[Senate Hearing 109-]
[From the U.S. Government Publishing Office]



 
DEPARTMENTS OF LABOR, HEALTH AND HUMAN SERVICES, EDUCATION, AND RELATED 
              AGENCIES APPROPRIATIONS FOR FISCAL YEAR 2006

                              ----------                              


                        WEDNESDAY, APRIL 6, 2005

                                       U.S. Senate,
           Subcommittee of the Committee on Appropriations,
                                                    Washington, DC.
    The subcommittee met at 9:30 a.m., in room SD-124, Dirksen 
Senate Office Building, Hon. Arlen Specter (chairman) 
presiding.
    Present: Senators Specter, Cochran, and Harkin.

                DEPARTMENT OF HEALTH AND HUMAN SERVICES

                     National Institutes of Health

STATEMENT OF ELIAS ZERHOUNI, M.D., DIRECTOR
ACCOMPANIED BY:
        DR. JAMES F. BATTEY, JR., M.D., Ph.D., DIRECTOR, NATIONAL 
            INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS
        DR. ANTHONY S. FAUCI, M.D., DIRECTOR, NATIONAL INSTITUTE OF 
            ALLERGY AND INFECTIOUS DISEASES
        DR. ANDREW VON ESCHENBACH, M.D., DIRECTOR, NATIONAL CANCER 
            INSTITUTE

               OPENING STATEMENT OF SENATOR ARLEN SPECTER

    Senator Specter. Good morning, ladies and gentlemen. The 
hour of 9:30 has--having arrived, we will proceed with the 
hearing of the Appropriations Subcommittee on Labor, Health and 
Human Services, Education. Today our hearing will focus on the 
work of the National Institutes of Health, which I have 
characterized as the crown jewel of the Federal Government, and 
perhaps the only jewel of the Federal Government.
    We have the distinguished director, Elias Zerhouni, Dr. 
Elias Zerhouni, with us today, and other members. We have in 
the past had all of the directors of the Institutes, and it is 
not realistic to hear from that number of witnesses, and 
knowing of the important work, we have decided this year to 
limit the witnesses to those who have presidential 
appointments. We have also included Dr. Battey because of some 
recent issues as to the new policy on ethics, which will be a 
subject of some of our discussion here today.
    Before proceeding further, just a word or two about my 
health. I have a lot of questions about my health. I had my 
fourth treatment last Friday and I am on the job. During the 2-
week recess when I could not travel abroad, I was in Washington 
most of the time, and aside from an involuntary new hair style, 
I'm accommodating to all of the rigors of the situation. I find 
that among all of the alternatives, the best alternative is to 
come to work and fight tigers, and we've got a lot of tigers 
around here, and fighting tigers is a great distraction and a 
great cure. So just that little bit of recommendation to the 
foremost scientists in the world, just how to handle one 
person's temporary medical problem.
    The work of the National Institutes of Health is a vital 
matter for America and for the world. Senator Harkin, who will 
be along in a few moments, and I, as is well known, have taken 
the lead on the increase in funding where we have moved from 
some $12 billion to $28 billion. This year the funding was 
almost flat, really not accommodating even inflation. Senator 
Harkin and I offered an amendment to add $1.5 billion to the 
budget resolution, which passed.
    It's been a long struggle. The first time we tried to add 
money to the budget resolution we lost 63 to 37, and we went 
back with a sharp pencil and established the priorities. That's 
become a virtual impossibility now with the very heavy demands 
on our subcommittee on education and health and community 
development block grants and many other items, and worker 
safety. It will be a battle to keep that extra $1.5 billion in 
terms of real dollars that we will have.
    We will want to discuss the issues of the new standards of 
ethics. When the issue came up before the House of 
Representatives, there was I think a, diplomatically stated, a 
pretty stern tone taken. When the matter came before this 
subcommittee, we reviewed the matter with Dr. Zerhouni and said 
we'd look forward to his response.
    But we also gave the people who were being charged an 
opportunity to come in and speak for themselves and to defend 
themselves on an extemporaneous basis. They were in the 
audience. They were welcome to come up and to do--and to talk. 
We had that hearing back on January 22, 2004.
    It's always a difficult matter to prescribe a cure, 
medically or politically or ethically. It may well be that 
there are some revisions which are necessary, and we're going 
to make some suggestions and engage in some dialogue. But the 
ultimate decisions have to rest with the professionals who are 
in the field.
    One word about stem cells, which we will take up in the 
course of the hearing. There is great concern about the Federal 
policy on stem cells contrasted with what is happening in the 
States with the $3 billion budget in California and the lure of 
top scientists to California. Now Massachusetts is coming in 
with a program. We have discussed in this subcommittee the 
concerns about a brain drain going to Europe. This is something 
that we have to deal with.
    There was very strong sentiment in the Congress about 
broadening the use of stem cells, moving away not necessarily 
from nuclear transplantation. We're not talking about creating 
another Dolly or about those sort of tactics, but just to use 
the stem cells which otherwise will be thrown away. There are 
hundreds of thousands which were created for in vitro 
fertilization and they're not being used, and they could be 
used to cure diseases.
    We understand the situation with the administration, Dr. 
Zerhouni, and the White House point of view, and I have 
suggested to you before that you might look for some greater 
latitude for advocacy within the administration. You're very 
respectful and you're very diplomatic and your voice might be 
heard and be influential.
    I've had an opportunity to talk to the President about the 
matter. He was in Pennsylvania 44 times during the campaign, 
and I was with him on most of the occasions. We had a lot of 
time to talk on the plane and in the car. His views are pretty 
firm, but so are mine, and so are, I think, a majority of the 
Congress, as you see with what's happening in the House. 
Senator Harkin, Senator Feinstein, Senator Hatch, Senator 
Kennedy, and I have re-introduced legislation. So that's a big 
matter for the research future of America and the world.
    That's longer than I usually talk, but since there are no 
other members present, I felt a little more latitude. Dr. 
Zerhouni, we welcome you here. We thank you for taking on this 
tough job and we look forward to your testimony.

               SUMMARY STATEMENT OF DR. ELIAS A. ZERHOUNI

    Dr. Zerhouni. Thank you, Mr. Chairman, and first and 
foremost, let me tell you about our admiration for your 
continuing service while you're fighting cancer, and we're 
looking forward to seeing you support NIH, support medical 
research as you have in the past for many years to come.
    I would like to also----
    Senator Specter. Is there any shortcut to--Dr. Zerhouni--to 
returning Arlen Specter the kind of head of hair that Elias 
Zerhouni has?
    Dr. Zerhouni. I would be very happy to share.
    Senator Specter. I hope the camera will focus on Dr. 
Zerhouni's hair, so we don't just get this verbally.
    Dr. Zerhouni. I will do everything to share that with you, 
sir.
    Senator Specter. I don't want share, I want my own, Dr. 
Zerhouni.
    Dr. Zerhouni. I have submitted for the record written 
testimony.
    Senator Specter. Your full statement will be made a part of 
the record, Dr. Zerhouni, and in accordance with our standard 
practice, to the extent you can summarize, that would be 
helpful to leave the maximum amount of time for questions and 
answers. We have a vote scheduled at 10:00 and we have the new 
Prime Minister of the Ukraine speaking. But this is a very 
important hearing and I will return after the vote so we do 
full justice to the issues which we have here today.

             THE PAST, THE PRESENT, AND THE FUTURE FOR NIH

    Dr. Zerhouni. Thank you. I will do so. First and foremost, 
let me summarize for us with a few slides where NIH is and 
where the budget is heading. Clearly, NIH has, as you said, 
been the crown jewel of medical research and of the Federal 
Government in promoting and advancing, through research, better 
health.



    I'll show you some results that I think all of us know. In 
heart disease, we've had a 60 percent reduction in mortality 
over the past 30 years, primarily due to discoveries in terms 
of metabolism, of cholesterol, in terms of inflammation, in 
terms of the management of hypertension. You can see over the 
slides there that we've seen for the first time a marked 
decrease in both mortality and morbidity, with 815,000 lives 
saved this year--in 2000.
    For the first time, over the past 10 years we're seeing a 
very real decrease in cancer mortality. The National Cancer 
Institute should really be commended for these results. We've 
seen, for example, mortality reduced in 11 of the 15 most 
common cancers in men and in 8 of the 15 most common cancers in 
women. We're continuing to see increased survivorship for 
cancer with a markedly increased number of Americans living 
with cancer today, from 3 to 9 million and rising.
    I think you can see the survival rates between 1974, 1976, 
1992, and 1999, and you can see improvements in all cancers. 
But you can see also in very specific cancers, survival rates 
right now in breast cancer are 87 percent, colon cancer 62 
percent, Hodgkin's disease 84 percent, and prostate cancer 98 
percent.
    We're continuing to do research on infectious agents and 
the new threats of biodefense agents. And you can see that in 
2003 for the first time we've developed an effective vaccine 
against ebola virus. Anthrax, we've crystallized the anthrax 
toxin and have identified new drug targets.
    In SARS, I'd like to remind you that because of the 
doubling of the budget that you have spearheaded and the 
research and the new tools that were made available to human 
genome research, we were able to identify the SARS virus in 
less than a month. Today there is the first vaccine in trial 
already in the works, and two more have been developed as well.
    So I think that the investment that you have really helped 
us with has paid off and is paying off. We're continuing to 
strengthen the NIH vision by doing systematic coordination 
across all the Institutes. In 2004 we presented the NIH Roadmap 
for Medical Research that involves all the Institutes and 
really engages in areas where no single Institute can do the 
job. In 2005, we announced the trans-NIH plan for obesity 
research, and in 2006, this year, the NIH neuroscience 
blueprint.
    The scope of the challenge is enormous, as you well know. 
We have hundreds of common diseases and 6,000 rare diseases to 
take care of. Clearly, the budget that we have is large, $28 
billion. But from our standpoint of scientists and physicians, 
we look at it on a per-American basis. When you look at that, 
what you realize is that we have to manage $96 per American per 
year. The NCI manages $16 per American per year to combat all 
cancer, NIAID $15, NHLBI $10. It is in this context that we 
have to invest our dollars to make the most impact on our 
health care costs, which are fast rising and come to $5,500 per 
American per year.
    Clearly, the budget this year is going to have to lead to 
difficult choices, and we've established priorities, such as 
the support of new and established scientists with new grants. 
We've increased the number of grants available for competition, 
obviously at the expense of inflation factors and other choices 
we had to make. We are accelerating research for treatments and 
prevention strategies through the NIH Roadmap for Medical 
Research. We're continuing to develop countermeasures for 
biological and chemical threats. This year we're announcing the 
neuroscience blueprint. We think that even though we have 
difficult budgets, it's important to do the right thing even if 
it's not the right budgetary time.
    Again, this year we have many new candidate vaccines----
    Senator Specter. What do you mean, Dr. Zerhouni, by doing 
the right thing even though if it's not the right budgetary 
time?

                        MAKING THE RIGHT CHOICES

    Dr. Zerhouni. What I mean is despite the fact that there is 
a flat budget there are scientific opportunities in 
neurosciences, behavioral sciences. And we believe, with the 15 
Institute directors that are primarily responsible for this 
area of science, that it was important to have a coordinated 
plan to advance our knowledge of the brain and the nervous 
system and the impact of behavioral--and behavioral factors on 
health.
    This year we have several new vaccines available for HIV/
AIDS that will need to be tested, and that is very costly. We 
have moved $100 million within our tight budget to the 
priorities that we believe in 2006 will allow us to test for 
the first time very promising vaccines for HIV/AIDS.
    Senator Specter. Where do you take that money from?
    Dr. Zerhouni. Basically we've moved it from all categories 
of the total AIDS budget over the past 2 years, as we predicted 
with Dr. Fauci, that in 2006 we will need to engage in larger-
scale clinical trials of HIV vaccines.
    Last, I think that it is clear that as the organization 
known as NIH has grown more complex, it is also important to 
coordinate and understand better the portfolio of investments 
we're making, especially when you consider that we are managing 
$96 per American per year. You want to make sure that all of 
that investment is maximally utilized. We are announcing the 
creation of a new Office of Portfolio Analysis and Strategic 
Initiatives in 2006 and requesting budgetary support for that 
office to do both strategic analysis of what is it we've done--
--

   PROPOSAL TO CREATE THE OFFICE OF PORTFOLIO ANALYSIS AND STRATEGIC 
                              INITIATIVES

    Senator Specter. What do you mean or need by budgetary 
support?
    Dr. Zerhouni. We've requested a budget line for the Office 
of the Director to create this office and support it.
    Senator Specter. How much is that line?
    Dr. Zerhouni. We've started with a $2 million request.
    Senator Specter. $2 million?

                          PREPARED STATEMENTS

    Dr. Zerhouni. Yes. This office is going to allow us to 
develop better coding, better understanding of our databases, 
and coordinate them across Institutes so that we can have a 
standard way of looking at the entire activities of the Agency. 
We will work through the Institutes and centers to coordinate, 
as we've shown in the past with the trans-NIH obesity plan, 
that we could in fact find areas of synergy and improve on 
them, and obviously evaluate whether or not we are. As you 
often ask us: ``What have we accomplished?'' I think we need to 
evaluate it systematically to show you and the American people 
supporting us the results of this research.
    [The statements follows:]

                Prepared Statement of Dr. Elias Zerhouni

    Mr. Chairman, Members of the Committee: I am pleased to present the 
fiscal year 2006 President's budget request for the Office of the 
Director (OD). The fiscal year 2006 budget includes, $385,195,000, an 
increase of $27,149,000 over the fiscal year 2005 enacted level of 
$358,046,000 comparable for transfers proposed in the President's 
request. 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 FOR MEDICAL RESEARCH

    The NIH Roadmap for Medical Research supports trans-agency research 
and training programs aimed at accelerating the pace of discovery and 
improving the translation of research findings into health 
interventions. The development of new tools and technologies will help 
scientists understand intricate cellular processes and will make large 
volumes of biologic data publicly available for analysis and use in 
other model systems. Nanomedicine concept development awards are 
defining the scope of future centers to explore molecular inventions 
and interventions for curing disease or repairing tissues. Innovative 
team approaches will facilitate the creation of new biomedical and 
behavioral interdisciplinary fields and contribute to our understanding 
of complex diseases and conditions. Studies examining outcomes such as 
pain, fatigue and obesity will be enhanced by NIH Roadmap projects 
supporting the integration of behavioral and social sciences with 
biomedical and physical sciences. The clinical research initiatives are 
exploring ways to promote the integration and extension of clinical 
research networks, support translational research, and facilitate the 
coordination and harmonization of clinical research policies across 
federal agencies. Critical to these new efforts will be an infusion of 
trained scientists and clinical researchers at all stages of their 
careers, able to apply interdisciplinary and multidisciplinary 
approaches to complex biomedical problems. And for the first time, 
physicians, nurses and dentists are being trained together to become 
leaders in this clinical research community. These and other projects 
will enhance the capacity of scientists to harness the knowledge base 
for specific applications in all areas of investigation. The fiscal 
year 2006 budget request for NIH Roadmap for Medical Research is 
$83,000,000, an increase of $23,280,000 over the fiscal year 2005 
level.

                      THE OFFICE OF AIDS RESEARCH

    The Office of AIDS Research (OAR) plays a unique role at NIH, 
establishing a roadmap for the AIDS research program. OAR coordinates 
the scientific, budgetary, legislative, and policy elements of the NIH 
AIDS research program. Our response to the AIDS 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. OAR oversees the development of the annual 
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 also identifies and 
facilitates multi-institute participation in priority areas of research 
and facilitates NIH involvement in international AIDS research 
activities. The fiscal year 2006 budget request for OAR is $60,899,000, 
which is the same as the fiscal year 2005 level.

                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 to facilitate analyses by sex/gender; and 
develops opportunities for the advancement of women in biomedical 
careers and investigators in women's health research. These ORWH 
efforts are in full partnership with the NIH Institutes and Centers. 
New research has been expanded in the ORWH-funded Specialized Centers 
of Research through interdisciplinary research in women's health and 
sex and gender factors and through the unique ORWH interdisciplinary 
career development program that fosters the mentored development of 
junior faculty and assists them in bridging advanced training towards a 
goal of research independence. The fiscal year 2006 budget request is 
$41,363,000, an increase of $148,000 over the fiscal year 2005 level.

         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 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.
    In response to a 2004 Institute of Medicine study entitled, 
``Improving Medical Education: Enhancing the Behavioral and Social 
Science Content of Medical School Curricula'', OBSSR developed a 
program to promote the design and implementation of medical school 
curricula with coverage of behavioral and social sciences. This program 
will provide a mechanism whereby medical school students will receive 
training about issues such as the influence of psychological, 
biological, and social factors on health and disease; the role of 
physicians' beliefs, behaviors, and values in patient care; managing 
difficult physician-patient interactions; and the impact of policy on 
health behaviors and patient care. In addition to the benefits realized 
by individual physicians in training, funded medical schools may 
develop the infrastructures to permanently integrate behavioral and 
social sciences into their curricula. To continue such groundbreaking 
work in the behavioral and social sciences, the fiscal year 2006 budget 
request for OBSSR is $26,185,000, an increase of $94,000 over the 
fiscal year 2005 level.

                    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 interventions to the 
public. The ODP has two additional specific programs/offices that place 
emphasis on particular aspects of the prevention and treatment of 
disease the Office of Dietary Supplements (ODS) and the Office of Rare 
Diseases (ORD).
    In fiscal year 2006, the ODS within ODP requests a budget of 
$27,078,000, an increase of $97,000 over the fiscal year 2005 level. 
ODS promotes the scientific study of the use of dietary supplements by 
supporting investigator-initiated research, and stimulating research 
through the conduct of conferences and presentations at national and 
international meetings. Other current ODS efforts include:
  --Sponsorship of systematic review of the relationship between omega-
        3 fatty acids and a number of clinical indications, 
        particularly coronary heart disease.
  --Collaborations for the development, validation, and dissemination 
        of analytical methods and reference materials for dietary 
        supplements.
  --Support and development of databases of dietary supplement 
        information including:
    --National Health and Nutrition Examination Survey (NHANES);
    --Collaboration with USDA to develop an analytically-based database 
            of dietary supplement ingredients;
    --Plan to contract for development of a dietary supplement label 
            database;
    --International Bibliographic Information on Dietary Supplements 
            (IBIDS);
    --CARDS, a database of federally funded research on dietary 
            supplements.
  --Collaboration with other federal agencies to develop a coordinated 
        approach to assessment of the health effects of bioactive 
        factors in food and dietary supplements. Publishes Fact Sheets 
        on dietary supplements for consumers.
    Another component of ODP, the ORD, was formally established through 
the Rare Diseases Act of 2002, Public Law 107-280. The budget request 
for fiscal year 2006 for ORD is $15,649,000, an increase of $56,000 
over the fiscal year 2005 level. The following are four highlights of 
ORD activities: (1) An Extramural Rare Diseases Clinical Research 
Network that involves 10 consortia, more than 70 sites, and 30 patient 
support organizations for almost 50 rare diseases. Thirty-three 
clinical protocols are under development. (2) The Rare Diseases 
Intramural Research Program is a collaborative effort between the ORD 
and the National Human Genome Research Institute at the NIH Clinical 
Center. Recently, the program initiated annual contracts for 25 
molecular diagnostic tests for specific rare diseases that will be made 
available by the contractor to the public at reasonable cost. (3) ORD 
also co-funds annually approximately 100 scientific conferences for 
scientific opportunities or where research is lagging or lacking. (4) 
The newly established Trans-NIH Rare Diseases Research Working Group is 
developing an assessment of rare diseases biospecimen collection, 
storage, and delivery issues, of genetic tests in extramural research 
programs, and plans for a conference on amyloidosis.

                    THE OFFICE OF SCIENCE EDUCATION

    The Office of Science Education (OSE) develops science education 
programs to enhance efforts to attract young people to biomedical and 
behavioral science careers and to improve science literacy in both 
adults and children. The OSE creates programs to improve science 
education in schools (the NIH Curriculum Supplement Series); creates 
programs that stimulate interest in health and medical science careers 
(LifeWorks Web site); creates programs to advance public understanding 
of medical science, research, and careers; and advises NIH leadership 
about science education issues. 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 Web site is a central source of information about 
available education resources and programs. http://
science.education.nih.gov. The fiscal year 2006 budget request for OSE 
is $3,878,000, the same as the fiscal year 2005 level.

                 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, intramural 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 and enhance the training of undergraduate students 
from disadvantaged backgrounds in biomedical research careers and 
employment at the NIH.
    The fiscal year 2006 budget request for OLRS is $7,213,000, the 
same as the fiscal year 2005 level.

         OFFICE OF PORTFOLIO ANALYSIS AND STRATEGIC INITIATIVES

    In fiscal year 2006, the NIH plans to create a new office within 
the Office of the Director--the Office of Portfolio Analysis and 
Strategic Initiatives (OPASI)--which will provide tools to facilitate 
planning for trans-NIH initiatives, including an improved process for 
collecting IC data on expenditures on various diseases, conditions, and 
research fields, and improvements in data about burden of disease. The 
office will also develop, with input from the ICs, common processes and 
formats, where necessary, for the conduct of NIH-wide planning and 
evaluation. For trans-NIH planning efforts, the office will seek broad 
public input--from the public, health care providers, policymakers, and 
scientists--in addition to soliciting advice from within NIH. The 
office will also coordinate and make more effective use of the NIH-wide 
evaluation process. The budget request for OPASI is $2,000,000.
    Thank you, Mr. Chairman for giving me the opportunity to present 
this statement; I will be pleased to answer questions that the 
Committee may have.

     NATIONAL INSTITUTES OF HEALTH 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 2006, a sum of $81,900,000.

                      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 four states. These facilities house researchers from the NIH 
Institutes' and Centers'(ICs) intramural basic, translational, and 
clinical research programs; science administrators who oversee NIH's 
grants; the NIH leadership, and various programs that support agency 
operations. The fiscal year 2006 B&F budget request focuses on the need 
for responsible utilization and stewardship of NIH's past and recent 
investments in the ``bricks and mortar'' of the research enterprise. In 
order to stay abreast of the changing needs of the NIH programs, it is 
imperative that we provide reliable, safe and secure research support 
facilities that are appropriately equipped, operated and maintained.
    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. Through this process, the 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 2006 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.
    The fiscal year 2006 B&F budget request is organized among three 
broad Program Activities: Essential Safety and Regulatory Compliance, 
Repairs and Improvements and Construction. The fiscal year 2006 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 2006.

                    FISCAL YEAR 2006 BUDGET SUMMARY

    The fiscal year 2006 budget request for Buildings and Facilities is 
$81.9 million. The B&F request contains a total of $14 million for 
Essential Safety and Regulatory Compliance programs composed of $2 
million for the phased removal of asbestos from NIH buildings; $5 
million for the continuing upgrade of fire and life safety deficiencies 
of NIH buildings; $1.5 million to systematically remove existing 
barriers to persons with disabilities from the interior of NIH 
buildings; $0.5 million to address indoor air quality concerns and 
requirements at NIH facilities; and $5 million for the continued 
support of the rehabilitation of animal research facilities. In 
addition, the fiscal year 2006 request includes $66.9 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; and $1 
million in Construction for pre-project planning including concept 
development studies and analyses of NIH-wide facility projects proposed 
in the facilities plan.
    My colleagues and I will be happy to respond to any questions you 
may have.
                        Office of AIDS Research

       FISCAL YEAR 2006 NIH AIDS RESEARCH BY-PASS BUDGET ESTIMATE

                              INTRODUCTION

    In its report on the fiscal year 2005 budget for the Department of 
Health and Human Services, the Senate Committee on Appropriations 
stated:

    ``The NIH Office of AIDS Research [OAR] coordinates the scientific, 
budgetary, legislative, and policy elements of the NIH AIDS research 
program. Congress provided new authorities to the OAR to fulfill these 
responsibilities in the NIH Revitalization Action Amendments of 1993. 
The law mandates the OAR to develop an annual comprehensive plan and 
budget for all NIH AIDS research and to prepare a Presidential bypass 
budget.'' (Senate Report 108-345, page 175)

    Public Law 103-43, the National Institutes of Health Revitalization 
Act of 1993, requires that ``the Director of the Office of AIDS 
Research establish a comprehensive plan for the conduct and support of 
all AIDS activities of the agencies of the National Institutes of 
Health.'' It also requires that the Director ``shall prepare and submit 
directly to the President, for review and transmittal to the Congress, 
a budget estimate for carrying out the Plan for the fiscal year . . .'' 
That budget ``shall estimate the amounts necessary for the agencies of 
the National Institutes of Health to carry out all AIDS activities 
determined by the Director of the Office to be appropriate, without 
regard to the probability that such amounts will be appropriated.''
    In accordance with the law, the Office of AIDS Research (OAR) has 
developed the fiscal year 2006 Professional Judgment (By-Pass) Budget 
Estimate for NIH AIDS Research to carry out the scientific priorities 
of the fiscal year 2006 NIH Plan for HIV-Related Research. This By-Pass 
budget estimate is based on the following criteria: the commitment to 
support only the highest quality research; and the urgent need to 
pursue priority scientific opportunities.

                                OMB PART

    The NIH AIDS program received an overall score of 83 in the 2005 
PART. This score included a 100 percent in the Program Purpose and 
Design section. The human and economic toll of the AIDS pandemic 
requires a unique response that is complex, comprehensive, multi-
disciplinary, and global. The NIH role in this response is 
unprecedented, comprising a comprehensive program of basic, clinical, 
and behavioral research on HIV disease to better understand the basic 
biology of HIV and develop effective therapies and prevention 
strategies. PART demonstrated that NIH provides effective scientific 
coordination and management of this diverse AIDS research portfolio 
through a comprehensive planning and budget development process, which 
was utilized to develop the fiscal year 2006 By-Pass Budget Request.

                         OAR COMPREHENSIVE PLAN

    The OAR has established a unique and effective model to develop a 
consensus on the scientific priorities of the annual comprehensive AIDS 
research plan, called the NIH Plan for HIV-Related Research, that is 
based on the most compelling scientific priorities that will lead to 
better therapies and prevention strategies for HIV infection and AIDS. 
The planning process involves the NIH Institute and Center Directors; 
NIH intramural and extramural scientists and program managers; 
scientists and researchers from other government agencies, academia, 
foundations, and industry; HIV-infected individuals; and other 
community representatives. The plan also is reviewed by the OAR 
Advisory Council.
    The NIH fiscal year 2006 Plan for HIV-Related Research is divided 
into five Scientific Areas including: Natural History and Epidemiology; 
Etiology and Pathogenesis; Therapeutics; Vaccines; and Behavioral and 
Social Science. The plan further addresses critical issues that cut 
across all of the scientific areas: Microbicides; HIV Prevention 
Research; Racial and Ethnic Minorities; Women and Girls; International 
Research; Training, Infrastructure, and Capacity Building; and 
Information Dissemination.
    The fiscal year 2006 NIH AIDS research agenda continues the 
following overarching themes: a strong foundation of basic science; HIV 
prevention research, including development of vaccines, microbicides, 
behavioral interventions, and strategies to prevent perinatal 
transmissions; 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 crucial research 
and training needs in developing countries; and research targeting the 
disproportionate impact of the AIDS epidemic on racial and ethnic 
minority populations in the United States.
    The Plan shapes NIH investments in biomedical and behavioral AIDS 
research and provides the framework to translate critical research 
findings to benefit populations desperately in need both in our country 
and abroad. The Plan serves as the framework for developing the annual 
NIH AIDS research budget; for determining the use of NIH AIDS-
designated funds; for tracking and monitoring AIDS-related 
expenditures; and for informing the scientific community, the public, 
and the AIDS-affected community about NIH AIDS research priorities. The 
entire plan can be found on the OAR web site: http://www.nih.gov/od/
oar/public/pubs/fy2006/00_Overview_fiscal year 2006.pdf

                     OAR BUDGET DEVELOPMENT PROCESS

    The Plan initiates the budget development process. Based on the 
objectives and priorities established in the Plan, the NIH Institutes 
and Centers (ICs) prepare their AIDS research budget requests, 
detailing new or expanded program initiatives for each scientific area. 
The OAR reviews the IC initiatives in relation to the Plan, to OAR 
priorities, and to other IC submissions to eliminate redundancy and/or 
to assure cross-institute collaboration. The OAR allocates the AIDS 
research budget levels to each IC based on the scientific priority of 
the proposed initiatives.
    This process allows the OAR to ensure that AIDS research funds will 
be provided to the most compelling scientific opportunities, rather 
than distribution based solely on a formula.

                     OAR BY-PASS BUDGET PRIORITIES

    The fiscal year 2006 NIH By-Pass Budget for HIV/AIDS Research 
responds to several crucial scientific opportunities and needs. In 
fiscal year 2005, OAR initiated a comprehensive trans-NIH review of all 
grants and contracts supported with AIDS-designated funds to ensure 
that these projects represent the highest scientific priorities and 
opportunities. This process also included: (1) a review of the 
appropriateness of definitions of HIV/AIDS research in the institutes 
(i.e., coding of research as AIDS or AIDS-related) and the mix of 
investments in key priority areas in view of the current epidemic; and 
(2) a series of meetings with IC representatives to assess their AIDS 
portfolios relative to AIDS and AIDS-related priorities. This process 
will result in the redirecting of AIDS funds to higher priority 
projects and new scientific opportunities in fiscal year 2006.
    NIH-sponsored HIV/AIDS research continues to provide the important 
scientific foundation necessary to design, develop, and evaluate new 
and better vaccine candidates, therapeutic agents and regimens, and 
prevention interventions. In particular, this By-Pass budget places a 
renewed priority on the discovery, development, and pre-clinical 
testing of additional HIV vaccine candidates. The NIH priority in AIDS 
vaccine research to date has resulted in approximately 70 clinical 
trials of nearly 40 vaccine candidates. The evaluation of an AIDS 
vaccine will require extensive testing in the United States and in 
international settings where there is a high incidence of HIV. High 
priority is placed in this budget on funding to move promising vaccine 
candidates into large-scale clinical trials to evaluate the potential 
for efficacy.
    In the area of AIDS therapeutics research, current therapeutic 
regimens have resulted in extended survival and improved quality of 
life for many HIV-infected individuals in the United States and Western 
Europe. However, a growing proportion of patients receiving therapy are 
demonstrating treatment failure, experiencing serious drug toxicities 
and side effects, and developing drug resistance. This By-Pass budget 
provides critical support for the development of new and better drugs 
using sophisticated structural biology, combinatorial chemistry, and 
macromolecular techniques. The goal of this research is to develop new, 
safe, less toxic, less expensive, and more effective therapeutic agents 
and regimens.
    The increasing incidence of metabolic disorders, cardiovascular 
complications, major organ dysfunction, and physical changes associated 
with current antiretroviral drugs underscores the critical need for new 
and better treatment regimens. Improved regimens also are needed to 
treat HIV co-infections such as hepatitis B and C, as well as other 
opportunistic infections to reduce drug interactions and problems with 
adherence to complicated treatment regimens.
    In fiscal year 2005, the Office of AIDS Research spearheaded a 
critical and unique multi-IC inter-disciplinary collaboration to 
formalize plans for the innovative restructuring of the NIH clinical 
trials networks for HIV therapeutics, vaccines and prevention 
interventions in fiscal year 2006. OAR convened meetings of relevant IC 
high-level staff, established an OAR Working Group of United States and 
international clinical trialists, and convened a public meeting of over 
145 participants from universities, medical schools, the pharmaceutical 
and biotechnology industries, professional scientific societies, 
community advisory boards, constituency groups, and NIH IC program 
staff to develop a set of principles to guide the development of 
Request For Application (RFAs) for these multi-IC supported clinical 
programs. This effort made a significant contribution to the process of 
the recompetition of these networks in fiscal year 2006 and to ensuring 
that they will operate effectively and cooperatively, making the best 
use of research funds.
    The alarming continued spread of the pandemic in Southeast and 
Central Asia, Eastern Europe, Latin America, and the Caribbean 
underscores the urgent need for more affordable and sustainable 
prevention and treatment approaches that can be implemented in 
resource-limited nations. The high incidence of Hepatitis B and 
Hepatitis C, malaria, and TB in many of these nations further 
complicates the treatment and clinical management of HIV-infected 
individuals. This budget provides increased funds for the development 
and evaluation of new regimens for these HIV co-infections that will 
allow the treatment of these diseases without serious drug interactions 
and toxicities.
    The By-Pass budget provides funds for NIH international AIDS 
research including: HIV vaccine candidates and chemical and physical 
barrier methods, such as microbicides, to prevent sexual transmission; 
behavioral strategies targeted to the individual, family, and community 
to alter risk behaviors associated with sexual activity and drug and 
alcohol use; drug and non-drug strategies to prevent mother-to-child 
transmission (MTCT); therapeutics for HIV-related co-infections and 
other conditions; and approaches to using Antiretroviral Therapy (ART) 
in resource-poor settings. Specific international infrastructure needs 
include: (1) developing research sites through establishment of stable, 
targeted cohorts, development of recruitment strategies, and 
enhancement of laboratory, clinical, and data management capabilities; 
(2) increasing the number of scientists, clinicians, and health care 
workers trained in basic, clinical, and behavioral research, data 
management, and ethical considerations; (3) developing research 
collaborations; and (4) transferring appropriate clinical and 
laboratory technologies.

                      OAR BY-PASS BUDGET ESTIMATE

    NIH is enhancing collaboration, minimizing duplication, and 
ensuring that research dollars are invested in the highest priority 
areas of scientific opportunity that will allow NIH to meet its 
scientific goals.
    The total fiscal year 2006 By-Pass budget estimate for all NIH AIDS 
research is $3.387 billion. This represents an increase of $442 million 
or 15 percent over the fiscal year 2005 current estimate of $2.945 
billion.
    The NIH Office of AIDS Research is providing the following 
materials: NIH fiscal year 2006 Plan for HIV-Related Research; NIH 
Research Mechanism Table; and Table of Funding by the NIH fiscal year 
2006 Plan for HIV-Related Research.

