence from other 
research studies, prompted issuance of an updated set of guidelines for 
hypertension management--the so-called JNC 7, or Seventh Report of the 
Joint National Committee on Prevention, Detection, Evaluation, and 
Treatment, of High Blood Pressure. An important feature of the 
guidelines is a reclassification of blood pressure levels that includes 
the new category ``prehypertension'' (120 to 139 mm Hg systolic and/or 
80 to 89 mm Hg diastolic blood pressure). Individuals with 
prehypertension are strongly encouraged to pursue lifestyle changes--
losing excess weight, eating a heart-healthy diet, increasing physical 
activity, quitting smoking--to forestall development of overt 
hypertension. To date, most behavioral interventions have focused on 
only one or two lifestyle changes at a time. However, findings from a 
recent clinical trial indicate that an all-in-one approach to lifestyle 
changes is feasible and effective in lowering blood pressure. Trial 
participants who addressed many elements of a healthy lifestyle 
simultaneously also significantly reduced their weight and became more 
fit providing even more incentive to undertake such changes.

              HYDROXYUREA THERAPY FOR SICKLE CELL DISEASE

    A breakthrough for patients occurred in 1995 when the NHLBI 
announced the results of a major trial of the first treatment for 
adults with sickle cell disease. The study found that use of the drug 
hydroxyurea slashed rates of painful crises and acute chest syndrome, 
and sharply reduced the need for blood transfusions and 
hospitalizations. A followup study of the trial participants recently 
reported that hydroxyurea not only protects patients from episodes of 
severe illness associated with their disease, but also prolongs their 
lives. Even the sickest patients--those who suffered three or more 
painful crises a year--benefitted. These results have important 
implications both for improving patient care and for decreasing health 
care costs associated with sickle cell disease.

            IMPROVING SURVIVAL FOR VICTIMS OF CARDIAC ARREST

    Cardiac arrest--in which the heart stops beating effectively, blood 
does not circulate, no pulse can be felt, and the victim collapses into 
unconsciousness--is a frequent occurrence in this country. Despite 
several decades of efforts to train members of the public to perform 
CPR (cardiopulmonary resuscitation), few victims of out-of-hospital 
cardiac arrest survive the experience. The NHLBI Public Access 
Defibrillation trial trained volunteer rescuers to use an automated 
external defibrillator, a device that shocks the heart back into normal 
rhythm. It found that use of CPR plus the defibrillator, compared with 
use of CPR alone, markedly increased survival of people who suffered 
cardiac arrest in various community settings, and caused no major 
injuries or serious safety problems. An important next step, currently 
under way with NHLBI support, is to determine the safety and 
effectiveness of providing defibrillators to families of heart attack 
patients for use when a cardiac arrest occurs at home. In addition, the 
Institute is establishing a research consortium of investigators, 
hospitals, emergency medical services, and local communities to 
investigate promising experimental strategies to resuscitate patients 
who experience out-of-hospital cardiac arrest.

                     COMBATING THE OBESITY EPIDEMIC

    Obesity is a problem of great concern to the NHLBI, as it strongly 
influences the risk for developing diseases and conditions such as 
coronary heart disease, hypertension, and diabetes. Thus, the Institute 
is strongly involved in the overall NIH effort to reverse the U.S 
obesity epidemic, and I have been especially pleased to serve as 
cochair of the NIH Obesity Research Task Force.
    The NHLBI recently launched a major study that addresses one of the 
most challenging aspects of weight control--keeping lost pounds off. 
The Weight Loss Maintenance Trial will initially assist overweight or 
obese adults participants in making lifestyle changes to reduce their 
weight and, subsequently, it will test various strategies to help the 
participants maintain their weight loss over the next several years. 
The trial focuses on persons who are being treated for high blood 
pressure or high blood cholesterol and, consequently, have particularly 
strong reasons to achieve and maintain a healthy weight.
    Another new initiative will assess the effectiveness of worksite 
interventions for preventing or controlling overweight and obesity in 
adults. Strategies to be considered include implementing environmental 
and policy changes to increase employees' physical activity (e.g., 
flextime or fitness-center discounts), offering healthful food choices 
in cafeterias and vending machines, providing information about 
nutrient and calorie content of foods at the point of purchase, and 
enhancing social support from fellow workers to encourage improved diet 
and physical activity.
    A third NHLBI initiative will explore the potential use of 
bioengineering approaches to address problems of obesity. For example, 
new methods for imaging body fat content may enable more specific 
identification of who needs to lose weight and their success in doing 
so. Bioengineering techniques may also offer a solution to the 
difficult technical challenge of obtaining precise measurements of 
energy intake and expenditure. One can envision development of a 
wristwatch-like gadget from which the wearer could easily determine 
whether an energy intake goal has been exceeded or an energy 
expenditure has been met. New approaches might provide accurate, 
convenient, easily understood, and inexpensive devices that would 
foster research, improve clinical management of adults and children, 
and help the public eat less and exercise more.

                               CONCLUSION

    These examples illustrate the extraordinary potential of clinical 
research, and particularly clinical trials, to address issues of major 
importance to the public health. The NHLBI will continue its commitment 
to stimulate and support clinical research, and to ensure that the 
knowledge thereby gained is rapidly, efficiently, and fully applied to 
disease treatment and prevention.

                            BUDGET STATEMENT

    The fiscal year 2005 budget includes $2,963.9 million, an increase 
of $172.1 million over the fiscal year 2004 enacted level of $2,791.8 
million.
    I would be pleased to answer any questions that the Committee may 
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 2005 budget 
includes $393,507,000 which reflects an increase of $11,561,000 and a 3 
percent increase over the fiscal year 2004 final conference level. 
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. NIDCD's mission 
includes the support of research to create assistive devices which 
substitute for lost and impaired sensory and communication function. 
Equally important to the NIDCD mission has been the discovery of 
genetic mutations that affect communication disorders. This work would 
not have been possible without the completion of the Human Genome 
project, supported in part by the National Institutes of Health. 
Enabled by this landmark accomplishment, scientists supported by the 
NIDCD have been studying the genes responsible for non-syndromic (not 
associated with any other problem) hereditary hearing impairment. 
Within the last 8 years, 54 genes have been identified, largely due to 
the contributions of NIDCD. Scientists are now focusing their efforts 
on identifying more genes, learning what role the genes have in 
deafness, and determining which genes affect certain populations of 
individuals. For example, recent studies have demonstrated that 
particular ethnic groups carry specific genetic mutations. Studying the 
genes that cause non-syndromic hereditary deafness will also permit 
early and more accurate genetic testing and foster the development of 
innovative intervention and prevention strategies, and more effective 
treatment methods for individuals with deafness and other communication 
disorders. My testimony today will primarily focus on the many genetic 
discoveries that have allowed NIDCD-supported scientists to learn more 
about the causes of communication disorders, a first step in prevention 
and treatment.

             NEW WAY TO IDENTIFY USHER SYNDROME IN CHILDREN

    Usher syndrome Type 1 is an inherited disorder. Children born with 
this disorder are deaf, suffer balance problems, and gradually lose 
their vision. Although Usher syndrome affects individuals of other 
racial and ethnic backgrounds, scientists have recently identified a 
clear pattern of its inheritance in Ashkenazi Jews, who are descendants 
of Jews from Germany, Austria and Eastern Europe. In 2003, a NIDCD-
supported scientist identified a mutation within the gene known to be 
responsible for Usher syndrome. The particular mutation seems to be 
responsible for most of the Usher syndrome seen in Ashkenazi Jews. 
Because scientists now know which mutation is responsible for this type 
of Usher syndrome, they can develop genetic tests to detect the 
mutation in Ashkenazi Jewish children who are born deaf. By identifying 
children destined to lose their sight, parents and doctors can help 
them learn to communicate and prepare them for blindness. Some of these 
children will be appropriate candidates to receive a cochlear implant. 
Cochlear implants are small electronic devices that enable individuals 
who are deaf or have severe hearing loss to detect sound. This research 
will now enable doctors to provide important quality of life 
improvements for children with Usher syndrome.

          GENE REPLACEMENT THERAPY CAN GENERATE NEW HAIR CELLS

    The sensory hair cells of the inner ear play an important role in 
detecting sound. People who lose hair cells due to excess noise, 
infections, or accidents often lose some or all of their ability to 
hear. Scientists have determined that many forms of inherited deafness 
are also due to problems with hair cells. The hair cells of the inner 
ear act like miniature amplifiers. Sound waves that enter the inner ear 
are converted into a series of chemical and electrical signals within 
the cells. These signals are ultimately transmitted to the brain via 
the auditory nerve and interpreted as sound. In the past, only birds or 
reptiles were thought to be capable of generating new hair cells. Now, 
NIDCD-supported scientists have discovered a way to use gene therapy to 
generate new hair cells in the ears of adult mammals. Scientists used a 
virus to transfer a gene called Math1 into the ears of guinea pigs. 
Math1 is expressed in developing hair cells, and its expression is 
thought to cause the cells to become hair cells, rather than becoming 
another cell type within the ear. The virus infects cells of the ear 
and causes them to produce the Math1 protein. Early experiments suggest 
that when the virus infects cells that do not normally express Math1, 
some of these cells become hair cells. In addition, the new hair cells 
also attract fibers of the auditory nerve, suggesting that the new 
cells may also be able to establish a link to the part of the brain 
that interprets sound--the auditory cortex. If this work can be 
duplicated in human beings, it may be the first step towards enabling 
scientists to use gene therapy to restore hearing to those who have 
lost it, or to enable deaf individuals to hear.

 NEW SHORT ELECTRODE WILL ALLOW GREATER BENEFIT FROM COCHLEAR IMPLANTS

    Cochlear implants are commercially available miniature hearing 
prostheses capable of assisting those who are profoundly deaf or 
severely hearing impaired. Approximately 60,000 individuals all over 
the world have received cochlear implants. The implant bypasses damaged 
or missing hair cells to send electrical signals through an array of 
electrodes within the cochlea (inner ear). Current cochlear implants 
send sound information that covers the entire frequency range. In order 
to send both high and low frequency information, the electrodes of the 
cochlear implant are inserted as far into the cochlea as possible. 
Unfortunately, inserting the electrodes into the cochlea compromises 
any residual (remaining) hearing the individual may have had prior to 
implantation. Consequently, scientists developed a new shorter 
electrode to help an additional population of individuals with hearing 
loss. These individuals have a considerable amount of residual hearing 
and their primary hearing loss is in sounds in the high frequency 
range. They are also experienced, yet unsuccessful, adult hearing aid 
users with severe-to-profound hearing impairment who would not have 
been conventional cochlear implant candidates. The short electrode is 
inserted into the base (or bottom) of the cochlea to restore hearing at 
high frequencies, while preserving low frequency hearing, or residual 
hearing, in the apex (or top) of the implanted ear.
    The preliminary data demonstrates residual hearing can be preserved 
with this short electrode, and provides evidence that this is most 
beneficial for understanding speech in a noisy background. Furthermore, 
the innovative short electrode may be an ideal treatment for those with 
presbycusis, which is the loss of hearing that gradually occurs in most 
individuals as they grow older. This new electrode design allows many 
more people with some degree of hearing loss to benefit from cochlear 
implant technology.

           IDENTIFYING GENES IMPORTANT FOR THE SENSE OF TASTE

    The worldwide obesity epidemic is causing health professionals to 
focus their attention on how people choose which foods to eat. Because 
taste plays an important role in food choice, scientists are interested 
in figuring out how taste buds tell the brain that they have tasted 
something, and which taste genes are responsible for sensing different 
food flavors. Vegetables such as broccoli, cauliflower, cabbage, and 
brussels sprouts contain compounds related to phenylthiocarbamide 
(PTC). For more than 50 years, scientists thought that the ability to 
taste PTC and similar compounds was determined by a single gene. If an 
individual inherited the PTC-tasting version of the gene, then they 
detected its bitter taste. If the tasting version of the gene was not 
inherited, the compound had no taste to that individual. Now NIDCD 
scientists, in collaboration with scientists in California and Utah, 
have identified a gene that regulates a person's sensitivity to the 
bitter taste of PTC. This explains why people seem to demonstrate a 
range of sensitivity to PTC's taste and may even influence whether or 
not an individual likes to eat broccoli and other vegetables containing 
PTC-like compounds. Because they determine an individual's sensitivity 
to a particular taste, inherited genes probably influence food choices. 
In the future, doctors may now be able to use this knowledge as part of 
a strategy to prevent and treat obesity and to overcome poor nutrition 
due to poor food choices. Increased knowledge about how taste cells 
tell the brain that they have detected a particular flavor may also 
help doctors restore the sense of taste to those who have lost it due 
to injury, disease or aging.

                          VOCAL FOLD PARALYSIS

    Vocal fold paralysis is a genetic disorder that can be inherited. 
The vocal folds are two bands of smooth muscle tissue that lie opposite 
each other and are located in the larynx or voice box. When at rest, 
the vocal folds are open to allow an individual to breathe. Voice is 
produced by vibration of the vocal folds. To produce voice, air from 
the lungs passes through the folds, causing vibration and thus making 
sound. The sound from this vibration then travels through the throat, 
nose, and mouth (resonating cavities). The size and shape of these 
cavities, along with the size and shape of the vocal folds, help to 
determine voice quality. Paralysis of the vocal folds impacts voice 
quality and inhibits an individual's ability to communicate. This 
disorder can also cause life-threatening breathing difficulties in 
affected newborn infants.
    Intramural scientists at the NIDCD and the National Institute of 
Neurological Disorders and Stroke are studying a family in which this 
disorder occurs and have found that vocal fold paralysis is due to 
degeneration of the nerves involved in movement. Weakness in the 
muscles of the arms and legs can also accompany this disorder. In the 
study, genetic analyses were used to locate the site of the causative 
gene to a section on chromosome 2. Further studies revealed that 
mutations in the dynactin gene, which resides at this location, are 
responsible for this disorder. Dynactin is a molecule that helps 
transport materials within nerve cells, and this research finding 
suggests that dynactin transport is essential for health and 
maintenance of at least some motor nerve cells.
    This finding allows for a genetic tool for diagnosing vocal fold 
paralysis, which can aid in the clinical and neonatal management of 
this disorder. In addition, these findings provide better understanding 
of motor nerve cells and the molecular mechanisms that cause motor 
nerve degeneration.

                              NIH ROADMAP

    The NIH Roadmap initiative to support interdisciplinary research 
and research training will advance the NIDCD mission because it 
encourages collaboration of scientists from seemingly unrelated 
disciplines. Interdisciplinary collaborations from a variety of 
scientific disciplines are necessary for developing assistive 
communications devices such as hearing aids and cochlear implants. The 
success of the development of the cochlear implant is a good example of 
successful interdisciplinary research as it involved the effort of 
physicists, chemists, material scientists, psychologists 
otolaryngologists, audiologists, speech-language pathologists, 
electrical engineers, and biomedical engineers We look forward to 
expanding upon that type of research in the coming years.
    Finally Mr. Chairman, I would like to thank you and Members of this 
Committee for giving me the opportunity today to speak to you about the 
exciting recent discoveries from the NIDCD. I am pleased to answer any 
questions that you have.

                                 ______
                                 
             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 2005, a sum of $325,147,000, which reflects an 
increase of $16,671,000 over the comparable fiscal year 2004 
appropriation.
    The National Library of Medicine continues to be the premier source 
of science-based medical information. Just 10 years ago the Library 
introduced its Web site one of the very first in the federal government 
and so began a decade of amazing growth in the amount and variety of 
medical information it made available. Today the Library's Web service 
not only provides free access to Medline/PubMed, the largest and most 
reliable database of scientific medical information in the world, but 
NLM has created information products designed specifically for 
patients, families, and the public.
    Despite its recent successes, NLM believes that the surface has 
barely been scratched and that the future holds the promise of many 
more valuable information products for the professions and the public. 
The Library's communications experts are at the cutting edge of new 
technology and, as more and more users have access to ever more 
powerful networks, the Library will put in place sophisticated yet easy 
to use information services that allow users free access to the world's 
burgeoning base of science-based health information. For scientists 
this means access not only to the growing published journal literature, 
but also electronically to scientific monographs and textbooks and to a 
variety of genomic information resources through NLM's National Center 
for Biotechnology Information (NCBI). For the general public, this 
means making even more consumer health information--from the National 
Institutes of Health and other reliable sources--available from the 
NLM's Web site.
    The new NIH Roadmap Initiative has the potential to have a profound 
and positive impact on how American medical research is conducted. The 
NLM sees itself has having an important role in the Initiative in three 
areas. Because the Roadmap recognizes that one of the most powerful and 
unifying concepts of 21st century biology is that of bioinformatics, 
the computerized bioinformatics databases and analysis tools of the 
NCBI will become even more central to the research enterprise. Second 
is the Roadmap's requirement to ``re-engineer the national clinical 
research enterprise.'' NLM's leadership role in working with biomedical 
vocabularies the Unified Medical Language System, the recently 
announced arrangement with the SNOMED clinical vocabulary, and NLM's 
expanding the NIH clinical trials database are all key aspects of 
improving clinical research. Finally, the Roadmap articulates NIH's 
responsibility to communicate research results to improve the quality 
of life for all people. The Library has a central role in collecting 
and communicating these results through Web-based information services 
and online databases. These are described in what follows.

             TOOLS FOR SCIENTISTS AND HEALTH PROFESSIONALS

    The NLM's Medline/PubMed is the most-used database of peer-reviewed 
medical information in the world. It contains more than 12 million 
references and abstracts to the world's medical literature published 
since the 1960s; an ancillary ``OldMedline'' extends the coverage back 
to the early 1950s. Each year millions of scientists and health 
professionals connect to Medline/PubMed (no registration or fee is 
required) and search for information they can use in the research or 
practice. More than a half billion such searches are done every year. 
The newest system, introduced in 1997, is constantly being improved. 
Several years ago NLM introduced links between Medline/PubMed 
references and publisher websites so users could retrieve the full text 
of articles. Today, more than 4,000 of the database's 4,600 
publications have such links.
    Another heavily used database is GenBank, the repository of all 
publicly available DNA sequences sent to the NLM from laboratories 
around the world. GenBank, and an increasing array of other valuable 
data resources, is the responsibility of the National Center for 
Biotechnology Information. The Center, which was created by the 
Congress in 1988 with the mandate to manage and disseminate genetic 
data, coordinates closely with the NIH Human Genome Project. GenBank 
today contains more than 27 million sequence entries totaling 33 
billion base pairs from over 130,000 species. NLM, through the Web 
operations of the NCBI, 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.
    A repository for chemical structure and assay data has been 
suggested as one aspect of NLM's involvement with the NIH Roadmap 
Initiative on ``small molecules'' to enhance research and develop new 
therapies. The NCBI is working on such a repository--called PubChem--
which will integrate into one open database, information from existing 
chemical structure databases at various NIH institutes as well as data 
supplied from industry and academic centers. By providing chemical 
structure validation and structure-structure matching and by linking to 
descriptions of the compounds in journal articles, PubChem will play an 
invaluable role in making this information useful to scientists.
    PubMedCentral, a digital archive, is an important component of the 
infrastructure needed to enhance access to the life sciences 
literature. Publishers electronically submit peer-reviewed research 
articles, essays, and editorials. NLM guarantees free access to the 
material; copyright remains with the publisher or the author. Access to 
PubMedCentral is free and unrestricted. The full text of more than 100 
life science journals, some going back decades, is now available, and 
more are added as they sign on to the system. Digitally archiving the 
scientific literature and guaranteeing access for future generations is 
an important NLM responsibility.

                  INFORMATION SERVICES FOR THE PUBLIC

    The National Library of Medicine has become a favorite destination 
of seekers of health-related information on the Web--people looking for 
answers to questions about their health or the health of their loved 
ones. MedlinePlus, the largest of NLM's Web offerings for the general 
public, now receives about 4 million unique visitors a month. 
Increasingly, they also find their way on the NLM Web site to other 
services created specifically for them--NIHSeniorHealth.gov, 
ClinicalTrials.gov, Genetics Home Reference, Household Products 
Database, and Tox Town are all recent examples. These Web sites contain 
or point to information created by NIH components and other reliable 
noncommercial sources. They require NLM librarians and information 
specialists to work closely with a wide variety of outside 
organizations. MedlinePlus, launched in November 1998, today is one of 
the most heavily trafficked Web sites containing health information for 
the public. It has more than 650 ``health topics,'' containing, for 
example, overview information, pertinent clinical trials, alternative 
medicine, prevention, management, therapies, the latest research, and 
the latest news from the print media. There are even links to the 
scientific literature through Medline/PubMed. In addition to the 650 
health topics, there are medical dictionaries, encyclopedias, 
directories of hospitals and providers, and interactive ``tutorials'' 
with images and sound. MedlinePlus en espanol was introduced in 2002 
and has grown to virtual parity with the English version. Both scored 
the highest marks of any Federal Web site in a recent outside 
evaluation. A new aspect of MedlinePlus is its plan to ``Go Local,'' 
that is, to link users with community helping services near them. North 
Carolina is the first MedlinePlus partner to go local.
    The National Library of Medicine is collaborating with the American 
College of Physicians in a unique ``Information Rx'' project that seeks 
to encourage practicing physicians who are members of the College to 
``prescribe'' MedlinePlus to their patients who need further 
information on a medical subject. After test runs in Georgia, Iowa, 
Virginia, and Florida, the Information Rx program will go nationwide 
later in 2004.
    MedlinePlus is not the only NLM information service directed at the 
consumer. Another very popular resource is ClinicalTrials.gov, which 
integrates previously fragmented information on human studies for 
different conditions into a single, coherent system, providing the 
public with an easy-to-use and convenient ``one-stop'' site for 
comprehensive information on clinical trials. The site, which is used 
not only by the public but by their health care providers, currently 
includes information on approximately 8,800 trials for hundreds of 
diseases and conditions conducted in about 90 countries. 
ClinicalTrials.gov receives approximately 16,000 visitors daily and 
over 3 million page views monthly.
    Late in 2003 another service for the public was launched: 
NIHSeniorHealth.gov. This site contains information in a format that is 
especially usable by seniors. For example, the site features large 
print and easy-to-read segments of information repeated in a variety of 
formats--such as open-captioned videos and short quizzes to increase 
the likelihood it will be remembered. NIHSeniorHealth.gov has a 
``talking'' function, which allows users the option of reading the text 
or listening to it as it is read to them. Another new NLM consumer 
service is the Household Products Database. This is a guide that 
provides easy-to-understand information on the potential health effects 
of more than 2,000 ingredients contained in more than 4,000 common 
household products. The database provides information on many of these 
substances and their potential health effects, in consumer-friendly 
language. For more technical information, users can launch a search for 
a product or ingredient from the product's page into NLM's TOXNET, a 
cluster of databases on toxicology, hazardous chemicals, and related 
areas.
    Another consumer health information resource introduced in 2003 is 
the Genetics Home Reference. Genetics is a complex subject, and much of 
the primary data and literature are difficult to understand without 
formal training. The Genetics Home Reference Website augments 
MedlinePlus with summaries of genetics information and an overview of 
the fundamentals of genetic science. The user can browse by a specific 
disease/condition or by gene. It also has a geographic list of genetic 
counselors and information for care-givers. The database has more than 
100 condition summaries and 80 gene summaries and new content is being 
added continuously.
    The Library launched Tox Town late in 2002. Tox Town looks at an 
ordinary town and points out many environmental hazards that might 
exist there. Users can click on a town location, like the school, and 
see a colorful dollhouse-style cutaway view of that building. Toxic 
chemicals that might be found in the school are listed, along with 
links to selected Internet resources about school environments. There 
are similar cutaways for offices, factories, parks, and other 
locations. NLM has plans to add new scenes, such as an urban community 
and a farming region.

                      SERVING SPECIAL COMMUNITIES

    With all these unique information resources, it becomes more and 
more important for the Library to engage in outreach to let citizens 
know what is available. The 5,100-member National Network of Libraries 
of Medicine is an important partner in these outreach endeavors. Many 
of the programs are directed at minority populations. For example, 
there are programs to assist in remedying the disparity in health 
opportunities experienced by African Americans, Latinos, Native 
Americans, senior citizens, and rural populations. A new NLM database 
introduced in 2003 has health information aimed at Asian Americans; 
2004 will see a similar database with information about the health 
concerns of Native Americans.
    Under a program with the Historically Black Colleges and 
Universities (HBCUs), NLM is helping to train people to use information 
resources in dealing with environmental and chemical hazards. The 
latest aspect of this outreach effort is NLM's collaboration with the 
United Negro College Fund Special Programs Corporation to work with the 
HBCUs in the area of consumer health to encourage the use of reliable 
electronic health information (such as that provided by the NLM) by the 
public.
    NLM also has been instrumental in reaching out to other countries 
around the world to help improve their access to scientific medical 
information. The oldest such program is that involving formal 
partnerships with major institutions in 20 countries. The NLM helps 
them obtain computerized access to the literature; the countries in 
turn help NLM receive the medical literature from that part of the 
world. The Library is also a key player in the Multilateral Initiative 
on Malaria, the multiagency effort to improve malaria research in 
African nations. NLM's role is to establish and maintain the first 
malaria research communications network, MIMCOM. There are now 19 
research sites in 9 countries participating, with full access to the 
Internet.