                ATTACHMENT 1.--OFFICE OF AIDS RESEARCH FISCAL YEAR 2006 BY-PASS SUMMARY MECHANISM
                                              [Dollars in millions]
----------------------------------------------------------------------------------------------------------------
                                                                       Fiscal years
                                        ------------------------------------------------------------------------
                                          2004  estimate    2005  estimate     2006  by-pass     2006 over 2005
                                        ------------------------------------------------------   dollar change
                                                                                              ------------------
                                           No.     Amount    No.     Amount    No.     Amount  Percent   Amount
----------------------------------------------------------------------------------------------------------------
Research Projects:
    Noncompeting.......................   2,245   $1,173    2,407   $1,268    2,370   $1,087     -14.3    -$181
    Administrative supplements.........     (14)      18      (16)      19      (20)      17     -10.5       -2
    Competing..........................   1,035      376      804      307    1,178      712     131.9      405
                                        ------------------------------------------------------------------------
      Subtotal, RPGs...................   3,266    1,567    3,195    1,594    3,528    1,816      13.9      222
SBIR/STTR..............................      91       31      103       35      105       41      17.1        6
                                        ------------------------------------------------------------------------
      Total, RPGs......................   3,357    1,598    3,298    1,629    3,633    1,857      14.0      228
                                        ========================================================================
Research Centers:
    Specialized/comprehensive..........      61      104       61      111       63      120       8.1        9
    Clinical research..................  .......      43   .......      45   .......      49       8.9        4
    Biotechnology......................  .......       6        1        7   .......       7   .......  ........
    Comparative medicine...............      17       48       17       52       17       65      25.0       13
    Research centers in minority         .......      10   .......      10   .......      11      10.0        1
     institutions......................
                                        ------------------------------------------------------------------------
        Subtotal, Centers..............      78      211       79      225       80      252   .......       27
Other Research:
    Research careers...................     235       30      240       31      235       34       9.7        3
    Cancer education...................  .......  .......  .......  .......  .......  .......  .......  ........
    Cooperative clinical research......      25       44       25       44       25       44   .......  ........
    Biomedical research support........       1        2        1        2        1        3      50.0        1
    Minority biomedical research              2        1        2        1        3        1   .......  ........
     support...........................
    Other..............................     115       62      114       64      115       72      12.5        8
                                        ------------------------------------------------------------------------
      Subtotal, Other Research.........     378      139      382      142      379      154   .......       12
                                        ------------------------------------------------------------------------
      Total, Research Grants...........   3,813    1,948    3,759    1,996    4,092    2,263   .......  ........
                                        ========================================================================
                 FTTPs
Training:
    Individual.........................      62        3       62        3       62        3   .......  ........
    Institutional......................     703       31      723       32      737       33       3.1        1
                                        ------------------------------------------------------------------------
      Total, Training..................     765       34      785       35      799       36       2.9        1
                                        ========================================================================
Research & development contracts.......     181      364      190      415      225      553      33.3      138
    (SBIR/STTR)........................     (10)      (2)     (10)      (2)     (10)      (1)    -50.0       (1)
Intramural research....................  .......     325   .......     331   .......     356       7.6       25
Research management and support........  .......      96   .......      99   .......     106       7.1        7
Construction...........................  .......       5   .......  .......  .......  .......  .......  ........
Library of Medicine....................  .......       7   .......       8   .......      10      25.0        2
Office of the Director.................  .......      61   .......      61   .......      63       3.3        2
Buildings and Facilities...............  .......  .......  .......  .......  .......  .......  .......  ........
                                        ------------------------------------------------------------------------
      Total, Budget Authority..........  .......   2,840   .......   2,945   .......   3,387      15.0      442
----------------------------------------------------------------------------------------------------------------


    ATTACHMENT 2.--OFFICE OF AIDS RESEARCH, FISCAL YEAR 2006 BY-PASS, FUNDING BY THE NIH PLAN FOR HIV-RELATED
                                                    RESEARCH
                                              [Dollars in millions]
----------------------------------------------------------------------------------------------------------------
                                                                        Fiscal year
                                         -----------------------------------------------------------------------
                                                                                            2006 over 2005
                                                                               2006  ---------------------------
                                           2002    2003     2004      2005      by-            Percent
                                          actual  actual  estimate  estimate   pass   Dollar      of     Percent
                                                                                      change  increment   change
----------------------------------------------------------------------------------------------------------------
Natural History and Epidemiology........    $276    $295     $293      $296     $315     $19       4.3       6.4
Etiology and Pathogenesis...............     685     727      716       728      812      84      19.0      11.5
Therapeutics............................     689     726      754       771      848      77      17.4      10.0
Vaccines................................     329     407      467       529      714     185      41.9      35.0
Behavioral and Social Science...........     346     370      402       408      457      49      11.1      12.0
Training and Infrastructure.............     121     137      165       169      191      22       5.0      13.0
Information Dissemination...............      53      55       43        44       50       6       1.4      13.6
                                         -----------------------------------------------------------------------
      Total.............................   2,499   2,717    2,840     2,945    3,387     442       100      15.0
----------------------------------------------------------------------------------------------------------------

                                 ______
                                 
               Prepared Statement of Dr. Anthony S. Fauci

    Mr. Chairman and Members of the Committee: I am pleased to present 
the fiscal year 2006 President's budget request for the National 
Institute of Allergy and Infectious Diseases (NIAID) of the National 
Institutes of Health (NIH). The fiscal year 2006 budget of 
$4,459,395,000 includes an increase of $56,554,000 over the fiscal year 
2005 enacted level of $4,402,841,000, comparable for transfers proposed 
in the President's request.
    NIAID conducts research to understand, treat, and prevent 
infectious and immune-related diseases. Infectious diseases include 
well-known killers such as tuberculosis and malaria, emerging or re-
emerging threats such as HIV/AIDS, SARS, West Nile Virus and influenza, 
and ``deliberately emerging'' threats from potential agents of 
bioterrorism such as those that cause anthrax and smallpox. Examples of 
immune-related diseases include autoimmune disorders such as type 1 
diabetes, systemic lupus erythematosus, rheumatoid arthritis, 
transplantation-related illnesses, asthma, and allergies.
    Historically, NIAID has accomplished its mission with a strong 
commitment to basic and targeted research in immunology, microbiology, 
and infectious disease. In the 57 years since NIAID was founded, this 
approach has led directly to new therapies, vaccines, diagnostic tests, 
and other technologies that have improved the health of millions of 
people worldwide. In recent years, however, the growing realization 
that the nation needs a stronger defense against both naturally and 
deliberately emerging infectious diseases has led NIAID to adopt a new 
research paradigm that accelerates the development of safe and 
effective medical countermeasures. To accomplish this, we have sought 
creative ways to modify our traditional process of research and 
development to move potential products ahead more rapidly while 
continuing to preserve the excellence in basic research that is a 
hallmark of NIAID, and all of NIH. The result is that we now take a 
much more proactive role in collaborating with academia, industry and 
other partners to move promising concepts into advanced product 
development and clinical testing.

                          BIODEFENSE RESEARCH

    In the wake of the 2001 terrorist attacks, NIAID substantially 
expanded and accelerated its biodefense research program. The fiscal 
year 2006 President's budget request for NIAID includes $1,664,505,000 
for these biodefense research and development activities. The NIAID 
Strategic Plan for Biodefense Research provides a blueprint for the 
construction of three essential pillars of the NIAID biodefense 
research program: infrastructure needed to safely conduct research on 
dangerous pathogens ($30,000,000 in fiscal year 2006); basic research 
on microbes and host immune defenses that serves as the foundation for 
applied research ($612,190,000 in fiscal year 2006); and targeted, 
milestone-driven research and development of medical countermeasures to 
create the vaccines, therapeutics and diagnostics that we would need in 
the event of a bioterror attack ($1,022,315,000 in fiscal year 2006).
    The investment Congress has made in the NIAID biodefense research 
program has already begun to return substantial dividends in all three 
of these aspects of biodefense research. Dramatic advances have been 
achieved in the development of medical countermeasures against an 
attack with biological agents, and, although there is much more to be 
accomplished, we are in a far stronger position today than we were only 
a few years ago. In September 2001, we had 15.4 million doses of 
smallpox vaccine available; today, we have more than 300 million doses. 
A next-generation smallpox vaccine called modified vaccinia Ankara 
(MVA) is in clinical testing and other vaccine candidates are in pre-
clinical development stages. A new oral form of the antiviral drug 
cidofovir is in advanced product development for use in the event of a 
smallpox attack, as well as to treat the rare but serious complications 
of the classic smallpox vaccine. For anthrax, NIAID has aggressively 
pursued development of a new vaccine called rPA; the Department of 
Health and Human Services (DHHS) has contracted with VaxGen, Inc. to 
purchase 75 million doses of rPA under the BioShield legislation passed 
last year. This vaccine is derived using molecular biological 
methodologies and is produced using modern vaccine manufacturing 
techniques and may require fewer doses than the currently licensed 
vaccine. New anthrax therapies that can neutralize the anthrax toxin, 
such as monoclonal and polyclonal antibodies, are being developed. 
Candidate antibody treatments for the toxin that causes botulism are in 
development, as is a new vaccine to prevent the disease. Finally, an 
Ebola recombinant DNA vaccine is in initial human clinical trials at 
the NIAID Vaccine Research Center.
    With regard to research infrastructure, many integrated research 
facilities are under construction to safely contain and study 
pathogens, including several new biodefense laboratories that will be 
owned and operated by NIAID. In addition, sites have been selected for 
the construction of two National Biocontainment Laboratories (NBLs) and 
nine Regional Biocontainment Laboratories (RBLs) at major universities 
around the United States. All of these research laboratories will 
provide the secure facilities needed to carry out the nation's expanded 
biodefense research program in settings that protect workers and the 
surrounding communities. NIAID also has funded eight Regional Centers 
of Excellence for Biodefense and Emerging Infectious Diseases Research 
(RCEs). This nationwide network of multidisciplinary academic centers 
will conduct wide-ranging research to better understand infectious 
agents that could be used in bioterrorism, and will develop 
diagnostics, therapeutics and vaccines needed for biodefense against 
these agents. In 2005, NIAID will fund two additional RCEs and three to 
four additional RBLs. NIAID also has developed and expanded contracts 
to screen new drugs against bioterrorism threat agents, developed new 
animal models for bioterrorism threat agents, and established a 
biodefense reagent and specimen repository.
    Advances in Medicine rest on a foundation of basic research into 
the fundamental properties and mechanisms of life. In biodefense, these 
basic studies include sequencing and understanding of microbial genomes 
(genomics) and their products (proteomics), deciphering how microbes 
cause disease (pathogenesis), and examining how the human immune system 
and pathogens interact (immunology). NIAID-funded basic researchers 
have made significant progress since 2001 in each of these areas. For 
example, researchers have now determined the genetic sequence of at 
least one strain of every pathogen identified as a potential bioterror 
threat, and NIAID has established the Pathogen Functional Genomics 
Resource Center to help researchers apply and analyze these new genome 
sequence data. In pathogenesis, NIH researchers recently determined the 
three-dimensional structure of the anthrax toxin bound tightly to a 
target cell surface receptor. This finding has provided new leads for 
the development of novel antitoxins that could save lives late in the 
course of anthrax disease when large amounts of toxin are present and 
antibiotics alone are no longer sufficient to save the patient. 
Finally, basic molecular and cellular studies of the human innate 
immune system, which is comprised of broadly active ``first responder'' 
cells and other mechanisms that are the first line of defense against 
infection, have been moving forward rapidly. These advances suggest it 
may be possible to develop fast-acting countermeasures that boost 
innate immune responses to mitigate the effects of a broad spectrum of 
bioterror pathogens or toxins. Manipulation of the innate immune system 
also could lead to the development of powerful adjuvants that can be 
used to increase the effectiveness of vaccines.
    The knowledge and products that will flow from the NIAID biodefense 
research program, including research results, intellectual capital, 
laboratory resources, and countermeasures in the form of diagnostics, 
therapeutics, and vaccines, will help us cope with naturally emerging, 
re-emerging, and deliberately released microbes alike. Recent 
experience tells us that knowledge developed to understand one pathogen 
invariably applies to others. For example, when HIV first emerged, 
antiviral drug development was in its infancy. Now, new technologies 
have led to the development of more than 20 antiretroviral drugs that 
can effectively suppress HIV replication and dramatically reduce AIDS 
morbidity and mortality. These same technologies, and the lessons 
learned about antiviral drug development, are being applied to the 
development of new generations of drugs against many viruses, including 
influenza, SARS, smallpox, and Ebola. Even if we are never confronted 
with another bioterror attack, the biodefense research and preparations 
being carried out now will without question prove to be very valuable.

                           HIV/AIDS RESEARCH

    Only a few statistics are needed to present a profoundly disturbing 
picture of the still-emerging HIV/AIDS pandemic. Approximately 40 
million people worldwide are living with HIV/AIDS, according to the 
Joint United Nations Programme on HIV/AIDS (UNAIDS). Every year, more 
than 5 million people worldwide are newly infected with the virus--
about 14,000 each day; more than 95 percent of these people live in low 
and middle income countries. In the United States, nearly one million 
people are living with HIV/AIDS, and approximately 40,000 new 
infections occur annually, according to the Centers for Disease Control 
and Prevention. The death toll continues to climb steadily; worldwide, 
more than 20 million people with HIV have died since the pandemic 
began, including more than 520,000 in the United States. In 2004, there 
were 3 million deaths due to HIV/AIDS. As shocking as these numbers 
are, they do not adequately communicate the physical and emotional 
devastation to individuals, families, and communities coping with HIV/
AIDS, nor do they capture the terrible impact of HIV/AIDS on the 
economies and security of nations, and indeed on entire regions.
    Even as the burden of HIV/AIDS continues to grow, recent progress 
in research is providing reasons for optimism. For example, several new 
antiretroviral drugs recently have entered the market, all of which 
were built on NIAID-sponsored research and/or were tested in NIAID 
clinical trials networks; many other new anti-HIV drugs are in clinical 
trials. Other novel approaches to anti-HIV drugs are in the research 
``pipeline.'' For example, NIAID scientists, in collaboration with 
extramural colleagues and with industry, recently conducted a clinical 
trial to test a product, anti-CCR5, that binds to a new therapeutic 
target, the HIV co-receptor, thus preventing HIV infection of host 
cells.
    The development of a safe and effective HIV vaccine is one of 
NIAID's highest priorities. The scientific barriers to the creation of 
such a vaccine are extraordinarily high, and better coordination, 
collaboration and transparency of research worldwide would help to 
overcome them. To facilitate such an approach, NIAID participated 
heavily in the creation of a new initiative called the Global HIV/AIDS 
Vaccine Enterprise, which was endorsed by President Bush and the other 
G8 countries at their June, 2004 Summit meeting in Sea Island, GA. The 
project creates a worldwide consortium of people and organizations with 
a stake in HIV vaccine research who agree to harmonize their individual 
HIV vaccine efforts by following a unified Strategic Plan for HIV 
vaccine development. This plan was published on a publicly-accessible 
website in February 2005.
    Other measures to prevent HIV transmission also are being 
vigorously pursued. For example, when I testified here last year I 
discussed our efforts to develop topically applied microbicides that 
women could use to protect themselves from HIV and other sexually 
transmitted pathogens. More than 50 candidate agents have shown 
activity against HIV and other sexually transmitted diseases in the 
laboratory, and several of these have been shown to be safe and 
effective in animal models. In February 2005, a large international 
study, sponsored by NIAID and involving more than 3,000 women at high 
risk of acquiring HIV in the United States and five African countries, 
opened for enrollment. If these microbicides are proven to be safe and 
effective, they likely will become a very important means of slowing 
the pace of the HIV/AIDS epidemic.

     RESEARCH ON OTHER EMERGING AND RE-EMERGING INFECTIOUS DISEASES

    Infectious diseases do not remain static, but continually and 
dramatically change over time. New pathogens, such as the Severe Acute 
Respiratory Syndrome (SARS) coronavirus, can emerge suddenly and 
familiar ones, such as influenza virus and West Nile virus, can re-
emerge with new properties or in unfamiliar settings. We must always be 
on guard for such changes and be prepared to react to them as quickly 
as possible. SARS is a prototypical example of a newly-emerging 
infectious disease. When SARS first came to the world's attention in 
early 2003 as an unknown, highly lethal and transmissible disease, 
researchers and public health authorities the world over immediately 
began to collaborate to understand it. In short order, NIAID-supported 
researchers and others in Hong Kong showed that SARS was caused by a 
previously unrecognized coronavirus, epidemiologists unraveled its 
modes of transmission, and public health authorities were able to 
contain the initial outbreak.
    Since then, NIAID has continued to pursue several approaches to the 
development of SARS antiviral therapies. For example, NIAID screening 
contracts have supported the evaluation of more than 20,000 chemicals 
for anti-SARS coronavirus activity. More than 1,400 compounds with 
activity against SARS coronavirus have been identified, including alpha 
interferon, a drug already approved by the FDA for the treatment of 
hepatitis B and C infections.
    NIAID scientists and grantees also are working on several 
approaches to a SARS vaccine, including one that entered human clinical 
testing in December 2004. It is truly remarkable that two years ago we 
were facing an unknown global health threat, and now we are already 
testing a promising vaccine that may help us to counter that threat 
should it re-emerge.
    When West Nile virus (WNV) first appeared in the Western hemisphere 
in 1999, NIAID immediately increased its basic research on the virus 
and undertook the development of new vaccines and treatments for the 
disease. NIAID currently supports the development of three types of WNV 
vaccine--one of which has entered initial clinical testing--and is 
developing candidate WNV therapies. For example, in 2004, NIAID 
expanded an ongoing clinical study in human volunteers that is 
evaluating the safety and efficacy of the administration of antibodies 
against the virus as a means of treating or preventing West Nile virus 
encephalitis.
    Influenza is a classic example of a re-emerging disease. Because 
the influenza virus continually changes, the U.S. influenza vaccine 
supply must be renewed each year. Although the egg-based technology 
currently in use has served us reasonably well for more than 40 years, 
it has limitations in flexibility in that surges in the need for 
additional or new vaccines cannot be readily accommodated due to the 
advance time that is required to provide for the annual requirement for 
hundreds of millions of fertilized chicken eggs to manufacture the 
vaccine. In addition, there is the ever present risk of contamination 
and the vicissitudes of yield of virus from this technique. The serious 
vaccine shortage that occurred this flu season underscores the 
difficulties we face in annually renewing the influenza vaccine supply, 
and highlights the pressing need to move toward adoption of newer 
vaccine manufacturing techniques to improve the flexibility and speed 
with which vaccines can be made.
    NIAID supports several research projects and other initiatives 
intended to foster the development of new influenza vaccines and 
manufacturing methods that are simpler and more reliable, yield 
products that work against multiple influenza strains, and provide 
greater protection. DHHS has requested $120 million in fiscal year 2006 
to help shift vaccine manufacture toward new cell-culture technologies, 
new production technologies, as well as to provide for year-round 
availability of eggs to provide for a secure supply and surge capacity. 
In addition, a technique developed by NIAID-supported scientists called 
reverse genetics allows scientists to manipulate the genomes of 
influenza viruses to make the process of development of seed viruses 
for vaccines faster and more predictable.
    Although the impact of influenza in a normal epidemic year is 
substantial, influenza viruses from animals occasionally cross into 
humans and, if the virus then acquires the ability to be easily 
transmitted between people, can cause a much more serious influenza 
pandemic. NIAID conducts a great deal of research to understand the 
viral biology and epidemiology that underpinned past pandemics and 
funds surveillance activities in Asia to detect the emergence of 
influenza viruses with pandemic potential. In addition, the DHHS draft 
Pandemic Influenza Response and Preparedness Plan directs NIAID to help 
develop and produce an effective vaccine as rapidly as possible that 
could be used should a pandemic alert be declared.
    In recent years, avian influenza virus strains that can infect 
humans have emerged; the most worrisome are known as H9N2 and H5N1. In 
1999 and 2003, an H9N2 influenza strain caused illness in people in 
Hong Kong. The H5N1 ``bird flu'' influenza strain was first detected in 
1997 and has spread widely among wild and domestic birds. This latter 
virus has infected at least 55 people and killed 42 since January 2004, 
and there has been at least one documented case of human-to-human 
transmission.
    NIAID has taken several steps to develop vaccines against both of 
these potential pandemic strains. NIAID contracted with Chiron 
Corporation to produce investigational batches of an inactivated H9N2 
vaccine, which will be evaluated clinically by NIAID this year. For 
H5N1, Aventis-Pasteur, Inc. and Chiron are both producing 
investigational lots of inactivated H5N1 vaccine preparations; 
additionally, DHHS has contracted with Aventis to produce up to 2 
million doses to be stockpiled for emergency use, if needed, to 
vaccinate health workers, researchers, and, if indicated, the public in 
affected areas. Development and evaluation of a combination antiviral 
regimen against these potential pandemic influenza strains are also now 
under way.

                  RESEARCH ON IMMUNE-MEDIATED DISEASES

    Immune-mediated diseases, including autoimmune diseases, allergic 
diseases, and asthma are important health challenges in the United 
States and abroad. One of the most promising strategies for developing 
treatments for a wide variety of these disorders is known as immune 
tolerance, in which researchers hope to selectively turn off injurious 
immune responses while leaving intact the protective responses needed 
to fight infection. To foster this research, NIAID sponsors the Immune 
Tolerance Network (ITN), a consortium of more than 80 investigators in 
the United States, Canada, Western Europe, and Australia dedicated to 
the clinical evaluation of promising therapies that can induce immune 
tolerance. The ITN will be recompeted in fiscal year 2006.
    Reducing the growing burden of asthma among inner-city minority 
children is another NIAID priority. NIAID-supported investigators 
recently reported the largest study of its kind, showing that an 
intervention to reduce exposure to indoor allergens and tobacco smoke 
substantially reduced asthma severity and healthcare utilization among 
inner-city children. In 2004, NIAID's Inner-City Asthma Consortium 
launched 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.
    In closing, Mr. Chairman, I would like to take a moment to remember 
John R. La Montagne, Ph.D., the former deputy director of NIAID, who 
died suddenly on November 2 while traveling to a meeting of the Pan 
American Health Organization in Mexico City. Human infrastructure, in 
the form of a highly trained and deeply committed work force, is a 
critical component of any kind of medical research. Throughout John's 
almost 30 years at NIAID, his leadership and dedication to improving 
global health, as well as his generosity, wit, even-handedness and 
kindness, made him a cornerstone of the human infrastructure at NIAID. 
Personally, he was a dear friend and one of the finest people I have 
ever known. He is sorely missed.
    Thank you, Mr. Chairman. I would be pleased to answer any questions 
that the Committee might have.
                                 ______
                                 
           Prepared Statement of Dr. Andrew C. von Eschenbach

    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's budget request for the National Cancer Institute (NCI) 
for fiscal year 2006. The fiscal year 2006 budget includes 
$4,841,774,000, an increase of $16,516,000 over the fiscal year 2005 
enacted level of $4,825,258,000 comparable for transfers proposed in 
the President's request.

                             LONG-TERM GOAL

    The accelerating progress that the National Cancer Institute (NCI) 
and its partners in the cancer community have made over the past three 
decades in understanding the molecular mysteries of cancer is now 
extending the years and enhancing the quality of patients' lives. Now 
we are closer to the reality of eliminating the suffering and death due 
to cancer--the goal that NCI set to be achieved by 2015. The fiscal 
year 2006 budget continues to accelerate the discovery, development, 
and delivery of the interventions that will transform our traditional 
view of cancer as a death sentence into a disease that we can prevent, 
eliminate, or control. Accomplishing this goal is the legacy we strive 
to leave our children.
    Our increased knowledge in several clinical approaches has led to 
new treatments approved for use. For example, our understanding of the 
molecular mechanisms required for tumors to develop the blood supply 
necessary for their growth led to the Food and Drug Administration's 
(FDA) approval of the monoclonal antibody Avastin as a first-line 
treatment for patients with metastatic colorectal cancer. Similarly, 
knowledge of the growth factors necessary to stimulate cancer cell 
proliferation led to development and approval of another targeted 
monoclonal antibody Erbitux for the treatment of metastatic colorectal 
carcinoma and to the accelerated approval of Alimta for locally 
advanced or metastatic non-small cell lung cancer. These are just a few 
of the new drugs offering fresh hope for patients with advanced cancer.
    We have made progress in preventing cancer from ever developing in 
the first place, especially in people at high risk. An example is the 
creation of a vaccine that has prevented women from becoming 
persistently infected with human papilloma viruses (HPV), an infection 
that is responsible for half of all cervical cancers.
    Now we must quicken the pace of progress because the trajectory is 
clear: discovery of cancer's genetic and molecular mechanisms leads to 
development of innovative interventions that--when delivered to 
patients--save lives. Building on this knowledge, the promise of 
tomorrow's advances is just over the horizon. This hopeful prospect 
will be realized by investing in strategic research areas, including: 
cancer genomics, biomarkers, molecular imaging, nanotechnology, and 
bioinformatics.

                    ADVANCED TECHNOLOGY INITIATIVES

    The technology revolution is speeding up and enabling the discovery 
process. Recent advances in molecularly-targeted imaging will allow us 
to locate very small tumors and interrogate their features. 
Nanotechnology has emerged as a key strategy for imaging molecular 
features of cancer that are notoriously difficult to detect. In one 
case, a team of NCI-supported scientists has crafted a nano-sized 
device--less than 1/80,000 the width of a human hair--to identify areas 
of new blood vessel growth, which is characteristic of growing tumors. 
Further, drugs attached to agents that seek out the proteins on cancer 
cells will target therapy to exactly where it is needed without damage 
to healthy cells.
    The development, integration, and coordination of advanced 
technologies are pivotal to enabling the biomedical and cancer research 
advances that are necessary to achieve NCI's 2015 goal. The Institute 
has played a crucial role in charting the path and collaborating in 
efforts to support bold new programs in this crucial arena.
    For instance, the National Advanced Technologies Initiative for 
cancer (NATIc) is a plan to create a nationwide ``virtual'' laboratory 
for cancer. The NATIc plan envisions a network of state and regional 
technology ``hubs'' focused on several strategic areas, including 
advanced computing, nanotechnology, and biorepositories.
    NCI has already begun development of the cancer Biomedical 
Informatics Grid (caBIG) to create a ``world-wide web'' for cancer 
research. The goal is to create a network of interconnected data, 
applications, individuals, and institutions that will redefine how 
cancer research is conducted and care is provided. During its initial 
year, the caBIG enterprise began bearing its first fruits with the 
release of NCI's caArray, a prototype software application that is made 
freely available to facilitate the sharing and analysis of microarray 
data by the medical research community. NCI and its partners in 
academia and industry are also developing an online information 
infrastructure to support clinical trials management and electronic 
drug approval submissions to the FDA. The first system module--the 
Federal Investigator Registry (Firebird)--starts pilot testing this 
spring.
    In addition, NCI has for the first time adopted a modern business 
model approach to our research and development program for cancer-
imaging technologies. This entailed creation of an Imaging Integration/
Implementation (I\2\) Team that recently submitted a proposed business 
plan for a new entity to be called I\2\ Imaging, Inc. The goal is to 
create distinct product lines to organize NCI's imaging program and 
clearly define measurable goals for each of the product lines. The plan 
includes four R&D programs encompassing imaging technologies for: (a) 
understanding of cancer biology and microenvironments; (b) cancer 
prevention and preemption; (c) development and preclinical validation 
of therapies; and (d) tools for clinical trial support.

                     STRATEGIC RESEARCH INITIATIVES

    Exponential advances in cancer research are defining, with ever 
increasing specificity, the many genetic, molecular, and cellular 
events that influence the cancer process. We now understand cancer as 
an ongoing process that can be interrupted at many stages--from 
susceptibility to initiation to disease progression. We are translating 
this new knowledge into innovative strategies to prevent cancer from 
developing, eliminate it early when it does occur, and modulate its 
devastating effects. This involves NCI making strategic investments in 
several research areas.
    Cancer prevention, early detection, and prediction.--New evidence-
based interventions encourage lifestyle improvements in diet and 
physical activity, discourage tobacco use, and promote safe and fully-
tested chemoprevention approaches for people at risk. Pioneering 
proteomic and biomarker advances, and the promise of nanotechnology, 
give us new hope for the early detection of cancer and prediction of 
patient responses to treatment.
    Development of strategic cancer interventions.--One of NCI's key 
strategies is to optimize the development and speed delivery of 
targeted cancer diagnostics, therapies, and preventives to patients. 
This is evidenced by NCI's investments into the Cancer Genome Anatomy 
Project, Academic Public-Private Partnership programs, and Rapid Access 
to Intervention Development (RAID).
    An integrated clinical trials system.--NCI provides leadership, 
resources, and expertise for clinical trials programs that span the 
discovery of novel molecules to the evaluation of new agents and 
interventions. To make clinical trials more efficient and to accelerate 
and improve the regulatory approval process, NCI is enhancing its 
working relationship with the FDA and the Department of Health and 
Human Services' (DHHS) Office of Human Research Protections to develop 
more streamlined policies and procedures for the conduct of clinical 
trials.
    Integrative cancer biology.--Integrative cancer biology is the 
study of cancer as a complex biological system. NCI's initiatives in 
this cutting-edge area include creating computational models of the 
complex networks within and among cancer cells, building our 
understanding of the tumor microenvironment, and studying the role of 
the tumor macroenvironment in cancer development.
    Molecular epidemiology.--NCI is developing novel ways to unravel 
the complexities of inherited and environmental contributions to cancer 
causation. Future investments will help scientists uncover risk 
factors, identify genetically susceptible individuals, and generate 
individual and public health strategies to avoid or mitigate adverse 
genetic exposures.

                       INTERAGENCY COLLABORATIONS

    Cancer is a large and complex problem with scientific, medical, 
social, cultural, and economic dimensions. Addressing this problem 
requires that NCI work across institutional and sector boundaries, 
share knowledge, and bring together the diverse members of the DHHS 
family of agencies, as well as other Federal offices, that can help 
develop systems-based solutions to the cancer problem. Just within the 
National Institutes of Health (NIH), NCI collaborates with virtually 
all of the 27 Institutes and Centers. Likewise, NCI also has many 
ongoing collaborations with several DHHS agencies. The ultimate 
beneficiaries of this continued cooperative effort will be cancer 
patients and their families.
    NCI and FDA created an Interagency Oncology Task Force (IOTF) to 
remove bottlenecks in the process of developing and approving safe, 
more effective cancer interventions. IOTF, which is comprised of senior 
representatives from both agencies, has been meeting regularly to 
define key areas of mutual interest and concern. As a result, the NCI-
FDA Cancer Training Fellowship Program was launched in 2005. The 
program will train a cadre of scientists in research and research-
related regulatory review so that they can develop skill sets that 
bridge the two distinct processes.
    NCI is also an active participant in the Medical Innovation Task 
Force established last year by DHHS. The group--which also includes the 
FDA, the Centers for Disease Control and Prevention, the Centers for 
Medicare & Medicaid Services, and the NIH--is weighing new ideas and 
solutions to encourage innovation in health care. The interagency panel 
seeks to speed the delivery to market of effective new medical 
technologies, such as drugs, biological products, and medical devices.

                              NIH ROADMAP

    NCI's contributions to NIH Roadmap initiatives will increase NCI's 
ability to support the collaborative research critical to cancer 
studies. Cooperation across the cancer continuum is vital for continued 
progress. The NIH Roadmap mechanisms support research in cancer biology 
that will also enhance continued interdisciplinary research to address 
vital questions related to cancer and the immune system, the interface 
of aging and cancer, and the role of microbial agents in the etiology 
of human cancers. By encouraging interdisciplinary teams to evolve in 
both directed and serendipitous ways, these new funding mechanisms 
complement and enlarge NCI's efforts toward the integration and cross-
fertilization of research efforts that span the cancer spectrum.

                      CHALLENGES AND OPPORTUNITIES

    In the coming years, we will face a number of critical challenges 
and opportunities. We stand on the brink of a new age of ``personalized 
oncology''--delivering the right treatment to the right patient at the 
right time to halt cancer-causing processes in the body before they 
cascade into advanced disease states. NCI is driven to meet the 2015 
challenge goal. Cancer is a public health and financial challenge for 
the United States. NIH estimates that in 2003, the total cost of cancer 
was over $189 billion: $64 billion in direct medical costs (much of it 
paid by Medicare) and $125 billion from lost productivity due to 
illness and premature death. More telling, 570,000 Americans lost their 
lives to the disease last year, according to the American Cancer 
Society. 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 future due to the 
aging and changing demographics of our population. NCI and its partners 
are committed to making progress toward the goal of eliminating 
suffering and death due to cancer in the next 10 years.
    Thank you, Mr. Chairman. I would be pleased to answer any question 
that the Committee may have.
                                 ______
                                 
  Prepared Statement of Dr. Barbara Alving, Acting Director, National 
                     Center for Research Resources

    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 2006, a sum of $1,100,203,000, which 
reflects a net decrease of $14,887,000 over the comparable fiscal year 
2005 appropriation. Within the total is $162,618,000 for AIDS research.
    I am delighted to have this opportunity to share with you the 
scientific advances achieved by NCRR-supported investigators and the 
future directions for NCRR programs. As the ``research resources'' 
component of the National Institutes of Health, NCRR's mission is to 
ensure that scientists have the necessary tools and access to research 
environments to conduct their progressively more complex research on 
human disease. With ready access to essential tools, our nation's top 
scientists may creatively explore promising new research avenues that 
will ultimately enhance human health.
    Because of its cross-disciplinary programs, NCRR supports research 
tools and infrastructure that enable all lines of biomedical inquiry, 
from studies of molecular structures to clinical trials that evaluate 
potential therapies. Most NCRR-supported research resources are shared 
and accessible to scientists nationwide. These shared resources include 
advanced instrumentation and novel technologies, animal models of human 
disease, and electronic networks for collaborations among investigators 
in less populated areas. In addition, through the Institutional 
Development Award program, NCRR provides support to institutions in 23 
states and Puerto Rico to develop new research facilities, equipped 
with state-of-the art research tools.
    NCRR encourages resource sharing because it broadens access to 
essential tools, is cost effective, and leverages precious federal 
research support. Each year, NCRR-funded research resources are used by 
more than 35,000 investigators who receive their primary research 
support from other NIH components, other federal agencies, and the 
private sector. Let me briefly describe just a few of the science 
advances that these researchers achieved over the past year.