                            SCIENCE ADVANCES

    Many scientists believe that molecular biology is the primary 
driver of medical advances in the 21st century. The rapidly increasing 
volume of molecular data and the need to decipher its cryptic and 
subtle patterns has created demanding requirements for computerized 
databases and analysis tools, special curatorial expertise, and unique 
physical facilities. The National Center for Biotechnology Information 
is a key player in ensuring that the outpouring of data from molecular 
biology laboratories around the world is turned to life-enhancing 
purposes. GenBank, as noted above, is growing rapidly with 
contributions received from scientists around the world. Scientists 
also avail themselves of sophisticated computational tools, such as the 
BLAST suite of programs, which lets scientists search enormous 
quantities of data for sequence similarities that will identify genes 
and genetic features. Another tool, Entrez, allows users to search DNA 
sequences and literature information with techniques that are fast and 
easy to use. The newest tool is the ``Reference Sequence Collection,'' 
which provides a centralized, integrated, non-redundant set of 
sequences that is integrated with other information for all major 
research organisms. Using the Reference Sequence Collection, time once 
spent on having to identify, gather, and analyze data can now be spent 
effectively on research.
    The Center is now also conducting research using the human genome 
sequence to begin exploring the history of human populations. NCBI 
researchers, working with other collaborators, first assembled a set of 
500,000 high-confidence variations and then compared the distribution 
of these variations on the genome to that predicted by several models 
of population history. They found that the data best fit a model in 
which the human population shrank dramatically about 40,000 years ago, 
a time when modern humans first appeared in Europe. The model suggests 
that the population subsequently grew about 30,000 years ago, 
consistent with archaeological evidence of a population expansion 
during that period. The results indicate that databases of genetic 
variation constructed alongside the human genome project can provide a 
unique insight into the history of human populations. This insight may 
also explain how these populations may respond differently to selective 
pressures such as infectious diseases.
    NLM's Lister Hill National Center for Biomedical Communications 
sponsors high-technology communications research projects in such areas 
as high quality imagery, medical language processing, high-speed access 
to biomedical information, developing intelligent database systems, 
multimedia visualization, data mining, and machine-assisted indexing. 
One prominent area of research has been the Visible Human Project. The 
project consists of two enormous (50 gigabytes) data sets, one male and 
one female, of anatomical MRI, CT, and photographic cryosection images. 
These data sets are available through a free license agreement to 1,800 
individuals and institutions in 47 countries where they are being used 
in a wide range of educational, diagnostic, treatment planning, virtual 
reality, artistic, and industrial applications. An ``Insight Toolkit'' 
has been developed and makes available a variety of open source image 
processing algorithms for computing segmentation and registration of 
medical data. The Visible Human Web site is one of the most popular of 
all NLM's Web offerings.
    NLM's Extramural Programs for more than 20 years has supported the 
training of medical informaticians at universities across the nation. 
In the early years the program focused on training of informaticians 
for clinical care. Today the training programs have added opportunities 
for training in bioinformatics, the field of biomedical computing for 
the large datasets characteristic of modern research. At present, NLM 
provides 18 grants to biomedical informatics training at 26 
universities, supporting 250 trainees. NLM also participates in the NIH 
Roadmap activities, almost all of which have major emphasis on 
biomedical computing. For example, training is an important requirement 
of the National Centers for Biomedical Computing, an initiative for 
which NLM is one of the key leaders. Training as embedded in Roadmap 
activities is expected to become a significant complement to NLM's 
traditional support of informatics training.

                               THE FUTURE

    In its role as the world's largest medical library, the NLM will 
continue to provide free access to the enormous literature of the 
health sciences, including even priceless historical treasures dating 
to the 11th century. As to the 21st century, the Library is making 
major contributions to the NIH Roadmap and is also applying its 
unparalleled collections and talents to ``BIOSHIELD,'' the Department 
of Health and Human Services' effort to combat bioterrorism. The 
ability to apply medical knowledge to make our citizens healthy and 
safe is to repay the investment of the nation in medical research. In 
this, the National Library of Medicine can be of great help.

                                 ______
                                 
                 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 2005, a sum of $441,911,000, which reflects an increase of 
$13,486,000 over the comparable fiscal year 2004 appropriation.
    As the recent NIAAA National Epidemiologic Survey on Alcohol and 
Related Conditions (NESARC) has shown, most cases of alcoholism are 
established by age 25, beginning as early as age 18.\1\ These new 
results, which are corroborated by studies not yet published, call for 
a major refocusing of research on youth as the most important target 
for preventing alcohol abuse and alcoholism on a public-health scale. 
We now know that youth and adolescence are the critical window of 
opportunity. The earlier one drinks in adolescence, the greater the 
likelihood that he or she will develop alcoholism.
---------------------------------------------------------------------------
    \1\ NIAAA National Epidemiologic Survey on Alcohol and Related 
Conditions, 2003, and unpublished data from the Collaborative Studies 
on the Genetics of Alcoholism.
---------------------------------------------------------------------------
    The public-health implications of preventing alcoholism before it 
becomes established in youth are large, given the magnitude of alcohol 
misuse and its consequences. The 2002 report of the World Health 
Organization ranks alcohol third as a preventable risk factor for 
premature death in developed nations. Only tobacco and cholesterol are 
greater risk factors.
    In the United States, almost 18 million American adults met the 
clinical diagnostic criteria for alcohol abuse or alcohol dependence in 
2002.\2\ Annual costs to U.S. society of the consequences of alcohol 
misuse are about $185 billion.\3\
---------------------------------------------------------------------------
    \2\ Grant BF, Dawson DA, Stinson FS, Chou SP, Dufour MC, Pickering 
RP. The 12-month prevalence and trends in DSM-IV alcohol abuse and 
dependence: United States, 1991-1992 and 2001-2002. Drug and Alcohol 
Dependence, in press, 2004.
    \3\ Harwood, H.; Fountain, D.; and Livermore, G. (2000). The 
Economic Costs of Alcohol and Drug Abuse in the United States 1992 
(updated for 1998). Report prepared for the National Institute on Drug 
Abuse and the National Institute on Alcohol Abuse and Alcoholism, 
National Institutes of Health, Department of Health and Human Services. 
NIH Publication No. 98-4327. Rockville, MD: National Institutes of 
Health.
---------------------------------------------------------------------------
    Heavy alcohol use in the American military is on the rise, with 
more than 19 percent of male personnel and more than 5 percent of 
female personnel reporting heavy use.\4\ (The Department of Defense 
defined heavy drinking as five or more drinks on one occasion, at least 
once a week, in its survey). This pattern of drinking is hazardous to 
the health and welfare of the individual, the family, and society. In 
the general population of the United States, alcohol-related illness 
and injury account for at least 8 percent of all emergency-room 
visits.\5\
---------------------------------------------------------------------------
    \4\ The 2002 Department of Defense Survey of Health Related 
Behaviors Among Military Personnel.
    \5\ McDonald III AJ, Wang N, Camargo Jr CA. U.S. Emergency 
Department Visits for Alcohol-Related Diseases and Injuries Between 
1992 and 2000, Archives of Internal Medicine, 2004;164:531-537.
---------------------------------------------------------------------------
                          ALCOHOL USE BY YOUTH

    Alcohol is the primary psychoactive substance of abuse by American 
children. As the NIAAA fiscal year 2005 Congressional Budget 
Justification notes, 78 percent of 12th graders, 67 percent of 10th 
graders, and 47 percent of 8th graders have used alcohol.
    The same source of those statistics, the National Institute on Drug 
Abuse's Monitoring the Future survey, also indicates that youth who 
report having been drunk at least once include 62 percent of 12th 
graders, 44 percent of 10th graders, and 21 percent of 8th graders. 
Roughly half of those percentages say that they drank heavily five or 
more drinks in a row in the past 2 weeks.
    The NESARC data show that most cases of addiction, not only to 
alcohol, but also to other drugs of abuse, first occur in youth, after 
which new cases drop off sharply. The same research shows that, by 
comparison, new cases of depression do not follow this trajectory, 
instead continuing to rise after adulthood.

                        REFOCUSING THE RESEARCH

    The new finding that youth is the stage of life during which 
alcoholism is most likely to begin calls for a shift in the emphasis of 
our research. By focusing even more strongly than we currently do on 
developing strategies to prevent the onset of alcoholism in this 
population, we have the potential to dramatically reduce, overall, the 
occurrence of this common disease.
    Likewise, shifting the focus of our medication development program 
to the early stages of the disease stands to improve the effectiveness 
of treatment. As with most diseases, early treatment for alcoholism 
could prevent a host of problems, including the medical sequelae of 
heavy alcohol use, which are estimated to cost $18.9 billion annually.
    Studies show that a combination of factors underlie drinking 
behaviors. Environmental factors--family and peers, for example--are 
the dominating influences on whether or not an individual first uses 
alcohol. Personality and temperament also influence the decision to 
begin drinking. These factors have a profound effect on youth.
    Whether or not drinking continues also is influenced by 
differences, from individual to individual, in the pharmacological 
effects (activities of genes, proteins, and metabolic products) that 
come into play once drinking has begun. When drinking progresses to 
alcoholism, alcohol's pharmacological effects will have become the 
dominant influence on drinking behavior.
    Identifying the pharmacological effects of alcohol is essential to 
our ability to design effective prevention and treatment strategies for 
youth. In childhood and adolescence, the pharmacological effects of 
alcohol are occurring at a time of rapid structural and physiological 
change in the brain. One of the major questions before us is how 
alcohol's pharmacological effects work in ways that specifically 
promote alcoholism during this vulnerable time of life. Two NIH Roadmap 
initiatives will be particularly informative in this regard, as 
follows.
    The Roadmap Metabolomics Technology Development Initiative will 
enhance our ability to identify metabolic processes that contribute to 
alcohol dependence (and alcohol-related organ damage). People have 
differences in the genes that regulate their cellular mechanisms, 
including the enzymes responsible for alcohol metabolism. These 
differences result in variations in how people respond to alcohol; for 
example, the choice to drink and the amount of alcohol consumed.
    Proteins, such as the receptors and transporters for 
neurotransmitters, play roles in virtually every step of alcohol's 
actions in the brain and other organs. Another Roadmap initiative, the 
National Technology Centers for Networks and Pathways, will remove 
barriers to defining how these proteins behave in the complex 
biological systems in which they interact. Such proteins are potential 
targets for medications, but efforts to alter the actions of proteins 
with potential medication compounds have thus far met with limited 
success in preventing and treating alcohol-use disorders in adults. 
This Roadmap initiative will provide much-needed tools that will help 
us track the interactions of specific proteins at specific points in 
time and cellular space an ability that will enable us to develop more 
precise targets for medications to treat the early stages of 
alcoholism.

                            ACTIONS UNDERWAY

    Our current research on drinking by youth includes studies of the 
neurobiological mechanisms of adolescent alcohol abuse; an initiative 
on preventing alcohol-related problems among college students; expanded 
testing of preventive interventions, from rural children to children in 
urban, diverse neighborhoods; and an initiative that is examining risk 
factors and testing community-based, longitudinal prevention programs 
among children in rural and small urban areas, in response to fiscal 
year 2004 House Appropriations Report language.
    Included in NIAAA's fiscal year 2005 Congressional Budget 
Justification is an expansion of the latter initiative among youth in 
rural and small urban communities, both of whom have high rates of 
alcohol use. Both biological and environmental studies, as well as 
studies of prevention strategies, will be included. The Substance Abuse 
and Mental Health Services Administration, the National Institute on 
Drug Abuse, the National Institute of Child Health and Human 
Development, the National Institute of Mental Health, and other NIH 
Institutes, as well as the Department of Education and other Federal 
agencies, will be invited to collaborate in this initiative.
    In addition to our research, we conduct outreach programs for 
youth. The Leadership to Keep Children Alcohol-Free has recruited 33 
Governors' spouses to spearhead a national prevention campaign. The 
Task Force on College Drinking has brought together university 
presidents and researchers, and is making headway in efforts to reduce 
drinking by college students and in evaluating those efforts.

                           THE LARGER PICTURE

    Alcohol abuse and alcoholism often result in behavioral outcomes 
such as property damage, legal problems, disrupted family lives, and 
derailed academic pursuits and professional careers. But its 
consequences also include medical sequelae. With prolonged, heavy use, 
it can act as a toxin, damaging virtually any organ in the body. For 
example, alcohol is a leading cause of liver cirrhosis and contributes 
to some kinds of cancer. Approximately 77 percent of the annual $185 
billion cost of alcohol misuse is health-related, generated by medical 
consequences and lost productivity associated with illness or death.
    Research leading to effective strategies for preventing and 
treating alcoholism early in life, when it is most likely to begin, can 
help avert many other costly problems. While we will increase our 
research on drinking by youth, we will continue our studies of the many 
other facets of alcohol use, such as fetal alcohol syndrome, as well as 
our research on the apparent protective effect of moderate drinking 
against certain chronic diseases.

                         CONNECTION TO OBESITY

    We will also conduct research on alcohol's role in the national 
obesity epidemic. In addition to acting as a drug, alcohol is a food--a 
highly caloric food. It has more calories per gram than do 
carbohydrates or proteins.
    In addition, alcohol acts on some of the same neurotransmitter 
systems that regulate appetite. Some medications that work to reduce 
appetite may also reduce alcohol intake. One of the highest priorities 
that NIH lists in its Government Performance and Results Act goals is 
human testing of the compound rimonabant for its potential to reduce 
alcohol use.
    Among the many neurotransmitter receptors that alcohol affects is 
the one receptor to which the active ingredient in marijuana binds. 
Stimulation of this receptor promotes appetite, and NIAAA animal 
studies show that blocking the receptor with rimonabant has the 
potential to reduce drinking in humans. NIAAA is preparing a human 
trial of rimonabant for treatment of alcoholism. Rimonabant made news 
in March of this year, when a French company announced the medication's 
effectiveness in reducing both weight and smoking.
    The anticonvulsant topiramate also is being tested for its 
effectiveness in reducing both obesity and alcohol use, through actions 
on another neurotransmitter system. The neurotransmitter gamma-
aminobutyric acid (GABA), among many others, is known to be an 
important intermediary of alcohol's actions in the brain.
    Obesity and alcohol are linked in yet another way, recent studies 
show. The livers of obese rats undergo more cell death and sustain more 
injury from heavy, periodic alcohol use than do those of their slimmer 
counterparts. In humans, liver damage is one of the most prevalent 
medical consequences of chronic drinking.\6\
---------------------------------------------------------------------------
    \6\ Carmiel-Haggai M, Cederbaum AI, Nieto N. Binge ethanol exposure 
increases liver injury in obese rats. Gastroenterology, 125(6):1818-33. 
Dec. 2003.
---------------------------------------------------------------------------
                              IMPLICATIONS

    On a large scale, epidemiology tells scientists where the action 
is. That is the case with our new findings on the stage of life when 
alcoholism is most likely to develop; that is, by age 25. We are 
beginning to take steps to greatly increase our focus on this period--
on how variations in genetic, biological, and environmental factors 
unfold to promote establishment of alcoholism during development. 
Meanwhile, the NIH Roadmap initiatives on metabolomics and proteomics 
are developing tools that can significantly accelerate our research.

                                 ______
                                 
              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 2005. The fiscal year 
2005 budget includes $394,080,000, an increase of $11,032,000 over the 
fiscal year 2004 level of $383,048,000 comparable for transfers 
proposed in the President's Request.

              DELIVERING ON THE PROMISE OF BASIC RESEARCH

    Although highly technical in nature, basic research provides the 
detailed molecular clues that scientists and clinicians can use to 
develop new strategies that more effectively prevent or treat disease. 
This year, I would like to highlight how NIDCR's investment in the 
basic sciences continues to yield important advances in oral and public 
health. I also would like to mention how NIDCR stands to benefit from 
the recently launched NIH Roadmap which has the potential to catalyze 
virtually all areas of oral health research and, most importantly, 
hasten the development of novel treatments that could greatly improve 
American oral health.

                 GENE TRANSFER AND THE SALIVARY GLANDS

    A prime example of basic research creating new clinical 
opportunities is the transfer of replacement genes into the salivary 
glands for therapeutic purposes. In the early 1990s, a team of NIDCR 
scientists published their initial paper on the technical feasibility 
of this approach. Thereafter, they began a unique long-term research 
interest in transferring replacement genes into the salivary glands of 
persons with Sjogren's syndrome and cancer patients whose salivary 
glands were damaged during radiation treatment. The hope was that the 
replacement genes would increase the production of saliva and eliminate 
the chronic parched sensation that plagues people with dry mouth 
conditions.
    The NIDCR scientists also began to apply their gene transfer 
studies to a third and seemingly less obvious therapeutic area: single-
protein disorders, such as type I diabetes, human growth hormone 
deficiency, and erythropoietin-responsive deficiencies. Frequently 
overlooked in the medical literature, salivary glands not only release 
saliva into the mouth, they routinely secrete digestive enzymes and 
other proteins into the circulatory system. As the scientists later 
would demonstrate, the salivary glands readily accept gene-carrying 
vehicles, or vectors. Thereafter, with minimal coaxing, the salivary 
glands act as natural protein factories, dutifully manufacturing the 
encoded replacement protein and pumping it at steady levels into the 
circulation. The approach has some built in advantages over gene 
therapy in other parts of the body, such as the liver. Salivary glands 
are easily accessible and any potential adverse effects would be non-
life threatening. Moreover, salivary gland cells are encapsulated to 
prevent leakage of the vector into the circulation and to other 
tissues.
    Recently, the group developed a new version of gene-carrying vector 
that entered the salivary glands of mice and produced the human protein 
erythropoietin for at least one year, a major step forward in the 
research. Just as importantly, the vector--a stripped down, 
bioengineered version of the harmless adeno-associated virus--did not 
trigger a sustained immune response, a common setback in gene therapy 
experiments.
    Building on this strong basic research base, NIDCR has developed a 
new initiative to evaluate the safety and efficacy of salivary gland 
gene transfer techniques in people with systemic single-protein 
deficiencies. The initiative will consist of three Phase I/II clinical 
trials. The first clinical trial will involve a prototype systemic 
single-protein deficiency disorder, adult growth hormone deficiency. As 
currently proposed, 21 patients will be enrolled in the study, which 
will be completed in four years. If successful, a second clinical trial 
will be conducted to treat people with erythropoietin-responsive 
deficiencies and ultimately a third clinical trial for those with 
Sjogren's syndrome and/or cancer patients with dry mouth.

                 PERIODONTAL DISEASE AND PRETERM BIRTH

    Another outstanding example of basic research creating new clinical 
opportunities is in the area of preterm pregnancy. In the United 
States, about one in eight babies is born prematurely,\1\ which is 
defined as a birth that occurs three or more weeks earlier than the 
expected due date. As all too many parents have tragically experienced, 
extremely preterm babies can be so small and underdeveloped that they 
must remain hospitalized for months and, if they survive, spend years 
battling chronic health problems.
---------------------------------------------------------------------------
    \1\ March of Dimes Defects Foundation. http://
peristats.modimes.org. Access on March 15, 2003.
---------------------------------------------------------------------------
    This serious and common problem has spurred scientists to identify 
``risk factors'' associated with premature births. These risk factors--
which now include smoking, low-income status, hypertension, diabetes, 
alcohol use, genitourinary tract infections--allow doctors to identify 
women who are more likely to deliver prematurely and thereby tailor 
their prenatal care to control or eliminate the risk factors.
    However, the list of risk factors remains a work in progress. An 
estimated one in four preterm births occur without any known 
explanation, and that has left scientists searching for additional 
susceptibility factors to help more mothers and reduce the estimated 
$13.6 billion per year spent in the United States on hospital stays for 
infants with a diagnosis of prematurity.\2\
---------------------------------------------------------------------------
    \2\ March of Dimes, PeriStats.
---------------------------------------------------------------------------
    In the mid 1980s, scientists began to suspect that periodontal 
disease might be one of these elusive risk factors. These NIDCR 
grantees and colleagues monitored women with more serious periodontal 
disease and found they were more likely to deliver early than those 
with mild or non-existent disease. They also have developed a plausible 
biological explanation to explain the possible association. Based on 
animal studies, the scientists hypothesized that certain bacteria from 
severe periodontal infections, most notably Porphyroma gingivalis, 
enter the bloodstream and eventually circulate to the womb. There, the 
oral pathogens colonize and irritate the uterine wall. This causes 
inflammation of the uterus and a rise in prostaglandins and other 
infection-signaling chemicals, which can induce early contractions and 
trigger premature labor.
    Left unanswered is whether treating women for periodontal disease 
during pregnancy will help them give birth to full term babies. The 
NIDCR recently launched two large randomized clinical trials to answer 
this important public health question. These national studies, which 
merge the disciplines of dentistry and obstetrics, will involve over 
2,600 women of various racial, ethnic, and economic backgrounds. What 
is unique about these clinical trials is there will be a yes-or-no 
outcome for each woman within 37 to 40 weeks, or the completion of the 
pregnancy. Women will not need to be tracked at great expense for 10 or 
20 years to get the final answer, as is often the case in clinical 
research. Once all the data are compiled and analyzed, which could take 
an estimated five years to assemble and analyze, researchers anticipate 
that they will have sufficient clinical data to offer sound scientific 
advice one way or the other on this critical public health issue.

                             PAIN RESEARCH

    In another example of the potential payoff from basic research, 
scientists are mapping in greater detail the multiple routes, or 
pathways, that sensory signals travel en route to the spinal cord and 
brain. This work has resulted in several new leads in how to more 
effectively manage pain. One of the most promising new leads stems from 
work conducted at the NIDCR. Our scientists found that an ultrapotent 
compound selectively eliminated an entire class of pain-sensing neurons 
from the peripheral nervous system of a living organism. The compound, 
called resiniferatoxin (RTX), killed the neurons, blocking inflammatory 
pain, thermal pain sensation, and reducing hypersensitivity to pain. 
Importantly, the animals maintained their ability to sense pain, in 
this case from a pinch, and they remained well coordinated, an 
indication that RTX did not affect sensory nerves in the muscles and 
joints. Since these initial reports, the investigators have assembled 
additional preclinical data and are moving rapidly toward evaluating 
RTX in human clinical trials.
    In order to seed additional discoveries in pain research and to 
help more Americans effectively manage pain, the NIDCR will begin an 
initiative to define the proteins and protein networks involved in 
processing pain-signal information in the orofacial region. This 
initiative encourages interdisciplinary studies that employ genomic and 
proteomic approaches, imaging technology, and computational biology to 
clarify the molecular events involved in chronic orofacial pain 
disorders.

                     PUTTING RESEARCH INTO PRACTICE

    To achieve our goal of improved oral health for all people, NIDCR 
must ensure that research advances are translated and adopted into 
clinical practice. Many of the unique questions faced by dental health 
professionals on a daily basis are most appropriately addressed in 
dental practice settings, among unselected patient populations. 
Practice-based research networks can generate important and timely 
information to guide the delivery of health care and improve patient 
outcomes. The NIDCR will launch an initiative to create dental 
Practice-Based Research Networks (PBRNs) to conduct clinical research. 
In time, linking the oral health practice-based research networks with 
existing medical networks will provide additional patients, 
professional expertise, and integration of resources for conducting 
research across a broad spectrum of health care specialties. By 
connecting practitioners with experienced clinical investigators, PBRNs 
will enhance clinical research supported by the NIDCR and produce 
findings that are immediately relevant to practitioners and their 
patients. The networks can support a variety of clinical studies with 
clear and easily defined outcome measures, and they typically draw on 
the experience and insight of practicing clinicians to help identify 
and frame the questions. Because research is conducted in the real-
world environment of dental practice, the results are more likely to be 
readily adopted by practitioners.

                              NIH ROADMAP

    The NIH Roadmap provides several additional opportunities to the 
oral-health research community. For example the goals of the initiative 
Building Blocks, Biological Pathways and Networks--are closely linked 
to NIDCR's molecular anatomy efforts to identify the full complement of 
genes, proteins and protein networks that are expressed in both oral 
cancer and periodontal disease. Advances in proteomic analysis 
platforms will be crucial for NIDCR to achieve its goal of defining the 
salivary proteome--a critical step in the Institute's long-term goal to 
exploit the salivary secretions for diagnostic purposes. The Molecular 
Libraries and Molecular Imaging initiative holds great promise for 
accelerating NIDCR's progress in defining the molecular pathways of 
pain reception and in elucidating new therapeutic targets to manage 
chronic pain. In addition, the initiative Research Teams of the Future 
will enable NIDCR's ongoing inter- and multi-disciplinary efforts to 
further expand and develop new ways to approach research questions. 
Finally, the integration of dentists into the new clinical research 
infrastructure that will be created by the Roadmap is key given that 
overall health and oral health are interrelated and that certain 
systemic conditions such as diabetes, Sjogren's syndrome, HIV/AIDS and 
osteoporosis have important oral symptoms, manifestations or 
complications.
    NIDCR envisions a clear path ahead for oral and craniofacial 
research. Many exciting new leads that have been reported in recent 
years makes it easy to imagine that the next wave of research advances 
will have a more profound and far reaching effect on oral health than 
ever before.

    Senator Specter. Thank you very much, Dr. Zerhouni.
    We have been joined by two members of the Appropriations 
Committee. Let me turn first to the distinguished chairman of 
the full committee, Senator Stevens.
    Senator Stevens. Well, Mr. Chairman, I am late. So I will 
just ask to put my statement in the record. I do greet our 
friends at the table and look forward to the comments and 
questions.
    Senator Specter. Without objection, the statement will be 
made a part of the record.
    [The statement follows:]

               Prepared Statement of Senator Ted Stevens

    Thank you Mr. Chairman. It's a pleasure to welcome Dr. Zerhouni and 
his distinguished colleagues who head up the Institutes at NIH here 
today.
    I'd also like to thank Dr. Andy von Eschenbach. Andy, I understand 
from my good friend Dr. Mike Phelps that you gave an excellent speech 
this past Sunday to the Academy of Molecular Imaging meeting in 
Orlando. As you know, PET and Molecular Imaging are special interests 
of mine.
    I must be brief since I have three other hearings where I must make 
an appearance. However, I want to commend Dr. Zerhouni for his efforts 
to develop the ``Roadmap'' initiative.
    That initiative aims to focus NIH's resources on several broad 
categories of medical research and to bring together different 
disciplines to make real, rapid and visible progress to determine the 
true basis of many diseases and then to treat them. The Roadmap, with 
its focus in the Director's office is important because no single NIH 
Institute can address these problems alone.
    I'm particularly pleased that you have chosen to focus early 
efforts of the Roadmap on the integration of nanotechnology, systems 
biology, and molecular imaging. By combining these three disciplines we 
hope to discover the molecular basis of diseases like cancers and then 
to develop targeted molecular therapies to arrest the progress of the 
disease and cure it.
    In the fiscal year 2004 appropriations legislation I sponsored an 
amendment to give the Director of NIH new authority to put together 
innovative collaborative approaches to medical research to help speed 
up the process. I hope that you, Dr. Zerhouni, will use that authority 
to take bold and visionary steps to help us find these cures.
    I've been a longtime supporter of large increases in funding for 
medical research. I continue that support, but I must warn you that it 
will be more and more difficult to sustain increases for medical 
research unless you do pursue bold new approaches such as nanosystems 
biology that have the potential to show real results that the American 
taxpayer can see. We must begin to show a return on our investment in 
order to continue it.
    Once again, I commend Dr. Zerhouni and the directors of the NIH 
Institutes for their leadership and efforts on behalf of all people.

    Senator Specter. Senator Cochran, do you have an opening 
statement?

               OPENING STATEMENT OF SENATOR THAD COCHRAN

    Senator Cochran. Mr. Chairman, thank you very much. I have 
submitted a statement as well and hope it will be included in 
the record.
    I want to commend the Director and his associates who are 
here today for the fine work that you are doing. I am 
particularly impressed with the work in health disparities and 
some of the research that is being undertaken now and funded by 
the National Institutes of Health.

                           PREPARED STATEMENT

    I notice an increase in the budget request for the National 
Center for Minority Health and Health Disparities. I think that 
is the entity that is supporting the Jackson Heart Study in my 
State where very meaningful work is being done in conjunction 
with the University of Mississippi Medical Center and Jackson 
State University and other educational institutions in our 
State to try to get at the bottom of some of the questions of 
why there is such a disparity in some kinds of heart diseases. 
This is being done in conjunction with the National Heart, 
Lung, and Blood Institute as well. But I think the need for 
more research, conducted in the places where we are 
experiencing health disparities or high incidences of chronic 
diseases, is something that is overdue, and I congratulate you 
for taking this initiative.
    [The statement follows:]

               Prepared Statement of Senator Thad Cochran

    Dr. Zerhouni, thank you for joining us today to discuss the budget 
for the National Institutes of Health. We have had great success in 
increasing NIH funding. It is my hope that we continue to support high 
quality research, and focus this research on the most pressing health 
issues of our country. Our goal should be to make sure NIH research 
benefits all Americans.
    I know you are familiar with the Jackson Heart Study, which looks 
at the reasons why African-Americans suffer disproportionately from 
heart disease. I hope the NIH will continue to take an active role in 
making sure research like this reaches underserved areas of our 
country. This relatively small investment has made a tremendous impact 
on my state. I am encouraged by the progress made by institutes, like 
the National Center for Minority Health and Health Disparities. I am 
pleased to support NIH in these efforts.

    Senator Specter. Thank you, Senator Cochran.
    We will now proceed with 5-minute rounds of questioning, as 
is the custom of the subcommittee.

                    FISCAL YEAR 2005 BUDGET REQUEST

    Dr. Zerhouni, your proposed budget will permit grant 
increases by only 1.3 percent instead of the inflationary 
increase of 3.5 percent. If NIH applied its usual policy of 
providing an average grant increase equal to the rate of 
inflation, it is my understanding that about 640 fewer 
competing grants would be funded than in 2004.
    First of all, is that accurate?
    Dr. Zerhouni. That is accurate, Senator.
    Senator Specter. After the increases which we have provided 
over the last 5 years, do you think the proposed budget is 
sufficient to maintain the momentum and bring discoveries from 
the laboratory to the doctor's office?
    A subset of that is, how much additional funding would be 
required to restore the usual NIH average cost policy, assuming 
the same number of grants which are now in the budget?
    Dr. Zerhouni. Ideally, Mr. Chairman, you would like to be 
sure not to fall behind inflation. However, this year, because 
of the very difficult budget environment, we had to make some 
difficult choices. We elected to maintain the number of grants 
to be able to provide as many scientists the opportunity to 
succeed in applying and made some sacrifices on the cost 
increases.
    If we had $220 million more--the number is $220 million--we 
could satisfy both conditions: have enough grants and 
inflationary increases.
    Senator Specter. If the Congress is willing to appropriate 
the additional $1.3 billion, what new research initiatives 
would NIH be able to conduct with these additional funds?
    Dr. Zerhouni. As you know, because of the doubling and the 
opportunities offered by the doubling, many of our institutes, 
if not all of them, have opportunities in translation in 
clinical research. This is the area of research generally that 
is difficult to undertake in a budget that is the budget that 
we are requesting.
    So when you look at the priorities that we would have to 
fulfill, if we had more resources, the first one would be to 
keep up with inflation. The second would be to continue our 
analysis and the framework for the Roadmap for medical 
research, accelerate that. We have some programs like the 
extramural construction programs, the IDeA program, that we 
would like to enhance over time, including training stipends. 
But the most important report from all the institutes is that 
there are some clinical trials in translational research that 
will have to be slowed down.
    Senator Specter. Well, I would like to have a more detailed 
answer for the record on what the impact will be on the 
administration's request contrasted with what the impact would 
be on an additional $1.3 billion. So we have specific 
information as to how many grants there would be, what will 
happen to the clinical programs.
    Let me turn now to the issue of stem cell research. You and 
I have discussed this at some length and the President made his 
famous statement back on August 9th of 2001 about certain stem 
cell lines being added. Some of those stem cell lines are 
contaminated with mouse feeder cells. Some of those stem cell 
lines are owned other places. We see Harvard with a $100 
million allocation, which is wonderful but nothing compared to 
the $28 billion you have. We see South Korea taking the lead. 
We see scientists leaving the United States because ideology is 
conflicting with medical research.
    [The information follows:]

      Research That NIH Could Fund With an Additional $1.3 Billion

    The fiscal year 2005 President's Budget requests an additional $764 
million for NIH, a significant increase to the program level given the 
competing priorities within the Federal budget. An additional $1.3 
billion over the request would provide $30.057 billion, an increase of 
7.2 percent over fiscal year 2004. With this additional funding, NIH 
would fund a larger share of the great research ideas that scientists 
submit to us. We would be able to fund about 700 more research project 
grants, increasing chances of a scientist's application being funded 
and increasing the currently expected ``success rate'' from the 27 
percent in the President's Budget to 29 percent. Additional priorities 
would include:
  --Accelerating implementation of Roadmap initiatives;
  --Implementing an interdisciplinary approach to neuroscience research 
        by completing the phase 2 of the Porter Neurosciences Building;
  --Providing average cost increases equal to biomedical inflation and 
        finance the committed levels for competing continuation grants;
  --Increasing support for research training awards; and
  --Increasing the amounts NIH pays on career awards.
    Examples of the new research initiatives and significant expansions 
of ongoing programs that NIH would conduct with these additional funds 
follow:

    TRANSDISCIPLINARY RESEARCH ON ENERGETICS AND CANCER (TREC) (NCI)

  --Novel initiative involving scientists from multiple disciplines and 
        encompassing projects spanning the biology and genetics of 
        energy balance to behavioral, sociocultural, and environmental 
        influences upon nutrition, physical activity, weight, energy 
        balance and energetics.
  --The TREC Centers would foster collaboration among transdisciplinary 
        teams of scientists with the goal of accelerating progress 
        towards reducing cancer incidence, morbidity and mortality 
        associated with obesity, low levels of physical activity and 
        poor diet.
  --Centers would also provide training opportunities for new and 
        established scientists who can carry out integrative research 
        on energetics, energy balance and its consequences.

            CANCER BIOMEDICAL INFORMATICS GRID (CABIG) (NCI)

  --Cancer research platform with common standards to expedite progress 
        by creating a network that links organizations, institutions, 
        and individuals to enable the sharing of cancer research 
        infrastructure, data, and tools.
  --All cancer researchers would have access to a common research 
        infrastructure that creates a plethora of opportunities to not 
        only make important new findings but to do so more quickly and 
        efficiently than ever before.
  --This new system would offer a library of tools and resources--from 
        clinical trial management systems to tissue bank and pathology 
        tools--that are all built to common standards and are 
        interoperable with other existing systems.
  --Study population data would be far more robust and researchers will 
        be able to mine data in a way that simply isn't possible at the 
        moment.
  --Joins the various fields of cancer research--from etiologic 
        research to prevention, early detection and treatment.

              UNDERSTUDIED CANCERS OF HIGH LETHALITY (NCI)

  --A key element to the elimination of death from cancer by 2015 would 
        be to focus on malignancies which are highly fatal, such as 
        pancreatic, esophageal, and liver cancers.
  --When these cancers are found, relatively little prolonging of life 
        or quality of life follows.
  --Understanding gene-environment interactions is important in 
        learning who is at elevated risk, and how that risk is 
        regulated.
  --Discoveries in these areas would lead to more accurate and cost-
        effective public health interventions aimed at eliminating 
        mortality.

  PATIENT NAVIGATION RESEARCH PROGRAM: ELIMINATING BARRIERS TO TIMELY 
       DELIVERY OF CANCER DIAGNOSIS AND TREATMENT SERVICES (NCI)

  --A major disconnect or gap exists between cancer Discovery and 
        Development research and Delivery for many Americans. Discovery 
        and Development research results in beneficial procedures for 
        cancer prevention, early detection, diagnosis, and treatment 
        that are intended for all Americans. Health disparities arise 
        when the Delivery system does not provide access to timely, 
        standard cancer care to everyone in the nation. NCI has 
        established the goal of eliminating suffering and death due to 
        cancer by 2015.
  --The NCI is challenging principal investigators to develop effective 
        patient navigation interventions. These interventions would 
        address access barriers to quality, standard cancer care. The 
        purpose of the Patient Navigation Research Program (PNRP) would 
        be to develop interventions to reduce the time to delivery of 
        standard cancer care services after identifying a cancer-
        related abnormal finding.
  --The patient navigator could assist patients and their families 
        through the cancer care continuum.
  --The research hypotheses are that navigated patients would: (1) 
        receive timelier, definitive diagnosis following screening and 
        abnormal finding; (2) receive more timely treatment following 
        positive diagnosis; (3) improve their satisfaction with the 
        health care system experience.

  STUDY TO IDENTIFY RISK FACTORS FOR CORONARY HEART DISEASE (CHD) IN 
                      HISPANIC POPULATIONS (NHLBI)

  --The nation's largest minority group.
  --Involve four community-based cohorts of adults, one each of 
        majority Cuban, Puerto Rican, Mexican American, and Central 
        American origin.
  --Examine the role of acculturation in the development of risk 
        factors and determine if any play a uniquely harmful role in 
        the development of CHD in Hispanics.
  --Include a closely integrated community and professional education 
        component to return the benefits of research results to the 
        participating communities.

 FIVE-YEAR RANDOMIZED CLINICAL TRIAL OF CHRONIC OXYGEN USE IN MODERATE 
TO SEVERE CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) PATIENTS (NHLBI)

  --COPD is the fourth most common cause of death in the United States.
  --Oxygen therapy is known to extend the life of patients with severe 
        COPD and hypoxemia.
  --Billions of dollars are spent in the United States each year to 
        provide oxygen for patients with moderate or severe COPD 
        without good evidence as to who benefits.
  --The trial would determine the effects of oxygen therapy on life 
        expectancy, hospitalization rates, independent living, and 
        quality of life.

 MULTI-CENTER CLINICAL TRIAL TO EVALUATE NEW TREATMENT APPROACHES FOR 
                          SARCOIDOSIS (NHLBI)

  --Sacroidosis is a multisystem disease that usually affects the 
        lungs, and is more common in black Americans.
  --Current treatment, which is based mainly on corticosteroids and 
        cytotoxic agents, is non-specific and has many dangerous side 
        effects.
  --An NHLBI Sarcoidosis Research Working Group and several patient 
        advocacy groups recommended support for a trial to test new 
        agents for sarcoidosis.

 IDENTIFY AND TEST APPROACHES TO REDUCING CARDIOVASCULAR DISEASE THAT 
 ARE SPECIFIC TO AMERICAN INDIAN AND ALASKA NATIVE POPULATIONS (NHLBI)

  --Such an initiative would test approaches to reducing cardiovascular 
        disease (CVD) risk factors in American Indian/Alaska Native 
        (AI/AN) populations that can be incorporated into clinical 
        programs of community health care systems or delivered through 
        other public health approaches in native communities.
  --Many AI/AN communities bear a heavy burden of CVD and modifiable 
        CVD risk factors.
  --AI/AN communities are concerned that few intervention studies have 
        been launched to test possible solutions.

     PRACTICE BASED RESEARCH NETWORKS OF DENTAL SPECIALISTS (NIDCR)

  --NIDCR's Practice Based Research Networks (PBRN) initiative would 
        otherwise be limited to networks of general dental 
        practitioners.
  --Networks provide an infrastructure for conducting multiple, 
        collaborative clinical trials and observational studies 
        relating to dental practice and oral health care.
  --Linkage of the oral health PBRNs with existing medical PBRNs would 
        provide additional patients, professional expertise, and 
        integration of resources for conducting clinical research 
        across a broad spectrum of health care specialties.

                  REGENERATIVE DENTAL MEDICINE (NIDCR)

  --Diseases and injuries that damage orofacial tissues have a serious 
        impact on quality of life.
  --Human stem cells would be utilized in combination with new bio-
        inspired materials to regenerate the complex structures of the 
        orofacial system.
  --Researchers would develop and test a number of stem cells and 
        biomaterial structures that mimic the multi-dimensional 
        architecture/function of tooth structures.

     PROSPECTIVE STUDIES ON CRANIOFACIAL PAIN & DYSFUNCTION (NIDCR)

  --Participants enrolled in this study would be followed over time to 
        identify risk factors associated with or predictive of the 
        onset of craniofacial pain and dysfunction.
  --Temporomandibular joint (TMJ) dysfunction is a condition of 
        particular interest.

                   CLINICAL RESEARCH TRAINING (NIDCR)

  --In the ``post-genomic era,'' translational and clinical research 
        plays an important role in bringing laboratory observations 
        into the clinical setting.
  --NIDCR's new program announcement would foster clinical research 
        training in multidisciplinary research settings for all members 
        of the clinical research team.

FULL-SCALE CLINICAL TRIAL OF PRIMARY INTERVENTIONS TO PREVENT OR DELAY 
          TYPE 2 DIABETES IN CHILDREN AND ADOLESCENTS (NIDDK)

  --Cases of type 2 diabetes are increasing in the pediatric 
        population, especially among adolescents and in certain 
        minority groups.
  --A school-based intervention approach may be an effective way to 
        prevent risk factors for type 2 diabetes in children and 
        adolescents.
  --Pilot studies for a multi-site, multi-component, school-based 
        intervention trial employing both environmental and behavioral 
        changes are under way; could launch the trial in fiscal year 
        2005.

  IMPROVE CLINICAL TRIALS FOR TREATMENT OF INFLAMMATORY BOWEL DISEASE 
                             (IBD) (NIDDK)

  --The conduct of new clinical trials in IBD is hampered by the 
        current need to rely on indirect diagnostic tests and 
        nonspecific clinical features.
  --The conduct of clinical trials and development of safer, more 
        effective treatments would be accelerated by research in 
        proteomics, to discover new biomarkers, and in molecular 
        imaging, to discover new non-invasive diagnostic imaging tests.

 STUDY THE ROLE OF THE INTRAUTERINE AND POSTNATAL ENVIRONMENTS IN THE 
                     DEVELOPMENT OF OBESITY (NIDDK)

  --A better understanding of aspects of the intrauterine environment 
        and a mother's medical status that contribute to future 
        overweight and obesity in offspring could lead to more 
        effective interventions before, during, or shortly after 
        pregnancy.
  --Strategies to prevent or treat obesity could also greatly benefit 
        from research on the impact of diet and other environmental 
        factors on the early development of brain pathways regulating 
        calorie intake and energy expenditure, and the permanence of 
        these effects in adulthood.
  --Tools are available to conduct these studies in appropriate animal 
        models, including primates.

EXPAND FEASIBILITY TRIAL OF DAILY DIALYSIS TO DETERMINE EFFECTS OF NEW, 
  MORE INTENSIVE DIALYSIS MODALITIES ON MORTALITY AND CARDIOVASCULAR 
                            DISEASE (NIDDK)

  --Clinical studies are needed to determine whether life expectancy of 
        persons with end-stage renal disease (ESRD), or chronic kidney 
        failure, can be improved by modifying standard dialysis 
        regimens.
  --Clinical centers have been established to test the feasibility of a 
        randomized clinical trial of more frequent dialysis.
  --The current frequent dialysis trial is limited by size and design 
        to measuring intermediate outcomes, such as blood pressure, 
        anemia, and quality-of-life.
  --An expansion of the trial could enable assessment of the effect(s) 
        of any change in dialysis regimen on hospitalization rate and 
        mortality, and on cardiovascular events--e.g., stroke, 
        myocardial infarction and heart failure--which often complicate 
        ESRD.

   INITIATE THE VERY LARGE PHASE III CLINICAL TRIALS FOR PARKINSON'S 
                            DISEASE (NINDS)

  --Necessary to adequately test one or more of the neuroprotective 
        drugs for Parkinson's disease (minocycline, creatine, coenzyme 
        Q10 and GPI-1485) that are being tested in pilot trials.

 CONDUCT A PHASE III CLINICAL TRIAL OF CEPHALOSPORIN FOR THE TREATMENT 
                 OF ALS (LOU GEHRIG'S DISEASE) (NINDS)

  --A screen of 1,040 drugs for potential use against neurodegenerative 
        diseases revealed one that may be particularly helpful for 
        ALS--the antibiotic cephalosporin.

   LAUNCH CHEMICAL COUNTERTERRORISM RESEARCH TO COMBAT NERVE AGENTS 
                                (NINDS)

  --A number of chemical agents and toxins that have served or could 
        serve as terrorist weapons that target the nervous system.
  --Research initiatives would focus on ameliorating the acute 
        neurologic responses to these chemical weapons as well as 
        alleviating any chronic neurodegenerative effects.

  EXPAND THE SPECIALIZED PROGRAMS OF TRANSLATIONAL RESEARCH IN ACUTE 
                       STROKE (SPOTRIAS) (NINDS)

  --From four to eight centers.
  --Would accelerate translation of basic research findings into 
        clinical practice in acute ischemic and hemorrhagic stroke.

               INITIATIVE FOR PANDEMIC INFLUENZA (NIAID)

  --Accelerate the development of next generation influenza antiviral 
        drugs and the production and clinical testing of up to four 
        pilot lots of candidate vaccines by up to one year or more.
  --Influenza routinely causes 36,000 deaths per year in the United 
        States; however, the ability of flu viruses to occasionally 
        jump from animals to humans poses an imminent threat of a 
        pandemic affecting millions of people--over 20 million people 
        worldwide is estimated to have died during the flu pandemic of 
        1918.
  --Research would also expand surveillance of emerging flu strains in 
        Asian animals to support development of new vaccines against 
        influenza strains with pandemic potential.

         CLINICAL TRIALS OF HIV/AIDS VACCINE CANDIDATES (NIAID)

  --Expand clinical trials to accelerate by one or more years clinical 
        evaluation of six promising HIV vaccine candidates.
  --Forty million people were estimated to have HIV/AIDS as of December 
        2003, with five million new infections occurring in 2003. 
        Another three million people died of the AIDS pandemic in 2003, 
        including 500,000 children, with a total of 70 million people 
        projected to die of the disease by 2020 if the current trends 
        continue.
  --As with other pandemic infectious diseases, a key component to 
        preventing the spread of HIV/AIDS, and to mitigating the long-
        range impact of the AIDS pandemic, is the development of an 
        effective HIV/AIDS vaccine. Critical challenges to developing 
        an effective vaccine include the need to clinically evaluate a 
        large number of promising HIV vaccine candidates in humans as 
        rapidly as possible to determine the toxicity and effectiveness 
        of the vaccine candidates. Factors contributing to the need to 
        clinically evaluate a large number of the most promising 
        vaccine candidates include the multitude of different HIV/AID 
        virus strains in existence and the frequency at which the virus 
        mutates and the fact that the virus infects and destroys the 
        immune system.

            CLINICAL TRIALS IN ORGAN TRANSPLANTATION (NIAID)

  --Expand and accelerate clinical trials to develop therapeutic 
        strategies to reduce the immune-mediated morbidity and 
        mortality of organ transplantation.
  --Over 25,000 people receive organ transplants each year. Although 
        the one-year survival for single-organ transplantation has 
        improved over the last 15 years to a level approaching or 
        exceeding 90 percent, there has been little success in 
        reversing the decline in long-term graft-vs-host disease and 
        patient survival (13 percent to 55 percent at 10 years, 
        dependant upon organ).
  --Studies would support both children and adults and will address the 
        barriers to short- and long-term success of transplant 
        procedures, including incompatibility between donor and 
        recipient, acute and chronic rejection, and complications of 
        long-term pharmacologic immune suppression.

            CLINICAL TRIALS OF TOPICAL MICROBICIDES (NIAID)

  --Expand existing support of clinical trials to accelerate the 
        clinical evaluation of four promising microbicide candidates 
        that have unique mechanisms of action to potentially protect 
        against sexually transmitted diseases (STD), including HIV/
        AIDS.
  --Topical microbicides are creams, gels or foams that can be applied 
        to the vagina or rectum and prevent STD-causing microbes, 
        including HIV, from invading the host. Pharmaceutical companies 
        have been reluctant to invest in research on microbicides 
        primarily because not enough data has been gathered through 
        large clinical studies in humans to provide a ``proof of 
        concept'' of any microbicide product.
  --A partially effective microbicide could avert more than 2 million 
        HIV infections over a 3-year span; also, microbicides could 
        play a critical role in reducing STD transmission from mother 
        to infant during childbirth.
       determine three-dimensional structures of proteins (nigms)
  --Partner with other Institutes.
  --Includes those related to cancer and emerging infectious diseases.
  --Would be useful for the design of new antibiotics or anti-cancer 
        agents.

   RESEARCH RELATED TO DETERMINING WHY DIFFERENT INDIVIDUALS RESPOND 
         DIFFERENTLY UPON TREATMENT WITH THE SAME DRUGS (NIGMS)

  --Would help physicians customize treatment to individual patients 
        and may guide the development of new drugs that are more 
        predictively effective in most people.
     development of tools for investigating model organisms (nigms)
  --Model organisms such as fruit flies, mice, and roundworms have 
        provided great insights into fundamental biological mechanisms 
        and into human disease.

            INNOVATIVE METHODS OF NEWBORN SCREENING (NICHD)

  --While ensuring protection of privacy and providing ethical 
        safeguards, the NIH could proceed with efforts to identify, at 
        birth, hundreds of genetic defects associated with mental 
        retardation, primary immunodeficiency diseases, and other 
        potentially disabling and fatal conditions.
  --Technologies generated by the Human Genome Project are available to 
        screen for hundreds of genetic diseases in newborns.
  --A database in rare genetic diseases could be developed to enable 
        scientists to identify unrecognized genetic defects in 
        newborns, to study currently untreatable disorders, and to 
        develop new therapeutics.
  --New screening techniques could allow clinical and preventive 
        interventions for currently treatable genetic disorders, such 
        as Severe Combined Immunodeficiency Disease (SCID), in time to 
        prevent or mitigate risks of early death or life-long 
        disability.

      GENOMIC AND PROTEOMIC RESOURCES FOR PREMATURE BIRTH (NICHD)

  --The NIH could establish a major consortium to create high-quality 
        data on human gene and protein expression, and to make this 
        information available on a publicly-accessible database that 
        will be dedicated to prematurity research. Investigators could 
        mine the database to advance their own research into the causes 
        of and ways to prevent premature birth.
  --Premature birth causes almost 70 percent of neonatal deaths and 
        reducing prematurity would reduce wide racial disparities in 
        infant mortality.
  --The depth and accessibility of the new genomic and proteomic 
        database could enable scientists to discover biomarkers for 
        premature birth and ultimately to develop early diagnostic and 
        effective treatment interventions.

 RESEARCH BASE TO ASSESS EARLY CHILDHOOD LEARNING AND SCHOOL READINESS 
                                (NICHD)

  --The NIH could develop, refine, validate, and scale-up tests to 
        assess how well preschool programs help young children--
        especially those at risk of school failure--to achieve ``school 
        readiness,'' cognitively, socially, and behaviorally.
  --Significant academic, public, and political attention is focused on 
        the educational achievement of all children, beginning with 
        preschoolers, with certain federal funds tied to school 
        systems' performance.
  --Preschool programs need scientifically-based tests to measure 
        accurately how well they prepare young children for later 
        school success. The programs especially need tests to measure 
        their performance with non-English speaking, ethnically 
        diverse, and educationally at-risk preschoolers. For the most 
        part, such tests do not exist, leaving preschool programs 
        unable to measure their performance for purposes of federal 
        funding.
  --The NIH is the primary research agency with the basic and applied 
        scientific expertise to produce these tests, which are now 
        lacking.

                 THE NATIONAL CHILDREN'S STUDY (NICHD)

  --The first two vanguard centers could be established for this 
        ground-breaking, congressionally-authorized, longitudinal study 
        of children's health and development. (There would be 
        significantly larger out-year costs.)
  --Extensive planning and selected feasibility studies enable vanguard 
        centers, for this large and complex research effort, to 
        investigate how environmental factors, broadly defined, may 
        influence children's health and development.
  --Primary care pediatric practices and other types of clinical sites 
        could become vanguard sites.
        new interventions to improve pregnancy outcomes (nichd)
  --The NIH could proceed with clinical trials and related studies to 
        prevent preterm births and improve neonatal outcomes.
  --An NIH research network recently discovered the first effective 
        intervention--progesterone treatment of high-risk women during 
        pregnancy--to prevent recurrent preterm birth. The new 
        treatment cannot be approved by the FDA until researchers study 
        children of mothers who received the experimental treatment to 
        detect any later-emerging adverse effect in the children.
  --A clinical trial is needed to affirm preliminary findings that a 
        nutritional supplement during pregnancy (an Omega-3 (n-3) 
        polyunsaturated fatty acid) is particularly efficacious in 
        preventing recurrent preterm birth in African American women, 
        for whom the experimental progesterone treatment was less 
        effective.
  --A clinical trial is needed to affirm preliminary findings that a 
        single, simple injection of tin mesoporphyrin can successfully 
        prevent complications of hyperbilirubinemia that can result in 
        severe, life-long disabilities. If not diagnosed and treated, 
        hyperbilirubinemia can lead to jaundice, brain injury and 
        kernicterus (a condition of severe neural symptoms, associated 
        with high levels of bilirubin in the blood).
   clinical trial for the treatment of inflammatory eye disease (nei)
  --Would be able to begin a clinical trial to evaluate a treatment for 
        uveitis that will greatly enhance patients' quality of life.
  --Uveitis is a group of ocular inflammatory disorders that represent 
        a major cause of vision loss and blindness in the United 
        States.
  --This new monoclonal antibody therapy could mean fewer side effects 
        than current therapies that require systemic, immuno-
        suppressive drugs, leading to an improved quality of life.