         OBESITY STUDIES AIDED BY ANIMAL AND CLINICAL RESOURCES

    Scientists who seek to determine the genetic defects of many human 
diseases are often stymied by the fact that common conditions--from 
obesity to psychiatric disorders--are influenced by multiple genes. 
Therefore, researchers have turned to inbred mice as a model system for 
detecting genetic regions that contribute to complex disease. Using 
unique mouse strains available through an NCRR resource, scientists 
examined genetic factors that affect many complex traits, including 
obesity and anxiety. With this approach about 150 previously 
undiscovered genetic regions were discovered. This effort may narrow 
the search for specific genes that contribute to obesity and also pave 
the way for finding similar genes in humans.
    NCRR's General Clinical Research Centers (GCRCs) provide an ideal 
research environment for studies of obesity, an increasing public 
health concern. Particularly valuable are the GCRCs' highly trained 
staff and state-of-the-art equipment that can analyze a patient's 
metabolism and track consumption of all foods, down to the level of 
micronutrients. At the University of California, Los Angeles, 
researchers depend on the GCRC for their carefully controlled studies 
of the hormones that affect appetite and metabolism. One study found 
that injections of the hormone leptin can reduce body weight by more 
than 50 percent in obese individuals born with leptin deficiency. At 
Yale University's GCRC, scientists evaluated hundreds of overweight 
children and adolescents and found that about half of the severely 
obese have a condition that raises their risk of heart disease and type 
2 diabetes. Ultimately, better understanding of the risk factors and 
potential therapies for obesity could lead to a leaner, healthier 
population.

                  ADVANCES IN TRANSPLANTATION RESEARCH

    As mentioned earlier, the GCRCs continue to have a significant role 
for advancing human health. For instance, the GCRCs enabled pioneering 
clinical studies related to transplantation, from the earliest 
successes with organ transplants in the 1960s to the current 
microtransplants of genes into cells. One recent success, reported in 
the Journal of the American Medical Association this past February, 
showed that islet cells from a single human pancreas can be 
transplanted into up to eight patients with type 1 diabetes, a 
condition in which the pancreatic islet cells do not make insulin. All 
eight transplant recipients achieved normal glucose levels without the 
need for insulin injections. Ongoing advances in transplantation 
illustrate how federally funded efforts--among molecular biologists, 
geneticists, animal researchers, and clinical investigators--lay a 
solid foundation for improving human health through the effort of a 
team of investigators.

                  BIODEFENSE AND TECHNOLOGY RESOURCES

    Besides clinical and comparative medicine resources, NCRR also 
supports biomedical technology centers that develop and provide 
scientists with access to innovative instruments, technologies, and 
computational tools. These technology centers have enabled recent 
advances to help scientists determine how infectious agents, like 
anthrax, induce their deleterious clinical effects. The anthrax 
bacterium is unusual because it produces large amounts of a toxin that 
can kill a patient even after the bacterium itself has been destroyed 
by antibiotics. A research team used x-ray data collected at an NCRR-
supported synchrotron resource to examine the structures of molecules 
that might disarm the deadly toxin. Synchrotrons are large machines 
(about the size of a football field) that accelerate electrons to 
almost the speed of light to produce intense x-rays with adjustable 
wavelengths that can be exploited to reveal the 3 dimensional 
structures of molecules. Further structural studies may lead to the 
development of effective toxin-blocking therapies for inhalational 
anthrax infections.
    In another study, scientists developed improved techniques for 
identifying microbes by their DNA ``fingerprints''--a critical advance 
in this age of bioterrorism and emerging diseases--and shorten the 
timeframe needed to identify the toxic agent. Using laser technology at 
an NCRR-supported flow cytometry resource, scientists analyzed and 
measured tiny samples of DNA from a Staphylococcus aureus bacterium. 
The analysis can be completed in just 30 minutes, compared to the 24 
hours normally required to analyze DNA. Advanced computational methods 
linked to the new technology may boost efforts to detect and track 
microbial threats and provide sufficient time to alert individuals at 
risk.

               INFORMATICS AND INTERDISCIPLINARY SCIENCE

    NCRR's shared resources provide a fertile environment for 
interdisciplinary collaboration. Such studies are essential for 
addressing important but complex research problems that scientists 
grapple with today. For instance, NCRR supports a large-scale 
interdisciplinary effort known as the Biomedical Informatics Research 
Network (BIRN). That effort draws on multiple resources to examine 
increasingly complex problems in neuroscience. BIRN is the nation's 
first test bed for online sharing of research resources and expertise, 
and for effective data mining for both basic and clinical research. The 
initial effort focuses on neuroscience, since that discipline holds the 
largest data sets and requires the capacity to transmit large, 
information-rich images of the brain. BIRN will be extended to other 
research areas. Ultimately, the network will enhance the translation of 
basic research to the patient.

                              NIH ROADMAP

    The NIH Roadmap complements many NCRR programs, and as a result 
NCRR staff members are involved in virtually every Roadmap Working 
Group. NCRR is leading the Exploratory Centers for Interdisciplinary 
Research program. These Centers are developing approaches that will 
allow researchers from very different scientific disciplines to work 
together to solve difficult biomedical or behavioral problems. NCRR is 
also leading the National Technology Centers for Networks and Pathways 
program that aims to develop new technologies to study molecular 
interactions within intact cells. NCRR has a significant role in 
another Roadmap initiative, the National Centers for Biomedical 
Computing, that will provide the infrastructure needed to promote 
productive interactions between computational scientists and biomedical 
researchers.

               STRATEGIC PLANNING AND FUTURE INITIATIVES

    This past year, NCRR published a new strategic plan for 2004-2008. 
Titled Challenges and Critical Choices, the plan was developed based on 
input from thousands of researchers and administrators for research-
intensive organizations nationwide. This strategic plan now guides 
NCRR's priorities for programmatic investments. I would like to briefly 
describe just a few of the initiatives that NCRR has launched, or plans 
to launch, to address the plan's recommendations.

Informatics for Clinical Research
    The scientists who participated in NCRR's strategic planning 
process highlighted cyberspace infrastructure that would significantly 
enhance information sharing, access to and management of vast datasets, 
and transmission of large data objects like brain images as a priority. 
NCRR has initiated an assessment to determine current capabilities and 
future requirements for electronic communication and information 
management across research centers, including the GCRCs, Research 
Centers in Minority Institutions, and biomedical technology research 
centers. One long-term goal is to support collaborations among 
investigators located in less densely populated states.

Enhance Protection of Clinical Research Subjects
    Another important trend identified during NCRR's strategic planning 
process involves the public's growing concern for the safety of 
participants in clinical research studies. NCRR created a Research 
Subject Advocate (RSA) program to assure appropriate safety monitoring 
of research subjects for GCRC-based studies and to ensure that 
investigators are aware of their responsibilities under State and 
Federal law. Because the RSA program has had such a positive impact, 
NCRR remains committed to strengthening the program.

Expand Availability of Nonhuman Primate Stem Cells
    Another NCRR initiative will focus on stem cells, which hold the 
potential for treating a variety of disorders. But extensive animal 
studies are needed to identify the molecules, cytokines or other agents 
that modulate stem cell differentiation. NCRR proposes to support 
research to identify these factors and to isolate several different 
embryonic stem cell lines from the rhesus macaque, baboon, and a few 
other nonhuman primate species. Isolated cell lines will be distributed 
to qualified scientists via a national resource, and a companion 
database will track relevant data for each cell line. Information 
gleaned from these studies may be applicable to the study of human stem 
cells.

                               CONCLUSION

    In closing, as biomedical research becomes more complex, 
specialized research resources are required to address emerging trends 
and build bridges across disciplines. NCRR plays a cross-cutting, 
trans-NIH role in biomedical research, supporting state-of-the-art 
resources that enable collaboration and stimulate scientific discovery. 
These research resources play an essential role in advancing human 
health.
    Thank you, Mr. Chairman. I would be pleased to answer any questions 
that the Committee may have.
                                 ______
                                 
Prepared Statement of Dr. Duane Alexander, Director, National Institute 
                 of Child Health and Human Development

    Mr. Chairman and Members of the Committee: I am pleased to present 
the fiscal year 2006 President's budget request for the National 
Institute of Child Health and Human Development (NICHD). The fiscal 
year 2006 budget includes $1,277,544,000, an increase of $7,223,000 
over the fiscal year 2005 enacted level of $1,270,321, comparable for 
transfers proposed in the President's request.
    With the continued support of this Committee, the National 
Institutes of Health has the unique ability to invest in complex 
medical studies that continue for many years. It is particularly 
satisfying to all of us when an investment in research cures a disease 
or eradicates a condition. With deep satisfaction, we report a major 
medical and public health achievement that the New York Times heralded 
a few weeks ago in a front page headline: U.S. is Close to Eliminating 
AIDS in Infants.
    This progress came in small incremental steps that arose from a 
large ambitious vision: to eliminate mother-to-child HIV transmission. 
Just a decade ago, a pregnant woman with HIV who lived in the United 
States had more than a 25 percent chance of passing the virus on to her 
child. In the early 1990s, the NICHD and the NIAID formed the Pediatric 
AIDS Clinical Trials Group to test promising new anti-HIV treatments. 
One of the first studies showed that the drug AZT administered to the 
mother and newborn infant at specific times could reduce HIV 
transmission from 25 percent to 8 percent. Subsequent research tested a 
drug combination known as highly active anti-retroviral therapy (HAART) 
and showed that the rate of transmission could be reduced even further. 
Today, with an expanded array of anti-HIV drug treatments, the chance 
of a pregnant woman in the United States passing the virus on to her 
child has plummeted to about 1.2 percent.

          COMPOUNDS IN MOTHERS' MILK PROTECT AGAINST DIARRHEA

    Human breast milk is known to protect infants from diarrhea, but 
the responsible components had not been known. Results of a routine 
investigation to understand the purpose of some complex sugar molecules 
found in human breast milk may lead to a way to prevent diarrheal 
diseases from occurring, not just in infants, but in older children and 
adults as well. The molecules, called oligosaccharides, are abundant in 
human breast milk. During the last decade, NIH-funded researchers have 
discovered that oligosaccharides can stop bacteria and viruses from 
binding to the cells in the intestinal wall, preventing diarrheal 
diseases from gaining a foothold.
    Oligosaccharides have been found to combat E. coli 0157, the deadly 
bacterium that can infect ground beef and other common foods. They also 
block the Norwalk virus, which incapacitates thousands of cruise ship 
voyagers every year, as well as rotavirus, one of the most common 
causes of diarrheal diseases in children. Oligosaccharides may also 
provide a means to overcome the problem of bacterial resistance. They 
function differently than do antibiotics, and bacteria do not appear 
able to develop resistance to the oligosaccharides.

               RESEARCH LEADS TO BETTER HEALTH FOR WOMEN

    Fibroids, or leiomyomas, are painful noncancerous growths that 
develop in the smooth muscle of the uterus. Women with fibroids may 
have painful menstrual periods, pain during intercourse, infertility, 
incontinence, and bowel obstruction. Women with fibroids are also more 
likely to go into labor prematurely and to experience a miscarriage. 
The exact number of women with fibroids is not known, but between 25 
and 40 percent of all U.S. women experience fibroid symptoms. Fibroids 
disproportionately affect African Americans. One study estimated that 
80 percent of African American women have fibroids by age 60. There are 
few effective ways other than hysterectomy to treat these tumors. 
Recently, however, NICHD researchers made some basic discoveries about 
fibroids that may lead to effective non-surgical treatments. In one 
study, researchers used sophisticated gene analysis technology to learn 
that fibroids contained abnormally high levels of a protein known as 
dermatopontin. That study led to another discovery that fibroids are 
largely made up of abnormal strands of collagen; thus, researchers are 
now searching for new drug treatments directed toward the abnormal 
collagen.
    Pregnancy and childbirth place women at higher risk for a disorder 
known as pelvic organ prolapse, which can be painful and disabling, and 
require surgical treatment. Although surgical procedures may correct 
the condition, many women may experience urinary incontinence as a 
result of such treatment, which may require a second surgery to 
correct. From early results of a clinical trial, NICHD-funded 
researchers have learned that performing an incontinence surgical 
procedure during the same operating room session as the prolapse repair 
markedly decreases the chances for incontinence, without adverse 
effects. Such findings not only have implications for improving the 
quality of life for women, but may have implications for helping to 
reduce the cost of care.

                       RESEARCH ENHANCES LEARNING

    After more than 30 years of careful research--using the same 
scientific rigor we use to test a new drug or medical procedure--the 
NICHD has identified the instructional methods that best help children 
learn to read. A recent brain imaging study has shown that these 
scientifically proven methods actually change the brain functioning of 
formerly poor readers so that it resembles the brain functioning of 
good readers.
    Unfortunately, however, many school districts still rely on 
instructional practices that are not based on scientific research. 
According to the National Center for Education Statistics, roughly 37 
percent of the nation's 4th graders read below grade level. In 
collaboration with the Department of Education, NICHD staff is working 
to communicate evidence-based research findings to provide school 
districts around the country with new approaches to teach reading. To 
be competitive in the years ahead, U.S. students will also need a 
thorough grounding in science. A recent study has challenged current 
thinking on the best way to teach science. The traditional belief was 
that students would better remember what they learn if they discovered 
on their own how to conduct an experiment rather than having someone 
teach it to them. In fact, the researchers found just the opposite: 
that students learned faster and retained more information if they were 
given explicit instructions about experimental procedures. The finding 
provides teachers with important information on how best to convey 
scientific concepts to their students.
    Our basic science laboratories continue to produce discoveries of 
potential clinical relevance to learning and mental retardation. NICHD 
scientists discovered that a single protein appears central to the 
formation of the long-term memories underlying all advanced learning. 
Two teams of NICHD scientists have discovered how the protein known by 
the acronym BDNF is produced in the brain and are studying whether 
defects in the BDNF protein system may lead to disorders of learning 
and memory. Other scientists have studied an animal model of the 
defective Rett syndrome gene that causes deterioration of cognitive and 
motor function in girls to learn how the gene causes anatomic and 
functional abnormalities. Studies also continue on the genetic and 
neurobiologic bases of autism.

               KIDS MAY SAY OTHERWISE, BUT PARENTS MATTER

    Several NICHD studies of child development provide strong evidence 
that parents can exert a direct and positive influence on the decisions 
that children and young adults make. For example, researchers had 
suspected for some time that extensive television viewing at an early 
age might be associated with decreased attention span in children. 
However, they had no data from long-term studies to support this 
observation. So NICHD-funded researchers designed a study to answer an 
important question: do children who watch increasing amounts of TV at 1 
and 3 years of age have increase attention problems at age seven? The 
researchers analyzed data from an ongoing study involving more than 
2,600 children and found that the more television very young children 
watched, the more likely they were at age seven to have attention 
problems. These findings do not mean that early television viewing is 
associated with clinically diagnosed attention-deficit/hyperactivity 
disorder (ADHD). However, the findings support the idea that parents 
could reduce the risk for attention problems by limiting children's 
television viewing in their early years.
    NICHD scientists have also developed a research-based tool that 
parents can use to significantly reduce the risks that young, 
inexperienced drivers face. Insurance companies have known for some 
time that motor vehicle crash rates are higher for teenagers than for 
older drivers and are the highest during the first 1,000 miles and the 
first 6 months of driving. The researchers developed and tested a 
program in which the central feature is a contract between the parent 
and new driver. As part of this contract, the newly licensed driver 
agrees to limit driving at night, driving with other teens in the car, 
driving on high-speed roads, and driving in bad weather. NICHD research 
showed that parents can greatly reduce the risks that new drivers face.

        REHABILITATION NETWORKS SEEK TO IMPROVE QUALITY OF LIFE

    Serious illness and injury may result in life-long impairment. The 
Traumatic Brain Injury Clinical Trials Network will evaluate new 
treatments and rehabilitation techniques for children and adults with 
brain injury. The Pediatric Critical Care Network will evaluate new 
treatments for children who have suffered a serious injury or illness. 
The Network will study the effectiveness of short-term treatment and 
its relationship to the rehabilitation that patients receive and to the 
long-term outcomes.

               THE BEST PHARMACEUTICALS FOR CHILDREN ACT

    The NICHD, as directed by law, in consultation with the FDA and 
experts in pediatric drug development, has identified and prioritized 
the most important drugs for further study in children. Currently, 
children are being recruited to study lorazepam for use as a sedative 
and anticonvulsant, and nitroprusside for controlling blood pressure of 
children undergoing surgery. In cooperation with the National Cancer 
Institute, data pertaining to the drugs vincristine and dactinomycin 
are being reviewed to provide the first evidence-based look at the 
efficacy, toxicity, and dosing of these two drugs. The evidence from 
this review will provide the basis for subsequent studies that will 
provide specific guidance on the use of these drugs in children. Drugs 
on the current priority list will form the basis of solicitations in 
2006.

                     THE NATIONAL CHILDREN'S STUDY

    NICHD scientists working collaboratively with the NIEHS, the CDC, 
and the EPA continue to make progress in planning the implementation of 
the National Children's Study as directed by Congress in the Children's 
Health Act of 2000. The Study, as currently planned, will involve about 
100,000 children and their families, and can form the basis of child 
health guidance, interventions, and policy for generations to come. 
Funds in the fiscal year 2005 budget are being used to establish four 
Vanguard Centers that will pilot recruitment strategies and the Study 
protocol. A data coordinating center will be established to provide the 
statistical analysis and reporting of the Study results. The protocol 
for this Study has been drafted and 101 sites across the United States 
have been identified to provide a population-based representative 
sample. These steps bring us closer to the point at which the full 
study could be implemented.

                              NIH ROADMAP

    The NIH Roadmap initiative is providing an important guide to help 
the NICHD achieve its research and programmatic goals. The initiative 
directed to Re-engineering the Clinical Research Enterprise is 
currently helping to develop future leaders in clinical research. The 
NICHD is leading several targeted efforts to enhance the training, 
development, and support of the clinical research teams of the future.
    Mr. Chairman and members of this Committee, I would like to thank 
you for your continued support of our research to improve the health 
and well being of women, children and families, as well as for your 
support in the critical task of developing tomorrow's research leaders. 
I will be pleased to answer any questions.
                                 ______
                                 
Prepared Statement of Dr. Jeremy M. Berg, Director, National Institute 
                      of General Medical Sciences

    Mr. Chairman and Members of the Committee: I am pleased to present 
the fiscal year 2006 President's budget request for the National 
Institute of General Medical Sciences (NIGMS). The fiscal year 2006 
budget includes $1,955,170,000, an increase of $11,103,000 over the 
fiscal year 2005 enacted level of $1,944,067,000 comparable for 
transfers proposed in the President's request.

      UNDERSTANDING DISEASE REQUIRES UNDERSTANDING NORMAL FUNCTION

    As we go about our daily lives, most of us probably forget about 
the biological processes that make our bodies work. Our cells are 
constantly making new components, dividing, moving, and even dying. 
Complex mechanisms underlie each of these processes and elaborate 
networks integrate them to promote normal, healthy function. If any of 
these processes break down, the result can be cancer, diabetes, 
Alzheimer's, or a host of other diseases.
    To improve our understanding of basic biological processes, we need 
to employ a wide range of approaches. These include conducting basic 
research, developing new technologies, and training tomorrow's 
scientists. In essence, this is the core mission of NIGMS. For more 
than 40 years, the Institute has focused on deepening understanding of 
critical life processes and the molecular underpinnings of disease. In 
this way, NIGMS lays the foundation for advances in the diagnosis, 
treatment, and prevention of many different illnesses.

             PARADIGM-SHIFTING IDEAS AND THEIR APPLICATION

    NIGMS has an impressive track record of investing in research with 
big payoffs. One indication of this success comes from the many 
prestigious awards our grantees receive for their research. In each of 
the last 8 years, at least one Nobel Prize has been given to an NIGMS 
grantee. This year continues the trend: The 2004 Nobel Prize in 
chemistry went to Irwin Rose, Ph.D., a biochemist at the University of 
California, Irvine, whose work has been supported by the Institute for 
several decades. He brings the number of NIGMS-supported Nobel 
laureates to 57.
    Rose shared the prize for his studies on how cells control the 
breakdown of unneeded proteins. The mechanism for this controlled 
breakdown underlies many processes in health and disease and is now the 
focus of literally thousands of research studies. The discoveries 
flowing from this basic research are increasingly being translated into 
new therapies. For example, Alfred Goldberg, Ph.D., an NIGMS grantee at 
Harvard Medical School in Boston, initiated research that led to a new 
drug called Velcade. This drug is used to treat multiple myeloma, a 
deadly type of bone marrow cancer. Velcade works by targeting the 
proteasome--the molecular machine that breaks down unneeded proteins 
that Rose and his coworkers discovered. Velcade is likely to be the 
first of a number of drugs based on the discovery of this process that 
is so fundamental to much of cell biology.
    The path to new approaches for promoting health and preventing and 
treating diseases has several key elements. These include creatively 
exploring a range of biological systems, developing tools for expanding 
knowledge, finding appropriate ways to integrate this knowledge into 
practical applications, and, of course, having a workforce of 
scientists who have the motivation and the knowledge to drive these 
advances.

           FROM CARNIVOROUS SNAILS TO A NOVEL PAIN TREATMENT

    It is tough to make a living as a carnivorous snail. A large family 
of such creatures, called cone snails, relies on extremely potent venom 
to paralyze prey almost instantly. Baldomero Olivera, Ph.D., a 
biologist at the University of Utah in Salt Lake City, has been 
studying cone snails for more than 25 years with NIGMS support, 
carefully separating the venom into its components and studying each 
one.
    Remarkably, the venom components are small proteins that target 
structures within the neuromuscular system with exquisite specificity. 
Because of the roles of their targets and this great specificity, these 
proteins are powerful research tools and show great promise as drugs. 
The first drug to result from this work, Prialt, was approved by the 
FDA in December 2004 to treat the chronic, intractable pain often 
endured by people with cancer, AIDS, or certain neurological disorders. 
One thousand times more powerful than morphine, this new pain 
medication is thought to be non-addictive.
    Other recently discovered pathways are leading to new drugs as 
well. The process of RNA interference, first characterized in 
roundworms by NIGMS grantees, can specifically silence individual 
targeted genes. Harnessing this process has allowed scientists to 
precisely control genes, leading to exciting new research tools and 
promising new ways to treat diseases including HIV, hepatitis, and 
cardiovascular disease. An RNA interference-based drug to treat the 
blinding eye disease of macular degeneration is currently in clinical 
trials.

                      THE SHAPES OF THINGS TO COME

    The human genome is expressed primarily through proteins, the 
molecules that perform virtually all of the body's activities. Based on 
their amino acid sequences, proteins fold into complex shapes that 
determine their functions, including which other molecules they bind to 
form complex assemblies. Powerful techniques have been developed for 
determining protein structures in great detail. Thousands of such 
structures have been determined, providing deep insights into how 
biological systems function in health and disease and driving the 
development of new drugs and other therapies. Much of this work has 
been performed by individual investigators working on individual 
proteins chosen based on their biological context. A productive 
laboratory might determine two to four structures per year. This 
approach continues to be effective, but it is too slow to keep up with 
the vast number of potential protein targets now accessible through 
genomic studies.
    To complement the contributions of individual investigators, NIGMS 
launched the Protein Structure Initiative (PSI) in 2000 with the goal 
of developing technologies and processes to enable researchers to 
quickly, cheaply, and reliably determine the three-dimensional 
structures of proteins. After 4 years, the nine PSI pilot centers can 
produce several structures each week, and the total number of 
structures solved by the PSI centers has now passed the milestone of 
1,000!
    With the second phase of the initiative beginning this summer, the 
PSI will use the tools and methods developed in the pilot phase to 
continue technology development and to determine more protein 
structures, including some that were too complex to tackle during the 
pilot phase. Researchers will use these structures to determine and 
understand protein function, predict the structures of other proteins, 
identify targets for drug development, design molecules to fit those 
targets, and compare proteins from normal and diseased tissues.
    An important activity related to the PSI is the structural biology 
component of the NIH Roadmap for Medical Research, which funded two 
Centers for Innovation in Membrane Protein Production to aid structural 
studies of this major class of proteins. Difficulties inherent in 
studying membrane proteins mean that we know relatively little about 
them, despite the fact that they represent up to a third of all 
proteins and are the targets for a large number of therepeutic drugs. 
NIGMS is actively involved in other Roadmap initiatives, as well, 
including those in the areas of high-risk research (specifically, the 
NIH Director's Pioneer Award), bioinformatics and computational 
biology, molecular libraries and imaging, and interdisciplinary 
research.

                    COMPUTERS MODEL COMPLEX SYSTEMS

    Today's biomedical research has moved beyond describing the parts 
of living systems to focusing on the complex, dynamic interactions of 
those parts. One of the best ways to approach this formidable challenge 
is to use computers to model and manipulate the systems.
    Among the places this is happening are the five NIGMS Systems 
Biology Centers. Multidisciplinary teams of researchers at these 
centers are addressing such fundamental questions as how cells divide, 
differentiate, and communicate and how different kinds of environmental 
stress affect cell and tissue function.
    At the other end of the spectrum, NIGMS-supported researchers are 
investigating how human systems contribute to the spread of infectious 
diseases. The researchers, part of the Institute's Models of Infectious 
Disease Agent Study (MIDAS) initiative, use computational approaches to 
simulate disease outbreaks, whether they occur naturally or result from 
bioterrorism. In much the same way as weather forecasters use computer 
models to predict the landfall of hurricanes, scientists can use the 
MIDAS models to make predictions about potential epidemics. These 
models will assist policymakers, public health workers, and other 
researchers in understanding and responding to new infectious disease 
outbreaks.
    Responding to the medical community's growing concern that avian 
influenza could cause the next flu pandemic, the MIDAS network 
currently is simulating the outbreak of a deadly bird flu strain in a 
hypothetical human community. The computer models incorporate data on 
population density and age structure, distribution of schools, 
locations of hospitals and clinics, travel, and the infectiousness of 
the virus. The models will predict the effects of different strategies 
to contain the spread of infection, such as vaccinating specific groups 
of people or restricting travel. Preliminary results from the avian flu 
modeling project should be available by mid-2005.

                       DIVERSITY DRIVES DISCOVERY

    To continue making rapid progress in biomedical research and 
improving human health, we need to ensure that the pool of biomedical 
scientists reflects the great diversity of our nation. This diversity 
can spark new research questions and offer different approaches to 
answering them. NIGMS promotes this diversity in a number of ways.
    Through our Division of Minority Opportunities in Research, we 
offer programs that encourage and prepare underrepresented minority 
students for research careers. Other programs enhance science curricula 
and faculty research capabilities at institutions with substantial 
minority enrollments.
    We require our institutional training programs to recruit and 
retain underrepresented minority students, as well. And we promote 
diversity of ideas through interdisciplinary training programs and 
through efforts to bring the expertise of researchers in a variety of 
fields, from the physical to the behavioral sciences, to bear on 
biomedical questions. One example is our partnership with the National 
Science Foundation that supports more than 30 research grants at the 
interface of biology and mathematics.

                         EXPANDING THE HORIZON

    Our increasing knowledge of the biological processes that underpin 
health and disease holds great promise for new drugs and better 
diagnostic techniques in the future. A more complete picture of how 
these processes work--and don't work--may lead to new methods for 
preventing illness altogether.
    At the same time, it is important to remember that breakthroughs 
are often based on years of scientific research, with each new result 
building on many previous ones. Each discovery pushes back the frontier 
and reveals intriguing new questions and avenues for future study. 
While we can't always predict what we'll find, we can guarantee that 
the journey will bring us closer to our goal of understanding human 
health and disease.
    Thank you, Mr. Chairman. I would be pleased to answer any questions 
that the Committee may have.
                                 ______
                                 
Prepared Statement of Dr. Francis S. Collins, Director, National Human 
                       Genome Research Institute

    Mr. Chairman and Members of the Committee: I am pleased to present 
the fiscal year 2006 President's budget request for the National Human 
Genome Research Institute (NHGRI). The fiscal year 2006 budget includes 
$490,959,000, an increase of $2,351,000 over the fiscal year 2005 
enacted level of $488,608,000 comparable for transfers proposed in the 
President's request.
    Cable News Network (CNN) recently named the completion of the Human 
Genome Project (HGP) the number one health news story of the past 25 
years. CNN reported, ``Much of the marvel of medicine has to do with 
discovery. Mapping the human genome, the complete sequence of DNA, gave 
scientists a blueprint for building a person, making it the No. 1 
medical story, according to a distinguished panel CNN gathered to rank 
the top 25 medical stories of the past quarter-century.'' As the leader 
of the HGP, the National Human Genome Research Institute (NHGRI) is 
very proud of this recognition, but as CNN also pointed out there is 
still a great deal more to learn.

                       ONGOING NHGRI INITIATIVES

Analysis of the Completed Human Genome Sequence
    In October 2004, the International Human Genome Sequencing 
Consortium, led in the United States by the NHGRI and the Department of 
Energy, published a description of the finished human genome sequence 
in the journal Nature. An international team worked to convert the 
draft genome, published in 2001, into a highly accurate form. The new 
analysis reduces the estimate of the number of human protein-coding 
genes from 35,000 to only 20,000-25,000--a surprisingly low number for 
our species, considering that only a decade ago most scientists thought 
there would be over 100,000 genes. We now focus on the more difficult 
task of understanding the function of each of these genes.

Use of Comparative Genomics to Understand the Human Genome
    The availability of the genome sequences of the human, the mouse, 
the rat and a wide variety of other organisms is driving the 
development of an exciting new field of biological research, 
comparative genomics. The NHGRI is funding research comparing the 
finished reference human genome sequence with that of other organisms, 
to identify regions of similarity and difference, thus dramatically 
increasing understanding of the structure and function of human genes 
to enable development of new strategies to combat human disease.

ENCyclopedia Of DNA Elements (ENCODE) project
    With the goal of identifying the precise location and function of 
all sequence-based functional elements in the human genome, the NHGRI 
launched the ENCyclopedia Of DNA Elements (ENCODE) project in the fall 
of 2003. The project is an international consortium of computational 
and laboratory-based scientists open to all investigators who agree to 
abide by the project's criteria and guidelines for participation. A 
manuscript describing the ENCODE project appeared in the October 22, 
2004 issue of Science, detailing the rationale and strategy behind the 
quest to produce a comprehensive catalog of all parts of the human 
genome crucial to biological function, including all protein-coding 
genes, non-protein-coding genes, regulatory elements involved in the 
control of gene transcription, and DNA sequences that mediate 
chromosomal structure and dynamics. All data generated for the ENCODE 
project are being deposited in free, public databases as soon as they 
are experimentally verified.

Progress with the HapMap
    All diseases have a hereditary component, but for most common 
diseases like diabetes, heart disease, and mental illness, the gene 
variants responsible for the increased risk have been difficult to 
identify. To solve this problem, an approach to scan large regions of 
chromosomes to find the genetic variants (called SNPs, or single 
nucleotide polymorphisms) that increase or decrease the risk of disease 
is needed. NHGRI has taken a leadership role in the International 
HapMap Consortium and the development of the HapMap (haplotype map), a 
catalog of human genetic variations and how that is organized into 
haplotype ``neighborhoods'' across the gene. Researchers are already 
starting to use the HapMap to find genes and variants that contribute 
to many diseases; it will also be a powerful resource for studying the 
genetic factors contributing to variation in individual response to 
disease, drugs, and vaccines.
    In February 2005, the International HapMap Consortium completed 
phase I of the project, ahead of schedule. Boosted by an additional 
$3.3 million in public-private support, the NHGRI announced plans to 
create an even more powerful map of human genetic variation than 
originally envisioned. The consortium's new goal is an improved version 
of the HapMap about five times denser than the original plan. This 
``Phase II'' HapMap will test another 4.6 million SNPs from publicly 
available databases and add that information to the map. The HapMap 
will be completed in the fall of 2005.

Gene Variants May Increase Susceptibility to Type 2 Diabetes
    Understanding the genetic basis of the more common, polygenic 
diseases has traditionally been very difficult. But the tools of 
genomics, especially HapMap, are beginning to reveal many details about 
the risk of common diseases that had previously been unapproachable. 
One disease for which excellent progress has been made towards 
understanding its genetic cause is Type 2 diabetes. Affecting about 17 
million people nationwide, it accounts for 90 to 95 percent of all 
diabetes cases in the United States. This past year, two international 
research teams, including one at NHGRI, each found variants in a gene 
that appears to predispose people to type 2 diabetes, the most common 
form of the disease. Homing in on a wide stretch of chromosome 20, the 
teams identified four genetic variants (SNPs) that are strongly 
associated with type 2 diabetes in Finnish and Ashkenazi Jewish 
populations and that appear to raise the risk of type 2 diabetes by 
about 20 to 30 percent. Translating this discovery into a treatment 
that benefits people with diabetes or those at risk is still years 
away, but this is a major step in that direction.

                            NEW INITIATIVES

Roadmap--Chemical Genomics
    The Molecular Libraries Roadmap initiative will offer public sector 
researchers access to libraries of novel small organic molecules that 
can be used as chemical probes to study the functions of genes, cells, 
and biochemical pathways. This marriage of chemistry and biology will 
provide new ways to explore the functions of major components of cells 
in health and disease. In June 2004, NHGRI announced the establishment 
of the NIH Chemical Genomics Center, and up to eight pilot extramural 
centers will be funded at academic institutions and other locations 
across the country in the spring of 2005. These will function as an 
integrated network, including a common publicly available database 
(PubChem, already activated in September 2004) which will display the 
results of all screens of chemical compounds.

Human Cancer Genome Project
    The dramatic drop in costs of DNA sequencing, catalyzed by the 
Human Genome Project, now makes it possible to use sequencing as a 
major tool for medical research. Doctors and research scientists have 
long known that cancer is, essentially, a genetic disease. Inherited 
mutations or acquired genetic alterations can set a normal cell on a 
path of uncontrolled growth and malignancy. It is now conceivable to 
identify the complete universe of genes involved in every type of 
cancer. That is the intent of a bold new NCI/NHGRI proposal for a Human 
Cancer Genome Project. Such a complete inventory of cancer genes will 
provide powerful new ways to prevent, diagnose, and treat every major 
form of the disease.

The $1,000 Genome Project
    The ability to determine the complete genome sequence of an 
individual could revolutionize medical care. In October 2004, NHGRI 
awarded more than $38 million in grants to spur the development of 
innovative technologies designed to reduce the cost of DNA sequencing 
dramatically. NHGRI's near-term goal is to lower the cost of sequencing 
a mammalian-sized genome to $100,000, which would enable researchers to 
sequence the genomes of hundreds or even thousands of people as part of 
studies to identify genes that contribute to cancer, diabetes, and 
other common diseases. Ultimately, NHGRI's vision is to cut the cost of 
whole-genome sequencing to $1,000 or less, which would enable the 
sequencing of individual genomes as part of medical care. The ability 
to sequence each person's genome cost-effectively could give rise to 
more individualized strategies for diagnosing, treating, and preventing 
disease. Such information could enable doctors to tailor therapies to 
each person's unique genetic profile.

The U.S. Surgeon General's Family History Initiative
    The U.S. Surgeon General's Family History Initiative was launched 
on November 8, 2004, with the NHGRI as the lead collaborating federal 
agency. The purpose of this national public health campaign is to: 
increase the awareness of the American public and their health 
professionals about the importance of family history in health; provide 
tools to gather, understand, evaluate, and use family history to 
improve health; give health professionals tools to communicate with 
patients about family history; and increase genomic and health 
literacy. A web based and print tool entitled ``My Family Health 
Portrait'' was developed in both English and Spanish to facilitate 
collection of family history data. To date, the initiative has been 
highlighted in more than 1,000 media stories and over 170,000 copies of 
the tool have been distributed via the World Wide Web and in paper 
form. This public health campaign is intended to be an annual event.

ELSI Centers for Excellence Program
    On August 31, 2004, the NHGRI's Ethical Legal and Social 
Implications (ELSI) research program announced the funding, with 
contributions from the Department of Energy and the National Institute 
of Child Health and Human Development, of four interdisciplinary 
centers as part of its Centers for Excellence in ELSI Research (CEER) 
program, a new initiative to address some of the most pressing ethical, 
legal, and social questions facing individuals, families, and 
communities in the genome era. Each of the centers, based at Duke 
University, Case Western Reserve University, Stanford University, and 
the University of Washington, will assemble a team of experts in 
several disciplines, such as bioethics, law, behavioral and social 
sciences, clinical research, theology, public policy, and genomic 
research.

                        OTHER AREAS OF INTEREST

Genetic Education for Health Care Professionals
    The NHGRI has developed numerous educational programs to prepare 
health care professionals for the integration of genomics into primary 
health care. A new effort by the NHGRI in this area in 2004 was its 
work with the American Academy of Family Physicians (AAFP) to develop 
the AAFP's 2005 Annual Clinical Focus program, which has Genomic 
Medicine as its theme.

Genetic Nondiscrimination
    Possibly the greatest impediment to the advancement of genomic 
science and its application to human health is the fear of genetic 
discrimination. The NHGRI has worked for ten years to realize a federal 
solution to this problem. The Secretary's Advisory Committee on 
Genetics Health and Society has also strongly supported the need for 
federal legislation. On February 17, 2005 the Senate passed the Genetic 
Information Nondiscrimination Act of 2005 (S. 306), which would address 
these fears, and the Bill has now been referred to the House. The Bush 
Administration has also issued a Statement of Administrative Policy in 
support of the legislation. This issue remains a high priority for the 
Institute.
    Thank you, Mr. Chairman. I would be pleased to answer any questions 
that the Committee might have.
                                 ______
                                 
    Prepared Statement of Dr. Patricia A. Grady, Director, National 
                     Institute of Nursing Research

    Mr. Chairman and Members of the Committee: I am pleased to present 
the fiscal year 2006 President's budget request for the National 
Institute of Nursing Research (NINR). The fiscal year 2006 budget 
includes $138,729,000, an increase of $657,000 over the fiscal year 
2005 enacted level of $138,072,000 comparable for transfers proposed in 
the President's request.
    I appreciate the opportunity to appear before you today to discuss 
the exciting work of the National Institute of Nursing Research (NINR) 
that provides important science to provide necessary improvements in 
the quality of patient care across the continuum of life. Unique within 
the NIH, our mission is structured around the science that connects 
health care providers to patients, their families, and caregivers.
    There are many components to our society's healthcare mosaic. Care 
is delivered through a variety of settings: conventional healthcare 
sites, community-based clinics, and homes. Patients with exceptional 
needs--from newborns, the disabled, individuals at the end-of-life--and 
the underserved, from urban to rural settings, rely on quality care. 
Through our studies, we seek to understand and manage the symptoms of 
acute and chronic illness, and thus, to find effective approaches to 
achieving and sustaining good health.
    Let me now share with you some examples of how our research is 
changing patient care and improving lives.

              MOTHERS AND THEIR YOUNG CHILDREN WITH ASTHMA

    Asthma, a chronic and sometimes life threatening condition, is 
associated with high health costs related to medications, outpatient 
management, and emergency room visits. Especially for younger children, 
good asthma management requires close vigilance by the parent or 
caregiver. Researchers in one study interviewed working mothers of 
young, inner-city asthmatic children, more than a quarter of whom 
reported that there was a smoker in the house. While most of the 
children were under the care of a doctor and were prescribed 
appropriate asthma medications, many still experienced frequent 
coughing, wheezing, or shortness of breath. The mothers often did not 
give medications for coughing, which can be an early sign of an asthma 
attack. While most were vigilant and strove to provide good asthma 
management, the study demonstrated that many mothers lack sufficient 
information on early asthma symptoms and need additional education 
about asthma in order to provide the best care for their children.

                HEALTH DISPARITIES IN RURAL COMMUNITIES

    The health care of rural populations is a concern because of 
poverty, lack of services and/or health vulnerability of the 
population. NINR's recently funded Rural Nursing and Health Care 
Research Center provides an interdisciplinary research infrastructure 
to conduct and disseminate nursing research to address the needs of 
rural populations. NINR has funded researchers who are making advances 
with technological interventions for the chronically ill rural 
populations. The Women to Women project is a computer-based 
communication intervention that is testing a program of health 
information and social support for women. The program provides 
educational tools for self-management skills and studies the risks of 
isolation and chronic illness. This project has influenced health 
outcomes by creating a more informed and self-managing patient 
population. The program may ultimately serve as a model to deliver 
support and education to remote or vulnerable populations.

                       CARING FOR THE CAREGIVERS

    Dementia-related conditions cause a progressive decline in memory, 
cognition, and physical function, and affect nearly 10 percent of 
persons over 65 years of age. The behavior of the patient with dementia 
can range from forgetfulness to dangerous and aggressive activities. 
Family caregivers often identify the management of this behavior as a 
major source of distress and burden.
    The Savvy Caregiver Program, an educational program for caregivers, 
increased the skill, knowledge, and confidence of caregivers. In 
addition, most caregivers reported a decreased sense of burden and 
improved ability to deal with dementia-related behavior of the patient. 
The caregivers underscored their belief in the benefits of caregiving, 
and stated they would recommend the program to others.
    When family caregivers cannot manage the patient with dementia at 
home, they often must place the person in a long term care facility. 
The Family Involvement in Care program was developed to help family 
members contribute to the care of the institutionalized patient. This 
project tested a program for the nurses and staff on the impact of 
dementia for the family, and on ways to support a continued family 
presence. Family members reported more positive feedback to the 
facility, while the staff participants reported positive outcomes 
regarding the family caregiving role.

                  RESEARCH ON CARE AT THE END OF LIFE

    The end-of-life process includes numerous challenges: physical, 
emotional, spiritual, and financial. There also are challenges in 
health care systems exacerbated by the lack of continuity among 
caregivers, disruption of social support networks, unshared clinical 
information, and multiple physical locations for care. Family members 
experience role changes, stress, and ultimately, bereavement as their 
loved one traverses life's continuum.
    The NINR is charged with leading the Institutes and Centers for 
advancing a trans-NIH research agenda on end-of-life care. In this 
role, we support a broad range of studies designed to improve the 
management of symptoms associated with the end of life; elucidate the 
broad issues that affect many families across the nation such as 
communication among patient, family, and care providers; enhance coping 
with terminal illness; and examine cultural and ethnic influences on 
end-of-life care.
    In one NINR study, researchers interviewed patients with terminal 
cancer and found that spiritual well-being helped reduce depression, 
hopelessness, thoughts of suicide, and the desire to hasten death. The 
investigators concluded that palliative care clinicians should assess 
the spiritual beliefs and needs of their terminal patients to help them 
cope with despair and achieve a sense of peace and meaning in their 
life.
    In December 2004, NINR cosponsored an NIH state-of-the-science 
conference on end-of-life. Nearly one thousand people from around the 
world came to NIH to review the existing knowledge base on end-of-life 
and to recommend opportunities for future research. These 
recommendations will feature prominently in NINR's forthcoming research 
plans in this area.

      PALLIATIVE AND END-OF-LIFE CARE IN RURAL AND FRONTIER AREAS

    Residents living in rural or frontier areas typically have limited 
access to health care services, particularly at end-of-life. In fiscal 
year 2006, NINR will initiate studies focused on understanding the 
scope of the problems associated with limited access to care in rural 
areas. These studies will examine ways to improve end-of-life care 
through the use of technology; develop new methods to use existing 
networks and services; design culturally appropriate interventions for 
palliative care; and identify possible alternative settings and methods 
for providing care and supporting family caregivers.

                   BUILDING NURSING RESEARCH CAPACITY

    As our nation is experiencing a shortage of nurses, we are also 
experiencing a shortfall in the number of nurse scientists. NINR is 
building research capacity with several innovative initiatives, 
collaborating with universities nationwide to rapidly develop 
baccalaureate-to-doctoral fast-track programs. The Graduate Partnership 
Program (GPP) in Biobehavioral Research, a new pilot training program, 
partners schools of nursing with the NIH intramural program to provide 
cutting-edge, mentored research training for outstanding doctoral 
students.
    NINR is also supporting Centers to stimulate research and research 
training opportunities. One example, the Nursing Partnership Centers to 
Reduce Health Disparities, together with the National Center on 
Minority Health and Health Disparities, partners research-intensive 
universities with minority-serving institutions.

                        NINR AND THE NIH ROADMAP

    NINR has identified two key areas of science within the NIH 
Roadmap, Interdisciplinary Research Teams of the Future and Re-
engineering the Clinical Research Enterprise, and integrated them 
within the nursing research agenda. NINR and its investigators have 
extensive experience in conducting interdisciplinary research projects. 
Currently, more than one-half of NINR-funded studies appear in non-
nursing journals. This shows the promise of future interdisciplinary 
collaborations and the value of nursing research findings by other 
disciplines. In the area of improving the clinical research enterprise, 
most of NINR's research is clinical in nature and research questions 
are evaluated from the clinical researcher's perspective. Investigators 
translate research findings into the clinical practice of healthcare 
providers and develop partnerships to speed new scientific knowledge 
into mainstream health care.

                               CONCLUSION

    In conclusion, NINR strives to improve the quality of life and 
quality of health through every stage of life, especially for the most 
vulnerable in our society. We are committed to training the next 
generation of nurse researchers, and to continuing to fund rigorous and 
innovative programs of research to enhance the health of our nation.
    Thank you, Mr. Chairman. I will be pleased to answer any questions 
that the Committee might have.
                                 ______
                                 
    Prepared Statement of Dr. Richard J. Hodes, Director, National 
                           Institute on Aging

    Mr. Chairman and Members of the Committee: I am pleased to present 
the fiscal year 2006 President's budget request for the National 
Institute on Aging (NIA). The fiscal year 2006 budget includes 
$1,057,203,000, an increase of $5,213,000, or 0.5 percent over fiscal 
year 2005 enacted level of $1,051,990,000 comparable for transfers 
proposed in the President's request.
    Thank you for the opportunity to participate in today's hearing. I 
am Dr. Richard Hodes, Director of the National Institute on Aging, 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, and this number is 
expected to rise dramatically in the coming decades. The mission of the 
National Institute on Aging (NIA) is to improve the health and well-
being of these older Americans through research. In support of its 
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 for research 
related to the all-important effort to prevent and treat Alzheimer's 
disease (AD). Finally, our education and outreach programs provide 
vital information to older people across the Nation on a wide variety 
of topics, including living with chronic conditions, maintaining 
optimal health, and caregiving.

           ALZHEIMER'S DISEASE AND THE NEUROSCIENCE OF AGING

    AD is a devastating condition with a profound impact on 
individuals, families, the health care system, and society as a whole. 
Approximately 4.5 million Americans are currently battling AD, with 
annual costs for the disease estimated to exceed $100 billion.\1\ 
Moreover, the rapid aging of the American population threatens to 
increase this burden significantly in the coming decades: By the year 
2050, the number of Americans with AD could rise to some 13.2 million, 
an almost three-fold increase.\2\
---------------------------------------------------------------------------
    \1\ Data from the Alzheimer's Association. See also Ernst, RL; Hay, 
JW. ``The U.S. Economic and Social Costs of Alzheimer's Disease 
Revisited.'' American Journal of Public Health 1994; 84(8): 1261-1264. 
This study cites figures based on 1991 data, which were updated in the 
journal's press release to 1994 figures.
    \2\ Hebert, LE et al. ``Alzheimer Disease in the U.S. Population: 
Prevalence Estimates Using the 2000 Census.'' Archives of Neurology 
August 2003; 60 (8): 1119-1122.
---------------------------------------------------------------------------
    These statistics lend an urgency to the NIA's efforts to better 
understand, prevent, and treat AD, and in the past year, we have made 
several important steps forward. For example, a priority for the NIA is 
to identify risk factors for AD, as interventions that impact the 
effect of a risk or preventative factor could potentially delay the 
onset of the disease or prevent it altogether. Results from several 
recent studies have associated diabetes, which affects about one in 
five persons over age 60 years,\3\ with increased risk of cognitive 
impairment, including AD, raising the possibility that prevention 
strategies for diabetes may also have major consequences for preventing 
or delaying AD.
---------------------------------------------------------------------------
    \3\ See http://diabetes.niddk.nih.gov/dm/pubs/statistics/index.htm. 
Statistics are taken from the 1999-2001 National Health Interview 
Survey and 1999-2000 National Health and Nutrition Examination Survey 
(estimates projected to year 2002).
---------------------------------------------------------------------------
    Evidence is also mounting that lifestyle choices may affect risk of 
AD. In one recent study, older dogs on a regimen of regular physical 
exercise and mental stimulation and a diet fortified with plenty of 
fruits, vegetables, and vitamins performed better on cognitive tests 
and were better able to learn new tasks than dogs in a ``control 
group.'' Although the results of this study need to be replicated in 
humans, they do provide evidence that diet and mental exercise may 
protect against late-life cognitive decline, and that they may work 
more effectively in combination than by themselves.
    An area of some controversy has been the effects of hormonal 
influences on cognitive aging in women, with some studies demonstrating 
a decreased risk for AD among users of hormone therapy and others, 
notably the Women's Health Initiative Memory Study (WHIMS), showing 
that post-menopausal women on certain regimens were actually at higher 
risk for cognitive decline. The risks and benefits of hormone therapy 
remain under study. One new avenue of inquiry is the use of selective 
estrogen receptor modulators (SERMs) to prevent cognitive decline. 
SERMs mimic estrogen's actions in some tissues but block the action of 
the body's naturally occurring estrogen in others, offering the 
benefits of traditional hormone therapy with fewer potential health 
risks. In a recent study, the SERM raloxifene (Evista), frequently 
prescribed for the prevention and treatment of osteoporosis, appeared 
to reduce the risk of cognitive impairment in postmenopausal women. 
More research is needed, but this is a promising area of research.
    The first NIH AD prevention trial, comparing the effects of vitamin 
E and donepezil (Aricept) in preventing AD in people diagnosed with 
mild cognitive impairment (MCI), often a precursor condition to AD, 
recently concluded. Preliminary data indicate that people with MCI 
taking donepezil were at reduced risk of progressing to AD for the 
first 18 months of the 3-year study when compared with their 
counterparts on placebo. The reduced risk of progressing from MCI to a 
diagnosis of AD disappeared after 18 months, and by the end of the 
study, the probability of progressing to AD was the same in the two 
groups.
    NIA is currently supporting over 20 additional AD clinical trials, 
including large-scale prevention trials, which are testing agents such 
as anti-inflammatory drugs, statins, homocysteine-lowering vitamins, 
and anti-oxidants for their effects on slowing progress of the disease, 
delaying AD's onset, or preventing the disease altogether. Trials are 
also assessing interventions for the behavioral symptoms (agitation, 
aggression, and sleep disorders) of people with AD. The Institute also 
supports the development of new agents for AD prevention and treatment, 
including chemical compounds to validate new drug targets, an activity 
with relevance to the ``Molecular Libraries'' area of the NIH Roadmap.
    This year, we have moved forward with two major AD initiatives. The 
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), was funded, with funding also identified for several ancillary 
studies. This ambitious initiative is being implemented jointly with 
several other NIH Institutes, academic institutions, and industry 
partners, and exemplifies the potential for scientific discovery that 
is the goal of the NIH Roadmap component on Public-Private 
Partnerships.
    The NIA is accelerating the pace of Alzheimer(s disease genetics 
research with its AD Genetics Initiative, a major new program to speed 
the creation of a large repository of DNA and cell lines from families 
with multiple AD cases. The goal of this initiative is to develop the 
resources necessary for identifying the remaining late-onset AD (LOAD) 
risk factor genes, associated environmental factors, and the 
interactions of genes and the environment. To aid recruiting efforts, 
the NIA Alzheimer's Disease Education and Referral Center worked 
closely with the Alzheimer's Association as well as several academic 
partners to publicize the initiative.
    In addition to AD, the NIA supports research on other neurological 
diseases, including Parkinson's disease, frontotemporal dementia, and 
prion diseases. For example, NIA investigators, along with researchers 
from the National Institute of Neurological Disorders and Stroke, were 
part of an international research team that identified a mutation that 
is believed to be the most common genetic cause of Parkinson's disease 
identified to date. This discovery could lead to the development of a 
test to detect the mutation in individuals at risk.

                      OTHER AGING-RELATED RESEARCH

    Diseases of aging continue to affect many older men and women, 
seriously compromising their quality of life. Diseases and conditions 
currently under study at the NIA include:
    Anemia.--Recently, NIA investigators found an overall prevalence of 
anemia of 11 percent in men and 10.2 percent in women ages 65 years and 
older, with prevalence increasing dramatically over age 85. The 
American Society of Hematology (ASH) has worked closely with several 
NIH institutes to establish a research agenda on anemia in the elderly. 
An ASH workshop, ``Clinical Implications of Anemia in the Elderly,'' 
was held in March 2004 to establish a research agenda on anemia in the 
elderly; a report of this workshop will be published in the journal 
Blood in spring 2005. Program staff from NIA and several other NIH 
Institutes participated in the ASH workshop and will work 
collaboratively to identify research priorities. In addition, the NIA 
is developing an initiative to stimulate a broad range of research on 
anemia in the elderly that will inform efforts to decrease the 
associated functional impairment, morbidity and decreased survival.
    Obesity.--According to the National Health and Nutrition 
Examination Survey, some 64 percent of U.S. adults are either 
overweight or obese. Excess weight and obesity are linked with an array 
of conditions, including diabetes, osteoarthritis, and cardiovascular 
disease. As we age, we tend to gain fat, which may interfere with the 
work of tissues in which it accumulates. For example, marrow in most 
bones becomes partially or wholly replaced by adipose (fat) cells, and 
fat accumulates around and infiltrates the bundles of muscle fibers in 
muscles of the limbs and trunk. The accumulation of fat in the muscle 
appears to be doubly dangerous, interfering with both mechanical 
function of the muscles and insulin sensitivity. The NIA is planning an 
initiative to stimulate research exploring adipogenesis in aging--i.e., 
the origin of the increased propensity to form fat cells, and its 
impact on tissues and systems. This area of research has the potential 
to broadly impact our understanding of both the decline in function of 
individual tissues in the musculoskeletal system, and the frequently 
seen changes in glucose metabolism and insulin sensitivity with age.
    Elder Abuse and Mistreatment.--Many older Americans are vulnerable 
to mistreatment, including physical and psychological abuse, neglect, 
and financial exploitation. However, the scope of the problem remains 
unknown. The National Research Council (NRC), at the request of the 
NIA, established a Panel to review risk and prevalence of elder abuse 
and neglect. The Panel's 2003 report, Elder Mistreatment. Abuse, 
Neglect, and Exploitation in an Aging America, outlines a number of key 
priorities, including the development of operational definitions of 
elder mistreatment and the development of reliable and valid measures 
of prevalence. To that end, the NIA is planning a pilot program to 
develop the tools to accurately assess the prevalence of elder abuse, a 
necessary first step in developing interventions.
    A number of the NIH Roadmap initiatives are particularly relevant 
to aging research. For example, small molecule development, by 
providing chemical compounds to validate new drug targets, is crucial 
to the development of drugs for a variety of age-related diseases, 
degenerative conditions, and disabilities. Another Roadmap initiative 
has established a network of investigators to improve the measurement 
of patient-reported outcomes, and ongoing projects of particular 
relevance to the aged population are addressing pain, fatigue, 
arthritis, psychiatric symptoms, including depression, and social 
functioning.

                  HEALTH COMMUNICATIONS AND PROMOTION

    Last year, the NIH launched NIHSeniorHealth.gov, a unique web site 
developed by NIA and the National Library of Medicine and geared toward 
the health needs of older adults. In its first year, the site was 
extremely successful, attracting some 380,000 unique visitors and 
garnering over three million page views. It was the only web site to 
receive an ``Industry Innovators Award'' from the International Council 
on Active Aging. A Spanish-language version of the site is currently 
under development.
    Meals on Wheels Initiative.--During a 2002 Congressional hearing, 
it was recommended that NIA and the Administration on Aging (AoA) work 
together to disseminate research-based consumer education materials to 
the thousands of seniors who participate in the Meals-on-Wheels (MOW) 
program. In participation with AoA, NIA conducted focus groups with the 
MOW Association of America to identify the types of information of 
greatest interest to MOW's clients and the best ways to deliver such 
information. Now, a new booklet entitled ``Take Your Medicines the 
Right Way--Everyday!''is being made available to MOW providers for 
their clients free of charge. The booklet is in easy-to-read language 
and covers important steps to help ensure safe and effective medication 
use.

                               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. The results of this research 
often have important implications for public policy. A major source of 
demographic data on aging is the 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. In 2004, the NIA added a 
cohort of ``Early Baby Boomers'' to this study; this will provide 
crucial information on the savings, retirement, and health behaviors of 
tens of millions of Americans now approaching retirement age.
    Thank you for the opportunity to testify before this Subcommittee. 
I would be happy to answer any questions you may have.
                                 ______
                                 
 Prepared Statement of Dr. Sharon H. Hrynkow, Acting Director, Fogarty 
                          International Center

    Mr. Chairman and Members of the Committee: I am pleased to present 
the fiscal year 2006 President's Budget for the Fogarty International 
Center (FIC). The fiscal year 2006 budget includes $67,048,000, which 
reflects an increase of $416,000 over the fiscal year 2005 enacted 
level of $66,632,000 comparable for transfers proposed in the 
President's request.
    Many years ago, President John F. Kennedy noted that ``A rising 
tide lifts all the boats. And a partnership, by definition, serves both 
partners, without domination or unfair advantage.'' These words serve 
to remind us of the importance of working in partnership with those 
around the world, on equal footing, and for the common good. 
Congressman John E. Fogarty, for whom our Center is named, also shared 
this belief and worked tirelessly to champion improved health of 
Americans in a healthier world--through international health research 
and training programs.
    Today, the vision of Congressman Fogarty continues to inspire the 
Center in building international partnerships on behalf of the National 
Institutes of Health (NIH) and in supporting research and training 
programs to advance the objectives of global health. FIC's unique 
mission and initiatives add value, complement NIH international 
programs and build scientific capacity around the world for the benefit 
of Americans and the global community.
    I welcome this opportunity to discuss briefly FIC's progress over 
the past year as well as our proposed plans for fiscal year 2006. 
Developed with the support and guidance of the Administration and this 
Committee, the Fogarty programs reflect our nation's enduring 
commitment to global health as well as vibrant, and equal, 
international collaborations.

                      GLOBAL BURDENS OF ILL HEALTH

    The health challenges we face as Americans and as members of a 
global community are many. HIV/AIDS and tuberculosis continue to rise 
at alarming rates. SARS, West Nile Virus, and avian flu are constant 
threats to global health and economies. At the same time, as chronic 
diseases such as cancer, cardiovascular disease, and mental health 
disorders increase year after year, taking enormous tolls in human 
suffering and economic costs, the development and deployment of more 
effective preventive and treatment measures is urgent.
    The Fogarty response to these challenges is to support a range of 
critical research and training programs, each designed to tackle 
specific health problems shared by United States and foreign 
populations. We work in partnership with universities in the United 
States, low- and middle-income nations, and our fellow Institutes at 
the NIH, the Centers for Disease Control and Prevention, the World 
Health Organization, and others to effect change. Fogarty supports over 
20 research and training programs in more than 100 countries, involving 
more than 5,000 scientists in the United States and abroad. HIV/AIDS, 
TB, maternal and child health, environmental health and bioethics are 
just a few of the priority program areas in which Fogarty and its 
partners are making an impact.

                       IMPACT OF FOGARTY PROGRAMS

    I want to share with you two examples to highlight the impact of 
Fogarty programs worldwide. The first is a genealogy of sorts of one 
scientist's career path and support by Fogarty. Dr. Lee Riley of the 
University of California at Berkeley traces his professional roots to 
Dr. Warren D. Johnson, Jr. of the Weill Medical College of Cornell 
University. Both have dedicated decades of their professional careers 
to understanding, preventing, and treating infectious diseases in the 
slums of Brazil. It all started in 1988 when Dr. Johnson received FIC 
support to train AIDS scientists in Brazil. When Dr. Riley joined the 
Cornell faculty in 1990, Dr. Johnson brought him into the AIDS training 
effort and allowed Dr. Riley to initiate additional training activities 
on tuberculosis diagnostics and pathogenesis. When Dr. Riley moved to 
the University of California at Berkeley in 1996, he competed 
successfully for his own training program in Brazil through Fogarty's 
International Training and Research in Emerging Infectious Diseases 
Program (ITREID). Dr. Johnson received a similar ITREID program grant 
at Cornell, enabling the two to coordinate and synergize their training 
activities. Dr. Riley's group ultimately expanded the ITREID program to 
other countries in Latin America as well as to Eastern Europe, and Dr. 
Riley competed successfully for a new FIC-supported grant on Global 
Infectious Disease Training and Research in Brazil.
    The results and impact of these 17 yearlong partnerships have been 
enormous. In terms of people and publications, thirty Brazilian 
investigators have been trained in the United States, 29 of whom are 
still active researchers in Brazil; 28 articles have been published in 
top scientific journals; 12 Ph.D. and 3 Masters degrees in public 
health have been conferred; and, a large number of allied health 
professionals, many of whom are or were residents of slums, have 
received project-related training. Just one of the trainees who has 
returned to Brazil, Dr. Albert Ko, has trained over 50 local staff--
both laboratory and field--over the last eight years, and he has now 
received his own FIC training award. Other trainees are applying for 
and are receiving funds from NIH and other research agencies.
    Critically, the wealth of knowledge generated has been enormous. 
New understandings have emerged of the causes and treatments of 
leptospirosis, a disease that impacts primarily young people. Patterns 
of the spread of tuberculosis in crowded situations have been 
uncovered, and prevention strategies deployed. Training of health 
scientists from Brazil through the FIC AIDS training programs led to a 
major research grant from the National Institute of Allergy and 
Infectious Diseases for the study of the pathogenesis of leishmaniasis 
in Brazil and for a subsequent Fogarty award in infectious disease 
training. Training through the FIC AIDS training programs has helped 
Brazil evaluate the effectiveness of antiretroviral therapy programs 
that have served as a model and inspiration to other developing 
countries. The partnerships have generated millions of dollars of 
additional support from Brazil, Spain, Mexico, and other nations to 
sustain the research and training activities. And, the relationships 
and partnerships that have been built over time are the ones that will 
allow future studies to move ahead expeditiously.
    The second example is from a research project involving a 1996 
pilot program in Orizaba, Mexico working to evaluate the impact of 
Directly Observed Therapy (Short-Course) (DOTS) in populations with 
drug-resistant tuberculosis. DOTS is the WHO recommended TB treatment 
regimen whereby TB patients are monitored daily to ensure that 
medications are taken properly. In this region, 21 percent of the new 
cases were resistant to at least one anti-tuberculosis drug and 3 
percent were multi-drug resistant (MDR) over a five-year period. The 
data collected demonstrated that DOTS could rapidly reduce transmission 
and the incidence of both drug-susceptible and drug-resistant 
tuberculosis. The case rates of multi-drug resistant tuberculosis were 
also reduced; however, the fatality rate was highest (12 percent) for 
patients infected with resistant strains. In a developing country with 
a moderate rate of drug-resistant tuberculosis, DOTS can rapidly reduce 
the transmission of both susceptible and resistant organisms. 
Additional studies are now under way to expand on these initial 
findings.

                      FISCAL YEAR 2006 INITIATIVES

    FIC will continue to support the NIH Roadmap for Medical Research 
in the 21st Century. Working with partners across NIH and universities 
around the world, FIC will foster interdisciplinary programs in 
clinical research training, identify novel technologies to combat 
global health threats, and expand efforts to bring experts from 
multiple disciplines together to advance NIH Roadmap goals. In keeping 
with the Roadmap, FIC will work in fiscal year 2006 to bring new 
partners into the global health enterprise. FIC will support the 
Framework Programs for Global Health to link multiple schools within 
the same university (or coupled universities) around the topic of 
global health, bringing business, journalism, social science, 
engineering, medicine, law, public health and other disciplines into 
the global health arena in the university setting. A second goal will 
be to energize the next generation of global health leaders through 
development of undergraduate and graduate curricula on global health. 
This effort will propel global health efforts forward in new ways in 
the United States and abroad.
    FIC will enhance its two main programs to address HIV/AIDS and 
related TB challenges. Fogarty's AIDS International Research and 
Training Program builds capacity in resource poor nations to tackle the 
AIDS problem through science and evidence-based policies. Working 
through 25 U.S. universities, educational programs support post-
doctoral, doctoral, Masters level work, and training for allied health 
professionals, including nurses, to advance research on vaccine 
development and microbicide development, to identify groups at high-
risk for exposure and to help support the development of interventions 
that make sense at the local and community levels. Nearly 2,000 
developing country researchers from over 100 countries have been 
trained in the United States, many at senior levels, and more than 
50,000 through in-country workshops and courses. More than 80 percent 
of those trained in the United States through this program returned 
home to pursue research and health efforts locally. And, recognizing 
the need for clinical and health systems researchers for AIDS and TB, 
FIC launched a unique International Clinical, Operational and Health 
Services Research Training Award program to meet these needs. Today, 
under this program, experts in Uganda, Haiti, Russia, and China are 
working with U.S. partners to advance AIDS prevention and treatment 
strategies through targeted training efforts and to monitor the 
effectiveness of AIDS drug delivery paradigms. These programs support 
the goals of the President's Emergency Plan for AIDS Relief and the 
Global Fund and will lead to useful insights about effective drug 
delivery approaches in resource poor nations.
    As a third emphasis area, FIC will expand in fiscal year 2006 its 
pilot program to support NIH Alumni Associations abroad. These 
Associations will serve an important role to junior scientists as they 
return home through support of networking activities in which to share 
information and expertise, and other activities. At the same time, they 
will allow U.S. scientists to maintain collaborative ties. Building on 
efforts in Brazil, Mexico, South Africa, India and China, FIC will 
expand this effort to include Central and Eastern Europe, Russia and 
Thailand.
    As a fourth emphasis area in 2006, FIC will expand efforts in the 
neurosciences. With the exception of sub-Saharan Africa, brain 
disorders are the leading contributor to the years lived with 
disability in all regions of the world. More than 150 million people 
suffer from depression at any point in time and nearly one million 
commit suicide each year. Worldwide, about 25 million people suffer 
from schizophrenia and 38 million from epilepsy. FIC, in partnership 
with the National Institute of Neurological Disorders and Stroke and 
other NIH Institutes, will continue its efforts to develop new 
knowledge and technologies to enhance the understanding of brain 
disorders in resource poor settings around the world. Much of the 
research funded by this program could have implications for how certain 
brain disorders are studied, diagnosed, and treated in the United 
States.

                               CONCLUSION

    The global health challenges we face are many, but the 
international partnerships supported by Fogarty and its partners are a 
bedrock upon which scientific progress will be made to the benefit of 
the American people and the global community.
    Thank you, Mr. Chairman. I would be pleased to answer any questions 
that the Committee may have.
                                 ______
                                 
Prepared Statement of Dr. Thomas R. Insel, Director, National Institute 
                            of Mental Health

    Mr. Chairman, and members of the Committee, I am pleased to present 
the fiscal year 2006 President's budget request for the National 
Institute of Mental Health (NIMH). The fiscal year 2006 budget includes 
$1,417,692,000, which reflects an increase of $5,759,000 over the 2005 
enacted level of $1,411,933,000 comparable for transfers proposed in 
the President's request. In my statement, I will call to your attention 
our Nation's immense burden of mental and behavioral disorders and 
include a brief review of our research activities and accomplishments.

                        BURDEN OF MENTAL ILLNESS

    The mission of the National Institute of Mental Health (NIMH) is to 
reduce the public health burden of mental and behavioral disorders. New 
scientific discoveries and powerful new tools are revealing the 
mechanisms involved in the pathophysiology of mental disorders. This is 
a vital step in the development of more effective strategies to manage, 
treat, and even prevent these debilitating disorders.
    The report of the President's New Freedom Commission: Achieving the 
Promise--Transforming Mental Health Care in America defined the 
challenge. The burden of these disorders is staggering, in terms of 
both morbidity and mortality. Mental illness represents 4 of the top 6 
sources of disability from medical causes for Americans ages 15-44 
according to the World Health Organization; suicide accounts for more 
deaths each year than either homicide or AIDS. Recent estimates in the 
President's report put the economic costs of treating mental disorders 
at $150 billion, with elements of these costs increasing beyond 20 
percent per year. The report called for a transformation of mental 
health care, with recovery as a goal. NIMH is working closely with the 
Substance Abuse and Mental Health Services Administration (SAMHSA) as 
it seeks to carry out this mandate.