   CLINICAL TRIALS NETWORK FOR THE TREATMENT OF AGE RELATED MACULAR 
                        DEGENERATION (AMD) (NEI)

  --Could launch a clinical trials network to test promising new 
        therapies for age-related macular degeneration.
  --A clinical trials network is needed to test a variety of new 
        treatment approaches targeting the full range of disease forms 
        and levels of severity of age-related macular degeneration.
  --Age-related macular degeneration is the leading cause of vision 
        loss among Americans over 65 years of age, the fastest growing 
        segment of the U.S. population.

   ROBUST PROGRAM TO EVALUATE THE TOXICOLOGY OF NANOSCALE MATERIALS 
                                (NIEHS)

  --Nanoscale materials are already appearing in commerce as industrial 
        and consumer products and as novel drug delivery formulations. 
        Commercial applications and resultant opportunities for human 
        exposure may differ substantially for nanoscale vs. ``bulk'' 
        materials.
  --Currently there is very little research focus on the toxicology of 
        manufactured nanomaterials. There are indications in the 
        literature that manufactured nanomaterials may distribute in 
        the body in unpredictable ways and that certain nanoparticles 
        have been observed to preferentially accumulate in particular 
        organelles.
  --The NTP/NIEHS research program would evaluate the toxicological 
        properties of major nanomaterials classes which represent a 
        cross-section of composition, size, surface coatings, and 
        physico-chemical properties, and use these as model systems to 
        investigate fundamental questions concerning if and how 
        nanomaterials can interact with biological systems.

USE OF METABOLOMICS TECHNOLOGIES FOR PREDICTING TOXICOLOGICAL RESPONSES 
                                (NIEHS)

  --Assessment of exposure and of risks from exposure could be greatly 
        improved by using metabolic indicators such as changes in gene, 
        protein or metabolite expression.
  --Research supported by this initiative would focus on the 
        application of metabolomics technologies to identify predictive 
        markers of exposure, toxicity and disease in animal and human 
        populations; link metabolic profiles with biological pathways 
        and mechanisms of environmentally-related exposures and 
        diseases; and develop computational and modeling approaches for 
        assessment and integration of metabolomics data in predictive 
        toxicology research.
  --This program would be a critically important application of the 
        basic methodology development work being undertaken as part of 
        the NIH Roadmap initiative on Metabolomics Technology 
        Development.

  PREVENTION TRIALS TO ASSESS THE POTENTIAL ABILITY OF NON-STEROIDAL 
  ANTI-INFLAMMATORY DRUGS AND A COMBINATION OF ANTI-OXIDANT VITAMINS 
                                 (NIA)

  --Prevent Alzheimer's disease and age-associated cognitive decline.
           development of a clinical trials consortium (nia)
  --Test testosterone therapy for older men with low testosterone 
        levels who experience weakness, frailty, or a specific 
        disability that may be related to low testosterone.

   NEW INTERVENTIONS FOR PREVENTION AND CONTROL OF HEART FAILURE IN 
                    PERSONS AGED 65 AND OLDER (NIA)

  --Fully develop and validate new interventions through clinical 
        trials.

    MULTIDISCIPLINARY IMAGING RESEARCH PARTNERSHIPS FOR ADDRESSING 
 IMPORTANT BIOLOGICAL OR MEDICAL RESEARCH PROBLEMS OF SKELETAL MUSCLE 
                   AND ASSOCIATED SOFT TISSUE (NIAMS)

  --Improved imaging techniques provide a non-invasive way to monitor 
        changes in muscle (including muscular dystrophy and other 
        muscle diseases) and soft tissue.
  --Multidisciplinary imaging research partnerships would stimulate the 
        development of novel imaging technologies that will help us 
        understand the genetic and molecular bases of musculoskeletal 
        soft tissue function, disease, and injury processes.
  --Improved visualization of skeletal muscle and associated soft 
        tissue would enable researchers to more accurately measure 
        change during treatment or recovery from injury.

 PURSUE THE RESEARCH NEEDS AND OPPORTUNITIES IDENTIFIED AT THE RECENT 
 NIH CONSENSUS DEVELOPMENT CONFERENCE ON TOTAL KNEE REPLACEMENT (NIAMS)

  --Approximately 300,000 total knee replacements are performed each 
        year in the United States for end-stage arthritis of the knee 
        joint, and the rate of total knee replacement procedures 
        increases each year.
  --While these replacements have shown outstanding success, 
        controversies still exist regarding implant designs and 
        treatment. Research studies suggest that there are particular 
        challenges that must be addressed in patients with Parkinson's 
        disease, rheumatoid arthritis, and diabetes mellitus, as well 
        as total knee replacements in younger patients.

INCREASE SUPPORT FOR TRANSLATIONAL RESEARCH--MAXIMIZING THE RESULTS OF 
            BASIC RESEARCH TO IMPROVE PUBLIC HEALTH (NIAMS)

  --To enhance and expand translational research, a new centers program 
        is currently being or would be created called centers of 
        research translation.
  --These centers would pair basic and clinical projects in 
        investigator-initiated and directed research that is centered 
        around particular diseases. Different diseases might require 
        different translation mechanisms and strategies.
  --The goal of the centers is the application of powerful tools and 
        knowledge from basic research to clinical research to improve 
        human health.

   ADDITIONAL STUDIES ON INNOVATIVE THERAPIES FOR RHEUMATIC AND SKIN 
                            DISEASES (NIAMS)

  --Would expand a successful program that the NIAMS instituted in 
        fiscal year 1999.
  --Would solicit investigator-initiated proposals for clinical trials 
        of innovative therapies or approaches for the treatment of 
        rheumatic and skin disease.
  --The previous program has produced a number of ongoing clinical 
        trials that form the cornerstone of NIAMS-funded trials in 
        rheumatic diseases.
  --It is anticipated that the trials may identify new therapies for 
        rheumatic and skin diseases.

                          OTITIS MEDIA (NIDCD)

  --Would initiate Phase One trials of vaccine candidates.
          initiate a definitive epidemiological study (nidcd)
  --Would establish the role of prenatal exposure to cytomegalovirus in 
        progressive hearing loss during childhood.

                    COMMUNICATION DISORDERS (NIDCD)

  --Would expand research to identify the hereditary basis.
    hair cell degeneration and regeneration in the inner ear (nidcd)
  --Would initiate new research to define the molecular basis.

 ENHANCE CAPACITY FOR DISASTER/TERRORISM MENTAL HEALTH RESEARCH (NIMH)

  --Could enlarge this currently small program to establish emergency 
        research protocols in conjunction with local public health 
        authorities and develop critically needed measures for use in 
        emergency/disaster research studies.

 RESEARCH INITIATIVE ON PEDIATRIC BRAIN-BEHAVIOR DEVELOPMENT VITAL TO 
         DIAGNOSING AND TREATING CHILD MENTAL DISORDERS (NIMH)

  --This initiative would result in the first-ever identification of 
        neuroimaging markers of specific child mental disorders which 
        will lead to improved diagnostics and potential for new 
        treatments in pediatric mental illnesses.

 USE NIMH CLINICAL TRIAL NETWORKS TO LAUNCH TRIALS ON SIMULTANEOUS USE 
   OF MULTIPLE PSYCHIATRIC MEDICATIONS FOR THE SEVERELY MENTALLY ILL 
                                 (NIMH)

  --Multiple medications is a widespread practice, but there is limited 
        scientific data about its health effects and implications.

                      ANOREXIA AND BULIMIA (NIMH)

  --Would expand research on understanding eating disorders.
          more research using brain imaging techniques (nida)
  --Would study how exposure to drugs of abuse can affect the 
        developing human brain.
  --Understanding precisely how brain changes relate to behavior, 
        especially during childhood and adolescence, is critical to 
        designing effective strategies for reducing drug use in the 
        United States.
  --Better treatment strategies targeting children and adolescents 
        would be developed through these efforts.

COLLABORATIONS OF ESTABLISHED CLINICAL TRIALS NETWORK (CTN) WITH OTHER 
                   ESTABLISHED NETWORKS AT NIH (NIDA)

  --NIDA CTN staff and staff from NCI's Community Clinical Oncology 
        Program have discussed the possibility of jointly supporting a 
        smoking cessation study. This study would bring these two NIH 
        clinical research networks together in a synergistic 
        collaboration and test the networks' interoperability.
  --CTN has also had discussions with NICHD to link the CTN to a 
        Network at NICHD that is studying adolescents and comorbidity.

  ENHANCE OUR UNDERSTANDING OF THE GENETIC OR HERITABLE RISK FACTORS 
 ASSOCIATED WITH DRUG ABUSE USING THE CTN AS A VALUABLE RESOURCE (NIDA)

  --The CTN could serve as a resource to acquire genetic information on 
        participants in clinical trials and to better characterize 
        different phenotypes associated with addiction.
  --As gene variants are identified in association with drug addiction, 
        research could be conducted to determine how this genetic 
        information can be used to tailor medications to an 
        individual's genetic needs. This knowledge could be 
        incorporated into ongoing medications trials in the CTN.

 EXPAND RESEARCH ON PREVENTING DRINKING BY YOUTH IN RURAL/SMALL URBAN 
                             AREAS (NIAAA)

  --Note: Partnerships have been formed with academic health centers, 
        abbreviated ``AHC,'' to conduct this research. AHC have in 
        place the disciplines required, as well as extensive service 
        networks in rural and small urban regions.
  --Would expand the number of AHC sites that would conduct the 
        research.
  --Would collect data on psychological and physical development, and 
        environmental/community circumstances, that are not routinely 
        collected in medical settings. A variety of biomedical, 
        psychosocial, and environmental factors act in concert to lead 
        to adverse outcomes, such as alcohol-related problems. We must 
        understand what all of these factors are and how they interact, 
        if we are to make real advances in preventing and treating 
        adverse outcomes of alcohol use among youth.

 EXPAND RESEARCH AIMED AT DEVELOPING MEDICATIONS FOR ALCOHOLISM (NIAAA)

  --Would develop animal models of response to alcohol that closely 
        predict efficacy of compounds to be tested in humans.
  --Would create a clinical-trials network for early Phase II human 
        trials. These trials could yield relatively quick results and 
        can indicate which compounds are worth the resources required 
        for IND approval and Phase III trials. Partnerships would be 
        sought with pharmaceutical companies interested in compounds 
        found to be successful in NIAAA early Phase II human trials.
             expand research on alcohol metabolism (niaaa)
  --Alcohol metabolism plays a crucial role in alcohol dependence and 
        in alcohol-induced organ damage.
  --Would form a bioinformatics data base, including data on gene 
        expression, proteomics, and metabolomics involved in alcohol 
        metabolism. This would be very important to our understanding 
        of which genes and proteins are involved in addictive behavior 
        and alcohol-induced organ damage, including cancer.
  --In human clinical studies, use metabolomics and proteomics to 
        generate information on biomarkers of early/late tissue damage, 
        and identify targets for medication development.
  --Using imaging technology, would determine if alcohol metabolism 
        occurs in the brain and, if so, determine what enzymes are 
        involved.
  --Would identify all adducts (especially those that promote 
        autoimmune reactions) that result from alcohol metabolism, and 
        their roles in addictive behavior and organ damage.
  --Would understand the interactions of alcohol metabolism with 
        comorbid conditions, such as obesity and diabetes.

             TISSUE ENGINEERED HUMAN MODEL SYSTEMS (NIBIB)

  --Would stimulate research and development in three-dimensional human 
        tissue model systems; engineered tissues for drug development; 
        and cell-based sensors for clinical diagnosis and treatment.
  --Tissue engineering holds the promise to repair and/or replace 
        damaged organs.
  --Tissue engineering strategies focusing on cell-based therapies, or 
        treatment modalities that rely on cells as the agents for the 
        treatment of diseases, have the potential to revolutionize 
        human therapeutics in the 21st century.

            MINIMALLY-INVASIVE, IMAGE-GUIDED SURGERY (NIBIB)

  --Would support research needed to rapidly develop computer-assisted, 
        image-guided microsurgery, which could replace traditional 
        surgery.
  --Image-guided, minimally-invasive surgical procedures involve less 
        patient risk and pain and result in reduced hospital stays and 
        shorter recovery periods.
  --Advances in surgical robots and microsurgical techniques could 
        enhance a surgeon's ability to perform complex tasks that 
        cannot be performed by hand.
  --Could support: integration of existing technologies and development 
        of new technologies to navigate human anatomy, obtain 
        diagnostic tissues, localize and treat human disease and 
        injury, and monitor responses to surgical interventions.
        chemistry of imaging agents and molecular probes (nibib)
  --Could support exploratory projects for the synthesis, physical 
        characterization, and initial demonstration of feasibility for 
        clinical imaging agents for physiological, anatomical, and 
        molecular imaging.
  --The ability to image molecular processes and cell function in vivo 
        provides an opportunity to understand biological processes as 
        they occur in their environment.
  --Knowledge gained may be used to advance early-stage disease 
        detection and individually-tailored therapeutic interventions.
  --The development of new clinical imaging agents requires focused 
        efforts by chemists and molecular biologists to discover new 
        compounds and materials suitable for in vivo imaging.

                 BRAIN-COMMUNICATION INTERFACE (NIBIB)

  --Could develop technologies to create a more functional and 
        convenient system for restoring movement to paralyzed 
        individuals.
  --Investigators have been successful in making Function Electrical 
        Stimulation (FES) a practical solution for restoring some 
        movement to paralyzed individuals.
  --Current systems allow individuals with spinal cord injuries to 
        stand and breathe, and can restore functional hand grasp and 
        arm movement to some individuals with severe spinal cord 
        injuries.
  --Recent developments in the technology of microelectrode design and 
        neurophysiological signal analysis open the possibility of 
        restoring greater control of motor function naturally--by 
        thinking about moving, a technique referred to as direct brain-
        communication interface.

SUPPORT PLANNING GRANTS TO DEVELOP AND OPTIMIZE MODELS FOR DEPARTMENTS 
         OF CLINICAL RESEARCH WITHIN SCHOOLS OF MEDICINE (NCRR)

  --Would provide tools to develop and test models.

 RESTORE THE EXTRAMURAL RESEARCH FACILITIES IMPROVEMENT PROGRAM (RFIP) 
                              FUNDS (NCRR)

  --Would support construction and renovation projects at National 
        Primate Research Centers, animal research facilities and for 
        modem research laboratories at smaller institutions and 
        institutions within IDeA states.

   ADDRESS THE SHORTAGE OF ADVANCED INSTRUMENTATION NEEDED TO PURSUE 
                CUTTING-EDGE BIOMEDICAL RESEARCH (NCRR)

  --The High End Instrumentation program is the only NIH program that 
        provides support for research equipment that costs at least 
        $750,000; awards may be up to $2 million.

   INTEGRATE TECHNOLOGY DEVELOPED THROUGH THE BIOMEDICAL INFORMATICS 
 RESEARCH NETWORK (BIRN) INTO CLINICAL RESEARCH AND OTHER NEW DOMAINS 
                     OUTSIDE OF NEUROSCIENCE (NCRR)

  --Some BIRN bioinformatics tools would be distributed and other tools 
        developed; hands-on workshops to inform investigators how to 
        use the tools for their research.
  --Information technologies would be critical for scientific 
        discovery.

         NCMHD COULD STRENGTHEN AND EXPAND ITS PROGRAMS (NCMHD)

  --Loan Repayment Program
  --Centers of Excellence Program
  --Research Endowment Program

 NCMHD COULD FULLY LAUNCH ITS COMMUNITY-BASED RESEARCH PROGRAM (NCMHD)

  --Would fulfill this Congressional requirement.

                        TRAUMA AND INJURY (FIC)

  --Would initiate a new program to support research training to 
        address the growing global burden of morbidity and mortality 
        due to trauma and injury related to road traffic accidents, 
        suicide and drowning, mental health consequences of war and 
        civil disorders, lack of emergency care and blood products and 
        other related conditions.
  --Training supported by the new program would lead to prevention 
        strategies and interventions in wound healing, development of 
        synthetic blood products, development of low-cost imaging 
        technologies, mental health strategies, and epidemiology to 
        assess risk factors as well as other activities to reduce the 
        impact of trauma and injury to individuals, families and 
        communities.
  --Would support the establishment of a global network of highly 
        meritorious research training centers to mitigate the impact of 
        trauma and injury.

 BRAIN DISORDERS IN THE DEVELOPING WORLD: RESEARCH ACROSS THE LIFESPAN 
                                 (FIC)

  --This program was begun through short term planning grants in fiscal 
        year 2003 with the intention to grow to full research project 
        grants in fiscal year 2005.
  --The program supports collaborative research and capacity building 
        projects on brain disorders throughout life relevant to low- 
        and middle-income nations. Brain disorders represent a fast 
        growing proportion of the global burden of disease.

     DEVELOP THE NEXT GENERATION OF INTERNATIONAL RESEACHERS (FIC)

  --It is imperative that the U.S. scientific community be prepared to 
        tackle new threats while at the same time be positioned to work 
        in partnership with colleagues around the world on shared 
        problems.
  --Would increase support to train U.S. medical students, graduate 
        students and post-doctoral students in methodologies needed to 
        tackle global health challenges.
  --Would extend and intensify efforts in resource-limited nations to 
        provide clinically appropriate, cost-effective, and sustainable 
        care of direct health and economic benefits for the global 
        community and mitigate the threat of disease crossing borders 
        to affect the U.S. population.

    COULD SIGNIFICANTLY EXPAND CAPABILITY TO ANALYZE, ANNOTATE, AND 
 CLASSIFY MASSIVE AMOUNTS OF RAW SEQUENCE AND PROTEIN DATA TO MAKE IT 
                  READILY USABLE BY RESEARCHERS (NLM)

  --Molecular biology is generating an unprecedented amount of genomic 
        data that have the potential to overwhelm researchers by sheer 
        volume.
  --The protein classification project provides a valuable method to 
        deduce the function of newly discovered proteins, greatly 
        accelerating research in the molecular basis of disease and 
        therapy.
  --The unique and comprehensive Reference Sequence Collection would 
        assist in studying the function of single genes and performing 
        large-scale comparative analyses of genes across multiple 
        organisms.

  COULD ACCELERATE PROGRESS TOWARD DEVELOPMENT AND IMPLEMENTATION OF 
 CLINICAL VOCABULARY STANDARDS THAT ARE CRITICAL TO RE-ENGINEERING THE 
                   CLINICAL RESEARCH ENTERPRISE (NLM)

  --The inability to share clinical data across systems impedes 
        clinical research and is responsible for a significant number 
        of medical errors.
  --An interlocking set of clinical vocabulary standards must be 
        developed that incorporate robust mappings between multiple 
        vocabularies used in clinical research and health care.
  --Research, testing, and demonstration projects would help to 
        determine best practices for incorporating vocabulary standards 
        into clinical research, health care, and public health.

    COULD WORK WITH OTHERS TO DEVELOP COMMON SOFTWARE PLATFORMS FOR 
ADVANCED CLINICAL AND EDUCATIONAL APPLICATIONS OF THE VISIBLE HUMAN AND 
                      OTHER IMAGE DATA SETS (NLM)

  --Investments in building a Visible Human Functional Atlas of the 
        Head and Neck and associated public software tools establish a 
        strong foundation for developing applications software, 
        including simulation and modeling, useful in medical training 
        and treatment.
  --Further research and testing would fully integrate the data, 
        software, and other technology in the teaching of embryology 
        and anatomy courses.

 DEVELOP AND SUPPORT WOMEN'S HEALTH INTERDISCIPLINARY RESEARCH CENTERS 
 ESPECIALLY IN THE AREAS OF: (OD--OFFICE OF RESEARCH ON WOMEN'S HEALTH)

  --Pharmacogenetic research that focuses on sex differences in drug 
        metabolism and biological pathways involved in the treatment of 
        diseases such as cancer, cardiovascular disease to provide the 
        much needed information to improve clinical outcomes, including 
        a better understanding of the impact of pregnancy or depression 
        on pharmacokinetics, pharmacodynamics, drug efficacy and 
        adverse effects of therapeutic agents.

  DEVELOP AND SUPPORT A CLINICAL TRIAL TO TEST A PROMISING INNOVATIVE 
TECHNIQUE THAT COULD REDUCE THE SIZE OF UTERINE FIBROIDS (OD--OFFICE OF 
                      RESEARCH ON WOMEN'S HEALTH)

  --Could result in less morbidity for the women who face potential 
        surgery or infertility as a result of this condition.

LAUNCH A TRANS-NIH INITIATIVE TO LEARN WHETHER EHEALTH TECHNOLOGIES ARE 
   EFFECTIVE IN ENHANCING HEALTH BEHAVIOR CHANGE AND CHRONIC DISEASE 
   MANAGEMENT (OD--OFFICE OF BEHAVIORAL AND SOCIAL SCIENCES RESEARCH)

  --Consumers, patients and providers are increasingly using eHealth 
        applications for making health care decisions, and for 
        obtaining and dispensing services.
  --These technologies offer a potentially low cost health delivery 
        system for underserved populations, as well as a means of 
        supporting provider adherence to evidence-based care.

    Senator Specter. I want to finish this question before my 
red light goes on to stay within the time limits. What is the 
status and availability and adequacy of stem cell lines for 
adequate stem cell research?

                           STEM CELL RESEARCH

    Dr. Zerhouni. We have 17 cell lines now available. As you 
know, we have worked aggressively in providing infrastructure 
funding to all the sources that we knew were eligible for 
Federal funding. NIH has done every effort to expand the 
availability of lines. We have spent intramurally dollars to 
create a characterization lab. We have gone from one laboratory 
2 years ago to nine laboratories doing research. So we are also 
realizing that training of scientists in these very difficult 
methods is very important. So we are doing everything we can to 
advance the field. So 17 lines are available to date, Senator.
    Senator Specter. Well, I am going to violate the red light 
for just one question. That is not enough, is it? Those are not 
enough, are they? It is a leading question.
    Are they?
    Dr. Zerhouni. Well, we have a Stem Cell Task Force and Dr. 
Battey really works very hard with the entire community to look 
at what is the impact of what we need to do today of the number 
of cell lines. The reports that we have is that we are learning 
tremendously at a very high pace what are the advantages and 
limitations. We are looking, for example, at these issues of 
genetic stability and genetic diversity.
    The Stem Cell Task Force at this point feels that we can do 
a lot of research with what we have. Can we do all of the 
research that will need to be done over the entire future of 
stem cell research? No one can say that that would be the case.
    Senator Specter. Well, I will pursue that with Dr. Battey. 
I do not consider that an adequate answer, Dr. Zerhouni. It is 
not often where I say your answer is not adequate, but I do not 
believe that is an adequate answer.
    We have been joined by the distinguished ranking member, 
and I will yield to him at this time for 5 minutes for an 
opening statement or questions or however he chooses to use his 
time.
    Senator Harkin. Mr. Chairman, thank you very much.
    Senator Specter. We will have second rounds, but we have 
Senator Stevens and Senator Cochran who are here.

                    STATEMENT OF SENATOR TOM HARKIN

    Senator Harkin. Well, thank you very much, Mr. Chairman. I 
apologize for being late. Some mornings you have to leave about 
5:00 in the morning to get here because of the traffic.
    It has been a privilege, Mr. Chairman, to work with you 
over the last 14, almost 15 years, on behalf of supporting, as 
you have said so many times, the crown jewel of our Federal 
Government, which is the National Institutes of Health. I want 
to thank you again for that working relationship, and I want to 
thank you for your great leadership, Mr. Chairman, in doubling 
the funding for NIH over that short period of time. It was a 
pleasure to work with you to do that and to continue to work 
with you on these crucial issues that impact the health and 
welfare of all of our people.
    Now, unfortunately, the budget we have submitted this year 
is a far cry from the doubling years. I am concerned what it 
means for the future health of NIH. We did not double the 
funding for NIH to then fall off a cliff. But that is a real 
possibility if we continue on with this kind of budget that we 
have.
    I want to welcome Dr. Zerhouni and the dozens of other NIH 
leaders who have joined us. I do not always get the time to 
hear from each of you, but I appreciate your being here and all 
the work that you do.
    All of you were involved in developing the NIH Roadmap. I 
want to commend you for that effort. The initiative should help 
break down the walls between the institutes and unite everybody 
at NIH behind common goals. And, Dr. Zerhouni, I thank you for 
your leadership in encouraging that and also for your 
leadership in encouraging more risk-taking in the kind of 
applications that NIH funds. We always have to be open to new 
ideas. To the extent that I can, I hope to back you up. People 
may say, well, why are you funding some of these far-out 
things? Well, because sometimes we want to take a look at them. 
And I really applaud you for doing that.
    I just got here to hear a little bit about the stem cell 
issue. We have discussed that many times before here. We know 
that this research offers enormous potential to help ease the 
suffering of people with Parkinson's and juvenile diabetes, 
ALS, Alzheimer's.
    I just had the occasion last evening to meet an old friend 
of mine who I had not seen in several years. I found out that 
he has Lou Gehrig's disease. It was just a startling thing for 
me to see that last evening. His words to me were, you have got 
to put more research into the stem cell research and find out 
what is going on here. To see someone that you have known for a 
long time and then you lost contact with him and then you see 
him and you know they are not going to be around very much 
longer and they are in middle stages of Lou Gehrig's disease, 
it is a tough thing to see.
    I am just concerned that the restrictive policies in this 
research are delaying the day when these diseases could be 
cured. Under the President's guidelines only those cell lines 
generated before the arbitrary date of August 9, 2001 at 9 
p.m.--not 9:30, not 8:45, but at 9 p.m., very arbitrary--can be 
approved for federally approved research. The President said 
then there were more than 60 eligible lines. Later we heard 
there were 78. Now I just think I heard from you there were 17 
that are available to researchers. Well, I will ask some 
questions about this during my period of time.
    These 17 were also grown on mouse feeder cells, all of 
them, which raises questions whether or not they can ever be 
used for any kind of human therapies.
    Meanwhile, scientists in other countries are moving ahead, 
but we cannot fund those. We cannot fund any of that kind of 
research because those lines were developed after August 9, 
2001 at 9 p.m. So again, I will get into that in my question 
and answer period.
    I thank you for letting me make my opening statement, and 
whenever I can get a chance to ask questions, I will----
    Senator Specter. Thank you, Senator Harkin. We will come 
back to another round.
    Senator Stevens.
    Senator Stevens. Thank you very much.
    Dr. Zerhouni, it is nice to see you here. I do not think we 
have ever had an opportunity to put visuals on all of these 
people that you have brought here with you today. So I want to 
thank you for coming and apologize to them for taking their 
time. I do not know of another group that is more important to 
the future of our country than maybe now the intelligence 
community might be that would have a similar impact in the long 
range, but this long-range impact of you and your colleagues is 
just staggering.
    I heard the comments of my friend, Senator Harkin. Senator 
Connie Mack came to me and urged me to support a concept of 
doubling the NIH budget, and we have done that, Senator. So the 
real question I think we have to do one of these days is 
analyze what have we achieved with that money. I do think that 
that is something that you and your assembled colleagues could 
help us on. We are currently looking to increase other areas 
now, the National Science Foundation for one and the 
intelligence community for another. So the doubling of those 
budgets in the next 5 years will take precedence I think 
because of the circumstances that exist in the country.