                            PRIORITY SETTING

    This past year NIMH searched for creative ways in which to optimize 
its impact on public health; the Institute and its stakeholders 
endeavored to reevaluate priorities for funding research. To help with 
this process, two workgroups of the National Advisory Mental Health 
Council were formed: one to review the NIMH extramural clinical 
treatment portfolio and one to review the basic sciences research 
portfolio.
    The goal of the clinical treatment workgroup was to help NIMH focus 
strategically in its support of therapeutics and interventions 
research. The workgroup's report describes clinical areas where more 
study is essential, and urges increased innovation and a sharpened 
focus on amplifying the impact of clinical trials on clinical practice. 
The report also cites the need to expand core resources and clinical 
trials infrastructure for NIMH to enhance its treatment development 
capacity.
    The workgroup reviewing the basic sciences research portfolio 
outlined specific tools and areas of research particularly ripe for 
increased investment, such as the pathophysiology of mental disorders 
and the translation of basic science discoveries into biomarkers, 
diagnostic tests, and new treatments.
    Translation of basic science to clinical issues and practice is now 
a major focus of the Institute. This past year, NIMH reorganized its 
extramural programs into five research divisions (from three) to focus 
on: basic science, translational research for adults, translational 
research for children and adolescents, behavioral effects on health 
(including HIV/AIDS spread and prevention), and psychiatric services 
and treatments. A key aim of the reorganization is accelerating 
translation of the best ideas in neuroscience and behavioral research 
into the clinics and out into the community.
    Rapid advances in mental health research are revealing the 
biological and environmental components of major mental illness. We now 
recognize that mental disorders are brain disorders, and we now have 
the tools to identify the brain circuits involved. Of note is recent 
research on improved detection of disease with biomarkers and 
development of personalized treatments.

           REVEALING THE BIOLOGICAL BASIS OF MENTAL DISORDERS

    A major goal for NIMH is to identify the biological basis of mental 
disorders to more precisely pinpoint targets for prevention and 
treatment. This means understanding the neural basis of the illness at 
all levels, from molecular to behavioral. For instance, imaging studies 
suggest that ischemia (restriction of blood flow in the brain due to a 
narrowed or blocked artery) may significantly contribute to the 
development of a form of depression. In a recent clinical trial, more 
than half of elderly depressed participants met the criteria for this 
newly recognized form of depression called ``ischemic depression.'' 
This realization should help improve diagnosis, and more effectively 
guide treatment for those with late-life depression.
    A recent NIMH study shows that in people with panic disorder, a 
type of receptor for serotonin (a mood-regulating neurotransmitter) is 
reduced by nearly a third in several structures of the brain that 
mediate anxiety. The finding is the first in living humans to show that 
this specific receptor, which is pivotal to the action of anti-anxiety 
medications, may be abnormal in the disorder and may help explain how 
genes might influence vulnerability for panic and anxiety disorders.
    A recent translational study on post-traumatic stress disorder 
(PTSD) was the first to demonstrate in humans the importance of a 
particular brain region in ``fear extinction''--the process by which a 
previously learned fear is extinguished by a new form of learning, 
rather than the forgetting of the original fear. The brain region is 
associated not with emotion, but with the regulation of higher 
cognitive functions. This will provide important contributions to the 
understanding and treatment of PTSD and other anxiety disorders.
    Several studies on depression have suggested that the formation of 
new neurons (neurogenesis) might be hindered in those with the 
disorder. In addition, animal studies have demonstrated that 
antidepressant medications are likely effective because they help 
increase neurogenesis. Several genes have been implicated in the 
susceptibility to schizophrenia and depression. In the past year, we 
have learned that common genetic variations bias the way the brain 
works, even in people who have not developed a major mental disorder. 
For instance, a gene variant that is especially common in people with 
depression is associated with a higher level of brain activation in 
response to threat or stress. A variant associated with schizophrenia 
appears to increase the amount of activity in the frontal lobe needed 
to perform complex attentional tasks. These kinds of studies reveal how 
subtle genetic variations may increase vulnerability to mental illness. 
Ultimately, this may provide a strategy for early detection and 
prevention of a psychotic or depressive episode based on identifying 
individuals at genetic highest risk, just as we routinely intervene in 
those with high blood pressure and high cholesterol to prevent a heart 
attack.
    Autism continues to be an increasing priority for NIH. We are just 
beginning to see the pay-offs of cross-Institute investments in several 
new centers and projects. Previous studies show that on average, autism 
is not diagnosed in children until after the age of 6, a relatively 
late age considering that early intervention is critical for the best 
treatment response. Thus, NIMH research will help develop new tools for 
detecting autism early, before age two. In addition, NIMH is part of a 
public/private research consortium focusing on the study of infant 
siblings of children with autism, to help identify early features and 
distinguishing characteristics of autism. NIMH and other NIH institutes 
are collaborating with voluntary and private funding organizations and 
government agencies internationally to develop a new research 
initiative ($21.5 million over 5 years) to identify specific gene 
variants that produce susceptibility to autism.

                        TREATMENTS FOR RECOVERY

    The first of several large, NIMH-funded clinical studies testing 
various treatment options for those with serious mental illnesses was 
completed last summer: a 13-site trial aimed at defining the most 
effective and safe treatment for children and adolescents with major 
depressive disorder. Depression is an important risk factor for 
suicide, the third leading cause of death among adolescents; it is also 
a major risk factor for long-term psychosocial impairment in adulthood. 
There has been much debate about whether a class of antidepressant 
medications, selective serotonin re-uptake inhibitors (SSRIs) can 
actually increase suicidal thinking. At present, fluoxetine (Prozac) is 
the only FDA-approved medication for depression in children and 
adolescents, and there have been conflicting results regarding its 
benefits and risks. The goal of the NIMH trial was to clarify the 
usefulness of treating adolescent depression with a type of 
psychotherapy called cognitive behavior therapy (CBT), or fluoxetine, 
or both. Results of the first 12 weeks found that a combination of 
fluoxetine and CBT was the most effective treatment (71 percent 
response rate). Of the other three treatment groups, fluoxetine alone, 
(60.6 percent response), but not CBT alone (43.2 percent response) was 
significantly better than placebo (34.8 percent response). Suicidal 
thinking, which was present in 29 percent of the participants at the 
beginning of the study, improved significantly in all four treatment 
groups, with those receiving medication and therapy showing the 
greatest reduction (below 8 percent). Soon we will know the 
effectiveness of these treatments over a six-month period from 
treatment initiation. It is critical for physicians and 
psychotherapists to closely monitor their young patients on 
antidepressant medications for signs of hurtful or suicidal behavior, 
particularly during the early phases of treatment.
     A central focus of NIMH treatment research has been finding a more 
tailored, individual approach to therapy. To personalize treatments, we 
need to know predictors of treatment response. Recent studies have 
begun to reveal some predictors that will help clinicians optimize 
care. For instance, studies of people with major depressive disorder 
reveal that standard antidepressant medication may be less helpful in 
those with a history of trauma, or specific genetic variations, or 
specific patterns of brain activation as seen on imaging scans. These 
same patients may respond well to cognitive behavior therapy. 
Similarly, patients with schizophrenia who have poor attentional 
processing and other cognitive deficits may report less satisfaction 
with anti-psychotic medications, which were not designed to treat these 
features of the illness. Ongoing research seeks to find markers that 
will guide individual treatment to optimize recovery.
    Other large trials to be completed within the next year will answer 
urgent questions about the choice of treatments in people with bipolar 
disorder, schizophrenia and Alzheimer's, and treatment-resistant major 
depression. NIMH continues its strong commitment to public 
dissemination of findings from these clinical trials by fostering 
partnerships with national and state organizations via the Outreach 
Partnership Program. Through this program, NIMH works with the National 
Institute on Drug Abuse and SAMHSA to bridge the gap between research 
and clinical practice.

                  BLUEPRINT FOR NEUROSCIENCE RESEARCH

    The NIH Blueprint for Neuroscience is a framework to enhance 
cooperation among the 15 NIH Institutes and Centers that have common 
interests in the nervous system. By pooling resources and expertise, 
the Institutes and Centers can take advantage of economies of scale, 
confront challenges too large for any single Institute, and develop 
research tools and infrastructure that will serve the entire 
neuroscience community. The Blueprint is developing a primary set of 
initiatives including a gateway to existing databases that permits more 
effective searches; training enhancement for basic neuroscientists; and 
expansion of ongoing pediatric imaging, gene microarray, and gene 
expression database efforts.

                              NIH ROADMAP

    NIMH has assumed a lead role on the Molecular Libraries and Imaging 
initiative of the NIH Roadmap, whose goal is to provide organic 
compounds called ``small molecules'' to scientists to use as tools to 
improve our understanding of biological pathways in health and disease. 
The potential of scientific discoveries of clinical relevance is 
enormous. The NIMH mission can be advanced by the identification of 
even one novel small molecule with biological activity in the brain, as 
it could provide invaluable information about brain circuits involved 
in mental illness and those that are altered by treatment.
                                 ______
                                 
Prepared Statement of Dr. Stephen I. Katz, Director, National Institute 
           of Arthritis and Musculoskeletal and Skin Diseases

    Mr. Chairman and Members of the Committee: I am pleased to present 
the fiscal year 2006 President's budget request for the National 
Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). 
The fiscal year 2006 budget includes $513,063,000, an increase of 
$1,906,000 over the comparable fiscal year 2005 enacted level of 
$511,157,000 comparable for transfers proposed in the President's 
request.
    Improving daily life is the driving force for the research that we 
support and conduct at the NIAMS. Virtually every home in America is 
touched by diseases affecting bones, joints, muscles, and skin. We are 
committed to improving our understanding, diagnosis, treatment, and 
prevention of these diseases and disorders that are typically costly, 
chronic, and disabling, many of which disproportionately affect women 
and minority populations. I am delighted to share highlights of our 
research progress as well as our plans.

                  THE NIH ROADMAP FOR MEDICAL RESEARCH

    The NIAMS is pleased to partner with other NIH components in the 
many dimensions of the NIH Roadmap, and the Institute has 
responsibility for the management of an initiative for a patient-
reported outcomes measurement information system--or PROMIS--network. 
The goal of this initiative is to develop ways to measure patient-
reported symptoms such as pain and fatigue and aspects of health-
related quality of life across a wide variety of chronic diseases and 
conditions. The PROMIS initiative will develop a publicly available 
computerized adaptive test for the clinical research community. Many 
diseases that compromise daily life involve pain, fatigue, and other 
difficult-to-measure quality of life outcomes, and the development of a 
test to measure changes in these symptoms will be of benefit to 
patients and their health care providers.

                          RESEARCH IN CHILDREN

    When arthritis and other rheumatic diseases affect children, they 
can significantly compromise a child's ability to enjoy an active life. 
NIAMS-supported researchers have launched a state-of-the-art genomics 
project, and the goal of this project is to take full advantage of the 
tremendous progress that has been realized in genetics and genomics, 
and to uncover gene expression patterns (groups of genes that are 
``turned on'' or ``turned off'') that contribute to the development of 
pediatric arthritis. The NIAMS and a chapter of the Arthritis 
Foundation and the Schmidlapp Trust are supporting this study of 
children newly diagnosed with a variety of pediatric diseases such as 
juvenile rheumatoid arthritis, juvenile ankylosing spondylitis (or 
spinal arthritis) and other related immune disorders. Identifying the 
gene expression patterns for different types of arthritis in children 
will help to improve diagnosis as well as to predict the severity of 
disease for affected children.
    In other studies supported by the NIAMS, the promise of genetic 
studies was underscored by the identification of a gene variant that 
increases susceptibility to juvenile arthritis. The NIAMS and the 
Arthritis Research Campaign funded researchers from around the world 
who worked collaboratively in collecting DNA samples from children with 
juvenile rheumatoid arthritis and their parents. Research findings 
suggest that there may be distinct genetic profiles for the disease 
that result in differences in age of onset as well as disease severity.

                         BIOMARKERS OF DISEASE

    Progress in identifying the onset and progression of disease is a 
challenge in many chronic diseases, and the NIAMS has taken the lead in 
three initiatives to address this challenge: the first is the 
Osteoarthritis Initiative--a public-private partnership that the NIAMS, 
the National Institute on Aging, several other NIH components, and 
three pharmaceutical companies support that is working to develop 
clinical research resources for the discovery and evaluation of 
biomarkers and surrogate endpoints for clinical trials on 
osteoarthritis (the most common form of arthritis). Data and images 
collected will be available to researchers around the world to speed 
the pace of research in biomarker identification, and this consortium 
is expected to serve as a model for initiatives in the future that 
involve public and private partnerships. We have already enrolled 1,900 
individuals to participate in this Initiative. The second initiative is 
the creation of the Osteoarthritis Biomarkers Network involving 
institutions in the United States and Sweden. This Network facilitates 
the sharing of clinical, biological, and human resources to more 
rapidly and more effectively identify biomarkers for osteoarthritis. In 
the third biomarker initiative, the NIAMS supports the Autoimmune 
Biomarkers Collaborative Network which includes efforts to identify and 
validate biomarkers for lupus--a serious and potentially fatal 
autoimmune disease that occurs with greater frequency and intensity in 
African American women, and that affects many organ systems of the 
body.

                 ARTHRITIS AND OTHER RHEUMATIC DISEASES

    Rheumatoid arthritis is an autoimmune disease, and affected 
individuals often must be treated with powerful drugs that may help to 
keep the disease better controlled, but also suppress the immune 
system--leaving patients particularly vulnerable to infection. NIAMS-
supported researchers have identified a potential treatment that will 
suppress the abnormal, autoimmune response that causes the rheumatoid 
arthritis, but does not diminish the patient's ability to fight 
bacteria and viruses. The treatment is a synthetic peptide (a chain of 
amino acids) called dnaJP1--a particular section of a protein that has 
the same characteristic amino acid sequence as that found in patients 
with rheumatoid arthritis. In initial studies a synthetic version of 
the dnaJP1 peptide was given to patients with rheumatoid arthritis with 
the goal of blocking the immune response, and the immune system 
responses were normal in these treated patients. The NIAMS partnered 
with the National Institute of Allergy and Infectious Diseases, the 
Royal Netherlands Academy of Arts and Sciences, and the Dutch 
Organization for Scientific Research in funding this study. A new 
larger study will be undertaken to pursue studies of this promising 
synthetic peptide for people with rheumatoid arthritis.
    Fibromyalgia is a disease that affects many systems of the body, 
affects women far more commonly than men, and is characterized by low 
pain thresholds at specific tender points in the body. NIAMS-supported 
researchers have furthered our understanding of fibromyalgia in recent 
studies that determined that fibromyalgia was strongly aggregated in 
families, and that the number of tender points as well as total muscle 
pain scores were strongly associated with fibromyalgia in families. In 
addition, there was an increase in the presence of mood disorders in 
relatives of fibromyalgia patients. This aggregation of fibromyalgia in 
families suggests that genetic factors may play an important role in 
this disease. The NIAMS supported a workshop in November 2004 that 
reviewed the state of the science and a view to future studies in 
fibromyalgia.

                   BONE AND MUSCULOSKELETAL DISEASES

    Osteoporosis is characterized by bone thinning that results in 
increased susceptibility to fracture. A particular clinical challenge 
has been that often the first indication of osteoporosis is when a 
person (most often a woman) has a bone fracture, and by then the bone 
has already thinned. Better methods are needed to screen for 
osteoporosis and for those who are at high risk for fractures. 
Researchers have recently learned that bony regions of conventional 
dental x-rays may be useful in evaluating both the current micro-
architecture of bone as well as following changes in bone over time. 
Bone quality plays a critical role in osteoporosis and other bone 
diseases, and the NIAMS has partnered with the American Society for 
Bone and Mineral Research in sponsoring a meeting in May 2005 to 
evaluate the current status of assessment methods to serve as 
surrogates for fracture and bone fragility, as well as to determine the 
next steps that must be taken to validate these methods and incorporate 
them into clinical trials. In other studies with relevance for 
osteoporosis, basic scientists have identified a particular gene 
(Alox15) that is strongly associated with changes in bone mineral 
density--a measure of vulnerability for osteoporosis. Researchers had 
previously identified the involvement of Alox15 in fat metabolism, so 
the identification of its role in bone links metabolic pathways and 
bone changes, and also provides a new drug target for osteoporosis.

                            MUSCLE DISEASES

    One of the most active and productive areas within the Institute's 
research portfolio is in the muscular dystrophies--a group of genetic 
diseases characterized by progressive weakness and degeneration of the 
skeletal or voluntary muscles which control movement. NIAMS research 
has made progress in defining the genetic mutations and in overcoming 
the current barriers to effective gene therapy of Duchenne muscular 
dystrophy, Facioscapulohumeral dystrophy, and other muscle diseases. 
For example, scientists supported by the NIAMS and the Muscular 
Dystrophy Association recently reported that a particular method of 
gene therapy was able to reach all damaged muscles in a muscular 
dystrophy (MD) mouse, with implications for delivering genetic therapy 
for MD and perhaps other diseases of the muscle or heart. Previous work 
showed that MD could be prevented from occurring in a mouse model of 
the disease by replacing the gene for dystrophin, which is defective in 
people with the Duchenne form of the disease with a corrected copy of 
the gene. However, until now, no one had found a way to deliver a new 
gene to all muscles of an adult animal, including muscles that had 
already developed MD.
    The NIAMS has teamed with the National Institute of Neurological 
Disorders and Stroke (NINDS) and the National Institute of Child Health 
and Human Development (NICHD) to bring a strong focus to basic and 
clinical studies of MD. Activities include the efforts related to the 
new Muscular Dystrophy Coordinating Committee (MDCC), and the Muscular 
Dystrophy Research and Education Plan for the NIH that was developed by 
the MDCC and released in September 2004. In addition, in fiscal year 
2003, the NIAMS, along with NINDS and NICHD, each funded a Muscular 
Dystrophy Cooperative Research Center for which additional funding was 
provided by the Muscular Dystrophy Association. In fiscal year 2004, 
the three institutes re-issued the solicitation for centers--now known 
as Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research 
Centers, and expect to fund two to three additional meritorious centers 
in fiscal year 2005.
    The NIAMS, NINDS, NICHD and the Centers for Disease Control and 
Prevention sponsored a workshop on the burden of muscle diseases in 
January 2005. The participants in this workshop identified existing 
data on the costs and scope of muscle diseases, with a focus on the 
muscular dystrophies, and recommended strategies for developing new 
information sources.

                             SKIN DISEASES

    Skin diseases significantly compromise daily life for millions of 
Americans, both physically and psychologically. Researchers supported 
by the NIAMS have made great progress in our understanding of basic 
skin biology as well as understanding the bases for skin diseases.
    A particular area of focus in the NIAMS portfolio is on the roles 
of genes in skin diseases, and scientists have advanced our 
understanding in a number of areas, including identifying two genes on 
chromosome 17 which are associated with psoriasis. Other studies have 
identified susceptibility genes for keloids, which are an abnormal form 
of scarring that disproportionately affects people of color. 
Investigators studying the physiologic basis for keloid formation were 
able to determine that a blood vessel growth factor was likely to be 
associated with keloid formation. This suggests that it may be possible 
to suppress keloid formation by topical application of an inhibitor of 
this molecule. In a third area of genetics research, investigators have 
identified a new mouse model of alopecia areata that has allowed 
genetic susceptibility studies to be undertaken, and two new regions on 
chromosomes 8 and 15 were identified. The availability of this new 
animal model will allow better identification of the genetic basis of 
alopecia areata as well as provide a basis for testing potential 
interventions.

                               CONCLUSION

    Significant progress has been made in our understanding of 
fundamental life processes and how they go awry in diseases of bone, 
joints, muscles, and skin. We are proud of the advances that scientists 
supported by the NIAMS have achieved, and we are excited about 
initiatives that we have launched. Our goal remains, as always, to 
improve the health of the American public--to reduce the burden of 
disease and to enrich the quality of life for all Americans.
    I will be happy to answer any questions that you may have.
                                 ______
                                 
Prepared Statement of Dr. Ting-Kai Li, Director, National Institute on 
                      Alcohol Abuse and Alcoholism

    Mr. Chairman and Members of the Committee: I am pleased to present 
the fiscal year 2006 President's budget request for the National 
Institute on Alcohol Abuse and Alcoholism (NIAAA). The fiscal year 2006 
budget includes $440,333,000, which reflects an increase of $2,056,000 
over the fiscal year 2005 enacted level of $438,277,000 comparable for 
transfers proposed in the President's request. The Centers for Disease 
Control and Prevention last year ranked alcohol the number-three 
preventable cause of death in the country. This finding echoed a report 
issued by the World Health Organization, which listed alcohol as the 
third leading preventable cause of healthy years lost to death and 
disability in developed nations during 2002. The high rate of death and 
disability associated with alcohol is the result not only of injury, 
but also of organ damage, including brain damage. Alcohol's biological 
actions are widespread in the body, and, when used in excess, it has 
the potential to contribute to conditions such as cancer and liver 
disease. Every age group is at risk of alcohol-related problems, from 
fetuses exposed to alcohol in the womb to the elderly. In the United 
States, the estimated annual cost of alcohol-use disorders (alcohol 
abuse and alcohol dependence), including indirect costs, such as lost 
productivity, is $185 billion.\1\
---------------------------------------------------------------------------
    \1\ 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. NIAAA's mission is to develop prevention and treatment 
interventions that reduce alcohol-use disorders and their consequences. 
To achieve this goal, we must understand the underlying biological, 
behavioral, and environmental factors and identify populations at risk. 
NIAAA research initiatives in four areas, in particular, are essential 
to this effort: medication development, neuroscience, metabolism, and 
youth.
---------------------------------------------------------------------------
                         MEDICATION DEVELOPMENT

    Development of more widely effective medications for alcohol-use 
disorders and organ damage is among NIAAA's highest priorities; it is 
among the 28 research outcome goals listed in the NIH Government 
Performance and Results Act report. Medications help prevent or reduce 
drinking by acting on one or more of the many brain systems through 
which alcohol exerts its actions. For example, some medications reduce 
craving for alcohol. We are testing promising compounds for treatment 
of alcohol-use disorders, by themselves and in combination with 
behavioral therapies, and for treatment of liver damage.
    Recent advances in science and technology have enabled remarkable 
progress in our understanding of neurobiological mechanisms that 
underlie behavior, and are revealing new molecular targets for 
medications for alcohol-use disorders. Likewise, advances in our 
understanding of organ injury are providing new opportunities for 
developing medications. These advances are reflected in unprecedented 
progress in NIAAA's medication development initiative.
    A special challenge for our initiative is to develop strategies 
that will increase translation of promising medications identified by 
NIAAA research into clinical applications. The pharmaceutical industry 
has been reluctant to develop medications for alcoholism, and the 
medical community has been reticent to use new pharmacotherapeutic 
modalities as an adjunct to traditional behavioral therapies for the 
treatment of this disease. For example, only 3 to 13 percent of 
patients treated for alcoholism receive a prescription for the 
medication naltrexone, although it has yielded positive results in 
NIAAA-funded studies published in medical journals. We need to increase 
the likelihood that compounds we identify as effective and safe will 
reach the market and that they will reach patients who can benefit from 
them. Research is underway to identify barriers and strategies to 
remove them.
    Our recently established collaboration with the Food and Drug 
Administration (FDA) will help to expedite progress. Together, NIAAA 
and FDA are developing standards for clinical trials of medications to 
be tested as alcoholism treatments. This will help ensure that NIAAA-
supported trials are in line with regulatory requirements, enabling 
them to proceed.
    Our two highest priorities for accelerating our medication program 
are (1) to develop animal models and human research paradigms that can 
predict the clinical success of potential medications. Having these 
predictive models in place will prevent spending time and money on more 
elaborate testing of compounds that would ultimately fail to be 
effective. (2) Another priority is to establish a network of sites for 
early stages of human testing of medications, to reveal whether or not 
a drug should be pursued in larger, more expensive trials. Medications 
in this system will be on a fast track, in which scientific elements of 
safety testing, etc., remain, but elimination of unnecessary 
administrative roadblocks will expedite the process.

                            IN THE PIPELINE

    Human trials of two particularly promising medications are 
underway. Among the studies being conducted is a collaboration with the 
National Institute on Drug Abuse (NIDA), to test the antiseizure drug 
topiramate's effectiveness in treating people addicted to both alcohol 
and cocaine. Antiseizure drugs act on neurotransmitter systems that 
modulate brain-cell activity, to restore their natural balance. Alcohol 
causes an imbalance in the glutamate and GABA neurotransmitter systems 
(among others) and topiramate's actions on these receptors are thought 
to ease some of the symptoms of alcohol withdrawal. The drug rimonabant 
is directed at a different neurotransmitter system (the cannabinoid 
system) and has shown considerable promise in animal studies. Several 
other kinds of medications that have shown promise in research settings 
are in various phases of clinical studies, including several 
collaborations with other NIH Institutes.
    Some populations are at particular risk, and we also are conducting 
studies specific to them. We are testing medications in youth, who have 
high rates of alcohol abuse. This group poses special challenges, since 
the biological changes that occur in the brain during adolescence might 
compromise the pharmacologic actions of medications used for adults.
    People with co-occurring alcoholism and psychiatric conditions are 
another high-risk group. Our studies of this population include 
collaborations with the National Institute of Mental Health. In a 
recent trial, a drug already used as an anticonvulsant and to treat 
bipolar disorder showed promise in treating alcoholism in bipolar 
people, who are generally resistant to current medications for 
alcoholism.
    A collaboration with the National Cancer Institute and NIDA is 
helping researchers to understand the biological interactions that 
occur between alcohol and nicotine, and to develop treatments for 
alcoholic smokers. Studies suggest that addiction to alcohol and 
nicotine involves some common underlying mechanisms.
    In addition to developing medications to treat alcohol-use 
disorders themselves, we are developing treatments for alcoholic liver 
disease. Alcohol is among the leading causes of death from liver 
disease in the United States.
    Pharmaceutical companies put aside many of the medications they 
develop. Even though they may be safe, they may not be optimally 
effective for treating the diseases or conditions for which they were 
developed. These medications are potentially useful for treatment of 
other diseases, and some act on neurotransmitters that we have 
identified as promising targets for treatment of alcoholism. We are 
encouraging pharmaceutical companies to collaborate with us in 
developing these compounds as potential alcoholism treatments.

                      NEUROSCIENCE AND METABOLISM

    The biology of the brain contributes to how we make decisions--to 
the choices we make in life and the behaviors in which they result. 
Neuroscience research is essential for understanding the biological 
basis of alcohol-related behaviors and for identifying molecular 
targets for therapeutic compounds that can alter alcohol's actions in 
the brain. Many different biological systems in the brain influence how 
people respond to alcohol, and chronic, heavy exposure results in brain 
adaptations that form the underpinnings of alcoholism.
    NIAAA-funded scientists are making important discoveries about 
genes and proteins active in these brain systems, whose variant forms 
increase or decrease the risk of alcohol-use disorders. For example, 
recent studies suggest that a gene that produces an appetite-regulating 
protein fragment, neuropeptide Y, also affects tolerance to alcohol, a 
predictor of alcoholism and a factor in its development.
    In 2006, NIAAA will take part in the NIH Blueprint for 
Neuroscience, a collaboration of 15 Institutes. We are particularly 
interested in the Blueprint's cross-training programs for the next 
generation of researchers and clinicians in neuroscience. One component 
trains physicians and scientists to work together toward translating 
neuroscience findings into clinical practice; others provide training 
in computer and neuroimaging technologies that offer unprecedented 
research capabilities. The Blueprint's project to target all of the 
genes in the mouse genome, to discover which of them are critical 
players in health or diseases of the nervous system, will benefit NIAAA 
research.
    Metabolism also has a profound effect on people's responses to 
alcohol. Variations in the genes and proteins involved in alcohol 
metabolism can, like those involved in brain function, increase or 
decrease risk of alcoholism. NIAAA's metabolism initiative is making 
progress in identifying these gene/protein variations and their impact 
on alcohol-related behaviors, particularly in regard to enzymes in 
alcohol-metabolism pathways. The NIH Roadmap Initiative on National 
Technology Centers for Networks and Pathways is contributing valuable 
information to the effort. Like our neuroscience research, our 
metabolism research is helping us to identify potential targets for 
therapeutic compounds.

                             YOUTH AT RISK

    Last year, we reported that new epidemiology data called for a 
major scaling up of efforts to prevent underage drinking. The data 
revealed that youth is the age of greatest risk of alcoholism; people 
18-to-25 years old have much higher rates of alcoholism than any other 
age group in the Nation. Previous studies had shown the extent to which 
youth engage in risky patterns of drinking, such as occasionally or 
frequently drinking too much, too fast. Alcohol is the largest 
contributor to unintentional injury, the leading cause of death of 
Americans under age 21. People who begin drinking earlier in 
adolescence have a much higher risk of alcoholism as adults, as 
compared with late starters. Children are beginning to drink at earlier 
ages, and youth from secondary-school age to college age have 
substantial rates of risky drinking. In the military, more than 26 
percent of underage personnel engage in ``binge drinking'' (five or 
more drinks in a row), according to a recent Department of Defense 
report. These and other epidemiology data indicated to us that (1) the 
problem of underage drinking required renewed emphasis and coordination 
in the research and service communities, and (2) we should approach 
alcoholism as having a developmental trajectory that begins in 
childhood and adolescence. In a recent report, Reducing Underage 
Drinking: A Collective Responsibility, the Institute of Medicine called 
for strategies to ameliorate these problems. Last year, NIAAA announced 
the addition of a major new initiative to its ongoing research on 
youth.

                            YOUTH INITIATIVE

    Research shows that brain development and maturation occur over a 
longer period than previously thought. A key question we are asking is: 
What brain systems differ in adolescents and adults such that youth 
tend to binge drink? The brain receives and sends chemical messages 
that influence when an individual has ``had enough'' and stops 
drinking. Are the brain systems that regulate these ``stop mechanisms'' 
not yet mature in the adolescent brain? Does alcohol alter their 
development? A collaboration with NIDA is stimulating studies on 
consequences of alcohol exposure and drug abuse on development of the 
brain and behavior.
    NIAAA has formed a steering committee that includes both scientists 
and policy and communication experts. The former chairman of the IOM 
committee on underage drinking is a member, as are two of the 60 
current and former governors' spouses leading a national NIAAA-
sponsored prevention campaign. In addition, the NIAAA sits on the newly 
established Interagency Committee on Prevention of Underage Drinking. 
This Committee cuts across agencies, from research to service, 
including the Substance Abuse and Mental Health Services 
Administration, in a major coordination of effort.
    Our initiative also is reaching out to health-care systems and 
communities. An area in critical need of attention is the response of 
health care systems to underage drinking. NIAAA's youth initiative is 
beginning to address this need, in part, with a project called Underage 
Drinking: Building Health Care System Responses. Rural academic health 
centers will use existing services and clienteles to conduct the 
studies.
    The youth initiative is responding to crisis levels of risky 
drinking on college campuses, as well. It includes fast-track approval 
of grant applications in response to campuses that request help, a 
recommendation issued in the NIAAA Task Force on College Drinking--a 
collaboration between scientists and college presidents. Seven approved 
and funded projects are underway; another application is nearing 
approval, and others are under review. The Task Force is about to 
release an updated report, which will reflect the latest research 
findings. Another new program under the youth initiative, the 
Mississippi River Delta Project, is examining whether a prevention 
strategy recommended for college students by the Task Force is 
effective for rural adolescents.
    One major question that must be addressed regarding underage 
drinking and its consequences is whether enforcement of existing laws 
can reduce these problems by reducing youths' access to alcohol. We 
recently began collaborating with the Office of Juvenile Justice and 
Delinquency Prevention to address this question in rural communities. 
NIAAA's role in this joint effort is to provide the research required 
for evaluation of the effectiveness of the 3-year program. Four 
projects are underway; three more are nearing approval.
    The leadership of the youth initiative is discussing collaborations 
with other potential partners. In Spring 2005, we will meet with 
leaders in the radio and television media about the effects of alcohol 
portrayal on youth behaviors. Navy leaders have requested a meeting 
with NIAAA, also to be held in Spring 2005, to discuss prevention and 
treatment strategies. We have begun discussions with the Department of 
Agriculture about the possibility of conducting research and outreach 
through the 4-H Club organization.

                           AT THE CROSSROADS

    The results of our research will be useful to the public to the 
extent that clinicians and communities apply them. We are at a 
crossroads, in which we are able to identify new medications, for 
example, while the pharmaceutical and medical communities are 
relatively unresponsive to new findings in alcohol research, and 
prevention and treatment are not reimbursed adequately by private 
insurers.
    At this juncture, a high priority for our Institute is to develop 
strategies that will increase the likelihood that clinicians, 
communities, and health-care systems will adopt findings from our 
investigations. Efforts are underway. Thank you Mr. Chairman. I would 
be pleased to answer any questions that the Committee may have.
                                 ______
                                 
Prepared Statement of Dr. Story C. Landis, Director, National Institute 
                  of Neurological Disorders and Stroke

    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 fiscal year 2006 President's 
budget request for NINDS. The fiscal year 2006 budget includes 
$1,550,260,000, an increase of $10,812,000 over the fiscal year 2005 
enacted level of $1,539,448,000 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. This 
mission is extraordinarily important and extraordinarily difficult. It 
is important because the burden of neurological disorders is immense, 
affecting all segments of society. Diseases of the nervous system kill 
people of all ages, disrupt essential bodily functions, cause pain and 
discomfort, and disturb all aspects of human ability, from perception 
and movement through emotions, memory, language, and thinking. It is 
difficult because hundreds of diseases affect the brain, spinal cord, 
and nerves of the body, each presenting unique challenges. Compounding 
the challenge, the brain and spinal cord are difficult to access, 
sensitive to intervention, reluctant to regenerate following damage, 
intricate in structure, and elusive in their normal workings.
    Despite these challenges, we are making progress. Prevention of 
stroke and of nervous system birth defects is having a major impact on 
public health. Better drugs and surgical treatments help relieve 
symptoms for people with Alzheimer's disease, Parkinson disease, 
epilepsy, chronic pain, multiple sclerosis, and other diseases. 
Improvements in genetic testing and brain imaging also enhance 
physicians' ability to diagnose disease and guide therapy for nervous 
system disorders.
    To continue this progress, the NINDS supports basic studies to 
understand the nervous system in health and disease, translational 
research to move from the laboratory toward the clinic, and clinical 
research, including clinical trials to test the safety and efficacy of 
treatments and preventive interventions. The Institute supports most 
research through extramural grants and contracts to physicians and 
scientists throughout the country. NINDS intramural investigators also 
conduct research on the NIH campus in Bethesda, Maryland.
    To complement investigator-initiated research, the Institute 
directs initiatives to public health needs, unusual scientific 
opportunities, or issues that Congress highlights as critical. NINDS 
initiatives for fiscal year 2006 focus on tuberous sclerosis, Rett 
syndrome, muscular dystrophy, neuro-AIDS, transmissible spongiform 
encephalopathies (TSEs), stroke, and Parkinson disease, as well as on 
cross-cutting issues including counterterrorism, neurological 
emergencies, and stem cells. Increasingly, NINDS initiatives and other 
programs are in cooperation with other components of the NIH.

                           CLINICAL RESEARCH

    The NINDS currently supports more than 1,000 research projects that 
involve human subjects, with more than 300,000 people expected to 
participate. For example, epidemiological studies are examining risk 
factors for stroke with special attention to Blacks and Hispanics; 
genetic studies have recently helped identify genes related to 
Parkinson disease, ALS, dystonia, Joubert syndrome, and cerebrovascular 
disease; and brain imaging research is revealing how the brain develops 
throughout childhood and adapts after damage. Among the findings this 
year are brain imaging data that will identify which stroke patients 
might benefit from emergency treatments to unblock blood vessels and 
preliminary indications that vitamin D might help prevent multiple 
sclerosis in women, a finding which researchers are following up.
    Of the NINDS clinical research studies, approximately 125, with 
more than 25,000 expected participants, are clinical trials of 
interventions to prevent or treat neurological disorders. Projects 
range from planning and pilot trials to large multi-center trials. In 
notable results this year, a small intramural clinical trial of 
multiple sclerosis patients who did not respond to interferon, the 
standard therapy, found that administering the genetically engineered 
antibody daclizumab improved outcome substantially. An extramural 
clinical trial found that ultrasound may improve the effectiveness of 
t-PA (tissue plasminogen activator) in breaking up clots and restoring 
blood flow to the brain. T-PA has been the only FDA-approved therapy 
for acute ischemic stroke since NINDS clinical trials demonstrated its 
effectiveness in the 1990's.
    In other clinical trials activities this year, the innovative 
Neuroprotection Exploratory Trials in Parkinson Disease (NET-PD) 
program is selecting drugs that show promise for slowing the course of 
Parkinson disease and testing them through a clinical trials network. 
From 59 drug candidates proposed by 42 scientists from 13 countries, 4 
drugs were selected for testing in phase II clinical trials, with 
results expected in the next few months. If results warrant, larger 
trials will follow quickly. To enhance drug selection in the future, 
the NINDS is establishing a contract animal testing facility. The NINDS 
Pilot Studies Network (NPTUNE) is also underway to expedite pilot 
trials of new treatments for rare neurological disorders, for which the 
lack of clinical trials infrastructure often blocks moving therapies 
forward. NPTUNE chose testing of phenylbutyrate for spinal muscular 
atrophy (SMA) as the first trial. Development of the Clinical Research 
Collaboration (CRC) has also begun, which will extend the reach of the 
NIH into more communities across the United States. The CRC will engage 
hundreds of community practice and academic neurologists to speed 
trials; minimize costs; make trials more accessible to patients; 
recruit a diverse spectrum of participants; facilitate trials of rare 
diseases; and improve transfer of research results to clinical practice 
in community settings. Complementing the CRC, the NINDS is building a 
network to develop emergency treatments for neurological disorders. 
Stroke, seizures, and traumatic injury are just a few of the 
neurological disorders that often require emergency treatment. This 
program brings together specialists in emergency medicine with experts 
in neurological disease and in clinical trials. Finally, the NINDS is 
fully engaged in Roadmap initiatives to address clinical research and 
trials issues that cut across all of medical science.

                         TRANSLATIONAL RESEARCH

    Translational research encompasses the many steps that move basic 
research findings to a therapy that is ready for testing in clinical 
trials. In 2002, the NINDS began a comprehensive translational research 
program that can apply to all diseases within its mission. The program 
solicits investigator-initiated proposals, evaluates them according to 
peer review criteria tailored to the needs of translational research, 
and monitors progress with milestone-driven funding, as is common in 
industry. The first major project in this program, the Parkinson's Gene 
Therapy Study Group, met critical milestones this year with the 
creation of a stable colony of parkinsonian non-human primates for 
testing therapies and the development of modified viral vectors that 
can deliver therapeutic genes under tight control.
    Complementing the broad translational research program and relevant 
Roadmap initiatives in areas such as molecular libraries are several 
specific NINDS efforts. In one such program, the Institute, working 
with academia and voluntary disease organizations, formed a consortium 
of 26 laboratories to screen a set of 1,040 known drugs with laboratory 
tests for potential use against neurodegenerative diseases. Most of the 
drugs in this set have been approved by the U.S. Food and Drug 
Administration (FDA) for other uses, and so might move more quickly 
toward clinical trials. Several drugs from this program have shown 
promise against neurodegeneration and moved forward to testing in more 
definitive mouse models of human diseases. One drug, ceftriaxone, has 
already proceeded to testing in a clinical trial for ALS early this 
fall.
    Because of the state of the science and the impact of SMA on 
children and families, the NINDS chose this disease as the focus of an 
innovative approach to expedite therapy development. The SMA Project 
uses a performance-based contract mechanism to accelerate all steps 
from recognition of a research need, through solicitation, review, and 
funding of targeted research subprojects. In its first year, the 
Project quickly developed detailed plans for SMA drug development and 
solicited targeted research subprojects. A September 2004 workshop 
engaged SMA researchers, clinicians, and voluntary health organizations 
on clinical trials. As the Project proceeds, the NINDS is evaluating 
whether the approach might be applied to other disorders. The NINDS 
continues to support teams of researchers focused on developing 
therapies for neurological diseases through several other programs. 
These programs emphasize basic, translational, or clinical research, as 
appropriate to the state of science for each disorder. Examples include 
the Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research 
Centers, the Morris K. Udall Centers of Parkinson's Disease Research, 
the Facilities of Research Excellence in Spinal Cord Injury, and the 
Specialized Programs of Translational Research in Acute Stroke.

                             BASIC RESEARCH

    Preventing and treating neurological disorders relies on 
understanding the normal workings of the nervous system and what goes 
wrong in disease. The emerging new modalities for combating disease 
highlight this: Stem cells and growth factors arose from fundamental 
studies of nervous system development. Deep brain stimulation, which 
shows promise for Parkinson, dystonia, Tourette syndrome, and other 
diseases, relies upon research techniques developed to monitor the 
activity of single nerve cells in the brain, and on basic knowledge of 
anatomical circuits that control movement. Studies of how the brain 
learns are leading to behavioral therapies that may enhance ``brain 
plasticity'' to repair damage and giving new insights into what causes 
chronic pain, epilepsy, and dystonias. Most current drugs for nervous 
system diseases target molecules identified for their role in normal 
brain function. Gene therapy, new understanding of the molecular basis 
of diseases, diagnostic tests, and animal models for testing therapies 
are among the many fruits of fundamental studies in neurogenetics.
    Basic neuroscience research is continuing to advance rapidly, and 
Roadmap initiatives in areas such as protein structure, computational 
biology, and nanomedicine will help to accelerate that pace. Among the 
many basic neuroscience findings this year are studies that give 
insights into what controls stem cells in the brain and how they might 
be used therapeutically, the role of estrogen in autoimmune disease, 
strategies to transfer therapeutic genes into muscles to treat 
dystrophies, insights into the molecular targets of nicotine, better 
understanding of how genes and experience interact in brain 
development, and a new approach to silencing harmful genes in diseases 
such as Huntington's and spinocerebellar ataxias.

              THE NIH BLUEPRINT FOR NEUROSCIENCE RESEARCH

    Over the last several years, the NIH Institutes and Centers that 
have an interest in the nervous system have increasingly joined forces, 
driven by advances in neuroscience that have revealed common issues 
that intersect their unique missions. The NIH Blueprint for 
Neuroscience is a framework to enhance that cooperation. Just as the 
NIH Roadmap addresses the roadblocks that hamper progress across all of 
medical science, the NIH Blueprint for Neuroscience takes on challenges 
in neuroscience that are best met collectively. By pooling resources 
and expertise, the 15 NIH Institutes and Centers that make up the 
Blueprint can take advantage of economies of scale, confront challenges 
too large for any single Institute, and develop research tools and 
infrastructure that will serve the entire neuroscience community. The 
Blueprint is developing an initial set of initiatives focused on tools, 
resources, and training that can have a quick and substantial impact 
because each builds on existing programs. These initiatives include an 
inventory of neuroscience tools funded by the NIH and other government 
agencies, enhancement of training in the neurobiology of disease for 
basic neuroscientists, and expansion of ongoing pediatric imaging, gene 
microarray, and gene expression database efforts. For fiscal year 2006, 
Blueprint initiatives focus on genetically engineered mouse strains to 
study the nervous system, neuroscience training programs, and 
specialized ``core'' resources that can be shared across many 
laboratories.
    Thank you, Mr. Chairman. I would be pleased answer questions from 
the Committee.
                                 ______
                                 
  Prepared Statement of Dr. Donald A.B. Lindberg, Director, National 
                          Library of Medicine

    Mr. Chairman and Members of the Committee: I am pleased to present 
the fiscal year 2006 President's budget request for the National 
Library of Medicine (NLM). The fiscal year 2006 includes $318,091,000, 
an increase of $2,945,000 over the fiscal year 2005 enacted level of 
$315,146,000 comparable for transfers proposed in the President's 
request.
    In a world that is increasingly digital, the National Library of 
Medicine plays a pivotal role in facilitating research, supporting safe 
and effective health care, and promoting healthy behavior. In addition 
to maintaining the largest physical collection of health science 
literature in the world, the Library builds and makes freely available 
immense databases of scientific information, identifies and organizes 
free Web-based consumer health information produced by the NIH 
institutes and other authoritative sources, and connects all of these 
resources in novel ways that increase their value to scientists, health 
care practitioners, and the general public. Each day, almost a million 
people access the National Library of Medicine's digital resources. By 
making the results of research--from DNA sequences to published 
scientific articles to patient and consumer health information--readily 
available, the Library magnifies the positive impact of NIH's 
investment in the creation of new knowledge.
    The Library is a key player in a number of important NIH and HHS 
initiatives that have current implications for the scientific 
community, health care providers, and the general public. These are 
described later, but briefly they are: the new policy to encourage the 
depositing of peer-reviewed articles supported by NIH grant in an 
archive maintained by the Library; the creation of PubChem, a new 
resource for scientists that is part of the NIH Roadmap Initiative; the 
movement to widen the registration of clinical trials in 
ClinicalTrials.gov, an NIH/NLM database; and the dissemination of 
standard vocabulary for electronic health records and research data 
within NLM's Unified Medical Language System (UMLS).

          INFORMATION FOR SCIENTISTS AND HEALTH PROFESSIONALS

    The Library's services have never been more central to the 
scientific enterprise. No scientist would think of embarking on an 
experiment without a careful review of the literature. Researchers rely 
on NLM databases for this. They search the Medline/PubMed collection of 
15 million journal article records, or perhaps utilize the GenBank 
collection of 40 million DNA sequences and associated molecular data. 
Research articles and biological databases are interlinked through 
NLM's Entrez retrieval system that provides seamless searching of a 
vast information space all from a user's desktop computer.
    The original role of the Library, to provide access to the 
published literature of the health sciences, remains the foundation of 
NLM's services, and the physical collection continues to expand 
steadily. Medline/PubMed is a Web-accessible database that now contains 
more than 15 million references and abstracts to articles in biomedical 
journals from the 1950s to the present. For most of the records now 
being entered, it is possible to link from the reference to the full 
text of the article. More than half a million records, from journals in 
many languages, are added each year. Medline/PubMed is free on the Web 
and in fiscal year 2004 there were 678 million searches done on the 
system.
    PubMedCentral, which was created by NLM's National Center for 
Biotechnology Information (NCBI), is a database that is a key in one of 
the special NIH initiatives mentioned earlier--archiving the full text 
of articles that represent work supported by the NIH. Today's 
technology has led to research that frequently generates an enormous 
amount of data that is associated with the publication of an article. 
To maximize the usefulness of such articles, the full text needs to be 
stored, with ancillary data, and with links to associated resources, in 
a data repository such as PubMedCentral. Under a new NIH policy, peer-
reviewed research articles are submitted electronically to 
PubMedCentral. There are now more than 350,000 current and 
retrospective articles available free of charge in this archive.
    NLM's NCBI also hosts over 40 databases providing researchers and 
students with easy access to molecular biology information--sequences, 
genome maps, 3-D protein structures, and gene functions. The 
integration of all these data coupled with Web-based analysis tools 
offers a virtual desktop laboratory to the 50,000 researchers and 
students who visit daily over the Internet.
    With the completion of the NIH genome project, an important new 
opportunity to explore the interactions of chemical substances with 
biological systems has opened. The Molecular Libraries component of the 
NIH Roadmap aims to exploit this opportunity by developing chemical 
probes that modulate biological processes. A new database created by 
the NCBI, called PubChem (the second major initiative noted earlier), 
integrates data from a variety of sources to enable researchers to link 
diverse information about chemicals and biological processes. For 
example, PubChem links chemicals to PubMed, so that users may 
investigate the relationship of screening-center results and biological 
activities reported in the biomedical literature. As such, PubChem is a 
research tool for expediting discovery of the biological basis of 
disease and the development of new therapeutic approaches.
    A new information system was introduced by NLM in 2004: the 
Wireless Information System for Emergency Responders (WISER). Available 
for downloading over the Internet, the system uses a hand-held PDA 
device to provide on-the-spot information for emergency personnel who 
first respond to situations where hazardous materials have been 
released into the environment. WISER extracts data from NLM's extensive 
electronic file of peer-reviewed hazardous substances information and 
makes it instantly and conveniently available.

                  INFORMATION SERVICES FOR THE PUBLIC

    The Library was first prompted to create information services for 
the general public in 1997, when it became apparent that consumers were 
in fact using the Medline/PubMed database of the scientific medical 
literature heavily. The following year the NLM Board of Regents 
formally recommended that the Library expand its mandate to include 
serving the public. Since that time, NLM has created a series of highly 
successful Web-based information services aimed at consumers.
    Foremost among these is MedlinePlus.gov. This service, begun in 
1998, has become a much-consulted information resource for the public, 
patients, and their families. Some 6 million people use MedlinePlus 
each month, viewing more than 60 million pages of health information 
written especially for consumers. Much of the data comes from the NIH 
institutes, a reliable source of authoritative health information for 
the public. Other HHS health agencies, professional societies, 
voluntary health agencies, and academic organizations are also sources 
of the information carried on MedlinePlus. Many users come to the site 
for access to extensive information on prescription and over-the-
counter medications, a medical encyclopedia, directories of physicians 
and hospitals, and ``health tutorials'' on common medical topics and 
procedures.
    With help from the medical library community and from the National 
Institutes of Health, MedlinePlus continues to expand its coverage. A 
``Go Local'' function has been introduced so that users of MedlinePlus 
can link directly to organizations and agencies in their locality to 
request needed health services. North Carolina and Missouri are now 
connected locally, and more states will soon be joining Go Local. 
Another popular service is MedlinePlus en espanol. This was introduced 
in 2002 and has grown rapidly to reach virtual parity with the English 
version. Both English and Spanish language MedlinePlus scored the 
highest marks of any Federal Web site in a recent evaluation by the 
American Customer Satisfaction Index.
    One popular feature of MedlinePlus is the ability to link from any 
of the health topics to the database, ClinicalTrials.gov. In the past, 
information about clinical research was not readily available to the 
public. Patients typically learned about studies only from their 
doctors. ClinicalTrials.gov, which now contains extensive information 
on more than 12,000 studies, is a one-stop Web site for patients, 
families, and members of the public. Each record includes the locations 
of a study, its design and purpose, criteria for participation, contact 
information, and further information about the disease and intervention 
under study. One of the special NIH initiatives mentioned at the 
beginning of this statement is about the need for a broad registry to 
track all trials and their results. Because ClinicalTrials.gov provides 
an established system for collecting, organizing, and displaying study 
information, expansion of its role is being considered.
    In addition to MedlinePlus and ClinicalTrials.gov, the Library in 
recent years has introduced a number of specialized information 
resources for different segments of the public. NIHSeniorHealth.gov, 
for example, created with the National Institute on Aging, has 
information in a format that is especially usable by seniors on topics 
they are concerned with, such as Alzheimer's, arthritis, hearing loss, 
exercise for older adults, and so forth. There are other information 
resources created by NLM especially for people living with AIDS, 
American Indians, those living in the Arctic, and Asian Americans.
    The public will also find useful NLM databases that contain health 
and safety information about the content of everyday household 
products, consumer information about genetic conditions and the genes 
or chromosomes responsible for those conditions, and the potential 
environmental hazards in ordinary communities (``Tox Town''). The 
newest database of interest to the public is TOXMAP, a system that 
allows the user to specify a chemical, or a location, and to create a 
map that shows the distribution of that chemical in a geographic area.
    The usage of the Library's databases, both those for scientists and 
for the public, continues to climb. NLM pursues a number of outreach 
projects to spread the word that these resources are available to 
everyone, free and without registration. The more than 5,000 member 
institutions of the National Network of Libraries of Medicine are 
valued partners in this endeavor. They hold workshops at public 
libraries and other community organizations, demonstrate NLM databases 
to the public, and exhibit at meetings and conventions on behalf of 
NLM, thus providing the personal element that can be so important to 
reaching populations affected by health disparities. Another special 
outreach project is the ``Information Rx'' program, a collaboration 
with the American College of Physicians (ACP) Foundation. This is a 
project to encourage physicians to make information referrals to 
MedlinePlus. Since patients trust their physicians to recommend good 
health information, the idea is to promote MedlinePlus as the ``Web 
site your doctor prescribes.'' NLM is also now working with the 
American Medical Association Foundation in a similar project for its 
members.

      RESEARCH TO IMPROVE INFORMATION PRODUCTS AND INFRASTRUCTURE

    In addition to the work of the National Center for Biotechnology 
Information, described earlier, NLM also sponsors research and 
development through the Lister Hill National Center for Biomedical 
Communications. This organization conducts advanced 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. More than 2,000 
individuals and institutions in 47 countries have licensed the data and 
are using them in a wide range of educational, diagnostic, treatment 
planning, virtual reality, artistic, and industrial applications. An 
``Insight Toolkit'' 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 
NLM's Web offerings.
    Another initiative of the Lister Hill Center is the Scalable 
Information Infrastructure program. Its purpose is to encourage, 
through 3-year research contract awards, the development of health-
related applications of scalable, network aware, wireless, geographic 
information systems, and identification technologies in a networked 
environment. The initiative focuses on situations that require, or will 
greatly benefit from the application of these technologies in health 
care, medical decision-making, public health, large-scale health 
emergencies, health education, etc.
    The Library has a program of grant assistance for research, 
training and fellowships, medical library assistance, improving access 
to information, and publications. For more than 30 years NLM has 
supported medical informatics research and the training of medical 
informaticians at universities across the nation. NLM funding has been 
instrumental in the development of pioneering electronic health record 
systems now considered models for the nation and for the training of 
generations of leaders in the field of informatics. Today the training 
programs also emphasize 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. A new 
initiative to expand the scope of these training programs is a 
collaboration between the NLM and the Robert Wood Johnson Foundation 
that is establishing public health training tracks at several of these 
sites. In this post 9/11 era the sophisticated use of public health 
information--whether for timely detection of disease outbreaks or rapid 
dissemination of information to clinicians and the public in an 
emergency--is a subject of great importance.
    An important contribution of NLM to the infrastructure of medicine 
is the Unified Medical Language System. This project develops and 
distributes multi-purpose electronic ``Knowledge Sources'' and 
associated lexical programs for system developers. The purpose of these 
UMLS databases and programs is to help computer systems behave as if 
they ``understand'' the meaning of the language of biomedicine and 
health. The UMLS Metathesaurus, the heart of the UMLS Knowledge 
Sources, contains more than 1 million concepts and 4.5 million unique 
concept names from more than 100 different biomedical vocabularies and 
classifications, including the three principal clinical vocabulary 
standards: SNOMED CT (Systematized Nomenclature of Medicine-Clinical 
Terms), LOINC (Logical Observation Identifiers, Names, Codes), and the 
RxNorm clinical drug vocabulary. NLM has been instrumental in making 
these standards freely available through U.S.-wide licensing contract 
support, or direct development.
    These resources are especially important to the Federal 
government's plans to achieve always-current, always-available 
electronic health records (EHRs) for most Americans within a decade. 
The lack of common, readily available electronic medical terminology 
standards has been a major obstacle to the widespread deployment and 
effective use of EHRs. NLM is playing an important role in remedying 
this situation with the national licensing of SNOMED CT and its uniform 
distribution with other clinical and administrative standards within 
the UMLS. It is now possible for software vendors, health care 
providers, hospitals, insurance companies, public health departments, 
medical research facilities, and others to incorporate uniform 
terminology into their information systems much more readily. This is 
an important step toward establishing interoperable electronic health 
records that can be made available wherever and whenever patients need 
treatment. In addition to improving the safety and quality of health 
care, standard electronic health data will assist in detecting and 
responding to public health emergencies and provide one of the key 
building blocks for a cost-effective national research infrastructure.
    In summary, the National Library of Medicine has a central part to 
play on today's health care scene. It continues to be a freely 
accessible archive of the world's published biomedical literature and 
collection of genomic data, relied on by scientists and health 
professionals around the world. Millions of people view the Library as 
a source of trusted consumer health information and access the 
MedlinePlus and other NLM resources for the public. And the U.S. health 
care system, as it evolves to take advantage of new information 
technologies, will rely on infrastructure advances made by the NLM in 
the area of standard and widely shared terminology.
    Thank you, Mr. Chairman. I would be pleased to answer any questions 
that the Committee may have.
                                 ______
                                 
  Prepared Statement of Elizabeth G. Nabel, M.D., Director, National 
                    Heart, Lung, and Blood Institute

    Mr. Chairman and Members of the Committee: I am pleased to present 
the fiscal year 2006 President's Budget request for the National Heart, 
Lung, and Blood Institute (NHLBI). The fiscal year 2006 budget includes 
$2,951,270,000, an increase of $10,069,000 over the fiscal year 2005 
enacted level of $2,941,201,000 comparable for transfers proposed in 
the President's request. I come to you with pride on behalf of the NIH 
component that is responsible for much of the gain in life expectancy 
that we have enjoyed over the past three decades in the United States, 
as shown in this chart. At the same time, however, I come with deep 
concern because the diseases under NHLBI responsibility still comprise 
three of the four leading causes of death in this country--heart 
disease, stroke, and chronic obstructive pulmonary disease (COPD). 
Clearly, we have come a long way, but we have far to go.

                  A VISION FOR THE FUTURE OF THE NHLBI

    As the NHLBI's first new director in 22 years, I would like to take 
this opportunity to share with the Committee my vision for the 
Institute. This vision is based upon a fundamental set of values--
excellence, integrity, innovation, respect, and compassion--that will 
permeate all activities in the NHLBI. I believe that scientific 
discovery provides the basis for progress and that the NHLBI is 
uniquely positioned to catalyze changes that must be made to transform 
our new scientific knowledge into tangible benefits for the people of 
this country. Within this framework, let me articulate four themes that 
will guide priority setting of our research agenda.

                          THEME ONE: DISCOVERY

    The first theme--stimulating basic discoveries of the causes of 
diseases--is vital to developing new, critically needed treatments. 
Basic research provides the foundation of the NHLBI portfolio and has 
been one of its great strengths. The typical model of investigation--
research conducted by single investigators or small groups of 
investigators on projects of their own inspiration--accounts for most 
of the unanticipated and major scientific discoveries in this country. 
I believe strongly that we must protect and nurture investigator-
initiated research. The NHLBI will continue to invest in the most 
talented scientists conducting the highest caliber research. Innovation 
and creativity using the most advanced biomedical technologies will be 
our goal.
    We have an exciting opportunity to support emerging new scientific 
fields. Major strides are being made in computer sciences, 
bioengineering, material sciences, chemistry, and other areas of study 
that vastly benefit medical research, and the pace of discovery in 
these disciplines should be accelerated. One approach is to develop 
funding mechanisms (e.g., for support of high-risk research) that 
encourage innovative thinkers to turn their attention to the major 
current challenges in heart, lung, and blood diseases.
    Another objective is to generate large, publicly available sets of 
reagents and data that could function as a ``tool kit'' for NHLBI 
investigators. Gene sequences and maps, cell lines, knockouts and 
knockdowns of genes in selected animals, reference sets of proteins, 
protein affinity reagents, and libraries of small molecules are 
examples of resources that will provide our investigators with the 
technologies required for innovative discoveries.

                         THEME TWO: TRANSLATION

    Our second task is to speed translation to clinical applications so 
that people can benefit as quickly as possible from the basic research 
enterprise. Clinical research, and more specifically, translational 
research (``bench to bedside'') are vital to our mission, so that we 
can translate basic discoveries into the reality of better health for 
our country.
    The NHLBI must further develop the infrastructure for clinical 
research so that it serves the evolving field of scientific discovery 
and provides a foundation for evidence-based clinical decision-making. 
Clinical research is critical to ensuring that new products and 
techniques are safe and effective before they are widely applied. 
However, clinical research is often time-consuming and inefficient, and 
is increasingly burdened by regulatory hurdles. Our challenge is to 
expand clinical research to complement the exciting basic science 
discoveries, while making it more efficient and cost-effective.
    We intend to develop a translational research agenda supported by 
clinical trials, clinical networks, and clinical workforce training. 
Key components will focus on increasing interactions between basic and 
clinical investigators and easing the movement of new tools from 
laboratories to clinics. We will build upon our rich experience with 
clinical trials and networks to develop new partnerships among 
organized patient communities, community-based physicians, and academic 
researchers. We will work on improving bioinformatics and clinical 
databases, standards for clinical research protocols, measures of 
clinical outcomes, and quality assessment. Translational research 
requires the expertise of many fields and should include analysis of 
health education, outcomes, health-care delivery, and health-care 
economics. This focus fits well with the Re-engineering the Clinical 
Research Enterprise of the Roadmap.
    The NHLBI must cultivate a cadre of clinical researchers who have 
skills commensurate with the complexity and needs of our research 
enterprise. Clinicians must be trained to work in the 
interdisciplinary, team-oriented environments that characterize today's 
research efforts. We further anticipate that specific training will be 
required in an array of disciplines important to clinical research, 
including genetics, epidemiology, biostatistics, and behavioral 
medicine.
    At the core of this vision is the need to develop new partnerships 
of research with organized patient communities, community-based health 
care providers, and academic researchers. We will rely on our 
partnerships to facilitate the conduct of this clinical research, to 
train our clinical investigators, and most important, to achieve our 
common goals of improved health for the public.

                       THEME THREE: INTERACTIONS

    The third theme is facilitating communication between scientists 
and physicians so that new ideas can be generated, shared, and 
advanced.
    Today's science is far more complex than that of yesteryear. 
Research, whether basic or clinical, is now commonly done by teams of 
scientists wherein each individual brings specific talents and 
expertise to the overall effort. We will stimulate and facilitate the 
conduct of interdisciplinary research, so that advances can be made 
more quickly. Principal-investigator status will be granted not to just 
one investigator, as is the norm, but to all key members of the 
research team. Integrated reviews of grants will take into account the 
melding of various disciplines to address the problem at hand, and 
interdisciplinary teams will be encouraged to evolve in both directed 
and unexpected ways.
    An essential component of our efforts in research collaboration 
will be community-based clinical trials, which enhance the conduct of 
clinical research at academic medical centers. An outstanding example 
is our ALLHAT (Antihypertensive and Lipid-Lowering to Prevent Heart 
Attack Trial), in which physicians from many types of medical 
settings--a total of 623 sites in 47 states, Puerto Rico, the United 
States Virgin Islands, and Canada--successfully enrolled over 42,000 
patients and followed them for 6 years. The physicians participated 
because they believed in the importance of the scientific questions 
being addressed with regard to patient care and because of the direct 
benefits of participation to their patients, including free 
medications. These community-based physicians conducted the trial at 
very high standards--follow up was over 97 percent. As part of our plan 
to disseminate the ALLHAT results, participating community physicians 
are now working with other doctors in their local communities to treat 
patients with high blood pressure.

                       THEME FOUR: COMMUNICATION

    Our fourth task is to effectively communicate our research advances 
to the public to improve understanding of new, promising science.
    The NHLBI has an outstanding history of outreach in the areas of 
high blood pressure, cholesterol, asthma, heart attack, obesity, sleep 
disorders, and women's cardiovascular health, and new efforts are under 
way with respect to COPD and peripheral arterial disease. I 
wholeheartedly support these programs that serve the mission of our 
Institute and the Nation. Education of our patients and the public 
regarding prevention and treatment of heart, lung, blood, and sleep 
disorders is one of my highest priorities.
    We will continue to work collaboratively with our colleagues in the 
DHHS, including the CDC and the FDA, to support prevention and control 
programs. We also have an unprecedented opportunity to build upon our 
partnerships with professional organizations, who have a large stake in 
developing and implementing practice guidelines and monitoring their 
effectiveness, and with patient advocacy groups. One of our most 
gratifying partnership programs has been The Heart Truth, which is 
successfully raising awareness nationwide that heart disease is the 
leading cause of death among American women. The ``reach'' of this 
campaign continues to expand as we forge additional fruitful 
partnerships with entities in the public and private sectors.
    Disparities in health status constitute a significant global issue. 
Research is essential to understand the diverse contributions of 
genetics, health behavior, diet, socioeconomic status, culture, and 
environmental exposures in the genesis of health disparities in heart, 
lung, and blood diseases and to formulate, evaluate, and disseminate 
well-conceived, focused intervention programs. This work will 
necessarily entail a vigorous effort to increase the representation of 
minorities in the ranks of NHLBI researchers. We are also cognizant of 
the need to improve and expand programs to prevent, manage, and treat 
diseases and conditions that disproportionately affect U.S. minority 
and underserved populations, such as cardiovascular disease and asthma, 
and to evaluate the effectiveness of our research, treatment, and 
education programs. A full resolution of the health disparities problem 
will occur only through committed and sustained efforts by many in our 
government, health centers, and society.

                                SUMMMARY

    The realization of this vision will require the efforts of many. We 
are engaged in a special form of public service, that is, the promotion 
of patient and public health. I will work diligently to preserve public 
trust in the Institute, the NIH, and the biomedical research 
enterprise, and to ensure that the NHLBI serves the public with the 
highest level of integrity. This trust is essential for meeting our 
common goals of making important new scientific discoveries and 
translating them to improve health in this country.
    Thank you, Mr. Chairman. I would be pleased to answer any questions 
that the Committee may have.
                                 ______
                                 
 Prepared Statement of Dr. Kenneth Olden, Director, National Institute 
                    of Environmental Health Sciences

    Mr. Chairman and Members of the Committee: I am pleased to present 
the fiscal year 2006 President's budget request for the National 
Institute of Environmental Health Sciences (NIEHS). The fiscal year 
2006 budget includes $647,608,000, an increase of $3,103,000 over the 
fiscal year 2005 enacted level of $644,505,000 comparable for transfers 
proposed in the President's request.

                              INTRODUCTION

    ``Genetics loads the gun, but environment pulls the trigger.''----
Judith Stern, University of California, Davis
    The Nation needs better information to promulgate evidence-based 
environmental health regulatory policies and to prevent or cure most 
chronic diseases. This paucity of information has an enormous impact on 
the world's economy, both in terms of costs associated with health care 
and with regulatory compliance. In large measure, this situation exists 
because we still do not understand what role the environment plays in 
human health and disease. The application of knowledge and technologies 
developed through the pursuit of the Human Genome Project offers great 
promise for elucidating mechanisms of gene-environment interactions in 
the development of complex diseases.
    For years, the environment was considered to have a minor role in 
the etiology of human illness. But, in recent years, the thinking has 
shifted in favor of gene-environment interactions. For example, recent 
studies show that no more than one-third of the cancer burden can be 
attributed to the action of genes alone (Verkasala, et al., 1999, Int. 
J. Cancer 83:743-749; Lichlenstein, et al., 2000, NEJM 343:78-85), only 
15 percent of Parkinson's Disease (Tanner et al., 1999, JAMA, 281:341-
346), and about a third of autoimmune diseases (Powell, et al., 1999, 
Env. Health Pers. 107 (Suppl. 5), 667-672). A more recent study 
reported that 90 percent of individuals with severe heart disease have 
at least one or more of four classic risk factors captured in the 
current definition of the environment (Khat et al., 2003, JAMA 290:899-
904). Because of these and other findings, it is now generally accepted 
that more informative, cost-effective, high-throughput methods for 
assessing and predicting risk resulting from environmental exposures 
will need to be developed. Otherwise, we will not be able to prevent or 
cure most chronic diseases, and the costs associated with health care 
and environmental regulatory compliancy will continue to escalate.
    Starting in 1997, NIEHS developed several new research initiatives 
to respond to this urgent need. Such programs include: the 
Environmental Genome-Project (Kaiser, 1997, Science 278:569-570; Brown 
and Hartwell, 1998, Nat. Genet. 18:91-93), the National Center for 
Toxicogenomics (Kaiser, 2003, Science 300:563), and the Mouse 
Sequencing Project (Nature 432: 5, 2004). While the results from these 
three initiatives will provide information relevant to most chronic 
diseases, other research programs have been developed to address 
specific diseases such as breast cancer, Parkinson Disease, and autism. 
Today, I will briefly describe several of these initiatives and their 
implications for human health and disease.