                            PROSTATE CANCER

    I am glad to see Dr. von Eschenbach here. My good friend, 
Mike Phelps, reported you gave a tremendous speech at the 
molecular imaging meeting in Orlando. Several of you know my 
continuing interest in PET and its application to various areas 
of your institutes. I do hope that we can be able to be very 
aggressive in the use of that, the total molecular imaging 
concepts, to Alzheimer's, which I believe is becoming a great 
problem as the baby boom generation reaches retirement age.
    But I have one specific question. Prostate cancer is also a 
personal interest. I am a survivor now for 12 years. I would be 
interested if Dr. von Eschenbach would comment upon finasteride 
and what's going to happen to that clinical trial. I understand 
the clinical trial was canceled and there were some problems. 
Was the FDA a problem or was it that the high rate of tumor 
growth in those taking the drug? What happened, Doctor?
    Dr. von Eschenbach. Well, thank you, Senator, for that 
important question because I think it really underscores and 
points out not only the tremendous progress that we are making, 
but also how the investment that you have been responsible for 
in biomedical research is really now making it possible for us 
to solve problems that before we did not even understand.
    The issue with regard to the prevention trial of prostate 
cancer using finasteride demonstrated that in fact the drug did 
reduce the number of men who developed prostate cancer. So in 
that regard, we stopped the trial because the endpoint had been 
achieved. We in fact did get the answer and got the answer 
earlier than we had hoped or anticipated and demonstrated the 
protective effect of finasteride for a number of men who were 
susceptible to prostate cancer.
    What we also recognized in that trial was that although 
fewer men developed prostate cancer on finasteride, the kind of 
prostate cancer that they developed appeared to be more 
virulent and more aggressive, and perhaps could even increase 
their risk of progression or dying from prostate cancer.
    So in addition to demonstrating the protective effect, what 
we have now launched into is a subsequent set of studies to 
understand the mechanisms of action and to determine the impact 
on virulence. That is now an ongoing part of our research 
investigation.
    Senator Stevens. Thank you very much on that.
    Mr. Chairman, I do have, unfortunately, on the schedule 
several other subcommittees meeting. Again, I want to thank you 
for bringing all of the directors of these institutes here. I 
urge you to let them go quickly so they can go back to work.
    Senator Specter. That concludes the hearing.
    Senator Stevens. It concludes my time too. Thank you all 
very much.
    Senator Specter. Thank you very much, Senator Stevens.
    I am going to step out for a moment down the hall to the 
Judiciary Committee to see if I am needed for a quorum there. I 
hope to return within the time allotted to Senator Cochran, but 
if I do not, we will turn to Senator Harkin. Senator Cochran.
    Senator Cochran. Mr. Chairman, thank you.
    Dr. Zerhouni, we are very pleased with the fact that you 
are exploring research possibilities in areas that have 
previously been, I think, relegated to a fairly low priority. 
Fundamental challenges such as understanding obesity, its 
effect on health, what can be done to both treat those symptoms 
and, more importantly, prevent that condition should be the 
subject of research. I wonder what emphasis is placed in the 
budget request with regard to research in this area.

                            OBESITY RESEARCH

    Dr. Zerhouni. This is a very important topic to us. 
Actually I would like to point out that NIH has been working on 
obesity for over 10 years. I actually have a little graph here 
that you could see whereby our investments started in 1996 
because already at that time, NIH had predicted that the 
obesity crisis will hit, and it became one of the top 10 topics 
of research.
    However, as you know, the rate of increase of obesity is 
actually greater than what we expected, so we are increasing 
our funding at the same level. In fiscal year 1996, we had $86 
million. Next year we will have $440 million funding. Last year 
I established a trans-NIH Obesity Task Force, led by Dr. Allen 
Spiegel and Dr. Barbara Alving. They have come up with a new 
strategic research plan for obesity, and despite the difficult 
budget environment, we are going to increase our funding from 
$400 million to $440 million in obesity research by $10 
million. So we have almost quadrupled our investment in obesity 
research while the rest of the NIH doubled to show you our 
commitment to it and also our ability to see proactively where 
research needs to be.
    Senator Cochran. I hope you will take into account the 
importance of concentrating some of this funding in areas that 
suffer from this in a disproportionate way compared to the rest 
of the country.
    Dr. Zerhouni. Actually, Senator, this is one of the 
priorities of the new plan. We are going to focus on childhood 
obesity which affects rural areas and minority areas to a much 
greater degree than other communities. So we will have an 
implementation to be able to study that pattern early on in 
life.

 ROLE OF THE NATIONAL CENTER FOR COMPLEMENTARY AND ALTERNATIVE MEDICINE

    Senator Cochran. One new phenomenon I know is the fact that 
millions of Americans are using dietary supplements and herbal 
products today. The National Center for Complementary and 
Alternative Medicine is playing a role in understanding the 
efficacy and the effects of these products. What are your plans 
for research with respect to these products?
    Dr. Zerhouni. If you allow me, I would like Dr. Stephen 
Straus, who is the Director of the National Center for 
Complementary and Alternative Medicine, to answer that. He has 
very definite plans and great strategies for that.
    Dr. Straus. Thank you. Mr. Cochran, our goal is to 
characterize the complementary and alternative medicine (CAM) 
products that Americans are using, understand why they have the 
activities they do, and then prove whether they are safe and 
effective. We are doing this in a multi-tiered approach, much 
of which is conducted in partnership with the other NIH 
Institutes and Centers because of their strong areas of 
thematic expertise.
    We are doing this with products that are used for 
neurodegeneration such as ginko biloba. In that regard, we have 
already enrolled, in partnership with the National Institute of 
Aging, the National Heart, Lung and Blood Institute and the 
National Institute of Neurological Disorders and Stroke, over 
3,000 patients in the largest study ever mounted of an herbal 
product, and at that time the largest preventative study 
conducted for dementia. The goal is to prevent the onset of 
Alzheimer's disease in otherwise healthy, aging Americans.
    At the same time we are studying mechanism, and in your own 
State, we have funded outstanding investigators at the 
University of Southern Mississippi who are showing us several 
different chemical constituents in ginko that prevent the death 
of neuronal cells in the brain. These are our strategies.
    Senator Cochran. Thank you very much.

    THE NATIONAL INSTITUTE FOR BIOMEDICAL IMAGING AND BIOENGINEERING

    I appreciate also the NIH's recognition of the role for new 
technologies in the detection and treatment of disease. The 
National Institute for Biomedical Imaging and Bioengineering 
was created specifically to enhance research in this area. Has 
this investment begun to show results, Dr. Zerhouni?
    Dr. Zerhouni. I think so. One of the most important 
meetings that the institute has had was actually organized at 
the University of Mississippi. It was a national strategic 
meeting to try to see where the direction of the field would 
go. Dr. Pettigrew is really a great leader and I would like him 
to comment, if you do not mind, Senator.
    Senator Cochran. Thank you.
    Dr. Pettigrew. Thank you, Senator, and I appreciate having 
the opportunity to respond to that question.
    There are many problems that physicians alone cannot solve. 
There are problems that also require the input of quantitative 
scientists. These would be scientists, which include not only 
imagers and physicists but also mathematicians and computer 
scientists.
    We have been very successful, I am pleased to report, in 
bringing physicians and quantitative scientists together to 
translate the fundamental discoveries from the technologically-
based scientists into meaningful clinical applications for 
patients. That is certainly our goal and we work very hard to 
achieve that.
    The progress to date has been quite remarkable given our 
short history of only 2 years. I would like to tell you about 
two examples in this area.

                            NIBIB'S PROGRESS

    The first is the development of a new technology called 
quantum dots. These are small nano crystals that are able to 
identify specific cells of interest in the body, for example, 
cancer cells in lymphnodes. Quantum dots could also be used to 
identify the deposition of plaque in arteries.
    We have also seen progress in an area that many people in 
the audience might appreciate. No doubt people here have had 
MRI scans. This is a marvelous technology, in fact, the subject 
of the Nobel Prize in Medicine this year. But some of our 
researchers have tackled one of the problems, which is the 
speed with which these scans can be made. These researchers 
have improved the speed of acquisition of images 10-fold. 
Studies that used to take several minutes to acquire can now be 
acquired in a matter of seconds. The value of this is not only 
in improved patient comfort, but also in opening up additional 
applications such as image-guided surgery where speed would be 
very important.
    These are examples of some of the technological innovations 
that we have been pursuing and have begun to bring to fruition 
for the benefit of us all.
    Senator Cochran [presiding]. Thank you. Thank you very 
much, Mr. Chairman.
    Senator Harkin, do you have questions?
    Senator Harkin. If you want to have a follow-up.
    Senator Cochran. No. Go ahead. I am trying to carry out the 
chairman's 5-minute rule here. No, go ahead, please proceed.
    Senator Harkin. Okay, thanks.

                            STEM CELL LINES

    I would like to get back to the stem cell issue, if I 
could, and I would like to direct some questions to Dr. Battey. 
I believe you are heading the Stem Cell Task Force.
    Dr. Battey. That is correct.
    Senator Harkin. Correct me if I am wrong, but I think you 
have said that under the best case scenario, only 23 lines will 
be available to federally funded scientists. Is it 23 or is it 
17? I am a little confused there.
    Be that as it may, even if it is 23, my question basically 
is will 23 be enough to realize the full potential of stem cell 
research?
    Dr. Battey. Let me begin by addressing the numbers issue 
that you have raised.
    The number 17 refers to the number of cell lines that are 
available today for Federal funding that can be widely 
disseminated across the research community, cells that--if you 
had a laboratory--you could order and get in your laboratory 
for experiments. There are six additional derivations located 
at institutions that hold NIH infrastructure awards for the 
purpose of developing such cell lines, expanding them, getting 
them ready to be distributed, going from a derivation to a 
useful cell line that can be distributed. And we are hopeful 
that all six of these will become distribution quality cell 
lines. When you add 17 and 6, one arrives at the figure 23.
    Now, there are 31 derivations located in five institutions 
in Korea, India, and Sweden that are eligible for Federal 
funding that are on the registry, but they have not sought an 
NIH infrastructure award to develop such cell lines. So we do 
not know the status of these derivations. They are privately 
held and we are not privy to that information.
    Senator Harkin. Let me get to my question there, Dr. 
Battey. Will 23 or 17 be enough to realize the full potential 
of stem cell research?
    Dr. Battey. I do not know the answer to that question, but 
there are reasons to be concerned. For example, there was a 
published paper in December showing that when some of the cell 
lines, some of the 17, are grown in some people's hands and 
passaged for prolong periods of time, they develop karyotypic 
abnormalities, chromosomal abnormalities. These abnormalities 
are some of the same abnormalities that are seen on occasion in 
teratocarcinomas, which are tumors of cells like embryonic stem 
cells. That is an issue of great concern and will need to be 
followed very carefully.
    While I have to say I do not know whether or not we will be 
able to do everything possible with either 17 or 23 or 46 or 98 
or 321 cell lines, I do know that if there is additional 
functional diversity it is difficult to imagine that more cell 
lines would be detrimental to research progress.

                        MOUSE FEEDER CELL LINES

    Senator Harkin. Could any of these 23 lines ever be used in 
human therapy since they have all been developed on mouse 
feeder cells?
    Dr. Battey. We have discussed this issue at great length 
with the Food and Drug Administration, who would be the 
organization overseeing the safety and efficacy of any clinical 
studies that were done with these cells, were these cells to 
ever be returned to patients in transplantation in an effort to 
treat some of these awful disorders like ALS that you have 
spoken about. When we talk to the FDA about this, they say that 
the mouse feeder cell layer is an issue and the issue of 
whether or not a retrovirus or some other bad thing might have 
been transferred from the feeder cell layer to the human 
embryonic stem cells is an issue that must be explored.
    It is not, however, a prohibitive issue. It is one of many 
issues, including the history of the cells, where they have 
been cultured, what kind of medium they have been cultured in, 
if there have been any serum or other biological additives, 
what the state and purity of those are. So there is no question 
the feeder cell layer is a safety issue, but it is one of many 
safety issues and I do not think should necessarily be drawn 
out of that context.
    Would it be preferable to have cells that were not growing 
on mouse feeder cell layers? I think the answer to that 
question is yes. Would it be preferable to have cells that were 
grown in a medium that had nothing but completely defined 
substances, purified additives? Absolutely. That would be 
better. In fact, the NIH is funding investigators to try to 
develop better culture conditions for human embryonic stem 
cells with the goal of ultimately moving the cell lines into an 
environment that poses less questions about biological safety.

                       ACCESS TO ADDITIONAL LINES

    Senator Harkin. The other question I had was basically 
would federally funded scientists benefit from having access to 
additional lines. I think you basically answered that. 
Obviously, the more you have and the more involved, I would 
assume the better the research would be. You would have just 
more lines out there to look at.
    Dr. Battey. We will understand much better what the 
significance of number of cell lines is when we have explored 
to a greater degree what we can do with the cells that are 
available and widely distributed for Federal funding. But as I 
said before, it is difficult to argue that a greater number 
with more potential functional diversity would be detrimental 
to the research effort.
    Senator Harkin. If they had access to additional lines--
lead me on. I just want to get a better understanding. How 
would this be not detrimental if they had more?
    Dr. Battey. Well, the problem here and the reason why I 
cannot be more specific in answering this question is that we 
are just at the beginning of exploring what we can do with the 
cell lines that are eligible for Federal funding. We are just 
beginning to learn the master switches that keep these cells in 
a pluripotent state and allow them to replicate indefinitely in 
the laboratory. We are just beginning to get our hands around 
the growth factors and gene expression profiles that are 
associated with differentiation towards a cell type that might 
be interesting for a therapeutic application such as a 
dopamine-producing neuron that might be lost in a patient with 
Parkinson's disease or a motor neuron that will be lost by your 
friend with ALS. We are only beginning to understand, and until 
we know more about what we can do with the cells we have, what 
their limitations are, what their possibilities are, it is hard 
for me as a scientist in a fact-based manner to give you a 
better answer than the one I have given, as much as I would 
like to do that.

                            STEM CELL POLICY

    Senator Harkin. Is it time to reevaluate the policy that 
has been in effect since August 2001?
    Dr. Battey. I think it is very important for there to be a 
continued dialogue between scientists, the National Institutes 
of Health, your subcommittee, and the administration about what 
the state of the science is. The decision to evaluate a 
presidential policy is a decision that is made at the level of 
the White House. Our role in this process, as I understand it, 
is to provide facts and information for the people who make 
policy, and we have a regular dialogue with individuals in the 
administration, as well as individuals on some of your staff 
about the state of the science in human embryonic stem cells. 
Just on a personal note, I am happy to come and talk to anybody 
who has questions or wants to know more about the state of the 
science in what I consider to be one of the most exciting areas 
of science for the future of biomedical research.
    Senator Harkin. Thank you very much, Dr. Battey.
    Senator Specter [presiding]. Thank you, Senator Harkin.
    Dr. Battey, the Congress also has a constitutional role in 
setting national policy and that starts with this subcommittee. 
Dr. Zerhouni and Dr. Battey, as the area of responsibility may 
fall, we would like to have a comprehensive report on what has 
happened to the original 60-some stem cell lines announced by 
the President back in August of 2001 and what has happened to 
them, how many are in private hands, how many of them are 
tainted with mouse feeders, how many of them can be used, what 
is happening at Harvard, what is happening in South Korea, what 
is happening in other countries so we can make an evaluation as 
to what the policy ought to be.
    [The information follows:]
                           Stem Cell Research
    Question. What is the status of human embryonic stem cell (hESC) 
derivations listed on the NIH Stem Cell Registry? How many are in 
private hands? How many have been grown on mouse feeder layers? How 
many are viable?
    Answer. All of the derivations listed on the NIH Human Embryonic 
Stem Cell Registry are privately owned by 15 different companies or 
academic institutions. The providers indicated by an asterisk (*) below 
are recipients of the NIH Infrastructure award to develop, characterize 
and distribute cell lines.
BresaGen, Inc., Athens, Georgia*
    4 derivations
    3 lines available
    The cells in derivation BG04/hESBGN-04 failed to expand into 
undifferentiated cell cultures.
Cell & Gene Therapy Research Institute (Pochon CHA University), Seoul 
        Korea
    2 derivations
    0 lines available
Cellartis (formerly Cell Therapeutics Scandinavia), Goteborg, Sweden*
    3 derivations
    2 lines available
    Cell line SA03/Salgrenska 3 was withdrawn by donor.
CyThera, Inc., San Diego, California*
    9 derivations
    0 lines available
    The cells failed to expand into undifferentiated cell cultures.
ES Cell International, Melbourne, Australia*
    6 derivations
    6 lines available
Geron Corporation, Menlo Park, California
    7 derivations, all duplicates of Wisconsin Alumni Research Fdn. 
derivations
Goteborg University, Goteborg, Sweden*
    16 derivations, reported to have not been exposed to mouse feeder 
layers
    0 lines available
Karolinska Institute, Stockholm, Sweden*
    6 derivations
    0 lines available
    The cells failed to expand into undifferentiated cell cultures.
Maria Biotech Co. Ltd.--Maria Infertility Hospital Medical Institute, 
        Seoul, Korea
    3 derivations
    0 lines available
MizMedi Hospital--Seoul National University, Seoul, Korea*
    1 derivation
    1 line available
National Centre for Biological Science/Tata Institute of Fundamental 
        Research, Bangalore, India
    3 derivations
    0 lines available
Reliance Life Sciences, Mumbai, India
    7 derivations
    0 lines available
Technion-Israel Institute of Technology, Haifa, Israel*
    4 derivations
    2 lines available
University of California, San Francisco, California*
    2 derivations
    2 lines available
Wisconsin Alumni Research Foundation, Madison, Wisconsin*
    5 derivations
    5 lines available

    Of the 78 entries on the Registry, 71 are from independent embryos 
and 7 are duplicates located at both WiCell (Wisconsin Alumni Research 
Fdn.) and Geron. The Geron cell lines are not being widely distributed 
to the research community.
    Of the 71 independent derivations:

  --16 have failed to expand into self renewing, pluripotent cell lines 
        (9 at CyThera, 1 at BresaGen, 6 at Karolinska), and 1 line was 
        withdrawn by the donor at Cellartis (formerly Cell Therapeutics 
        Scandinavia, CTS). NIH provided Infrastructure support in 
        failed attempts to expand these 16 derivations into 
        distribution-quality cell lines.
  --Of the remaining 54 independent derivations, 21 are available for 
        shipment, after expansion and characterization using NIH 
        Infrastructure grant awards. The 21 that are currently 
        available are:

    BresaGen, Inc.--BG01, BG02, BG03
    Cellartis--SA01, SA02
    ES Cell International--ES01, ES02, ES03, ES04, ES05, ES06
    MizMedi Hospital--MI01
    Technion-Israel--TE03, TE06
    UCSF--UC01, UC06
    WiCell--WA01, WA07, WA09, WA13, WA14

  --Of the remaining 33 independent derivations, 2 more are at 
        institutions with NIH Infrastructure awards. If these 2 were 
        developed into distribution quality cell lines ready for 
        shipment, there would be 23 independent cell lines available to 
        the research community. The 2 cell lines under development are:

    Technion-Israel--TE04, TE07

  --The remaining 31 independent derivations are all at institutions 
        located outside of the United States that have not applied for 
        NIH Infrastructure awards to develop their cell lines. Any 
        plans to develop these derivations into cell lines that are 
        available to the research community are unclear at this time. 
        The 31 derivations at institutions that do not have 
        Infrastructure awards are:

    Pochon CHA (Korea)--2 derivations
    Goteborg Univ. (Sweden)--16 derivations
    Maria Biotech (Korea)--3 derivations
    National Centre for Biological Sciences (India)--3 derivations
    Reliance Life Sciences (India)--7 derivations

    As far as we know, all derivations have been exposed to mouse 
feeder cells, with the exception of the 16 derivations at Goteborg 
University (Sweden).
    Information on the detailed characteristics of each of the 
derivations is available on the NIH Human Embryonic Stem Cell Registry, 
http://escr.nih.gov.
    Question. What is Happening at Harvard University?
    Answer. On March 25, 2004, Harvard University announced the 
derivation of 17 hESC lines in an article published in the New England 
Journal of Medicine. Funding for the derivations and distribution of 
these lines is being provided by the Howard Hughes Medical Institute, 
Juvenile Diabetes Research Foundation and Harvard University.
    On April 23, Harvard University announced the establishment of the 
Harvard Stem Cell Institute. According to Harvard, the Institute will 
encourage adult and embryonic stem cell research using both animal and 
human stem cells. The Institute has two co-directors: Harvard Medical 
School Professor David Scadden, who also directs Massachusetts General 
Hospital's Center for Regenerative Medicine and Technology, and Douglas 
Melton, the Thomas Dudley Cabot Professor of the Natural Sciences and a 
Howard Hughes Medical Institute investigator.
    Research at the Institute will be focused on five areas of disease 
for which stem cell therapy seems most promising. The diseases all 
result from some sort of organ or tissue failure and include: diabetes, 
neurodegenerative diseases, blood diseases, immune diseases, 
cardiovascular disease, and musculoskeletal diseases.
    Although research on the 17 new human embryonic stem cell (hESC) 
derivations are not eligible for Federal funding, NIH is currently 
supporting several scientists at Harvard University whose hESC research 
use lines eligible for Federal funding. Dr. Doug Melton is working to 
identify the genes involved in hESC self-renewal and differentiation. 
Dr. George Daley is studying hematopoietic development from hESCs. Dr. 
Howard Green is working to develop the culture conditions to coax hESCs 
to become the keratinocytes that make up human skin(s epidermis. Dr. 
Jeffrey Harper is analyzing the signals that control hESC division.
    Question. What is Happening in South Korea? What is Happening in 
Other Countries?
    Answer. On February 12, 2004, South Korean researchers published 
the first scientifically credible report of the creation of a cloned 
human embryo in the laboratory by means of somatic cell nuclear 
transfer (SCNT) (Science 303: 1669-1674.) These scientists, supported 
by the South Korean government, then used these cloned embryos to 
establish a human embryonic stem cell line. They combined the DNA of a 
woman's ovary cell with her donated egg, from which the nucleus had 
been removed, and then stimulated the newly combined cell to divide. 
The resulting very early embryo was then allowed to develop to the 
blastocyst stage (five to nine days), at which point it was 
disaggregated and the highly potent stem cells of the inner cell mass 
were removed. These stem cells were then treated to produce a stem cell 
line to be used for various kinds of biomedical research. Subsequent to 
the publication of the SCNT study, the South Korean government voted to 
ban the creation of cloned human embryos, but might allow cloning for 
biomedical research on a case-by-case for medical treatment subject to 
approval by a National Bioethics Advisory Commission. Scientists will 
be permitted to use spare frozen embryos, left over from infertility 
treatments and kept in laboratories for at least five years, for 
limited stem cell research into treatments for hard-to-cure diseases. 
The regulations banning human cloning are expected to come into effect 
after President Roh Moo-hyun signs the bill. The regulations on stem 
cell research will go into effect in 2005.

                 OTHER INTERNATIONAL STEM CELL EFFORTS

    International Society for Stem Cell Research (ISSCR).--The 
International Society for Stem Cell Research is an independent, 
nonprofit organization established to promote and foster the exchange 
and dissemination of information and ideas relating to stem cells, to 
encourage the general field of research involving stem cells and to 
promote professional and public education in all areas of stem cell 
research and application. Opinions on the legitimacy of experiments 
using human embryos vary among members of the European Union (EU) 
according to the different ethical, philosophical and religious 
principles in which they are grounded. EU member states have taken very 
different positions on the regulation of human embryonic stem cell 
research and cloning for biomedical research. More information about 
the regulations and policies of EU members can be found on the website 
of the ISSCR at the following link: http://www.isscr.org/scientists/
legislative.htm.
    The International Stem Cell Forum (ISCF).--The ISCF was founded in 
January 2003 to encourage international collaboration and funding 
support for stem cell research, with the overall aim of promoting 
global good practice and accelerating progress in this vitally 
important area of biomedical science. The Forum's long-term aim is to 
help stem cell scientists achieve a range of revolutionary medical 
advances that will benefit people throughout the world. The ISCF is led 
by the United Kingdom's Medical Research Council and consists of 14 
leading supporters of stem cell research from around the world. Member 
organizations are based in the United States, Finland, Australia, 
Canada, Germany, France, Israel, Netherlands, Japan, Singapore, Sweden, 
Switzerland, and the United Kingdom. Within ISCF, the United States is 
represented by the NIH. The Juvenile Diabetes Research Foundation 
International (JDRF) is also a member of the ISCF. One short term goal 
of the ISCF is to compare different stem cell lines from the member 
organizations. As part of this goal, NIH's federally approved stem cell 
lines will be compared to those of other member organizations. 
Information about the stem cell research efforts of the member 
organizations can be found on the website: http://mrc.live.tmg.co.uk/.