     GENETIC DIFFERENCES IN SUSCEPTIBILITY TO DRUGS AND ENVIRONMENT

    Individuals vary, often significantly, in their response to 
environmental agents. This variability provides a high ``background 
noise'' when scientists examine human populations to identify 
environmental links to disease, often masking important environmental 
contributors to disease risk. Fortunately, the Human Genome Project 
created tools that can help identify the genetic variations in 
environmental response genes that can lead to such wide differences in 
disease susceptibility. NIEHS developed the Environmental Genome 
Project (EGP) to catalogue these genetic variants (polymorphisms) and 
to identify the ones that play a role in human susceptibility to 
environmental agents. This information is already being used in 
epidemiological studies to better pinpoint environmental contributors 
to disease. Also, several important variants have been discovered that 
are associated with risk for chronic illnesses such as leukemia, 
cardiovascular disease, and neuronal dysfunction.

            ANIMAL MODELS PREDISPOSED TO ENVIRONMENTAL RISK

    The usefulness of the susceptibility data generated in the EGP is 
enhanced by the availability of animal models with the exact sequence 
variations discovered by resequencing of the human environmental 
response genes. Therefore, NIEHS developed a university-based Mouse 
Genomics Centers Consortium to create mice with such variations and 
provide them to the scientific community. To date, approximately 20 
well-characterized mouse models have been developed. These models 
represent a variety of disease endpoints, including: Werner's syndrome 
(aging disorder), diabetes, mammary cancer, gastrointestinal and 
bladder cancer, prostate cancer, and skin cancer.

              EFFORT TO IMPROVE RELEVANCE OF ANIMAL MODELS

    Environmental health scientists often use mice to predict how 
environmental agents might affect people. Although mouse studies can 
indicate the potential of an exposure to cause cancer and other 
diseases, there is no way to precisely extrapolate these study results 
to the risk in humans. Information on the similarities and differences 
in homologous genes between human and mouse is important to improve 
accuracy in predicting human risk. While laboratory mice might look 
alike, the 100 different strains used in medical research differ 
significantly in their behavior, physiology and susceptibility to drugs 
and environmental agents (e.g., carcinogens), and scientists are eager 
to discover the differences in the genetic sequences that underlie 
these traits, with the goal of finding counterparts in humans. NIEHS 
initiated a mouse sequencing project to decipher the genomes of the 15 
mouse strains used most frequently in research to predict human risk. 
Such data will improve environmental risk assessment decisions and will 
help researchers in choosing the most appropriate strain for studying 
toxicity.

                     SISTER STUDY OF BREAST CANCER

    A unique study exploring gene-environment interactions in breast 
cancer development has begun nationwide recruitment. It will look at 
how genes, activities of daily life, and environmental exposures affect 
breast cancer risk. To get the information quickly, this study is 
recruiting 50,000 symptom-free women who have a sister that had breast 
cancer. These women are at increased risk of breast cancer, share many 
genes with their affected sibling, and would have experienced many of 
the same exposures. For these reasons, it is expected that a sufficient 
number of women will develop breast cancer within 10 years and their 
genes and exposures can be compared with those of women in the study 
who did not develop the cancer. A broad range of exposures will be 
examined, including personal care and household products, workplace 
exposures, and dietary factors, along with genetic analysis. The 
principal investigator has the active support of the American Cancer 
Society, Sisters Network, Inc., the Susan G. Komen Breast Cancer 
Foundation, and the Y-ME Breast Cancer Organization.

                          PARKINSON'S DISEASE

    A major impediment in Parkinson's Disease (PD) research has been 
the lack of rapid communication between epidemiologists, laboratory 
researchers, and clinicians which prevents the type of 
multidisciplinary approach this field needs. To encourage advances in 
this important area of study, NIEHS developed a multidisciplinary 
Collaborative Centers Program for Parkinson's Disease Environmental 
Research. This multi-institutional approach is designed to accelerate 
the identification of genetic and environmental factors leading to PD. 
Collectively, the three centers have expertise in basic neurosciences, 
human genetics, clinical research, and epidemiology, as well as long-
standing interactions with patient groups. Accomplishments to date 
include: efforts to discover new PD susceptibility genes; development 
of a registry in California to track the disease; development of mouse 
models with specific alterations in genes suspected of playing a role 
in PD, and efforts to develop a primate model of PD that exhibits the 
most prominent clinical features of the disease.

                                 AUTISM

    Autism is a devastating behavioral disorder that most likely arises 
from underlying genetic susceptibilities interacting with specific 
environmental exposures during pre- or post-natal development. A number 
of people have suspected that the mercury-containing compound 
thimerosal, used to preserve childhood vaccines, could be an 
environmental trigger for autism development, based on the established 
neurotoxicity of higher doses of mercury. Extensive epidemiological 
studies, however, have failed to provide any association between 
vaccines and autism. It is possible, however, that only a subset of 
children are susceptible to mercury effects, perhaps when coupled with 
an immunological challenge. Preliminary animal studies have provided an 
intriguing clue to possible susceptibilities that NIEHS is now 
pursuing. In these studies, different mouse strains were exposed to 
thimerosal at ages and doses that corresponded to the standard protocol 
for childhood vaccinations. Only the immunologically deficient strain 
of mouse exhibited a response. In these mice, behavioral effects were 
reported and morphological changes were observed in the brain. However, 
this study did not have sufficient power to be definitive. Fortunately, 
the NIEHS already had two Children's Environmental Health and Disease 
Prevention Research Centers devoted to autism. Thus, the Institute 
provided a supplement to one of these Centers to do more extensive 
testing of thimerosal in autoimmune-prone (SJL) mice. This Center has 
expertise in evaluating critical social behaviors, as well as the 
ability to conduct state-of-the-art stereology to measure brain effects 
such as volume changes and changes in cell number occur. This more 
extensive look at thimerosal-immune co-contributors to brain damage may 
provide better insight into this disorder than previous studies have. 
In addition, the same Center is recruiting a cohort of 700 autistic 
children, and appropriate control subjects, to further examine the role 
of gene-environment interactions in the etiology of autism.

                   OBESITY AND THE BUILT ENVIRONMENT

    Obesity is a major contributor to human disease and rising health 
care costs. NIEHS is collaborating with the Robert Wood Johnson 
Foundation to examine how community design influences physical 
activity. This so-called Active Living Design Program is working with 
local governments to influence city planning and land use decisions. 
The program's impact on physical activity, obesity, and other health 
indicators will be assessed. The Institute is also encouraging research 
to evaluate the role of ``in utero,'' neonatal, and pre-puberty 
exposures to environmental estrogens and other compounds in the onset 
and development of obesity, as well as examining gene-environment 
interactions that favor weight gain.

                             NANOTECHNOLOGY

    Nanotechnology is an exciting area of research with broad 
implications for multiple industries, including medicine and 
communication. For example, nanoscale devices have the potential to 
deliver therapeutic and imaging agents to specific cells and tissues in 
ways not presently possible. However, when bulk material is converted 
to ultrafine nanoparticles, its physical, chemical, and biological 
properties can be altered in ways that might adversely affect health. 
So, while many laboratories are focused on exploiting the rich 
potential of these agents, there is little activity to assess their 
toxicological properties. NIEHS, under the auspices of the National 
Toxicology Program (NTP), has initiated a program to evaluate the 
toxicological properties of the major classes of nanoscale materials 
and will investigate fundamental questions such as: How are nanoscale 
materials absorbed, distributed in the body, and taken up by cells? Are 
there novel toxicological interactions? What are the appropriate 
detection and quantification methods for nanoscale particles?

             NIH ROADMAP AND ENVIRONMENTAL HEALTH RESEARCH

    The ability to investigate and understand issues in environmental 
health requires collaboration between many scientific disciplines: 
epidemiology, toxicology, molecular biology, clinical sciences, and 
many others. Thus, Roadmap initiatives such as the Interdisciplinary 
Research Planning Centers will greatly enhance NIEHS' work. Examples 
include: the use of geographic/spatial methodologies to address 
combined genetic, social, and environmental factors on child health and 
development, and an effort to redefine computational genomics with 
emphasis on gene-environment interactions in alcoholism, 
atherosclerosis and breast cancer. Both projects have strong ties to 
other significant NIEHS-funded programs at the same institutions.
    Thank you for the opportunity to comment on the important work 
supported by the NIEHS. I will be happy to answer any questions you 
might have.
                                 ______
                                 
  Prepared Statement of Dr. John Ruffin, Director, National Center on 
                 Minority Health and Health Disparities

    Mr. Chairman and Members of the Committee: I am pleased to present 
the fiscal year 2006 President's budget request for the National Center 
on Minority Health and Health Disparities (NCMHD). The fiscal year 2006 
budget includes $197,379,000, an increase of $1,220,000 over the fiscal 
year 2005 enacted level of $196,159,000 comparable for transfers 
proposed in the President's request.
    The NCMHD has just entered its fourth year of operation. Much has 
been accomplished during this time. However, much remains to be done. 
Racial and ethnic minorities and other health disparity populations 
continue to suffer a disproportionate burden of illness, disability and 
premature death. Health disparities cover a broad spectrum of health 
conditions and diseases that include cancer, mental illness, infectious 
diseases, autoimmune diseases, endocrine diseases, vascular diseases, 
infant mortality, diabetes, HIV/AIDS, obesity and nutritional 
deficiencies. There are many factors that contribute to health 
disparities such as genes, biology, culture, race, environment, 
socioeconomics, and health behavior. Due to the interaction of these 
complex factors, the elimination of health disparities requires a 
multifaceted approach.

                 NIH HEALTH DISPARITIES STRATEGIC PLAN

    The Congress has charged the NCMHD to lead the Federal effort in 
health disparities research, research capacity building, and outreach. 
The NCMHD guides the NIH efforts in collaboration with NIH Director, 
the other NIH Institutes and Centers, and the NCMHD's Advisory Council 
in revising the NIH Health Disparities Strategic Plan annually. The 
plan represents the trans-NIH health disparities vision and strategy to 
eliminate health disparities through research, research infrastructure, 
capacity building, and community outreach.
    The NIH Institutes and Centers (ICs) are committed to educating 
minority patient populations on disease management and quality care. 
Several of the ICs plan to increase the number of culturally relevant 
health educational materials and to develop and expand linkages with 
minority organizations and professional societies to increase 
dissemination of research advances to minority-serving institutions, 
and racial and ethnic minority and health disparity communities. For 
example, the National Institute of Allergy and Infectious Diseases 
(NIAID) will produce a series of low-literacy fact sheets on sexually 
transmitted infections, HIV/AIDS, and tuberculosis. The NINDS expanded 
its health education program, Know Stroke. Know the Signs. Act in 
Time., to populations at high risk for stroke--African Americans, 
Hispanics, and seniors--in communities that have the health care 
systems in place to treat them. The National Center for Complementary 
and Alternative Medicine (NCCAM) will employ multimedia technology, 
such as web chats, teleconferences, and minority-focused media to 
disseminate information about complementary and alternative medicine.
    The National Cancer Institute (NCI) is achieving significant 
progress toward understanding and addressing the needs of the Hawaiian 
and Pacific Basin populations through a five-year cooperative agreement 
with Papa Ola Lokahi, a Native Hawaiian owned-and-operated community-
based health organization. Through this agreement, the NCI funds a 
variety of culturally competent cancer awareness, research, and 
training activities.
    The National Heart, Lung and Blood Institute (NHLBI) is initiating 
a new program to address the substantial and growing burden of 
Cardiovascular Disease (CVD) in American Indians and Alaska natives. 
This initiative will develop and test culturally appropriate 
interventions to promote the adoption of lifestyles and behaviors that 
are known to reduce biological and CVD risk factors, such as high blood 
pressure and cholesterol levels, obesity, glucose intolerance, and 
diabetes.

                    NCMHD HEALTH DISPARITIES IMPACT

    In addition to developing the NIH Strategic Plan, the NCMHD has 
focused attention on the pressing need to establish its programs. The 
national reach of the NCMHD extends to more than 100 institutions and 
more than 500 individuals that have received awards to train for health 
professions careers, conduct health disparities research, build 
research capacity and advance outreach efforts.
    The NCMHD Health Disparities Centers of Excellence (Project EXPORT) 
program currently funds seventy-one institutions in 29 states engaged 
in multidisciplinary research. Priority research focus areas include 
cancer, cardiovascular disease, stroke, diabetes and the health of 
mothers and their infants.
    Communities nationwide in states such as Alabama, New York, 
Pittsburgh, Montana and Hawaii are being encouraged and equipped for 
participation in clinical studies and for partnering in the conduct of 
evidence-based disease prevention and intervention activities. The 
Clemson University-Voorhees College Project EXPORT partnership has 
three studies focused on obesity. Using a network of community-based 
partners, each study examines diet and/or physical activity levels of 
rural residents or students. The objectives of the studies are to 
identify the socio-cultural factors influencing choices and determine 
how environmental effects and knowledge of nutrition and physical 
activity impact choices about diet and exercise.
    Culturally competent health care is an essential component in 
defeating health disparities and requires a distinct sense of urgency. 
In a recent study on cultural competence among physicians treating 
Mexican Americans who have diabetes, supported by a NCMHD-Center of 
Excellence, scientists determined that physicians can increase cultural 
competence and effective care by becoming self-aware of their 
knowledge, views, and attitudes about cultures and ethnic groups, and 
by engaging in culture-focused educational activities. Recognizing that 
culturally appropriate actions can be predicted, based on a provider's 
awareness that culture is relevant to medical care and that negative 
preconceptions can hinder the effectiveness of health care delivery, is 
an important finding for improving cultural competence and reducing 
health disparities.
    The NCMHD Research Endowment Program, unique within the NIH, is 
best described as inclusive and diverse. Fourteen institutions receive 
NCMHD endowment funds to enhance research capacity and infrastructure 
for research and training. The activities of the institutions involve 
strengthening teaching programs in the biomedical and behavioral 
sciences; establishing endowed chairs and programs; obtaining state-of-
the-art equipment for instruction and research; and enhancing the 
recruitment and retention of student and faculty from health disparity 
populations. A NCMHD Endowment Program award to the University of 
Kansas has enabled the university to develop a K-12 pipeline to recruit 
students through summer programs; retain and graduate 95 percent of 
underrepresented minority medical students; increase underrepresented 
minority faculty members from 24 to 39; and provide opportunities for 
48 underrepresented minority students to participate in health 
disparity research over the summer.
    The NCMHD supports two loan repayment programs--the Health 
Disparities Research Loan Repayment Program (HDR) and the Extramural 
Clinical Research Loan Repayment Program for Individuals from 
Disadvantaged Backgrounds (ECR), to promote a diverse and strong 
scientific workforce by alleviating the financial barriers that often 
discourage many talented health professionals from health disparity, 
medically underserved and disadvantaged communities from pursuing a 
research career.
    The NCMHD funds are supporting the deployment of 466 emergent 
researchers to 42 states and the District of Columbia to conduct health 
disparities research. These programs are the foundation for developing 
a lasting relationship with talented and committed health disparities 
scholars. Fifty-six percent of the awardees in the HDR program are 
members of a health disparity population. The loan repayment programs 
exemplify the multidisciplinary approach needed to address health 
disparities. For example, epidemiology, pharmacology, linguistics, 
etiology, ethnography, health policy, and behavioral science are among 
the program's research disciplines. Research includes: identifying 
barriers to health care access; race and long-term diabetes self 
management in an HMO; a comparison of androgen receptor for 
polymorphism in African American and Caucasian women with breast 
cancer; and reducing HIV/STI risk in young adult minority populations.
    The number of participating institutions in the Research 
Infrastructure in Minority Institutions (RIMI) Program has tripled 
since 2001. Program accomplishments include faculty seminar series on 
health disparities research; research on the health and developmental 
impact of methamphetamine production in New Mexico children, and the 
establishment of a Natural Toxins Research Center. The NCMHD will 
continue to build upon the RIMI program by exploring partnerships among 
tribal colleges, community/junior colleges, and non-research intensive 
four-year institutions with major research-intensive colleges and 
universities.
    The Minority Health and Health Disparities International Research 
Training Program (MHIRT) positions the NCMHD in collaboration with the 
NIH Fogarty International Center, to extend its health disparities 
research and training capacity across borders. The MHIRT program 
enables students and faculty from health disparity populations to 
participate in international research training opportunities in 
countries such as South Africa, Sweden, Italy, Mexico, Bulgaria, 
Thailand, Trinidad, China, Australia, Brazil, and Senegal. Research 
efforts include cancer epidemiology, reproductive biology, 
parasitology, malaria, ethnopharmacology and neurobiology.

          COMMUNITY-BASED PARTICIPATORY RESEARCH AND OUTREACH

    The NCMHD recently established an Office of Community-Based 
Participatory Research and Outreach, and launched a new program that 
will support collaborative partnerships between academic institutions 
and community-based organizations for research studies looking at the 
interface of physical and psychological environments and their health 
impacts on communities of color and the medically underserved; 
methodology research looking at effective methods of measuring racism 
and community level outcomes; evaluation of outcomes; and impact of the 
research. This program will build on the NCMHD existing community-based 
research and outreach initiatives through its Project EXPORT program.

                    FEDERAL RESEARCH COLLABORATIONS

    In addition to its core programs, the NCMHD has continued to fund a 
broad range of collaborations with the other NIH Institutes and 
Centers, the Department of Health and Human Services, and other Federal 
agencies. Recently, the NCMHD launched a new initiative to support 
research relevant to the Mississippi Delta Region and its medically 
underserved populations. This endeavor involved the collaboration of 
eight NIH Institutes and Centers with the NCMHD supporting 
approximately $8 million in research projects.

                               CONCLUSION

    Working with our many research partners, the top priority of the 
NCMHD is to build a solid and diverse national biomedical research 
enterprise of individuals, institutions, and communities dedicated to 
eliminating health disparities. The NCMHD will sustain and expand its 
primary strategies. Research capacity building will extend beyond 
academia to involve community and faith-based organizations, 
individuals, and business at local and grassroots levels. Training and 
the diversification of the health, scientific, and technological 
workforce will remain key areas of focus in developing innovative 
projects. Prevention, treatment, cultural competency, and health care 
delivery for urban and rural communities will be approached more 
aggressively. We will continue to strive for an America in which all 
populations will have an equal opportunity to live long, healthy, and 
productive lives.
                                 ______
                                 
    Prepared Statement of Dr. Paul Sieving, Director, National Eye 
                               Institute

    Mr. Chairman and Members of the Committee: I am pleased to present 
the fiscal year 2006 President's budget request for the National Eye 
Institute (NEI). This budget includes $673,491,000, an increase of 
$4,421,000 over the fiscal year 2005 enacted level of $669,070,000 
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.

                    GLAUCOMA AND OPTIC NEUROPATHIES

    Glaucoma is a group of eye disorders that causes optic nerve damage 
that can lead to severe visual impairment or blindness. Elevated 
intraocular pressure (IOP) is frequently, but not always, associated 
with glaucoma. Glaucoma is a major public health problem and published 
studies find it is the most common cause of visual impairment and 
blindness in African Americans.
    The prevalence of glaucoma is three times higher in African 
Americans than in non-Hispanic whites.\1\ Additionally, the risk of 
visual impairment is much higher and the age of onset is earlier than 
in Whites. An NEI-supported follow-up study to the Ocular Hypertension 
Treatment Study (OHTS) found that early treatment of elevated IOP 
reduces the risk of developing glaucoma in African Americans. Of the 
participants in the treatment arm of the study, 8.4 percent developed 
glaucoma whereas 16.1 percent in the observation group developed the 
disease. Additionally, the OHTS follow-up study found that certain 
biological characteristics of the eye including corneal thickness are 
helpful in predicting who will likely develop glaucoma and who will 
benefit from therapy. This study provides important treatment and 
prognostic information for clinicians in caring for this at risk 
population.
---------------------------------------------------------------------------
    \1\ The Eye Diseases Prevalence Research Group: Prevalence of open-
angle glaucoma among adults in the United States. Arch Ophthalmol 
122:532-538, 2004.
---------------------------------------------------------------------------
                            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). This year, NEI supported 
laboratory researchers made great strides in developing therapies for 
these diseases. For example, a recent NEI study found that eye 
injections of bone marrow stem cells from adult animals prevented 
vision loss in two rodent models of retinitis pigmentosa (RP). These 
findings raise the possibility of a therapy in which patients could 
receive an injection of their own bone marrow stem cells to preserve 
vitally important central vision.
    Age-related macular degeneration (AMD) is a leading cause of 
blindness and visual disability in older age Americans. The inability 
to prevent the development of AMD and its complications is largely due 
to an imprecise understanding of the pathologic mechanisms of the 
disease. Genetic and environmental factors have previously been 
implicated in the disease. A recent NEI supported study in animal 
models has found evidence that inflammation may also play a role. These 
animal models suggest that the immune system contributes to the disease 
and offer new insights into possible mechanisms of the disease. The 
availability of animal models of the disease will also allow for the 
testing of new intervention strategies.

                            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 eye 
care professionals, and are some of the most painful ocular disorders.
    The epithelial cells of the cornea form a surface barrier that 
protects the underlying tissues from the external environment. When 
this layer is damaged, the epithelial cells normally respond quickly to 
close the wound and reform the barrier. In some cases, however, this 
response is defective, leading to the formation of persistent and 
painful corneal ulcers. Development of more effective treatments for 
this condition has been hampered by the limited information about the 
cellular and biochemical events that regulate corneal wound closure. 
This year, scientists at the NEI discovered that an enzyme called Cdk5 
plays a central role in regulating the migration of epithelial cells to 
close corneal wounds. More importantly they discovered that drugs which 
inhibit Cdk5 promote cell migration and wound closure. These findings 
suggest a new therapeutic approach for treating persistent corneal 
ulcers and other conditions that impair wound healing. Animal studies 
are in progress to determine whether inhibitors of Cdk5 can safely be 
used in the eye to enhance wound healing.

                                CATARACT

    Cataract, an opacity of the lens of the eye, interferes with vision 
and is the leading cause of blindness in developing countries. It is 
also a major public health problem in this country. Throughout life, 
the lens carries out a process of continued growth with epithelial 
cells dividing and differentiating into fiber cells. As epithelial 
cells differentiate into fiber cells they become denuded of certain 
cell components so they will not interfere with vision or cause 
cataracts. NEI supported scientists have recently discovered that the 
epithelial cells ``borrow'' enzymes involved in programmed cell death, 
or apoptosis, to mediate the destruction of these cell parts. Apoptosis 
is a normal biologic process that guides an orderly destruction of 
cells that are no longer functional or needed. This study defines a 
critical step in how fiber cells are formed and will spark further 
investigation into whether alterations in apoptotic enzymes play a role 
in cataract formation.

              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, 
published data estimates that more than 3 million Americans suffer from 
visual processing disorders not correctable by glasses or contact 
lenses.
    It is estimated that 20 percent of preschool children ages 3-4 have 
a treatable eye condition.\2\ While many states are developing 
guidelines for preschool screening programs, none of the commonly used 
vision tests have been evaluated in a research-based environment to 
establish their effectiveness. Initial results from the NEI-sponsored 
Vision in Preschoolers (VIP) Study found that 11 commonly used 
screening tests vary widely in identifying children with symptoms of 
common childhood eye conditions such as amblyopia, strabismus, and 
significant refractive error. When the best tests are used by highly 
skilled personnel in a controlled setting, approximately two-thirds of 
children with one or more of the targeted disorders were identified. 
These better tests were able to detect 90 percent of children with the 
most severe visual impairments. The ongoing VIP study will continue to 
provide state and local agencies with data to select the most effective 
vision screening exams that are currently available. The VIP study will 
also help ensure that more children are detected and treated at an 
early stage when therapy is most effective.
---------------------------------------------------------------------------
    \2\ Comparison of preschool vision screening tests as administered 
by licensed eye care professionals in the Vision in Preschoolers Study. 
Ophthalmology 111(4): 637-50, 2004.
---------------------------------------------------------------------------
    A fundamental issue in neuroscience has been the inability of nerve 
cells to regenerate. If researchers could develop therapies that 
overcome this limitation, the deleterious effects of many neurologic 
diseases and central nervous system (CNS) injuries might be reversed or 
greatly improved. NEI-supported researchers provoked nerve cell 
regeneration in rodents by activating a nerve cell's natural growth 
capacity and using gene therapy to suppress the effects of growth-
inhibiting factors. Although vision was not restored, this combined 
approach stimulated nerve cell regeneration three times greater than 
prior attempts. Regeneration of the mature CNS would provide an 
opportunity to treat blindness and other neurologic diseases.

                           HEALTH DISPARITIES

    Census 2000 data indicate that 12.5 percent of residents in the 
United States, or 35 million people, are Latino. Based on these data, 
it is estimated that by the year 2025, 61.4 million Latinos will live 
in this country, making this the fastest growing minority population. 
However, there is little available data to ascertain the prevalence and 
severity of major eye diseases in this population. Results from the 
NEI-sponsored Los Angeles Latino Eye Study (LALES) suggest that Latinos 
have some of the highest rates of visual impairment and blindness in 
the United States. The prevalence of visual impairment and blindness in 
Hispanics increased with age and women were more frequently affected 
than men. From a socio-economic perspective, Latinos who were 
unemployed, divorced or widowed, or less educated had increased rates 
of visual impairment and blindness. The prevalence statistics, coupled 
with the socio-economic data from LALES concerning the factors that 
negatively influence access to health care, will aid the NEI, through 
its public education programs, to devise strategies that better target 
these at-risk populations.

                              NIH ROADMAP

    A major theme of the NIH Roadmap, Re-engineering the Clinical 
Research Enterprise, is aimed at accelerating and strengthening the 
clinical research process. This Roadmap theme is consonant with the 
NEI's own goal of supporting the highest quality clinical research. The 
NEI and vision research community have anticipated these opportunities 
by creating networks such as the Pediatric Eye Disease Investigator 
Group (PEDIG) and the newly launched Diabetic Retinopathy Clinical 
Research Network. Continuation and expansion of these initiatives 
should facilitate and hasten the translation of research discoveries 
from the laboratory to the clinic for the benefit of those afflicted 
with a range of eye disorders and diseases.

                       NIH NEUROSCIENCE BLUEPRINT

    The NIH Neuroscience Blueprint was launched in 2004 to further 
enhance cooperation among 15 NIH Institutes and Centers that support 
research on the nervous system. Blueprint participants are developing 
an initial set of initiatives focused on tools, resources, and training 
that can have a quick and substantial impact because each builds on 
existing programs. Among the Blueprint initiatives for fiscal year 
2006, NEI will participate in the systematic development of genetically 
engineered mouse strains for research on the nervous system and 
training in neuroimaging and computational biology. NEI will also 
participate with other Institutes in an initiative to provide 
specialized neuroscience resources such as animal model, imaging, gene 
sequencing and screening facilities.
    Mr. Chairman, this concludes my prepared statement. I would be 
pleased to respond to any questions you or other members of the 
committee may have.
                                 ______
                                 
    Prepared Statement of Dr. Allen M. Spiegel, Director, National 
        Institute of Diabetes and Digestive and Kidney Diseases

    Mr. Chairman and Members of the Committee: I am pleased to present 
the fiscal year 2006 President's budget request for the National 
Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) a sum 
of $1,872,146,000, which includes $150,000,000 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 
$8,562,000 over the fiscal year 2005 enacted level of $1,863,584,000 
comparable for transfers proposed in the President's request.
    I appreciate the opportunity to testify on behalf of the NIDDK. Our 
Institute supports research to combat a wide range of debilitating 
chronic health problems, including diabetes and other endocrine and 
metabolic diseases; digestive diseases; kidney and urologic diseases; 
blood diseases; and obesity. Through vigorous support of investigator-
initiated research and Institute-initiated efforts, the NIDDK will 
continue to elucidate the fundamental biology underlying health and 
disease and to explore new strategies for disease diagnosis, treatment, 
and ultimately, prevention.

           FROM THE LABORATORY BENCH TO THE PATIENT'S BEDSIDE

    In recent years, ever-advancing technologies have led to an 
explosion of biomedical knowledge. It is imperative that scientists 
harness new discoveries to improve medical care. Thus, in addition to 
supporting critical basic and clinical research, the NIDDK is also 
bolstering ``translational'' research, to accelerate the progression of 
scientific discovery from basic to clinical studies to directly benefit 
patients. In one stage of translational research, insights gained at 
the laboratory ``bench'' spur the design of new strategies for 
prevention or intervention, which investigators then test in clinical 
studies--at the patient ``bedside.'' In a second stage of translational 
research, investigators explore ways to bring successful interventions 
and lifesaving knowledge from the clinical research setting into the 
realm of healthcare practice.
    With the goal of directing NIDDK translational research investments 
to enhance efforts on multiple diseases, I established a Trans-NIDDK 
Translational Research Working Group to identify research obstacles and 
opportunities. The Working Group charted the progression from basic to 
clinical research to medical practice for a number of health conditions 
to identify common themes for future research. These analyses were 
considered by NIDDK's National Advisory Council; external advice was 
also received at other scientific meetings.
    By way of example, translational research relating to the 
assessment of blood sugar (glucose) levels has greatly benefited 
diabetes care. Scientists discovered that levels of a variant of the 
red blood cell protein hemoglobin, called hemoglobin A1c (HbA1c), 
correlate with blood sugar levels. In the 1990s, a landmark NIDDK-
supported clinical trial demonstrated that people with type 1 diabetes 
can reduce the risk of eye, kidney, and nerve complications by lowering 
their HbA1c levels through intensive treatment of blood sugar. As a 
result of this research, target levels for HbA1c were set, thus 
improving patient care by encouraging medical practitioners to use a 
combination of methods to better control blood sugar. This research 
further led to the FDA's acceptance of the HbA1c level as an end-point 
sufficiently robust to define clinical benefit in clinical trials. 
``Biomarkers,'' such as the level of HbA1c, can facilitate clinical 
trials and thus stimulate the development of new therapeutic agents. 
Many new drugs for diabetes have now been FDA-approved based on HbA1c 
as an outcome.
    In another example of successful bench-to-bedside research, NIDDK-
supported investigators elucidated the biological defect responsible 
for the devastating inherited metabolic disease, MPS I; discovered a 
naturally-occurring dog model for the disease; and tested a potential 
therapy in dogs. Following clinical testing, this therapeutic agent is 
now produced by industry and available on the market to treat this 
disease. These two examples illustrate the critical role of NIH 
investment in research from bench-to-bedside. Both also spanned several 
decades from the initial basic research discoveries to clinical 
application. Thus, a critical goal of NIDDK's new translational 
research efforts is to accelerate this process.
    In one planned translational research effort, the NIDDK will pursue 
the development of new biomarkers. Examples of diseases or conditions 
for which such biomarkers would be valuable include acute kidney 
failure, liver and kidney fibrosis, type 1 diabetes, and insulin 
resistance--which is associated with type 2 diabetes. The NIDDK will 
also foster research on biomarkers for interstitial cystitis, including 
the evaluation of a potential diagnostic marker that emerged from prior 
NIDDK-funded research.
    Among other translational research efforts, the NIDDK will 
strengthen research to bring new non-invasive imaging techniques from 
the laboratory to the clinical setting to enhance clinical research on 
liver, pancreatic, kidney, and urologic diseases. The Institute will 
also encourage the development of new animal models suitable for 
preclinical testing of diagnostic, preventive, or therapeutic 
interventions for diseases within NIDDK's mission. Although a wealth of 
information about human biology has been and continues to be gleaned 
from studies of mice and other animals, in many cases existing animal 
models are insufficient for preclinical testing. Other translational 
research efforts are capitalizing on fundamental knowledge about how 
proteins assume their proper structures. This approach, informed by a 
recent NIDDK-sponsored conference, will help propel the search for 
therapies for cystic fibrosis and certain liver and kidney diseases, 
which are caused by defects in protein ``folding'' or ``processing.'' 
Translational research promoted by the NIH Roadmap will synergize with 
these NIDDK efforts to accelerate progress.
    Insights gained from clinical observations can open new avenues for 
basic research studies, which, in turn, will spur new clinical research 
endeavors. Several NIDDK initiatives are fostering increased 
collaboration between basic and clinical researchers, including support 
for ancillary studies to major ongoing NIDDK clinical trials. Such 
studies will also maximize the Institute's investment in these trials. 
As part of our new efforts to enhance our research centers programs, 
the NIDDK will encourage basic and clinical research partnerships to 
take advantage of the opportunities of research centers.
    In addition to the bench-to-bedside research just described, the 
NIDDK is pursuing strategies to best translate successful clinical 
research results from patient study volunteers to the public. These 
efforts include, for example, translating the results of the Diabetes 
Prevention Program (DPP) clinical trial, which demonstrated that people 
at high risk for type 2 diabetes can dramatically reduce risk of 
disease onset through modest weight loss and exercise. To promote these 
positive findings, the NIDDK launched its campaign, ``Small Steps. Big 
Rewards. Prevent Type 2 Diabetes,'' with tailored messages and 
materials developed for ethnic groups at high risk for type 2 diabetes, 
older adults, and a general audience. In parallel, the Institute is 
supporting research demonstration and dissemination projects to explore 
new strategies for effectively translating the DPP results, from 
clinical trial to community. This research includes testing programs 
that target different age groups and minority populations.
    New translation efforts to combat kidney disease are building upon 
the recent finding that even modestly-impaired kidney function 
increases risk of cardiovascular disease and premature death. Avoiding 
these devastating outcomes requires early awareness of kidney disease 
and appropriate treatment. Critically important is detection of 
deterioration in the kidneys' filtering capacity, the glomerular 
filtration rate (GFR). While GFR is difficult to measure directly, it 
can be estimated from routinely measured serum creatinine. The NIDDK's 
National Kidney Disease Education Program (NKDEP) is thus encouraging 
laboratories that measure serum creatinine to provide clinicians with 
GFR values. The NKDEP recently launched an education campaign 
emphasizing the importance of early detection and treatment, and 
targeting this message to primary care providers and those at high risk 
for kidney disease.