    Senator Specter I have discussed it with the President and 
he has a view on it. The facts are very important in 
formulating all of our views. So let us proceed to bring all 
the facts to this subcommittee.
    Dr. Zerhouni. You have my commitment to do so, Senator.

                           BIODEFENSE AGENTS

    Senator Specter. Thank you very much.
    On the issue of biodefense, the concerns about another 
attack are with us imminently as we sit here. We have seen an 
acceleration of the venom and hatred from Wahabes and Islam 
fundamentalism and we have a long chronology of attacks going 
back to 1983 when 283 Marines were killed in Lebanon, what 
happened in Mogadishu, what happened in Africa in August 1998, 
what happened with the Cole, what happened on 9/11. We have to 
be prepared.
    Dr. Fauci, you and I have discussed this on other 
occasions. This year's request includes $1.7 billion toward 
biodefense research activities. What are the principal 
bioweapons that we are working to defend against?
    Dr. Fauci. The principal bioterror agents that we are 
involved in pursuing from the standpoint of developing 
countermeasures remain the category A agents that we have 
discussed before this committee on several occasions. High 
among those are still smallpox, anthrax, botulism toxin, 
tularemia plague, and the hemorrhagic fevers including Ebola. 
We are pleased to report, as Dr. Zerhouni mentioned in his 
opening statement, that over the past year with the resources 
that this committee has generously given us, we have made 
extraordinary progress in having available, either already in 
the stockpile or in contract on its way either in phase I/II or 
purchase, countermeasures in the form of vaccines for smallpox, 
anthrax, and soon Ebola.
    Senator Specter. If there was to be an attack on anthrax, 
how well prepared are we?
    Dr. Fauci. We are extraordinarily better prepared today 
than we were in the anthrax attacks in the fall of 2001 with 
the following issues. A, the stockpile of antibiotics right now 
to treat prophylactically for the entire 60-day period with 
ciprofloxacin or doxycycline is now able to meet a substantial 
attack, God forbid that were to occur. And also, we are now 
well into the development of the second generation of a 
recombinant protective antigen anthrax vaccine that could be 
used to vaccinate people who would go in to clean up, the 
hazmat people, health workers, and those who would be required 
to have an extended period of antibiotics. So the anthrax 
situation is dramatically different than it was in this 
building a year and a half, 2 years ago.
    Senator Specter. Adequate?
    Dr. Fauci. I believe adequate. I think we still have a ways 
to go on every issue, but the progress that is being made 
particularly in the arena of anthrax is striking.
    Senator Specter. My red light is about to go on. So I would 
like you to supplement in writing the details as to the other 
threats, what we have done, whether it is adequate, and what 
more needs to be done.
    Dr. Fauci. I would be happy to do that.
    Senator Specter. This is something we have to address 
forcefully and promptly.
    Dr. Fauci. Will do.
    [The information follows:]

   Research in Medical Countermeasures Against Category A Biological 
                                 Agents

    The accompanying table provides a summary on the status of research 
and development of medical countermeasures for Category A biological 
agents. These biological agents and the countermeasures that are 
currently available for them are identified in the first two columns. 
Recent NIAID accomplishments are identified in column three (complete 
details of these and additional accomplishments can be found in the 
NIAID Biodefense Research Agenda for CDC Category A Agents Progress 
Report).\1\ Candidate countermeasures that are at an advanced research 
stage where rapid development of the countermeasures is scientifically 
feasible are identified in the fourth column. Finally, many of the 
countermeasures that are the focus of early research efforts are 
identified in the last column.
---------------------------------------------------------------------------
    \1\ See http://www2.niaid.nih.gov/Newsroom/Releases/
biodefensereport2003.htm for a detailed report on research progress 
made to date for CDC Category A Agents.
---------------------------------------------------------------------------
    I would like to add that we continue to support a national, 
comprehensive biodefense research and development program. It includes 
the development of other biodefense countermeasures to combat 
Categories B and C biological agents, as well as a broad range of basic 
research activities. 



    Senator Specter. Senator Harkin.
    Senator Harkin. Thank you, Mr. Chairman.

                       FUNDING OF RESEARCH GRANTS

    Dr. Zerhouni, our staff has brought to our attention this 
issue of the number of research grants that we are funding this 
year. It is a question we always ask. What are we doing in 
terms of the number of grants and the funding for these grants?
    I have found--and you correct me if I am wrong on this--
that fiscal year 2004 marked the first time in 8 years that the 
number of new competing grants went down. It dropped from 
10,393 in fiscal year 2003 to 10,135 in fiscal year 2004. That 
is the bad news. We might say, well, but the good news is the 
President's 2005 budget calls for raising that number back to 
the 2003 level of 10,393. So I said, okay. How do we do that?
    As you know, when researchers get approved for NIH grants, 
for the second, third, fourth years, there is an automatic 3 
percent increase. Well, what I found out is that this 
longstanding commitment by NIH to these researchers is 
necessary so that they can pay their staff and give them their 
annual salary increases or get new equipment and so forth in 
the second, third, and fourth years. Now, that is 3 percent. 
And this year's budget calls for an increase of 1.9 percent to 
the second, third, and fourth year researchers. As a result, 
the researchers will receive less money than what NIH committed 
to providing them.
    I am wondering about the effect this is going to have. 
Could it force them to change the scope of their work in 
midstream?
    Now, again, I think that you and all of us are opposed to 
breaking NIH's commitment to its grantees. Once you make a 
commitment, you make a commitment. And I am concerned that this 
budget is changing this policy, and I am wondering why are we 
changing this policy. Why are we going to 1.9 percent rather 
than 3 percent?
    Dr. Zerhouni. These are very important questions and those 
are the questions we have grappled with in a very difficult 
budget environment and we had to make tough choices.
    But let me address your first question which was that a 
decrease between 2003 and 2004 and then recovery in 2005 in 
numbers of grants. Fiscal year 2003 was the last year of the 
doubling of the budget.
    Senator Harkin. Right.
    Dr. Zerhouni. We actually gave more grants in 2003 than we 
planned to do so that is why the number in 2003 was higher. In 
2004, we were planning on keeping that level or even go up a 
little bit, but certain budgetary events occurred.
    One, was the .59 percent cut across the board. That was in 
conference.
    Second was the reshifting of extramural construction, $119 
million we had not requested. It was then put back into the 
extramural construction.
    Last but not least was what we call the planning and 
evaluation tap, 2.2 percent of the NIH budget is used to fund 
AHRQ, for example. So all of these elements decreased the funds 
available for the grant pool in 2004.
    Now we come to this year and we have a budget envelope of 
2.6 percent. So we had to make tough choices.
    I agree with your policy principle. This is something that 
I have told all the Institute and center directors--that our 
word is our bond. We should really commit to maintaining 
research grants at least at an inflationary level so that they 
do not lose the ability to purchase research, if you will.



                             SUCCESS RATES

    But on the other hand, we also have a marked increase in 
terms of applications and new scientists are coming to us 
asking for grants. So we had to make a tough decision. I have 
the information here to show you on the screen. If you looked 
at our success rate at the beginning of the doubling, our 
success rate was 32 percent here. The number of applications we 
received in 2001 was 28,000. Senator, the number of 
applications we are receiving is now 38,000. This year alone 
our Center for Scientific Review will receive 66,000 
applications for all types of grants for NIH as well as some 
from CDC, AHRQ, FDA, and SAMHSA.
    Senator Harkin. Excuse me, Dr. Zerhouni, but that 38,000 
and the 37,000 and the 34,000 I see, are those the ones that 
actually make it through the peer review process?
    Dr. Zerhouni. Those are the ones that are applied for. They 
are new and competing in that year. Only one-third of them will 
get funded.
    So, for example, if you go back to 2001, Senator, we had 
28,000 grants. Thirty-two percent of those were funded. Then we 
had 30,000 applicants. Thirty-one percent of those were funded. 
And then in 2003, we had 34,700 applications.
    So from my standpoint, as you look at the budget and you 
look at the number of scientists out there who are coming up 
with great ideas, we had to make a choice. Can we shave the 
cost increases to allow more of these increasing numbers of 
scientists to apply and be successful? So those are the 
tensions, Senator, that I had to deal with in making the tough 
decisions.
    Senator Harkin. Well, I understand the dilemma you were 
faced with. I guess under the budget we have got a choice, 
either increase the number of new grants and cut back on the 
increases for those that are already approved, or keep the 
increases in and not have new grants.
    Dr. Zerhouni. That's right.
    Senator Harkin. That seems to be the dilemma.
    Well, I do not know. Maybe we made the right decision, but 
I just think we all ought to be aware, Mr. Chairman, of the 
tradeoff that we have made with this budget. Now, I am 
preaching to the choir here because this person right next to 
me here keeps going on the floor trying to get our budget up 
for NIH and I have backed him every time we have tried to do 
that. But because of this budget, you have had to make almost a 
devil's choice here in terms of the tradeoff. As you say, you 
want to keep your word. You want to keep your commitment to 
these researchers. But then the President's budget--it is his 
budget--wants to have all these new starts, so then you have to 
trade that off. I think that is why we need to actually get 
this budget back up again so that that does not happen.

                      PROJECTING OUT-YEAR BUDGETS

    Now, I am particularly concerned, as I said in my opening 
statement, about the years ahead. According to OMB, NIH's 
budget is expected to drop in actual dollars by 2 percent in 
fiscal year 2006. If that goes through, do we have any idea 
what that is going to mean in the number of grants and this 
dilemma we are facing right now? What is that going to mean?
    Dr. Zerhouni. At this point I heard the same thing that you 
heard. So we queried and we asked are there decisions made in 
our out-year budgets. To this moment, I am not told of any 
formal decisions that were made by OMB that would imply those 
cuts in the NIH budget.
    Senator Harkin. I got it from OMB.
    Dr. Zerhouni. I understand. There were projections, but 
from the standpoint of our interactions with OMB, we are told 
that those are projections and estimates that were made, not 
policy decisions.
    Senator Harkin. Well, I know they are projections. This is 
what OMB is projecting. I have got the figures right here, a 2 
percent cut in fiscal year 2006. That is next year. That is 
what we are going to be confronting next year, and we are going 
to be here next year.
    So, again, I am just asking. We need some information. What 
would this mean if OMB's projection goes through and we have 
this 2 percent cut in fiscal year 2006 and we are confronting 
that, what does it mean for grants, commitments to researchers, 
size of grants? I mean, we need to know what the impact of that 
is going to be.
    Dr. Zerhouni. We definitely are willing to provide you with 
those projections from the standpoint of the agency, and I will 
provide that to you for the record.
    Senator Harkin. I do not need them right now, but we are 
going to need them sometime because we are going to start 
getting into this sometime this year. But we should have some 
handle on that as to what that might mean, so that we can at 
least, as we have been saying here, get the facts out as to 
what this would mean. Before the budget actually comes out is 
what I am saying, we ought to have this out there so people 
that are devising the budget know what it is going to mean.
    Dr. Zerhouni. But again, we checked and those figures are 
not decisional figures. They are not decisions made. They are 
projections.
    Senator Harkin. I understand that, but we have got to know 
what those projections mean in real terms if in fact they 
follow through on them.
    Dr. Zerhouni. Definitely.
    [The information follows:]

                 2 Percent Decrease in Fiscal Year 2006

    As indicated, while there are mechanically calculated numbers in 
the OMB computer system that reflect the Administration's overall 
budget targets in the outyears, no specific funding decisions have been 
made for NIH or most other domestic programs. In answer to your 
question, if the NIH budget were to decrease by 2 percent in fiscal 
year 2006 from the fiscal year 2005 Budget Request, the number of 
competing research projects grants (RPGs) would decrease by an 
estimated 2,000 to 2,500 depending on the average cost assumptions 
used.

    Senator Harkin. Thank you, Dr. Zerhouni. Thank you, Mr. 
Chairman.
    Senator Specter. Thank you, Senator Harkin.

                            OBESITY RESEARCH

    Dr. Zerhouni, the issue of obesity is one of enormous 
importance. In 15 years, obesity has increased by over 50 
percent among adults; in 20 years, 100 percent among children 
and adolescents. We would like a written response as to what 
can be done by NIH, how this subcommittee might be effective on 
diet or education. We have both Health and Human Services and 
Education to try to confront this growing problem.
    [The information follows:]

                            Obesity Research

    The NIH Obesity Research Task Force, which was established in April 
2003 to accelerate research on this escalating health problem, has 
developed a Strategic Plan for NIH Obesity Research in broad 
consultation with external scientific and lay experts. We believe that 
implementation of this Plan is the best way that the NIH can contribute 
to arresting the obesity epidemic. Combating obesity must be a broad 
national effort to which the NIH can contribute new and important 
scientific insights. As noted, the fiscal year 2005 President's Budget 
request for the NIH reflects a 10 percent increase for obesity 
research, which would bring total NIH funding for this area to $440 
million. The proposed 10 percent increase includes additional new 
funding to begin implementation of obesity research in specific areas 
identified in the Strategic Plan because of their scientific 
opportunity and public health challenge. With respect to your specific 
reference to diet and education, the NIH has also recently created a 
new obesity research website http://www.obesityresearch.nih.gov), which 
contains links to science-based information generated by many of the 
NIH Institutes and Centers for the public, patients, and providers. Two 
helpful programs are the NIDDK's Weight Control Information Network and 
the NHLBI's Obesity Education Initiative.

           MEDICATION TO LOWER PLASMA LIPOPROTEIN (A) [LP(A)]

    Senator Specter. Last year I asked Dr. Lenfant about 
research on medication to lower Lp(a). Dr. Alving of the Heart, 
Lung and Blood Institute, is there anything new that you can 
inform the subcommittee about on the status of research toward 
a medication to lower Lp(a)?
    Dr. Alving. Yes. Thank you very much.
    Since the past year, there has been no really new 
information on Lp(a). It is still defined as an emerging risk 
factor. But there has been certainly very new information on 
the importance of lowering LDL, even below the guidelines of 
less than 100 milligrams per deciliter.
    Senator Specter. We see the LDL research all the time on 
the front pages.
    Dr. Alving. Yes.
    Senator Specter. But how about Lp(a)? That has been 
identified as a very problemsome factor. We have asked you 
about it repeatedly. What efforts are you making to identify 
what can be done about it?
    Dr. Alving. The efforts to identify it have been in terms 
of our ATP III Guidelines Committee, which has been reviewing 
all of the literature and has been closely focused on the 
latest guidelines and the latest research.
    Senator Specter. Aside from reviewing literature, is there 
active research being undertaken in the field?
    Dr. Alving. There are R01 grants that include Lp(a), but it 
has not really been able to be classified as a true risk 
factor. But what I would like to do----
    Senator Specter. How many grants?
    Dr. Alving. What I would like to do is reply for the record 
with an actual listing of the R01 grants so that I can give you 
very specific information about all of our research.
    Senator Specter. That would be fine. We would appreciate it 
if you would specify the grants, what they are doing, what 
their success has been, what more you need to do.
    Dr. Alving. Yes. I will be happy to do that, Senator.
    [The information follows:]

                      Research Activities on Lp(a)

    The NHLBI supports a variety of grants and contracts related to the 
cardiovascular disease (CVD) risks associated with elevated 
concentrations of Lp(a), factors that influence Lp(a) levels, 
mechanisms by which Lp(a) may affect CVD, and Lp(a) metabolism. 
Beginning in 2005, the NHLBI will support measurement of Lp(a) in the 
next four years of the National Health and Nutrition Examination 
Survey.
    The NHLBI supports the following R01 grants related to Lp(a):
  --APEX: Adiposity Prevention by Exercise in Black Girls (Medical 
        College of Georgia).
  --Biology of Proteolytic Derivatives of Lp(a) (University of 
        Chicago).
  --Epidemiology of Coronary Artery Calcification (University of 
        Michigan at Ann Arbor).
  --Genetic Determinants of Lp(a) Concentration (University of Texas 
        Southwestern Medical Center).
  --Genetic Epidemiology of Blood Lipids and Obesity (University of 
        Pittsburgh).
  --Lifestyle, Adiposity, and Cardiovascular Health in Youths (Medical 
        College of Georgia).
  --Macronutrients and Cardiovascular Risk (Johns Hopkins).
  --Regulation of Lp(a) Metabolism in Humans (University of California-
        Davis).
    The Institute also supports a K08 clinical investigator development 
award for a project on Lp(a), Homocysteine, and Cardiovascular Risk in 
End-Stage Renal Disease (Johns Hopkins).
    Lp(a) is a subject in several epidemiologic studies supported 
through NHLBI contracts:
  --Atherosclerosis Risk in Communities Study (ARIC) (Baylor College of 
        Medicine, Johns Hopkins, Mississippi Medical Center, University 
        of Minnesota--Twin Cities, University of Texas Health Sciences 
        Center, University of North Carolina at Chapel Hill).
  --Cardiovascular Health Study (CHS) (Johns Hopkins, University of 
        Washington, University of Vermont, University of Pittsburgh, 
        University of California--Davis, University of Wisconsin, Wake 
        Forest University).
  --Coronary Artery Risk Development in Young Adults Study (CARDIA) 
        (Harbor-UCLA Research and Education Institute, Kaiser 
        Permanente Division of Research, Northwestern University, 
        University of Minnesota--Twin Cities, University of Alabama at 
        Birmingham, University of California--Irvine).
  --Framingham Heart Study (Boston University Medical Center).
  --Jackson Heart Study (Jackson State University, Mississippi Medical 
        Center, Tougaloo College).
    Two NHLBI-supported cooperative agreements related to 
cardiovascular disease risk factors in Alaska Natives and Native 
Americans also include Lp(a) measurements:
  --Genetics of Coronary Artery Disease in Alaska Natives (GOCADAN) 
        (MedStar Research Institute).
  --Strong Heart Study (MedStar Research Institute, Missouri Breaks 
        Research Inc., Southwest Foundation for Biomedical Research, 
        University of Oklahoma Health Sciences Center, Weill Medical 
        College of Cornell University).
    In 1998, the NHLBI initiated a 4-year Lp(a) Standardization Program 
to enable accurate and consistent measurement that may help to 
reconcile various findings. Following completion of the program, a 
workshop was held to present the new results, evaluate current 
understanding of Lp(a) as a risk factor for CVD, and design future 
studies. The workshop report was published in the journal Clinical 
Chemistry in November 2003.
    In summary, the following statements can be made with respect to 
Lp(a).
  --In general, research has found only a modest association between 
        Lp(a) levels and CVD risk.
  --Compared with plasma LDL, Lp(a) concentrations are relatively 
        resistant to alteration by pharmacologic and lifestyle 
        interventions.
  --Lp(a) is a complex and heterogeneous protein, and measurement 
        challenges have created difficulties in comparing data from 
        different sources or assessing the impact of findings on the 
        severity of disease.
  --Measurement of Lp(a) is not currently recommended as part of CVD 
        risk assessment in patients.

    Senator Specter. We are going to try to bring this hearing 
to a close, following Senator Stevens' admonition. We are 
keeping a lot of scientists away from their laboratories here 
and there is a lot of work to be done.

                        SPINAL MUSCULAR ATROPHY

    Dr. Landis, on the issue of spinal muscular atrophy 
therapeutics, could you bring us up to date on when that will 
be ready for clinical trials?
    Dr. Landis. We are actually running three pilot clinical 
trials right now based on previous data. This is a network that 
is set up by Susan Iannaccone. In addition, the new project 
looking at additional compounds is well underway. The advisory 
committee has created a flow plan, and the first set of awards 
to come up with an animal model that would be used for 
preclinical studies will be awarded in the next week or 2.
    In addition, two further solicitations have been put out, 
one that would that would look for cell culture models again 
being used to solicit better mechanisms to look at therapeutic 
molecules, and the second to come up with a satisfactory way to 
measure the protein that is missing. So I think, between what 
pilot trials are ongoing and this new therapeutics initiative, 
we are making significant progress.
    Senator Specter. Would you supplement your answer with a 
written report about how you project activities of NIH to 
proceed in this line looking toward some ultimate answer?
    Dr. Landis. I would absolutely be pleased to do so.
    [The information follows:]

                        Spinal Muscular Atrophy

    The NINDS has developed a new program, called the SMA Project, to 
accelerate the development of therapies for this disease. The SMA 
Project uses a performance-based, milestone driven, contract mechanism 
to shorten the cycle time from recognition of a need or opportunity for 
research to getting research underway on those issues and finding 
answers. We awarded the primary contract in September 2003. This is an 
extremely ambitious project in a very challenging area of medical 
science, and scientific progress is not predictable. However, we have 
explicitly designed the SMA Project to respond quickly to unanticipated 
obstacles and to emerging opportunities, in the hopes of achieving our 
goal of identifying a therapeutic candidate for SMA, and completing the 
required preclinical research and development by late 2007.
    One very important aspect of this program is that we are 
coordinating the research centrally, calling for targeted research 
projects to meet specific needs identified by an overall plan, and 
carefully monitoring progress. The program is guided by a superb 
Steering Committee, with scientists from academia, industry, the Food 
and Drug Administration, and the intramural and extramural programs at 
the NINDS. The Committee has already developed a plan and a sample 
timeline showing all of the steps necessary to meet the goal of 
bringing a candidate therapeutic to investigational new drug (IND) 
status that is necessary for clinical trials, within four years. The 
sample timeline and other detailed information about this program are 
available to the public on a website at http://smaproject.org.
    A crucial aspect of the SMA Project is the rapid turnaround from 
identifying a research opportunity or need, to solicitation for 
research proposals, to funding. The first targeted solicitation for 
research subprojects, focused on mouse models for testing therapies, 
was issued in December of 2003. These applications have been reviewed, 
and expect awards to be issued by June 1, 2004. Two further 
solicitations were issued in March, on cell culture models and on 
measuring the crucial protein that is lacking in SMA. Full length 
proposals are due in May, notification of subcontract awards is 
scheduled for June and funding for July. These initial proposals have 
been focused on generating the necessary research tools to identify a 
candidate treatment that has the highest probability of success in the 
clinic. Future solicitations will be aimed at stimulating new drug 
identification; the development of gene therapy; and establishing 
centralized testing facilities to conduct the activities required in 
the flow plan, such as evaluating compounds in animal and cellular 
models of SMA.
    In addition to the contract-based SMA therapeutics development 
project, we are currently supporting the short term, open label pilot 
clinical trials, being conducted by Dr. Iannaccone, of three drugs that 
have shown promise either in patients or in models of SMA. We will be 
looking to see if these results warrant larger trials. We are also 
planning a workshop on clinical trials for SMA to be held later this 
year. This workshop is intended to ready the SMA clinical community to 
test interventions that result from the SMA Project, by promoting 
collaboration and high quality trial design. In preparation, we are 
moving forward to work with the community on identifying and evaluating 
drugs now available that may slow the progression of SMA and be ready 
for testing in clinical trials.
    So, we are exploiting the best existing opportunities in the short 
term for slowing the disease, and at the same time we are developing 
the best possible treatments for the future through the SMA Project. 
Finally, I want to emphasize that the SMA Project is not replacing our 
traditional investigator-initiated grant programs and our intramural 
program on SMA; we are continuing to support this research as well. We 
also have extensive research programs in cross-cutting areas such as 
gene therapy, drug screening, and stem cells that may ultimately have 
an impact on SMA.

    Senator Specter. Thank you. Dr. Spiegel, in your field we 
had a high visibility attention-getter when NBA basketball star 
Alonzo Mourning was seeking a kidney transplant and was forced 
to retire early on glomerular disease that damages filters in 
the kidney that cleanse the blood. We were asked to hold a 
separate hearing which was just too much to do. Could you give 
us an update on where that stands?
    Dr. Spiegel. Yes, Senator, I would be happy to do that.
    The glomeruli are tiny units that cleanse the blood in the 
kidney and they are comprised of kidney membranes and small 
capillary blood vessels. There are really two types of injuries 
that occur. One is glomerulonephritis, which is caused by the 
immune system. Many institutes at NIH work together to direct 
attention to preventing kidney failure from glomerulonephritis.
    The form that you are referring to, focal segmental 
glomerulosclerosis, affects children, and as you implied in the 
case of Alonzo Mourning, can affect African Americans 
disproportionately. We have intensive research efforts together 
with patient advocacy groups such as the NephCure Foundation. 
In fact, we have launched a clinical trial directed at new and 
more effective therapies for this important disorder, and we 
are hopeful that from that trial, new, safer, and more 
effective medication will emerge. But at the same time, we are 
also reinforcing our basic research to understand the basis for 
the injury that occurs in glomerulosclerosis.
    Senator Specter. Thank you very much.

                 AGE-RELATED MACULAR DEGENERATION (AMD)

    Dr. Sieving, with respect to macular degeneration, how are 
you moving ahead on the clinical trial networks for advancing 
AMD research?
    Dr. Sieving. AMD is a leading cause of vision loss and, in 
fact, one of the leading causes of disability in the elderly. 
It is a neurodegenerative disease. A part of the mission of the 
institute is to form alliances, scientific alliances and 
communication related to other neurodegenerations, including 
Parkinson's and Alzheimer's disease, because there are some 
common features that mutually these two multiple areas can 
learn.
    Now, the AMD network specifically is going to tackle the 
opportunities presented by existing and new compounds to modify 
the effects of and the course of AMD. One such opportunity--it 
is not actually a network, but one recent success came from the 
finding reported about a year ago that antioxidant nutrients 
and zinc can decrease the risk of progressing to end-stage 
vision loss. That is a very important finding in the aggregate 
for the American population. Now it is our task to take that 
bedside finding back to the bench to help understand on a 
molecular and cell biological basis why this is happening.
    Back on the AMD networks, we are proceeding with that. 
Applications are coming in, will be reviewed, and we hope that 
we will be able to successfully fund this venture.

                            AUTISM RESEARCH

    Senator Specter. Dr. Insel, with respect to autism, could 
you bring us up to date on the research activities of your 
department and what success you have had and what your 
projection is for the future?
    Dr. Insel. I would be happy to, Senator.
    We have in the past year launched a total of eight STAART 
centers. These are interdisciplinary centers to bring both a 
research effort and an intervention effort to autism. This is a 
program that will go over the next 4 to 5 years. It involves 
five of the institutes that are here today. It is, we think, a 
great national effort that will, by coordinating efforts across 
many different sites, lead to some very new insights into this 
troubling and still very mysterious illness.
    Senator Specter. We have quite a number of questions for 
the record. We very much appreciate your coming. We appreciate 
even more the outstanding work you are doing. We are committed 
to doing our utmost to help you on the funding. When the other 
research entities come forward with their requests, it 
continues to be my view that it is a very, very solid capital 
investment for the United States and we will continue to push 
on all lines.
    Anything further, Senator?

                     SPINAL MUSCULAR ATROPHY (SMA)

    Senator Harkin. Yes, just one thing, Mr. Chairman.
    Dr. Landis, on the SMA issue and what you are sending up to 
us, I tried to listen to your answer, but would you also look 
ahead as to how soon we might be going to clinical trials, and 
what the--I hate to use the word ``Roadmap'' but what that time 
line might be?
    Dr. Landis. We would be pleased to do that. The projection 
is 4 years for this new initiative to come to fruition with 
optimally selected compounds, but I will certainly give you a 
detailed answer.
    Senator Harkin. I will take a look at that.

                      TRANS-NIH OBESITY TASK FORCE

    Back on the issue of obesity, I met with Dr. Gerberding 
last week at CDC. They have said that now it may be surpassing 
tobacco usage as the biggest health menace that we face as 
Americans. Again, I am wondering how, Dr. Zerhouni, you are 
approaching this in terms of NIH's role in looking at obesity.
    Again, it always seems to me that it is easier for people 
who have never been obese to not be obese than it is for 
someone who becomes obese to lose weight and hold it down. That 
is just the facts.
    So how do we prevent it in the first place? It seems to me 
that one of the links in child health, Dr. Alexander, as kids 
develop and as they learn and grow--it seems to me some 
research ought to be done on that, what hkids eat and how they 
develop. And there may be some genetic problems too. I do not 
know. Dr. Collins could be involved in that.
    I guess what I am getting at is this seems to lend itself 
to some kind of an inter-institute kind of task force to look 
at how we get to the prevention end of it, not just to the 
cure, but what are some of the forces that might go into 
preventing this in the first place.
    Dr. Zerhouni. You are absolutely correct, Senator. As I 
indicated to you in the past through this graph, NIH started 
investing in obesity 10 years ago. But more importantly is the 
relevancy of the question you are asking. Last year I asked 
that we form a trans-NIH Obesity Task Force that is led by Dr. 
Spiegel. This year we are going to increase funding in obesity 
research by 10 percent. Here on the screen I can actually show 
you what that 10 percent is going to be related to [see figure 
3]: $3.5 million will be the prevention and treatment of 
childhood obesity in primary care settings; $3.5 million will 
be site-specific approaches to prevent and treat pediatric 
obesity.



    In a nutshell, we are going to focus on the aspects of 
prevention and understanding the evidence that we need to, in 
fact, stop the leading edge of the epidemic which is, we agree, 
in childhood. The earlier we intervene, the more likely we are 
to dampen the epidemic as we see it. So we are focusing those 
efforts exactly on that. We are widening our portfolio. We have 
quadrupled our investment on obesity research because we knew 
already a while back that it would become a public health 
problem.
    In addition to that, the other part of the new plan, which 
is on the web site, is receiving public comment, which is 
related to exactly what you are asking, this trans-NIH view, 
the other end of the spectrum is most of the diseases that are 
developed because of obesity are what we call comorbidities, 
diabetes, hypertension. Those are the ones that really hit the 
patients hard. Those do not occur to the same degree at every 
level of overweight. They occur disproportionately in the very 
morbid, high obesity patient with a BMI index of 33, 34, 35. So 
the other component of our strategy is to look at the front 
end, children, and look at those who are very likely to develop 
the co-morbidities and understand how you stop obesity from 
giving diabetes to patients and what is the relationship there, 
what is the relationship with hypertension, and so on.
    Dr. Spiegel, who is leading the trans-NIH task force, will 
be happy to provide you more detailed information. But we agree 
with you. It is a multi-prong strategy that we need to 
implement across all Federal Departments and NIH needs to 
attack now the leading edge and the trailing edge of what we 
know are the most important points of action that we should 
take.
    Senator Harkin. Well, I appreciate it. From my own 
standpoint, it is the leading edge is where you ought to focus. 
I hope what I am not hearing, Mr. Chairman, is that somehow or 
other we are going to do research into finding out how you can 
be obese, but we can have some kind of blockers to keep you 
from getting diabetes. I think more research ought to be into 
the front end to keep you from getting obese in the first 
place. That is my unscientific statement on that.
    Thank you.
    Dr. Zerhouni. Thank you, Senator.
    Senator Specter. Thank you, Senator Harkin. Thank you all 
very much.

                      PREPARED STATEMENT RECEIVED

    We have received the prepared statement of Senator Mary L. 
Landrieu which will be placed in the record.
    [The statement follows:]

             Prepared Statement of Senator Mary L. Landrieu

    Thank you, Mr. Chairman. Thank you, Dr. Zerhouni, for joining us 
today to discuss the National Institutes of Health (NIH) and its 2005 
budget, as proposed by the President. The National Institutes of Health 
are an integral component to our nation's health and safety. Within the 
twenty-seven Institutes and Centers at the National Institutes of 
Health, research is being conducted and studies are beginning to show, 
new and exciting ways to prevent, detect, diagnose, and treat the 
diseases and disabilities which plague our country and the world. 
Fostering communication and collaboration, the National Institutes of 
Health provide grant and research opportunities to universities, 
medical schools, hospitals, and other research institutes in addition 
to conducting their own federal research. Through these collaborations, 
the National Institutes of Health position themselves as the world's 
foremost medical research center and the focal point for domestic 
medical research.
    The President's fiscal year 2005 budget request provides $28.8 
billion for the National Institutes of Health. This number represents 
an increase of $764 million, or 2.7 percent, over fiscal year 2004 
levels. As a member of the Senate Appropriations Subcommittee on Labor, 
Health, Human Services and Education, I was proud to lend my support to 
doubling the National Institutes of Health budget in just five years. 
By steadfastly keeping the National Institutes of Health funding on 
track, my colleagues and I enabled the National Institutes of Health to 
support far more promising research than it was ever able to before, 
and to advance into new areas of science. While I am very proud of this 
aggressive increase and commitment to funding, we must not fall back on 
our commitment to medical research.
    Research at the National Institutes of Health has a real and direct 
impact on my state of Louisiana. The Centers for Disease Control and 
Prevention (CDC) reports that 9,306 people have been affected by the 
West Nile Virus in the United States this year. 240 of those infected 
have died. Of those cases, the state of Louisiana has reported 123 
cases and 8 deaths this year. Mosquito-borne diseases, such as the West 
Nile Virus, represent one of the most serious and preventable public 
health threats for many states. With the recent outbreak of the West 
Nile Virus in the United States, the National Institute of Allergy and 
Infectious Diseases at the National Institutes of Health have 
accelerated their research efforts into the West Nile Virus, possible 
vaccines, and treatment options. We have not yet developed a vaccine to 
combat the West Nile Virus but with the proper funding, researchers at 
NIH are committed to finding one.
    In addition to West Nile, Louisianians also find themselves 
battling another deadly epidemic, obesity. Currently in the United 
States there are 127 million adults that are overweight, 60 million of 
whom are obese, and 9 million who are severely obese. For children ages 
6-11, 30.3 percent are overweight and 15.3 percent are obese. These 
numbers have more than doubled in the last thirty years. This epidemic 
threatens the health of our Nation and increases the incidence of type 
2 diabetes, fatty liver disease, kidney failure, as well as many other 
diseases. I am pleased to learn that the fiscal year 2005 budget for 
the National Institutes of Health supports an expansion of $40 million 
to its obesity research portfolio but this is not nearly enough to 
reverse a trend of this magnitude. I hope that we can do more in the 
near future to end this epidemic. It is imperative that we work to 
understand the neurobiological, genetic, behavioral, and environmental 
basis of obesity and develop strategies to maintain healthy weight in 
adults and children.
    In conclusion, I would like to speak briefly about the flu epidemic 
that has recently taken a toll on our country and the global community. 
The CDC estimates that 10-20 percent of Americans come down with the 
flu each year. Of these numbers, more than 100,000 people are 
hospitalized and approximately 36,000 Americans die from the flu and 
its complications each year. While we have not experienced a flu 
pandemic since 1968, each fall and winter brings with it a new strain 
of the flu. Research institutions and health departments around the 
world are cooperating to track flu outbreaks and to determine the many 
different types, strains, and causes. The National Institute of Allergy 
and Infectious Diseases (NIAID) at NIH currently supports research into 
how the flu virus works and into developing better vaccines to prevent 
and treat the infection. By supporting this research at NIH we can hope 
to better track the development of flu strains and arm ourselves with 
the proper vaccines and treatments that will prevent deadly outbreaks.
    While these are but a few examples of the impact of NIH research on 
the state of Louisiana, I think they make it clear that the research 
being funded through the National Institutes of Health has a real and 
immediate impact on the citizens of our country. By wisely investing in 
medical research that advances the prevention and treatment of 
diseases, we in fact are saving money that would otherwise have to be 
used to diagnose and treat these diseases. I know that my colleagues 
agree that funding a cure is perhaps the best use of government 
resources there is. It is my hope that we will continue to increase the 
National Institutes of Health budget so that our children and 
grandchildren can truly benefit from the cures and medical advances 
made every day at NIH.

                     ADDITIONAL COMMITTEE QUESTIONS

    Senator Specter. 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 by Senator Herb Kohl
                                obesity

    Question. Dr. Crawford, both USDA and FDA have recently announced 
new efforts to combat the increasing problem of obesity. FDA announced 
the ``Calories Count'' program, and USDA has money in several programs, 
including WIC, to help battle this problem. However, for all of the 
government's efforts, all of the money being put into this effort pales 
in comparison to the food industry's billions of dollars worth of 
advertising. How can the government successfully get its message out 
when, at first glance, its efforts appear to be dwarfed by the food 
industry? How do your agencies compete with that?
    Answer. In support of the President's Healthier U.S. initiative, 
the DHHS established a complementary initiative, Steps to a Healthier 
U.S., which emphasizes personal responsibility for the choices 
Americans make for healthy behaviors. One aspect of this initiative 
focuses on reducing the major health burden created by obesity and 
other chronic diseases. Following DHHS' July 2003 Roundtable on Obesity 
and Nutrition, on August 11, 2003, FDA established an Obesity Working 
Group, or OWG, to prepare a report that outlines an action plan to 
cover critical dimensions of the obesity problem from FDA's perspective 
and authorities. This report was released on March 12, 2004.
    There is no simple answer to the problem of obesity. Achieving 
success in reducing and avoiding obesity will occur only as a result of 
efforts over time by individuals as well as various sectors of our 
society. It should be noted, however, that most associations, agencies, 
and organizations believe that diet and physical activity should be 
addressed together in the fight against overweight and obesity.
    The OWG report provides a range of short and long-term 
recommendations to address the obesity epidemic with a focus on a 
``calories count'' emphasis for FDA actions. These recommendations are 
based on sound science and address multiple facets of the obesity 
problem under FDA's purview, including developing appropriate and 
effective consumer messages to aid consumers in making wiser dietary 
choices; establishing educational strategies and partnerships to 
support appropriate messages and teach people, particularly children, 
how to lead healthier lives through better nutrition; developing 
initiatives to improve the labeling of packaged foods with respect to 
caloric and other nutrition information; encouraging and enlisting 
restaurants in efforts to combat obesity and provide nutrition 
information to consumers, including information on calories, at the 
point-of-sale; developing new therapeutics for the treatment of 
obesity; designing and conducting effective research in the fight 
against obesity; and continuing to involve stakeholders in the process.
    Regarding food labeling, the OWG report contains several 
recommendations based on sound science. I will provide these 
recommendations for the record.
    [The information follows:]
    Publish an advance notice of proposed rulemaking, or ANPRM, to seek 
comment on the following:
  --How to give more prominence to calories on the food label, for 
        example, increasing the font size for calories, including a 
        column in the Nutrition Facts panel of food labels for percent 
        Daily Value for total calories, and eliminating the listing for 
        calories from fat;
  --Whether to authorize health claims on certain foods that meet FDA's 
        definition of ``reduced'' or ``low'' calorie. An example of a 
        health claim for a ``reduced'' or ``low'' calorie food might 
        be: ``Diets low in calories may reduce the risk of obesity, 
        which is associated with type 2 diabetes, heart disease, and 
        certain cancers.''
  --Whether to require additional columns on the Nutrition Facts panel 
        to list quantitative amounts and percent Daily Value of an 
        entire package on those products and package sizes that can 
        reasonably be consumed at one eating occasion--or declare 
        quantitative amounts and percent Daily Value of the whole 
        package as a single serving if it can reasonably be consumed at 
        a single eating occasion; and,
  --Which, if any, reference amounts customarily consumed of food 
        categories appear to have changed the most over the past decade 
        and hence require updating.
    In addition, FDA will file and respond in a timely way to petitions 
the agency has received that ask FDA to define terms such as ``low,'' 
``reduced,'' and ``free'' carbohydrate; and provide guidance for the 
use of the term ``net'' in relation to carbohydrate content of food--
these petitions were filed on March 11, 2004.
    FDA will also encourage manufacturers to use dietary guidance 
statements, an example of which would be, ``To manage your weight, 
balance the calories you eat with your physical activity.'' In 
addition, the Agency will encourage manufacturers to take advantage of 
the flexibility in current regulations on serving sizes to label as a 
single-serving those food packages where the entire contents of the 
package can reasonably be consumed at a single eating occasion and 
encourage manufacturers to use appropriate comparative labeling 
statements that make it easier for consumers to make healthy 
substitutions.
    FDA believes that if the report's recommendations are implemented 
they will make a worthy contribution to confronting the nation's 
obesity epidemic and helping consumers' lead healthier lives through 
better nutrition.
    FDA also believes that the regulatory scheme for claims in food 
labeling, whether health claims, nutrient content claims, or other 
types of claims, are science based, and we continue to consider 
modifications to our regulations to keep up with recent scientific 
developments. A benefit of standardized, science-based terminology, as 
with other terms that FDA has defined that consumers may use to make 
health-based dietary choices--e.g., terminology concerning fat 
content--is that it allows consumers to compare across products and it 
encourages manufacturers to compete based on the nutritional value of 
the food. However, FDA does not regulate television and other media 
marketing of food products. Some of the modifications FDA is currently 
considering are described above in the list of topics to be covered by 
the ANPRM the agency intends to issue.
    With respect to conveying the report's messages to the public, FDA 
believes that all parties, including the packaged food industry, 
restaurants, academia, and other private and public sector 
organizations in addition to government agencies at all levels, have an 
essential role to play. On April 22, 2004, FDA's Science Board focused 
on specific recommendations from the OWG report. These recommendations 
call on FDA to work through a third-party facilitator to engage all 
involved stakeholders in a dialogue on how best to construct and convey 
obesity messages in the restaurant setting and in the area of pediatric 
obesity education.
    This approach is one example of how the Agency intends, by means of 
public and private partnerships, to leverage its ability to convey 
appropriate messages on obesity to the public with the goal of changing 
behavior and ultimately reversing obesity trends in the United States.

                           IMPORT INSPECTIONS

    Question. Dr. Crawford, the FDA budget this year includes a $7 
million increase to fund 97,000 food import examinations. This is a big 
increase in inspections over any previous year--still, however, less 
than one percent of all of the food imported into this country will be 
inspected. How would you respond to charges that you still aren't 
inspecting nearly enough imported food, especially in light of events 
during the past year where bad food has gotten in and people have died? 
How do we ensure consumers that their food is indeed safe?
    Answer. FDA is appreciative of the additional funding we have 
received for the inspection of domestic firms and for inspections of 
imported foods. FDA believes it is more effective to focus our 
resources in a risk-based manner than to focus simply on increasing the 
percentage of imported food shipments that are physically inspected. It 
is important to note that every shipment of FDA-regulated food which is 
entered through Customs and Border Protection as a consumption entry is 
electronically reviewed by FDA's Operational and Administrative System 
for Import Support to determine if it meets identified criteria for 
further evaluation by FDA reviewers and physical examination and/or 
sampling and analysis or refusal. This electronic screening allows FDA 
to concentrate its limited inspection resources on high-risk shipments 
while allowing low-risk shipments to proceed into commerce.
    Due to constantly changing environments of operation, e.g., 
counterterrorism and BSE, our domestic inspection and import strategy 
cannot be defined in terms of a percentage of coverage through 
inspections, physical examinations and sample analyses. It needs to be 
a flexible blend of the use of people, technology, information and 
partnerships to help protect Americans from unsafe imported products. 
Accordingly, the Agency is developing and using strategies for 
mitigating risks prior to importation through partnerships and 
initiatives based on best practices and other science based factors 
relevant to the import life cycle, i.e., from foreign manufacturer to 
the U.S. consumer. Recently this principle has been applied in the 
``Canadian Facility Voluntary Best Management Practices for Expediting 
Shipments of Canadian Grains, Oilseeds and Products to the United 
States'' implemented February 24, 2004, and designed to mitigate the 
potential of mammalian protein prohibited from being fed to cattle or 
other ruminants under BSE-prevention regulations promulgated by CFIA 
and FDA.
    Another piece of the long term solution to a higher level of 
confidence in the security and safety of food products lies in 
information technology that will merge information on products and 
producers with intelligence on anticipated risks to target products for 
physical and laboratory examination or refusal. This strategy would 
rely on data integrity activities that reduce the opportunity for 
products to be incorrectly identified at ports. It would also rely on 
cooperation from producers so that FDA can identify sources that are 
unlikely to need physical testing. However, even with such targeting, 
improvements are limited by the available methodologies for assessing 
threat agents and our ability to predict which tests ought to be used.
    We are ramping up our food inspections, but we recognize that we 
also need to inspect smarter, not just inspect more. That is why FDA is 
making significant investments in technology and information resources 
such as the development of the Mission Accomplishment and Regulatory 
Compliance Services System, MARCS. MARCS is a comprehensive redesign 
and reengineering of two core mission critical systems at FDA: FACTS 
and the Operational and Administrative System for Import Support, 
OASIS. OASIS supports the review and decision making process of 
products for which entry is sought into the United States. We are using 
funds to work to further improve targeting and using force multipliers 
such as IT.
    FDA also has a proof of concept project, called ``Predict,'' with 
New Mexico State University under a Department of Defencse contract 
which is being designed to enhance agency capability to rapidly assess 
and identify import entries based on risk using relevant information 
from various sources including regulated industry, trade, other 
federal, State, and local entities, and foreign industry and 
governments. This project, if successful, will greatly enhance FDA's 
capability to be smarter in directing field activities on products of 
greater risk to public health and safety. The proof of concept project 
is projected to be completed in the Fall of 2004. The relentless growth 
in the volume of domestic as well as imported food products, which are 
increasingly in ``ready for consumer sale packaging.'' Food imports are 
now growing at 19 percent per year. FDA needs to use all the potential 
tools available to improve its efficiency in food security and safety 
coverage.
    In addition, FDA has several strategic initiatives to enhance 
safety. One of these is ``Agency Initiatives to Improve Coverage,'' 
which includes the creation of the Southwest Import District to better 
coordinate import activities on the southern border. Another is 
reciprocal FDA and U.S. Customs and Border Protection training to 
improve product integrity of goods offered for import and increase 
enforcement actions by Customs to deter willful violations of U.S. laws 
and regulations. While foreign inspections and border operations 
provide some assurance that imported foods are safe, the agency 
continues to work to foster international agreements and harmonize 
regulatory systems. For instance, we actively participate in the 
Canada/U.S./Mexico Compliance Information Group, which shares 
information on regulatory systems and the regulatory compliance status 
of international firms to protect and promote human health.
    It is very important that American consumers trust the safety of 
the food supply. FDA has made fundamental changes in how we implement 
our mission of protecting the food supply, so that all Americans can 
have confidence that their food has been handled under secure 
conditions that provide assurance of its safety.

                           FDA FOIA POLICIES

    Question. Dr. Crawford, my office has been working with a non-
profit patient advocacy group, the TMJ Association, in their efforts to 
have two FOIA requests that are well over a year old responded to. 
Their original FOIA request was made on November 1, 2002 (request 
number 02017071), more than 17 months ago, and the subsequent request 
was made on March 25, 2003 (request number 03004361). They have not yet 
received the information requested, and have been unable to get a date 
commitment by FDA as to when the information will be provided. It is my 
understanding that they have been informed that FOIA requests are 
severely backlogged, and the FDA has no idea when they will be able to 
process their request. What is the current backlog for FOIA requests?
    Answer. As of April 28, 2004, FDA has 19,369 pending FOIA 
requests--17,555 have been pending more than 20 days and 1,814 have 
been pending 20 days or less. The Denver District Office is responsible 
for responding to the two requests from the TMJ Association. As of 
April 28, 2004, Denver District Office has 369 pending FOIA requests--
357 requests have been pending more than 20 days, and 12 requests have 
been pending 20 days or less.
    Question. How many FDA staff are responsible for handling these 
requests? Is this their sole responsibility, or do they have other 
responsibilities as well?
    Answer. For fiscal year 2003 the total number of personnel 
responsible for processing FOIA requests was 91 FTE, 75 full time 
employees, and 16 FTE work years representing personnel with part-time 
FOIA duties in addition to other responsibilities.
    Question. Does FDA need additional staff or resources in order to 
process these requests on a timely basis?
    Answer. In some agency components FOIA is a collateral duty. For 
example, in most FDA field offices, Compliance Officers whose primary 
responsibilities are related to the Agency's regulatory enforcement 
activities also perform FOIA duties as permitted by time and regulatory 
workload. Additional staff devoted to FOIA could shorten the amount of 
time for processing requests.
    Question. What do you believe is a reasonable length of time for a 
group to wait for an information request to be processed and responded 
to?
    Answer. Requests are processed by the agency component that 
maintains the requested records. There are a number of factors that 
must be considered in order to predict a reasonable amount of time for 
a request to be processed. Those factors include the volume of requests 
received by the component, the complexity of requests received, the 
amount of time required to search for records, the amount of time 
require to review the records to determine whether information is 
releasable under FOIA, and the resources available to process requests.
    Question. What is the average length of time it takes to process a 
FOIA request? Can you please explain the severe delay in processing 
this specific one, which has taken over two years and apparently has no 
end in sight? Can you please provide me a timeframe within which the 
FDA will respond to these two particular FOIA requests?
    Answer. Under the Electronic Freedom of Act Amendments of 1996, 
agencies are permitted to establish multiple tracks for processing FOIA 
requests based on the complexity of the requests and the amount of work 
and time required to process requests. Some FDA components have 
established multiple processing tracks. Requests are processed on a 
first in, first out basis within each track. The median number of days 
to process requests in the simple processing track is 19 days. The 
median number of days to process requests in the complex processing 
track, for more complicated requests, is 363 days. For requests that 
are not processed in multiple processing tracks, the median number of 
days to process is 44 days.
    Due to a heavy load of regulatory cases in the Denver District 
Office that must be handled by the Compliance Officers in addition to 
staff shortages, FOIA work in the Denver District is being performed by 
one individual on a part-time basis. This has resulted in a significant 
backlog of FOIA requests. The Denver District Office expects to fill 
request 02-17071 from the TMJ Association in six months, and request 
03-4361 in one month.
    Question. What additional efforts can this group undertake in order 
to speed up their request?
    Answer. The Denver District Office expects to fill request 02-17071 
from the TMJ Association in six months, and request 03-4361 in one 
month.
    In addition, the Denver District is reviewing and evaluating its 
FOIA workload and will develop a strategy aimed at reducing the backlog 
of FOIA requests.
    Question. What is the FDA's policy on charging for FOIA requests 
made by non-profit patient advocacy groups?
    Answer. The FOIA sets forth criteria that agencies must follow with 
respect to charging for processing FOIA requests. Non-profit 
organizations are considered Category III requesters. Such requesters 
receive 100 pages of duplication and two hours of search at no charge. 
If the number of pages exceed 100 and/or if the amount of search time 
exceeds two hours, Category III requesters are charged based on the 
FOIA fee schedule of the Department of Health and Human Services. The 
fee for duplication is $.10 per page, and the fee for search is based 
on the grade level of the individual who processes the request. I will 
be happy to provide the current grade rates for the record.
    [The information follows:]

                          CURRENT GRADE RATES

    GS-1 through 8--$18.00 per hour
    GS-9 through 14--$36.00 per hour
    GS-15 and above--$64.00 per hour
    In addition, requesters may make a request for waiver or reduction 
of fees if their request meets the following criteria: disclosure of 
the information is in the public interest because it is likely to 
contribute significantly to public understanding of the operations or 
activities of the Government; and, disclosure is not primarily in the 
commercial interest of the requester.

                          IMPLICIT PRE-EMPTION

    Question. Adverse reactions to prescription drugs and other 
medicines take the lives of more than 100,000 Americans each year, and 
millions more are seriously injured. For many years, state tort laws 
have enabled some victims to receive compensation for their injuries. 
It has been brought to my attention that the Food and Drug 
Administration (FDA) has stepped in to protect drug companies from 
liability in some of these lawsuits, potentially robbing individuals of 
their only means of compensation. FDA's actions are even more troubling 
when you consider that these lawsuits have other important purposes, 
such as deterring future bad behavior and providing the American public 
with access to important health and safety information. How many times 
has the FDA interfered in lawsuits, arguing that implicit pre-emption 
prohibits a plaintiff from receiving compensation for their injuries? 
In how many of these cases has a court held that the plaintiff's tort 
claim was implicitly pre-empted by federal law?
    Answer. In the past several years, the Department of Justice (DOJ) 
has represented the United States in four cases involving state-law 
challenges to the adequacy of FDA-approved risk information 
disseminated for FDA-approved new drugs.\1\ In each case, DOJ contended 
that the state-law claim was preempted by federal law. In addition, in 
some cases, DOJ argued that the state-law claim was not properly before 
the court by operation of the doctrine of primary jurisdiction.\2\
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    \1\ FDA also periodically becomes involved, through the Department 
of Justice, in cases involving preemption of state-law requirements 
under the medical device provisions of the FDCA, which include an 
express preemption provision, 21 U.S.C. 360k(a).
    \2\ Primary jurisdiction allows a court to refer a matter to an 
administrative agency for an initial determination where the matter 
involves technical questions of fact and policy within the agency's 
jurisdiction. See, e.g., Israel v. Baxter Labs., Inc., 466 F.2d 272, 
283 (D.C. Cir. 1972); see also 21 CFR 10.60.
---------------------------------------------------------------------------
    The legal basis for preemption in these cases is FDA's careful 
control over drug safety, effectiveness, and labeling according to the 
agency's comprehensive authority under the FDCA and FDA implementing 
regulations. If state authorities, including judges and juries applying 
state law, were permitted to reach conclusions about the safety and 
effectiveness information disseminated with respect to drugs for which 
FDA has already made a series of regulatory determinations based on its 
considerable institutional expertise and statutory mandate, the federal 
system for regulation of drugs would be disrupted. I will be happy to 
include information on the four cases for the record.
    [The information follows:]

Bernhardt
    In 2000, two individual plaintiffs filed product liability actions 
in a New York court against Pfizer, Inc., seeking a court order 
requiring the company to send emergency notices to users of the 
prescription antihypertensive drug CARDURA (doxazosin mesylate) and 
their physicians. The notices would have described the results of a 
study by a component of the National Institutes of Health (NIH) that, 
the plaintiffs alleged, demonstrated that Cardura was less effective in 
preventing heart failure than a widely used diuretic. FDA had not 
invoked its authority to send ``Dear Doctor'' letters or otherwise 
disseminate information regarding a drug that the agency has determined 
creates an ``imminent danger to health or gross deception of the 
consumer.'' (21 U.S.C. 375(b).) The plaintiffs, nevertheless, filed a 
lawsuit under state common law seeking relief that, if awarded, would 
have pressured the sponsor to disseminate risk information that FDA 
itself had not disseminated pursuant to its statutory authority.
    FDA's views were submitted to the federal district court in the 
form of a Statement of Interest.\3\ The Statement relied on the 
doctrine of primary jurisdiction. The Statement also took the position 
that the plaintiffs' request for a court order requiring the 
dissemination of information about NIH study results to users and 
prescribers of CARDURA was impliedly preempted. According to the 
Statement, the court order ``would frustrate the FDA's ability 
effectively to regulate prescription drugs by having the Court 
substitute its judgment for the FDA's scientific expertise.'' The 
Statement also noted that, if the court granted the requested order, a 
direct conflict would be created between the information required to be 
disseminated by the court and the information required to be 
disseminated by FDA under the FDCA (in the form of the FDA-approved 
labeling).
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    \3\ Statement of Interest of the United States; Preliminary 
Statement, Bernhardt v. Pfizer, Inc., Case No. 00 Civ. 4042 (LMM) 
(S.D.N.Y. filed Nov. 13, 2000).
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    The Statement contended that state law could not provide a basis 
for requiring a drug manufacturer to issue drug information that FDA 
had authority to, but did not, require. Importantly, the submission did 
not argue that the state-law claim was preempted because FDA had 
reached a determination that directly conflicted with the plaintiff's 
view. Nor did it assert that FDA had specifically determined that the 
information on the NIH study requested by the plaintiffs was 
unsubstantiated, false, or misleading. In this sense, the Statement of 
Interest in Bernhardt was the most aggressive, from a legal 
perspective, than the three subsequent DOJ submissions on FDA's behalf 
in preemption cases made during the present Administration.
    The United States District Court for the Southern District of New 
York accepted the primary jurisdiction argument made on FDA's behalf. 
(Bernhardt v. Pfizer, Inc., 2000 U.S. Dist. LEXIS 16963, *9 (whether 
the additional warnings sought by the plaintiffs were appropriate ``is 
a decision that has been squarely placed within the FDA's informed 
expert discretion'')). It did not address the preemption issue. The 
case was voluntarily dismissed on April 22, 2003.

Dowhal
    In 1998, an individual plaintiff in California asked that State's 
attorney general to initiate an enforcement action against SmithKline 
Beecham and other firms marketing OTC nicotine replacement therapy 
products in California. (These products are marketed pursuant to an 
approved new drug application.) The plaintiff contended that the FDA-
approved warnings for the defendants' products did not meet the 
requirements of a state statute called the Safe Drinking Water and 
Toxic Enforcement Act (Cal. Health & Safety Code  25249.5 et seq.), 
also known as Proposition 65. From 1996 through 2001, FDA had 
repeatedly advised the defendants that they could be liable under the 
FDCA for selling misbranded products if they deviated from the FDA-
approved warning labeling for their products. FDA also advised the 
state attorney general in writing in 1998 that the defendants' warning 
in the labeling clearly and accurately identified the risks associated 
with the products and, therefore, met FDA requirements under the FDCA. 
After receiving the letter, the attorney general declined to initiate 
enforcement action.
    Nevertheless, in 1999, the individual plaintiff initiated a lawsuit 
of his own in California state court under Proposition 65's ``bounty-
hunter'' provision, which empowers individuals to file enforcement 
actions under that statute on behalf of the people of the State of 
California. The lawsuit asked the court to award civil money penalties 
and restitution, and to issue an injunction requiring the defendants to 
disseminate warnings for their products that differed from the warnings 
required by FDA. In 2000, the plaintiff filed a citizen petition with 
FDA requesting that the agency require the defendants to change their 
warnings to reflect the language sought by the plaintiff in the 
lawsuit. FDA rejected the proposed language, determining that it lacked 
sufficient support in scientific evidence and presented a risk of 
mischaracterizing the risk-benefit profile of the products in a way 
that threatened the public health. Although the trial court found for 
the defendant, the California Court of Appeal rejected the defendant's 
contention that the plaintiff's claim was preempted under the FDCA, and 
allowed the lawsuit to proceed. (Dowhal v. SmithKline Beecham Consumer 
Healthcare, 2002 Cal. App. LEXIS 4384 (Cal. Ct. App. 2002), argued, 
Case No. S-109306 (Cal. Feb. 9, 2004).)
    FDA's views were presented to the Court of Appeal of California in 
an amicus curiae (``friend of the court'') brief and to the Supreme 
Court of California in a letter brief and an amicus brief.\4\ All three 
documents explained that the warning language sought by the plaintiffs 
had been specifically considered and rejected by FDA as scientifically 
unsubstantiated and misleading. Including the language would, 
therefore, misbrand those products and cause the defendants to violate 
the FDCA. The documents explained, further, that principles of conflict 
preemption applied to the plaintiffs' claim because it was impossible 
for defendants to comply with both federal and state law and because 
the state law posed an obstacle to the accomplishment of the full 
purposes and objectives of the FDCA.
---------------------------------------------------------------------------
    \4\ Letter from Robert D. McCallum, Jr., Ass't Attorney General, et 
al., to Frederick K. Ohlrich, Supreme Court Clerk/Administrator, Dowhal 
v. SmithKline Beecham Consumer Healthcare LP, et al., Case No. S-109306 
(Cal. filed Sept. 12, 2002); Amicus Curiae Brief of the United States 
of America in Support of Defendants/Respondents SmithKline Beecham 
Consumer Healthcare LP, et al., Dowhal v. SmithKline Beecham, Case No. 
A094460 (Cal. Ct. App. filed Mar. 22, 2002); Amicus Curiae Brief of the 
United States of America in Support of Defendants/Appellants SmithKline 
Beecham Consumer Healthcare LP, et al., Dowhal v. SmithKline Beecham, 
Case No. S109306 (Cal. filed July 31, 2003).
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    The California Court of Appeal rejected the preemption argument. 
(Dowhal v. SmithKline Beecham Consumer Healthcare, 2002 Cal. App. LEXIS 
4384, ***16-17 (Cal. Ct. App. 2002) (reversing trial court decision 
granting summary judgment for defendants on preemption grounds)). On 
April 15, 2004, the California Supreme Court reversed the appeals court 
decision, finding a direct conflict between FDA requirements and the 
state-law warning requirement advocated by the plaintiff. (Dowhal v. 
SmithKline Beecham Consumer Healthcare, 2004 Cal. LEXIS 3040.)
Motus
    Also in 2000, an individual plaintiff sued Pfizer in a California 
court alleging, among other things, that the company had failed to 
fulfill its state common law duty to warn against the risk of suicide 
the plaintiff alleged was presented by ZOLOFT (sertraline HCl), an FDA-
approved drug in the selective serotonin reuptake inhibitor (SSRI) 
class indicated to treat depression (among other things). On numerous 
occasions, FDA had specifically considered and rejected such language 
for SSRIs as scientifically unsupportable and inconsistent with FDA 
determinations as to the safety and effectiveness of the products.
    The United States District Court for the Central District of 
California (to which the case had been removed on the ground of 
diversity) rejected the defendant's preemption argument, allowing the 
lawsuit to proceed. (Motus v. Pfizer Inc., 127 F. Supp. 2d 1085 (C.D. 
Cal. 2000).) The court later granted the defendant's motion for summary 
judgment on non-preemption grounds (196 F. Supp. 2d 984, 986 (C.D. Cal. 
2001)), and the plaintiff appealed. DOJ submitted an amicus curiae 
brief to the United States Court of Appeals for the Ninth Circuit on 
FDA's behalf.\5\ The brief's arguments were essentially the same as the 
arguments advanced in Bernhardt. In contrast to the situation in 
Bernhardt, however, in Motus, FDA had specifically considered, and 
rejected, the language requested by the plaintiff under state law. The 
appeals court affirmed the trial court's decision earlier this year 
(2004 U.S. App. LEXIS 1944 (9th Cir. February 9, 2004)).
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    \5\ Amicus Brief for the United States in Support of the Defendant-
Appellee and Cross-Appellant, and in Favor of Reversal of the District 
Court's Order Denying Partial Summary Judgment to Defendant-Appellee 
and Cross-Appellant, Motus v. Pfizer, Case Nos. 02-55372 & 02-55498 
(9th Cir. filed Sept. 3, 2002).
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In re PAXIL
    In 2001, individuals filed suit in a California court on behalf of 
past or current users of PAXIL (paroxetine HCl) against the drug's 
manufacturer, GlaxoSmithKline (GSK), alleging that the company's 
direct-to-consumer (DTC) broadcast advertisements for the drug failed 
adequately to warn about the consequences of discontinuing the drug. In 
reviewing the new drug application for the drug, FDA had found no 
evidence that it was habit-forming and did not require GSK to address 
that risk in FDA-approved labeling. FDA did, however, require GSK to 
include in labeling statements regarding discontinuation syndrome, and 
the labeling consequently recommends that doctors gradually reduce 
dosages and monitor patients for syndrome symptoms. FDA reviewed 
proposed DTC advertisements GSK had submitted for Paxil that said that 
the drug was not habit-forming. The agency at no time determined that 
this statement was misleading. In August 2002, notwithstanding FDA's 
determination, the court issued a preliminary injunction prohibiting 
GSK from running DTC advertisements stating that Paxil is not habit-
forming. (In re Paxil Litigation, 2002 U.S. Dist. LEXIS 16221 (C.D. 
Cal. Aug. 16, 2002))
    On reconsideration, the court declared that the preliminary 
injunction challenged only ``FDA's . . . determination that the public 
is not likely to equate the words not habit forming' as used in 
direct[-]to[-]consumer advertisements with no withdrawal symptoms.''' 
According to the court, ``The question of how members of the general 
public are likely to interpret (or misinterpret) a statement is within 
one of the courts' core competencies.'' Declaring itself ``unwilling to 
blindly accept FDA's ultimate determination here,'' the court rejected 
the defendants' preemption and primary jurisdiction arguments. It 
nevertheless denied the injunction on the ground that the plaintiff was 
not likely to succeed in demonstrating that ``non-habit forming'' 
statement in the advertisement is misleading. Thus, although the court 
ultimately declined to award the injunctive relief sought by the 
plaintiff, it continued to distinguish between FDA's determinations as 
to the adequacy of drug warnings under federal law, and its own view of 
warnings adequacy under state common law. (In re Paxil Litigation, 2002 
U.S. Dist. LEXIS 24621 (C.D. Cal. Oct. 16, 2002).)
    DOJ submitted to the court a Statement of Interest and a brief 
asserting preemption.\6\ The Statement of Interest contended that a 
court order requiring GSK to remove the ``non-habit-forming'' claim 
from its advertisements for Paxil would be inconsistent with FDA's 
determination that the company's advertisements were proper and that 
Paxil is not, in fact, ``habit-forming.'' The brief contended that the 
court should find the plaintiff's state-law request for a court order 
preempted because it poses an obstacle to achievement of the full 
objectives of Congress ``by attempting to substitute th[e] Court's 
judgment for FDA's scientific expertise.'' As the brief pointed out, 
FDA had specifically reviewed the advertisements, made suggestions 
concerning the proper manner of presenting information relating to 
whether Paxil is ``habit-forming,'' and, in the exercise of its 
scientific and medical expertise, found the advertisements acceptable. 
The brief also included a primary jurisdiction argument. The court 
reversed its earlier award of an injunction prohibiting the 
manufacturer from running advertisements that had been reviewed and 
approved by FDA, but the reversal was based on a ground other than 
preemption. (In re Paxil Litigation, 2002 U.S. Dist. LEXIS 24621 (C.D. 
Cal. 2002).) \7\
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    \6\ Statement of Interest of the United States of America, In re 
PAXIL Litigation, Case No. CV 01-07937 MRP (CWx) (C.D. Cal. filed 
August 20, 2002); Brief of the United States of America, In re PAXIL 
Litigation, Case No. CV 01-07937 MRP (CWx) (C.D. Cal. filed Sept. 4, 
2002).
    \7\ In December 2003 (296 F. Supp. 2d 1374), the litigation, 
consisting of twelve action in eleven federal judicial districts, was 
centralized for pretrial proceedings in the United States District 
Court for the Central District of California.
---------------------------------------------------------------------------
Conclusion
    As these cases illustrate, courts entertaining lawsuits filed under 
state law do not always defer to FDA on matters that Congress has 
placed squarely within the agency's authority. In FDA regulatory areas 
characterized by comprehensive regulation and requiring a careful and 
expert evaluation of scientific data and public health issues, state 
coregulation can stand as an obstacle to or directly conflict with the 
agency's administration of its statutory mandate. Preemption is the 
constitutionally prescribed mechanism for resolving these conflicts.
    The practice of citing preemption and primary jurisdiction under 
the FDCA in litigation in which the United States is not a party is 
well-established and substantially predates the current Administration. 
DOJ and FDA participation in these cases is unusual. In the current 
Administration, DOJ has participated in private state-law actions on 
FDA's behalf only following a judicial finding that the action should 
proceed, and only to address a state-law finding that, left 
undisturbed, would undermine FDA's execution of its statutory mission 
or directly conflict with federal law. Responsibility for making final 
decisions whether to make submissions in private lawsuits, on 
preemption, primary jurisdiction, or any other issue, rests with the 
Department of Justice--not FDA itself.
    Question. These arguments conflict with long-standing FDA policy. 
The law appears to contradict what the FDA has argued. What motivated 
FDA to change its policy?
    Answer. The Government's participation in cases arising under 
state-law and presenting preemption issues is consistent with past FDA 
practice and with the pertinent law.
    The principal enabling statute of the Food and Drug Administration 
is the Federal Food, Drug, and Cosmetic Act, FDCA. Under this statute, 
FDA has broad authority to protect the public health by ensuring that 
foods are safe, wholesome, sanitary, and properly labeled, and that 
drugs and medical products are safe and effective. (See 21 U.S.C.  
393(b)(2)(A)-(C).) By operation of the Supremacy Clause of the United 
States Constitution (U.S. Const. Art. VI, clause 2), the FDCA nullifies 
conflicting requirements established by the States in legislation, 
regulations, or common law. (See Gibbons v. Ogden, 22 U.S. (9 Wheat.) 
1, 211 (1824) (Marshall, C.J.).)
    In the past, FDA has addressed conflicting state requirements in 
the context of rulemaking. In 1982, for example, FDA promulgated 
regulations requiring tamper-resistant packaging for over-the-counter 
drugs. In the preamble accompanying the regulations, FDA stated its 
intention that the regulations preempt any state or local requirements 
that were ``not identical to . . . [the rule] in all respects.'' (47 FR 
50442, 50447; Nov. 5, 1982.) Similarly, in 1986, FDA issued regulations 
requiring aspirin manufacturers to include in labeling a warning 
against use in treating chicken pox or flu symptoms in children due to 
the risk of Reye's Syndrome. In the accompanying preamble, FDA said the 
regulations preempted ``State and local packaging requirements that are 
not identical to it with respect to OTC aspirin-containing products for 
human use.'' (51 FR 8180, 8181; Mar. 7, 1986.) In 1994, FDA amended 21 
CFR 20.63 to preempt state requirements for the disclosure of adverse 
event-related information treated as confidential under FDA 
regulations. (59 FR 3944; Jan. 27, 1994.)
    In addition, for many years, conflicting state requirements have 
been addressed by FDA through case-by-case participation in selected 
lawsuits to which the United States has not been a party. Because FDA 
lacks independent litigating authority, this participation has been by 
the Department of Justice (DOJ) on FDA's behalf. The practice of 
addressing conflicting state requirements through participation in 
litigation dates back many years. For example, DOJ participated on 
FDA's behalf in favor of preemption in both Jones v. Rath Packing 
Company, 430 U.S. 519 (1977), and Grocery Manufacturers of America, 
Inc. v. Gerace, 755 F.2d 993 (2d Cir. 1985). In addition, as discussed 
in our response to the previous question on preemption, FDA has 
recently participated in several cases involving state-law requirements 
for the communication of risk information for prescription drugs. Of 
note, the first--and most aggressive, from a legal perspective--of 
these submissions occurred during the previous Administration--
Bernhardt case included in materials for the record.

                                 NARMS

    Question. What is the total amount of funding for NARMS, and from 
what account does it come?
    Answer. The total amount of funding for NARMS in fiscal year 2004 
is $7.634 million. This funding is located in the Salaries and 
Expenses, or S&E, account.
    Question. How much is FDA giving to USDA and CDC in fiscal year 
2005? How does that compare to fiscal year 2004? Please describe what 
factors are used to determine the division of funds.
    Answer. At this time, FDA has not determined the exact funding for 
CDC and USDA for NARMS for fiscal year 2005 but plans to make decisions 
by Fall 2004. In fiscal year 2004, FDA funding on NARMS will be reduced 
due to government-wide rescissions. In fiscal year 2004, FDA provided 
funds of approximately $1.6 million to USDA and $2 million to CDC. It 
is important to point out that a large portion of the funds provided to 
CDC is given to the states for the collection, isolation and 
identification of bacterial isolates, which are then shipped to CDC and 
the Food and Drug Administration's Center for Veterinary Medicine--
NARMS retail arm--for susceptibility testing. In determining the funds 
provided to CDC and USDA, we analyze the entire NARMS program, 
including the retail food arm of NARMS, and strive to fill in data gaps 
and avoid duplication of organisms to be tested.
    Question. How much NARMS money is currently being spent in foreign 
countries, specifically Mexico? How is this money being used?
    Answer. FDA is not spending any current year NARMS funding in 
Mexico or other foreign countries.
    Question. Does USDA or CDC spend any of their NARMS money in 
foreign countries?
    Answer. In fiscal year 2004 FDA is providing USDA and CDC, $1.6 
million and $2 million respectively. FDA does not keep detailed records 
of USDA and CDC funding for NARMS.

                           COUNTERFEIT DRUGS

    Question. In February, FDA released a report on combating 
counterfeit drugs. Several new technologies were mentioned that could 
be used to this effect, including Radiofrequency Identification 
tagging, color shifting inks, and holograms. Specifically regarding 
color shifting inks, which I understand are currently available, has 
FDA taken any action, or do you have any plans to pursue this option?
    Answer. It is true that color shifting ink technology is currently 
available for use on drug packaging and labeling. However, we heard 
uniformly from all stakeholders that this technology is expensive and 
requires significant investment of resources and time prior to 
implementation. Due to the wide variety of products, packaging, and 
labeling on the market, we heard from manufacturers, wholesalers, and 
retailers that the decision to use color shifting inks, or any other 
authentication technology, should be made by the manufacturer after a 
manufacturer initiated product risk assessment. Without such an 
analysis, use of color-shifting ink, or other authentication 
technology, could lead to an unnecessary increase in the cost of drugs 
to consumers. For example, we heard that color-shifting ink could be 
appropriate for use on a very expensive, high volume brand name drug 
product that is likely to be counterfeited, but not on a generic or low 
volume drug product that is less likely to be counterfeited.
    Based on our discussions with manufacturers, we estimate that it 
would take a minimum of six to twelve months to implement a technology 
such as color shifting ink from the time a decision is made to use the 
authentication technology on the packaging and/or labeling of a drug 
product. It could take longer if the technology, e.g., color-shifting 
ink, is used on the product itself because safety studies might have to 
be performed to ensure that the technology, e.g., the ink, does not 
affect the safety or stability of the product.

                        ANIMAL DRUG COMPOUNDING

    Question. Dr. Crawford, on February 10, I submitted a letter to Dr. 
McClellan regarding FDA's new Compliance Policy Guidelines, issued July 
14, 2003, regarding animal drug compounding. I received a response from 
FDA on March 31st, and I thank you for that. However, I do have a few 
more questions in light of the response.
    First, the letter stated that FDA issued the CPG for immediate 
implementation because of the ``urgent need to explain how it intended 
to exercise its enforcement discretion regarding compounded drugs for 
animal use in light of Thompson v. Western States Medical Center.'' 
However, this case dealt only with compounding in human drugs, not 
animal drugs. How does this create an urgent need to deal with animal 
drugs?
    Answer. After the Western States decision, FDA revised its 
enforcement policy on pharmacy compounding of human drugs. FDA was 
concerned that without updated guidance regarding compounding of animal 
drugs, the public would remain uncertain about whether and how FDA 
would change its enforcement policy with respect to compounded animal 
drugs. In addition, agency staff would lack clear guidance on 
enforcement matters.
    As FDA stated in its letter, although prior public comment was not 
sought in this case, pursuant to the good guidance practices 
regulations the public was invited to comment on the CPG when it was 
issued and may comment on it at any time (68 FR 41591 (July 14, 2003)). 
FDA has been reviewing those comments and will revise the guidance as 
appropriate upon completion of our review.
    Question. Second, the response states that two federal appeals 
court decisions have held that ``the Federal Drug & Cosmetic Act does 
not permit veterinarians to compound unapproved finished drugs from 
bulk substances, unless the finished drug is not a new animal drug. 
These cases support FDA's position that new animal drugs that are 
compounded from bulk substances are adulterated under the FD&C Act and 
may be subject to regulatory action.'' I have been informed that the 
cases cited deal only with veterinarians compounding drugs, not 
pharmacists. Why do you limit pharmacists as well as veterinarians? Is 
this supported by any congressionally-enacted statutory authority, 
legislative history or case law?
    Answer. The principle established by the courts applies equally to 
compounding by pharmacists and veterinarians.
    Veterinary medicine has not traditionally utilized the services of 
compounding pharmacies to the extent that they have been utilized 
within human medicine. The increasing activities and presence of 
compounding pharmacies in veterinary medicine is a relatively recent 
development.
    The Federal Food Drug and Cosmetic Act, or ``the Act'', and its 
implementing regulations do not exempt veterinarians or pharmacists 
from the approval requirements in the new animal drug provisions of the 
Act, 21 U.S.C. Section 360b. In the absence of an approved new animal 
drug application, the compounding of a new animal drug from any 
unapproved drug or from bulk drug substances results in an adulterated 
new animal drug within the meaning of section 21 U.S.C. Section 
351(a)(5). The compounding of a new animal drug from an approved human 
or animal drug also results in an adulterated new animal drug within 
the meaning of 21 U.S.C. Section 351(a)(5), unless the conditions set 
forth in 21 CFR 530.13(b) relating to extralable use are met.
    FDA is concerned about veterinarians and pharmacists that are 
engaged in manufacturing and distributing unapproved new animal drugs 
in a manner that is clearly outside the bounds of traditional pharmacy 
practice and that violates the Act--such as compounding that is 
intended to circumvent the drug approval process and provide for the 
mass marketing of products that have been produced with little or no 
quality control or manufacturing standards to ensure the purity, 
potency, and stability of the product.
    Pharmacists and veterinarians who engage in activities analogous to 
manufacturing and distributing drugs for use in animals may be held to 
the same provisions of the Act as manufacturers.
    Question. Finally, the final paragraph of the FDA response states 
``Accordingly, the regulations that implement AMDUCA provide that 
extralabel use by compounding applies only to compounding of a product 
from approved drugs, and that nothing in the regulations is to be 
construed as permitting compounding from bulk drugs.'' Is there in the 
agency's view anything in AMDUCA's regulations or the Act that is to be 
construed as not permitting compounding from bulk substances?
    Answer. As previously noted, under the Federal Food, Drug and 
Cosmetic Act, in the absence of an approved new animal drug 
application, the compounding of a new animal drug from a bulk substance 
results in a new animal drug that is adulterated as a matter of law. 
This has been FDA's longstanding position, which is supported by two 
federal appeals court decisions, United States v. Algon Chemical Inc., 
879 F.2d 1154 (3d Cir. 1989) and United States v. 9/1 Kg. Containers, 
854 F.2d 173 (7th Cir. 1988).

                         CONCLUSION OF HEARINGS

    Senator Specter. Thank you all very much for being here. 
That concludes our hearings.
    [Whereupon, at 10:48 a.m., Thursday, April 1, the hearings 
were concluded, and the subcommittee was recessed, to reconvene 
subject to the call of the Chair.]