          EXAMPLES OF BASIC AND CLINICAL RESEARCH ENHANCEMENTS

    Underscoring a growing health crisis among our Nation's children, 
this past year an NIDDK-supported pilot study of middle school students 
uncovered high levels of the ``metabolic syndrome,'' which is a cluster 
of health problems associated with obesity and increased risk for 
diabetes and cardiovascular disease. To address the health threats 
posed by obesity, we developed and published a Strategic Plan for NIH 
Obesity Research. Informed by extensive input from scientific and lay 
experts, the Strategic Plan was developed by the NIH Obesity Research 
Task Force. Since its inception by the NIH Director, I have had the 
privilege of co-chairing the Task Force with the NHLBI Director, with 
the aims of synergizing and accelerating obesity research across the 
NIH. Consistent with the goals of the Strategic Plan, the NIDDK is 
pursuing a multifaceted obesity research agenda, from basic molecular 
investigations to novel intervention studies to translational research. 
For example, the NIDDK is spearheading a new trans-NIH initiative to 
study how factors such as maternal weight during pregnancy can lead to 
obesity in offspring. This research has important implications for 
public health.
    In the area of digestive diseases, the Action Plan for Liver 
Disease Research has now been published. It was developed through 
NIDDK-led efforts with broad external input from the research, 
professional, and patient-advocacy communities. Examples of the many 
areas addressed by the Action Plan include developing or improving 
therapies for hepatitis C; developing tools for early liver cancer 
detection; and research on living donor liver transplantation. The 
Action Plan will direct new liver disease research; the NIDDK will also 
continue major ongoing clinical studies on hepatitis C; biliary 
atresia, a disease that strikes children; and non-alcoholic 
steatohepatitis, a fatty liver disease.
    The Action Plan for Liver Disease Research is part of a larger 
planning process for research on digestive diseases, which have an 
enormous burden on the U.S. population. For inflammatory bowel disease, 
external advice received in previous planning efforts will continue to 
inform the NIDDK research agenda. New planning efforts will aim to 
strengthen research on irritable bowel syndrome and other functional 
gastrointestinal disorders, which are debilitating and highly prevalent 
but not well understood. Following focused planning efforts relevant to 
gastroparesis, the NIDDK will establish a new clinical research 
consortium to study this debilitating syndrome of nausea, vomiting, 
bloating, and other symptoms which complicates diabetes and other 
diseases.
    In the areas of kidney and urologic diseases, in addition to the 
efforts described earlier, the NIDDK will encourage partnerships to 
pursue promising new therapies for polycystic kidney disease, and will 
launch a new clinical intervention study of children with 
vesicoureteral reflux, a bladder condition which can impair kidney 
function.
    I have highlighted today examples of NIDDK's many and diverse 
research plans and efforts. These reflect our strong commitment to 
improving human health.
    Thank you, Mr. Chairman. I would be pleased to answer any questions 
that the Committee may have.
                                 ______
                                 
Prepared Statement of Dr. Stephen E. Straus, Director, National Center 
               for Complementary and Alternative Medicine

    Mr. Chairman and Members of the Committee: I am pleased to present 
the fiscal year 2006 President's budget request for the National Center 
for Complementary and Alternative Medicine (NCCAM). The fiscal year 
2006 budget includes $122,692,000, an increase of $587,000 over the 
fiscal year 2005 enacted level of $122,105,000 comparable for transfers 
proposed in the President's request.
    In 2004 NCCAM celebrated its first 5 years by reflecting on its 
contributions to the science of complementary and alternative medicine 
(CAM) and crafting a second strategic plan that articulates the 
Center's plans for 2005-2009. The plan is a collaborative effort that 
was developed with extensive input solicited from the public, CAM 
practitioners, and experienced scientific investigators; it articulates 
NCCAM's agenda for researching CAM healing practices, training CAM 
researchers, and conducting outreach.
    It is noteworthy that an independent analysis released in January 
2005 of the major scientific and policy issues surrounding CAM use, 
which was undertaken by conventional and CAM investigators for the 
Institute of Medicine (IOM) of the National Academies, identified many 
of the same research and training priorities as had NCCAM in its 
strategic planning process. The IOM report emphasized that evidence-
based science must inform all health care practices, both conventional 
and CAM.
    In accord with the philosophy articulated by the IOM, scientific 
rigor has been and will remain the foundation upon which NCCAM advances 
its research agenda. In its first 5 years, NCCAM funded more than 1,200 
projects at some 260 CAM and conventional research institutions. The 
results of these projects are being published in leading medical 
journals, affording the public and their health care providers better 
data on which to base decisions on CAM use. The following are a few 
highlights of NCCAM's recent scientific advances, ongoing activities, 
and plans that illustrate the Center's progress and future directions.

                   UNDERSTANDING WHO USES CAM AND WHY

    Understanding who uses CAM and why they do so informs NCCAM's 
research goals, initiatives, and collaborations. In 2004, NCCAM 
reported results based on survey data collected in partnership with the 
Centers for Disease Control and Prevention from more than 31,000 
Americans. The data revealed that 62 percent of survey respondents used 
CAM in 2002. Back pain was the single most common reason respondents 
used CAM, followed by respiratory infections. To track trends in CAM 
use, NCCAM and the CDC have agreed to undertake a followup survey in 
2007. Additional NCCAM-funded survey analyses are also under way to 
examine in greater detail CAM use in diverse minority populations.

                 DETERMINING THE EFFECTS OF ACUPUNCTURE

    Acupuncture is among the top ten most popular CAM practices in the 
United States. In spite of its venerable traditions as a therapeutic 
practice in Asia, scientific research on acupuncture and how it might 
work is a relatively recent phenomenon. The recent report on the 
efficacy of acupuncture for osteoarthritis demonstrates the power and 
promise of the research strategies developed and implemented by NCCAM.
    More than 20 million Americans have osteoarthritis, a frequent 
cause of pain and disability among aging adults. In 2004, NCCAM-funded 
investigators, building on the results of previous smaller studies, 
reported the results of the largest randomized, controlled Phase III 
clinical trial of acupuncture ever conducted. This study of 570 
patients demonstrates that acupuncture is an effective complement to 
conventional treatments in patients with osteoarthritis of the knee.

                      EXPLORING MIND-BODY MEDICINE

    Recognizing the important role of social and behavioral factors in 
illness and health, NCCAM's new strategic plan describes further growth 
in the Center's investments on mind-body medicine for a range of 
diseases. One such study already under way is a clinical trial 
examining the use of meditation to achieve weight loss and enhance 
overall health and well-being among obese men and women. Also, in 2004 
NCCAM funded a mind-body center as part of its research centers 
program.
    To further stimulate the field of mind-body medicine research, 
NCCAM is co-funding an initiative with the NIH Office of Behavioral and 
Social Sciences Research to encourage interdisciplinary collaborations 
to elucidate processes underlying mind-body interactions and health and 
to develop health promotion and disease prevention and treatment 
interventions.

              INVESTIGATING DIETARY SUPPLEMENTS AND FOODS

    As reported in the NCCAM/CDC survey, herbal products are among the 
most popular CAM therapies. Although many believe these products to be 
safe because they are ``natural'' or have been used for centuries, few 
of these products have undergone sufficient study of their safety and 
effectiveness. Research on botanicals is a priority area, and NCCAM 
funds numerous studies ranging from basic laboratory investigations to 
large Phase III clinical trials, to gather data on the nature, safety, 
and efficacy of popular herbal remedies.
    For example, NCCAM supports several interrelated studies of 
cranberries for preventing urinary tract infections (UTIs), which 
afflicts approximately 25 percent of women at least once in their 
lifetime. These include Phase II clinical trials to identify the 
optimal cranberry formulation, dose, and treatment duration in studies 
on UTI prevention as well as other smaller studies on the basic 
mechanisms, pharmacokinetics, and renal clearance of cranberry's major 
chemical components.
    Another priority for NCCAM's dietary supplement research portfolio 
is chronic liver disease, which claimed the lives of more than 20,000 
Americans in 2002 and disproportionately affects minorities. Through 
the Small Business and Innovative Research program, NCCAM supports 
development of a standardized milk thistle product, the most promising 
CAM therapy for liver disease. In collaboration with the National 
Institute of Diabetes and Digestive and Kidney Diseases, NCCAM will 
undertake early phase studies of safety and tolerability of milk 
thistle to determine if a Phase III trial is likely to be successful, 
and if so, the optimal research design for its implementation.
    NCCAM grantees are also examining the potential therapeutic 
properties of foods such as soy--especially as it relates to 
alleviating menopausal symptoms and promoting bone health. Last year 
NCCAM-supported scientists reported that in a study of pain induced by 
bone cancer, soy-fed mice experienced less pain than those in a control 
group. A better understanding of how dietary constituents and plant-
based nutrients moderate pain may yield further treatments to help 
patients with chronic pain.
    Benefiting NCCAM's botanical research agenda is its partnership 
with the NIH Office of Dietary Supplements (ODS). This year NCCAM and 
ODS have renewed their partnership in funding Botanical Research 
Centers to promote interdisciplinary collaborative studies on dietary 
supplements.

           MEETING THE DIVERSE NEEDS OF SELECTED POPULATIONS

    NCCAM has a broad-based research portfolio, reflecting the 
diversity of individuals who use CAM for help in managing an array of 
diseases and conditions. For example, understanding how racial and 
ethnic minorities use CAM is a focus of the Center's research agenda in 
health disparities. Initiatives are under way to examine the interplay 
of race, ethnicity, age, gender, and locale to understand how they 
affect minorities' use of CAM to manage chronic illnesses such as 
diabetes or asthma. Examining these practices will help direct future 
research to answer why specific populations use certain CAM practices--
for cultural reasons, because of access issues, for economic reasons, 
or for effectiveness--which in turn will help health care providers 
better meet the needs of these groups.
    Diseases and conditions predominately affecting the elderly are 
major targets of ongoing investments. For example, NCCAM is supporting 
the largest randomized Phase III clinical trial to date of Ginkgo 
biloba to prevent dementia in the elderly. Cardiovascular disease 
(CVD), the leading cause of death in the United States, is also a 
research priority for NCCAM. Investigations are ongoing of the ability 
of green and black tea extracts (Camellia sinensis) to reduce 
cholesterol absorption and biosynthesis in postmenopausal women and 
patients at high risk for CVD.
    In 2004, NCCAM grantees reported results from a clinical trial in 
children affected with upper respiratory infections (URI). In the 
trial, over 400 healthy 2- to 11-year-olds received a placebo or an 
echinacea product, an herbal identified by the NCCAM/CDC survey as 
widely used, to determine objectively whether it would reduce the 
severity of URIs over the 4-month study period. The researchers 
observed no differences between the two groups in the duration, 
severity, number of days with fever, and rate of adverse events except 
for an increased incidence of rashes in children receiving echinacea. 
Given the widespread use of this product, NCCAM is following up on this 
research, focusing on prevention of infection, which is how echinacea 
is usually taken, and studying the mechanisms by which echinacea may 
have health effects.
    In the wake of the Women's Health Initiative, NCCAM is developing a 
diverse research portfolio to explore use of CAM in treating menopausal 
symptoms, including hot flashes and osteoporosis. Some studies are 
examining the safety and efficacy of a range of CAM modalities women 
now use to treat these symptoms; others address more basic science 
questions, such as a therapy's mechanism of action. NCCAM's research 
portfolio also addresses other important health conditions exclusive to 
women--endometriosis and premenstrual syndrome (PMS)--as well as those 
that affect more women than men, such as UTIs, osteoporosis, 
fibromyalgia, osteoarthritis, breast and other cancers, and 
cardiovascular disease.

                 PARTICIPATING IN TRANS-NIH INITIATIVES

    NCCAM co-chairs a critical component of the NIH Roadmap for Medical 
Research Activity, Reengineering the Clinical Research Enterprise, to 
develop a more effective and cost-efficient model of translational 
research to move basic research into safe, well-designed clinical 
trials. In addition, NCCAM is actively involved in the NIH 
Neurosciences Blueprint, a trans-NIH initiative to accelerate the 
efficiency and pace of neurosciences research. Also, as part of the 
Trans-NIH Obesity Initiative, NCCAM is co-sponsoring efforts on 
childhood obesity and obesity prevention and treatment.

                        CHARTING NCCAM'S FUTURE

    NCCAM has accomplished much in its first 5 years. The first NCCAM-
supported large-scale clinical trials are nearing completion; these 
findings are appearing in the nation's leading medical journals. NCCAM 
also has developed a comprehensive communications program to inform the 
public and health care professionals about CAM research findings. And 
the Center has created new opportunities in CAM research training for 
young scientists and has forged linkages between CAM institutions and 
conventional research centers. With its second strategic plan as a 
guide, NCCAM looks forward to making ongoing contributions as the 
nation's lead CAM research agency.
    Thank you Mr. Chairman. I would be pleased to answer any questions 
that the Committee may have.
                                 ______
                                 
    Prepared Statement of Dr. Lawrence A. Tabak, Director, National 
             Institute of Dental and Craniofacial Research

    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 2006. The fiscal year 
2006 budget includes $393,269,000, an increase of $1,440,000 over the 
fiscal year 2005 level of $391,829,000 comparable for transfers 
proposed in the President's Request.

  THE ROAD AHEAD: MERGING SCIENTIFIC VISION AND TECHNOLOGY DEVELOPMENT

    Many of the opportunities that now face our nation's oral health 
researchers have never been more exciting or scientifically 
challenging. For the first time, we can envision a day when early stage 
tooth decay will be reversible with remineralizing solutions that patch 
the tooth and halt the disease process before a filling is required. 
Researchers will soon begin to learn how to engineer teeth and their 
constituent parts in the laboratory and transplant them into the mouth 
to replace a missing tooth or damaged tissue. The day also is 
approaching when saliva will be a reliable diagnostic fluid to detect 
systemic diseases, providing a rapid, non-invasive alternative to 
blood-based tests. These are but a few of the many opportunities that 
await us. And yet, as important as these visions of the future are in 
setting the course toward improved public health, it is abundantly 
clear that the road ahead will be blocked unless we develop new tools 
and technologies for working within the complex microenvironments of 
the human body. It is this merging of scientific vision with technology 
development that the NIDCR is fostering within our nation's oral 
research community and which I would like to highlight.

                EARLY DIAGNOSIS TO PREVENT DENTAL CARIES

    Let me begin with one of the examples just mentioned. Despite 
dramatic reductions in tooth decay in the United States over the last 
half century, dental caries remains a significant public health 
problem, particularly among disadvantaged population groups. Dental 
decay also is an unexpected impediment to timely deployment of military 
personnel. At a time when our nation remains at war, dental readiness 
has been cited in testimony by the Reserve Officers Association as the 
number one deployment problem for National Guard and Reserve members. 
In a 2002 Department of Defense study, 34 percent of military personnel 
required dental care before they could be deployed, compared to only 16 
percent in 1998.
    The NIDCR will soon launch an initiative to evaluate the ability of 
emerging technologies to accurately and reproducibly measure extremely 
subtle changes in dental enamel that signal the earliest phases of 
dental caries. While this initiative may sound highly technical, its 
outcome could play an essential role in transforming dental care. 
Treatments with the potential to remineralize tooth surfaces in the 
very earliest stages of decay, long before a filling is needed, are 
emerging. In anticipation of the required clinical trials to rigorously 
evaluate these treatments, NIDCR will soon launch an initiative to 
ensure that microscopic changes in a tooth's mineral content can be 
measured accurately and reproducibly. Through this enabling research, 
the evaluation of these treatments will be firmly grounded in science, 
ensuring the greatest possible benefit to the public.

                    BIOENGINEERING: BUILDING A TOOTH

    Tooth loss has been a public health problem in the United States 
since the days of George Washington and Thomas Jefferson. Despite 
revolutionary advances in oral health over the last half century, tooth 
loss remains a problem, particularly among disadvantaged groups. In 
addition, tooth agenesis--the lack of one or more permanent teeth--is 
the most common congenital malformation in humans. While dental 
implants or dentures are often effective replacements, science has 
progressed to the point that it may be possible to generate replacement 
teeth from scratch, which would mark a truly historic advance in oral 
healthcare and in our understanding of human biology.
    Whereas just a few years ago tooth regeneration was far beyond the 
reach of science, which is no longer the case. An historic opportunity 
now awaits dental science to learn to seed and reproducibly control the 
complex, tightly orchestrated cellular and molecular interactions 
involved in producing a tooth and its supporting structures. The 
crucial first steps will be to: identify existing gaps in our knowledge 
of tooth formation; pursue viable solutions from throughout the 
biological and physical sciences to bridge these gaps; and, based on 
these comprehensive analyses, formulate blueprints for a complete 
tooth. Relying on the best of these blueprints, interdisciplinary teams 
of scientists will begin the process of engineering replacement teeth. 
It is likely that these investigations will initially yield viable 
replacement parts, such as enamel, dentin or periodontal ligament, but 
the ultimate goal is complete tooth regeneration.

                  LAB ON A CHIP: SALIVARY DIAGNOSTICS

    Another particularly exciting area of research is salivary 
diagnostics. Scientists have long recognized that our saliva serves as 
a ``mirror'' of the body's health, in that it contains the full 
repertoire of proteins, hormones, antibodies, and other molecular 
substances that are frequently measured in standard blood tests to 
monitor health and disease. Saliva is easy to collect and poses none of 
the risks, fears, or ``invasiveness'' of blood tests. The problem has 
been that the needed technologies have not existed to adequately 
develop salivary diagnostics on a large scale.
    The Institute continues to support a major research effort that 
will further develop these needed technologies and create the first 
comprehensive baseline catalogue of all proteins found normally in oral 
fluids. This is the initial step in building the needed scientific 
infrastructure required to expand salivary diagnostics. Already, 
scientists have begun to evaluate which of the myriad gene products in 
saliva correlate with various disease processes.
    The NIDCR envisions that this basic research could one day 
translate into miniature, hi-tech tests, or so-called ``labs'' on a 
silicon chip, which rapidly scan oral fluids for the presence or 
absence of multiple proteins linked to various systemic diseases and 
conditions. Given the ease of sample collection and the breadth of 
protein markers that could be arrayed on the silicon chip, salivary 
tests have the potential to revolutionize how diseases are diagnosed. 
Physicians and dentists would continue to diagnose diseases. But they 
would be in the position for the first time to monitor a patient's 
health, producing a comprehensive molecular print out of that 
individual's health status that can be assessed over time.
    Salivary diagnostics will have benefits far beyond medicine and 
dentistry as well. Law enforcement agencies could employ saliva tests 
in the field to determine rapidly whether a person is intoxicated or 
has recently used illegal drugs. These tests may also be beneficial in 
determining exposures to environmental, occupational, and biological 
substances, such as anthrax.

          ORAL CANCER: EARLY DETECTION IS KEY TO SAVING LIVES

    The field of salivary diagnostics recently yielded exciting early 
findings related to oral cancer detection. According to the American 
Cancer Society and the Centers for Disease Control and Prevention, oral 
cancer is the seventh most common cancer among U.S. males and ranks 
fourth among African American men. Unfortunately, survival rates have 
not improved significantly in decades. A patient's chance of survival 
is improved significantly with early detection and treatment. A team of 
NIDCR-supported scientists at the University of California at Los 
Angeles recently reported that they could measure elevated levels of 
four distinct cancer-associated molecules in saliva and distinguish 
within 91 percent accuracy between healthy people and those diagnosed 
with oral squamous cell carcinoma. This ``proof-of-principle'' study 
marks the first report in the scientific literature that distinct 
patterns of ``messenger RNA'' are not only measurable in saliva, but 
can indicate a developing tumor. These initial results highlight the 
potential clinical value of saliva and hold out exciting possibilities 
for development of commercially available tests capable of delivering 
early, reliable, non-invasive detection of developing tumors.

               PAIN: TRANSLATING TARGETS INTO TREATMENTS

    Sizeable gaps exist in our understanding of some of the most basic 
cells involved in the pain process. Prime examples are the glial cells. 
For decades, scientists assumed that glial cells primarily played a 
supportive role in the central nervous system and had no direct 
influence on the transmission of sensory signals to the brain. But, as 
more powerful analytical molecular tools have emerged in recent years, 
scientists now realize that glial cells play a far more important role 
in pain than was previously appreciated. With this new awareness, it 
becomes imperative to better define the biology of these cells and 
their roles in regulating certain aspects of nervous system function.
    The NIDCR will launch an initiative that will stimulate needed 
research into the basic biology of glial cells and their interactions 
with neurons in causing orofacial pain disorders, such as 
temporomandibular joint disorders. The initiative will encourage 
multidisciplinary studies in a variety of areas to define more broadly 
than ever important aspects of the pain process. Based on this broad 
investigative approach, key aspects of the pain process will be more 
clearly defined, pointing the way to unique and highly specific 
molecular targets for drug development. Without identifying these 
additional targets, it will be impossible to ever adequately control or 
treat pain, particularly among the estimated 10 percent of Americans 
who suffer from chronic pain.

                              NIH ROADMAP

    The NIH Roadmap themes are synergistic with NIDCR research 
initiatives and provide added impetus to the efforts of oral health 
researchers. For example, the theme Re-engineering the Clinical 
Research Enterprise is particularly relevant to the development of 
NIDCR-sponsored dental Practice Based Research Networks. Similarly, the 
goals of the initiative Building Blocks, Biological Pathways and 
Networks are closely linked to NIDCR's own bioengineering initiative, 
``Building a Tooth.'' Research Teams of the Future provides an 
opportunity to further integrate dentists into the new clinical 
research structure, and highlights NIDCR's longstanding efforts to 
encourage multi- and interdisciplinary approaches to research 
questions.
    With the above-mentioned examples and other research progress, such 
as in salivary gene transfer, defining the oral biofilm, and the 
molecular targeting of oral cancer, NIDCR has never faced more exciting 
opportunities. By merging our vision of the future with technology 
development, the road ahead will lead this nation to a new generation 
of progress and improved oral health.
    Thank you, Mr. Chairman. I would be pleased to answer any questions 
that the Committee may have.
                                 ______
                                 
 Prepared Statement of Dr. Jack Whitescarver, Director, Office of AIDS 
                                Research

    Mr. Chairman and Members of the Committee, I am pleased to present 
the fiscal year 2006 President's budget request for the NIH AIDS 
research programs, a sum of $2,932,992,000, which is an increase of 
$12,441,000 above the comparable fiscal year 2005 appropriation.

                           WORLDWIDE PANDEMIC

    AIDS is the deadliest pandemic of modern times. More than 20 
million people have already died of AIDS, and more than 60 million 
people around the world have been infected with HIV. AIDS is the 
leading infectious cause of death worldwide, surpassing tuberculosis 
and malaria.\1\ Its impact is profound, affecting families, 
communities, agriculture, business, healthcare, education, military 
preparedness, and economic growth. 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 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.'' \3\ A 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.\4\ Foreign Affairs magazine 
stated: ``. . . 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.'' \5\ Dramatic increases in HIV 
infection also are occurring in Eastern Europe, Central Asia, Latin 
America, and the Caribbean.
---------------------------------------------------------------------------
    \1\ Report on the Global HIV/AIDS Epidemic: July 2002, (UNAIDS/WHO, 
Geneva, Switzerland, 2002).
    \2\ The Impact of AIDS (Department of Economic and Social Affairs, 
United Nations, 2004).
    \3\ The Impact of AIDS (Department of Economic and Social Affairs, 
United Nations, 2003).
    \4\ Intelligence Community Assessment: The Next Wave of HIV/AIDS: 
Nigeria, Ethiopia, Russia, India, and China. (CIA, 2002).
    \5\ The Future of AIDS, Foreign Affairs, November/December 2002.
---------------------------------------------------------------------------
                           THE U.S. EPIDEMIC

    In the United States, according to CDC, the decline in death rates 
observed in the late 1990s, due largely to expanded use of new 
antiretroviral therapies (ART), has now leveled off. The use of ART has 
now been associated with a serious 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.\6\ This means that the overall 
epidemic is continuing to expand.\7\ \8\ \9\ CDC reports that 
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.\10\
---------------------------------------------------------------------------
    \6\ Characteristics of Persons Living with AIDS and HIV, 2001, HIV/
AIDS Surveillance Supplemental Report (CDC, 2003).
    \7\ 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\ Cases of HIV Infection and AIDS in the United States 2003, HIV/
AIDS Surveillance Report (CDC, 2004).
    \10\ Frequently Asked Questions and Answers about Co infection with 
HIV and Hepatitis C Virus (CDC, 2002).
---------------------------------------------------------------------------
    For the past several years, we have cautioned in our testimony that 
the appearance of multi-drug resistant strains of HIV presents an 
additional serious public health concern.\11\ \12\ \13\ \14\ \15\ In 
just the past few weeks, we have had a new warning about that 
potential. The New York City Health Department reported the possibility 
of a more virulent and aggressive multi-drug resistant HIV strain \16\ 
focusing attention again upon the nature of the infection, the 
associated immune decline, and the behaviors linked to HIV 
transmission. It is too early to determine if this is some newly 
virulent form of HIV. A series of highly sophisticated tests is now 
underway to examine how the virus replicates in cells, as well as the 
efficiency and mechanisms of viral attack. The fact that the individual 
infected by this virus progressed more rapidly to immune decline may be 
reflective of a number of factors, some unrelated to the viral strain, 
such as host factors, native immune system function, or genetics. We 
have much more to learn about this case. However, it highlights a 
number of lessons about the active and ongoing U.S. HIV epidemic. HIV 
infection does not occur in a vacuum or in isolation--it occurs in the 
context of behaviors, including alcohol and drug use (the use of 
crystal methamphetamine in the New York City case), that require a 
contextually appropriate and interwoven response. This case underscores 
the importance of access to quality care that may need to include HIV 
resistance testing, and closer monitoring for immune decompensation in 
the setting of appropriate treatment. Most importantly, this case is a 
wake-up call, a reminder that the ability to interrupt HIV 
transmission, as well as the cycle of pain and suffering associated 
with HIV disease, is directly related to the robustness of HIV care, 
treatment and research infrastructure in the communities impacted by 
this disease. This expanding and evolving U.S. epidemic continues to 
present new and complex scientific challenges.
---------------------------------------------------------------------------
    \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\ ``New York City Resident Diagnosed with Rare Strain of Multi-
Drug Resistant HIV that Rapidly Progresses to AIDS,'' New York City 
Health Department Press Release 2/11/2005.
---------------------------------------------------------------------------
                     ROADMAP FOR NIH AIDS RESEARCH

    In response to this worldwide crisis, NIH is the world's leader in 
the magnitude and quality of our AIDS research effort--a comprehensive 
program of basic, clinical, and behavioral research on HIV infection, 
its associated co-infections, opportunistic infections, malignancies, 
and other complications. No other disease so thoroughly transcends 
every area of clinical medicine and scientific investigation, crossing 
the boundaries of nearly all of the NIH Institutes and Centers. The 
Office of AIDS Research (OAR) plays a unique role at the NIH, 
establishing a roadmap for the AIDS research program. OAR coordinates 
the scientific, budgetary, and policy elements of the NIH AIDS program, 
prepares an annual comprehensive trans-NIH strategic plan and budget 
for all NIH-sponsored AIDS research; facilitates NIH involvement in 
international AIDS research activities; and identifies and facilitates 
multi-institute participation in priority areas of research. These 
legislative authorities are critical to identify and ensure support for 
the areas of highest scientific priority.

              COMPREHENSIVE AIDS RESEARCH PLAN AND BUDGET

    The OAR planning process is inclusive and collaborative, involving 
the NIH Institutes, 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. 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; 
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. The Institutes and Centers submit 
their AIDS budget request to OAR, and the OAR establishes their AIDS 
research budgets, in accordance with the priorities of the Plan, at 
each step of the budget development process.

                 FUNDING FOR HIGHEST PRIORITY RESEARCH

    To develop the fiscal year 2006 request, OAR initiated a 
comprehensive trans-NIH review of all grants and contracts supported 
with AIDS-designated funds to ensure that these projects represent the 
highest scientific priorities and opportunities. OAR carefully reviewed 
the mix of investments in key priority areas of research in view of the 
current epidemic. This budget request reflects OAR's redirecting of 
AIDS funds to the highest priority projects and new scientific 
opportunities in fiscal year 2006.
    This budget request places highest priority on the discovery, 
development, and testing of additional HIV vaccine candidates, 
including funding to move promising vaccine candidates into large-scale 
clinical trials to evaluate the potential for efficacy. The NIH 
priority in AIDS vaccine research to date has resulted in approximately 
70 clinical trials of nearly 40 vaccine candidates. The evaluation of 
an AIDS vaccine will require extensive testing in the United States and 
in international settings where there is a high incidence of HIV.
    In the area of therapeutics research, current drug regimens have 
resulted in extended survival and improved quality of life for many 
HIV-infected individuals in the United States and Western Europe. 
However, a growing proportion of patients receiving therapy are 
demonstrating treatment failure, experiencing serious drug toxicities 
and side effects, and developing drug resistance. The increasing 
incidence of metabolic disorders, cardiovascular complications, major 
organ dysfunction, and physical changes associated with current 
antiretroviral drugs underscores the critical need for new and better 
treatment regimens. Improved regimens also are needed to treat HIV co-
infections such as hepatitis B and C, as well as other opportunistic 
infections to reduce drug interactions and problems with adherence to 
complicated treatment regimens. The goal of this research is to develop 
new, safe, less toxic, less expensive, and more effective therapeutic 
agents and regimens.
    OAR spearheaded a multi-IC inter-disciplinary collaboration to 
formalize plans for the restructuring of the NIH clinical trials 
networks for HIV therapeutics, vaccines and prevention. This effort 
resulted in a set of principles to guide the development of the Request 
for Applications (RFAs) for the re-competition of these essential 
multi-IC supported clinical programs in fiscal year 2006, designed to 
ensure that they operate effectively and cooperatively, making the best 
use of research dollars.
    Our prevention research priorities include the development of 
vaccines, topical microbicides, strategies to prevent mother-to-child 
transmission, including a better understanding of risk associated with 
breast-feeding, management of sexually transmitted diseases (STDs), and 
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.

                      INTERNATIONAL AIDS RESEARCH

    NIH bears a unique responsibility to address the global epidemic, 
with priority on the urgent need for more affordable and sustainable 
prevention and treatment approaches that can be implemented in 
resource-limited nations. The high incidence of Hepatitis B and C, 
malaria, and TB in many of these nations further complicates the 
treatment and clinical management of HIV-infected individuals. NIH 
international AIDS research includes: development of HIV vaccine 
candidates and chemical and physical barrier methods, such as 
microbicides; behavioral strategies; strategies to prevent mother-to-
child transmission; therapeutics for HIV-related co-infections and 
other conditions; and approaches to using ART in resource-poor 
settings. NIH supports international training programs and initiatives 
that help build research infrastructure and laboratory capacity.

                          WOMEN AND MINORITIES

    In the United States, the rate of diagnoses for African Americans 
was almost 10 times the rate for whites and almost 3 times the rate for 
Hispanics. The rate of AIDS diagnoses for African American women was 25 
times the rate for white women.\17\ Women experience HIV/AIDS 
differently than 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. NIH is 
exploring research questions 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.
---------------------------------------------------------------------------
    \17\ HIV/AIDS Surveillance Report 2003, Vol. 15 (CDC, 2004).
---------------------------------------------------------------------------
    We are focusing on the need for comprehensive strategies to 
decrease HIV transmission in affected vulnerable populations, and 
improve treatment options and treatment outcomes, including 
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 
continues to make 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 NIH's leadership role in the response to the AIDS pandemic is 
fundamental and unprecedented, and we have established a research 
program that is complex, comprehensive, multi-disciplinary, inter-
disciplinary, and global. Further, this research investment is reaping 
even greater dividends, as AIDS-related research is also unraveling the 
mysteries surrounding many other infectious, malignant, neurologic, 
autoimmune, and metabolic diseases. The legislative authorities of the 
OAR allow NIH to pursue a united research front against the global AIDS 
epidemic. NIH is enhancing collaboration, minimizing duplication, and 
ensuring that research dollars are invested in the highest priority 
areas of scientific opportunity that will allow NIH to meet its 
scientific goals. We are deeply grateful for the continued support the 
Administration and this Committee have provided to our efforts.

    Senator Specter. Well, that is a good juncture to discuss 
that, Dr. Zerhouni. My colleagues look at the increases in the 
NIH budget and compare them with what is done generally or in 
other research lines, the National Academy of Sciences. NIH has 
gotten a much greater increase than anyone, and I think that's 
because this subcommittee has taken an interest in the subject 
and we have seen what you can do.
    How can you quantify the good use of the money? Because 
many of my colleagues say, well, we don't know the details of 
NIH, but they've gotten too much money too fast to be 
efficient. Are you efficient?
    Dr. Zerhouni. Well, this is----
    Senator Specter. I know what the answer's going to be, but 
tell me why it's yes.
    Dr. Zerhouni. I'm going to give you very simple numbers, 
sir. I believe in facts. Are we efficient? Do we have too 
much--have we received too many resources? $96 per American per 
year is what we invest in research and development and 
knowledge faced to a $5,500 per year spending in health care, 
rising at a much faster rate than inflation.
    This ratio is really the key. We need to accelerate our 
knowledge so that we can change the paradigm of how we treat 
patients today. It would be more effective if we could develop 
methods of intervening years before the disease develops, 
rather than do what we do today, which is intervene after the 
disease has struck.
    Senator Specter. Give me an illustration of that.

                RESULTS FROM ACCELERATING OUR KNOWLEDGE

    Dr. Zerhouni. A good illustration of that, I showed you the 
statistics on heart disease. You've seen how the mortality has 
dropped. That's because we've used as a preventive measure 
drugs that reduce high blood pressure and drugs that reduce 
cholesterol. Those two actions have led to a half of the 
reduction in mortality. That's a good example.
    In stroke, we've reduced the mortality of stroke by 50 
percent, just because we've used methods to reduce the impact 
of high blood pressure.
    In cancer, screening for cancer, in colon cancers, is 
responsible for the majority of the reduction in mortality from 
colon cancer. So there are things we can do as we learn more 
about the genetics----
    Senator Specter. Would you amplify your response on cancer?
    Dr. Zerhouni. Well, in cancer you can see, for example, in 
breast cancer--I'll give you one example in breast cancer--with 
the use of tamoxifan and the use of new drugs, we've reduced 
the occurrence, the reoccurrence of breast cancer by 50 
percent. We believe that in high risk populations, as we can 
identify them, and the National Cancer Institute is working on 
these factors, we'll be able to ultimately reduce the number of 
patients altogether who develop cancer. The same is true in 
colon cancer.
    Senator Specter. How will you do that?
    Dr. Zerhouni. Primarily by understanding----
    Senator Specter. Why haven't you done it before now?
    Dr. Zerhouni. I think we did not know the genetics of 
breast cancer or colon cancer until 10, 15 years ago. We 
started to know it, and our knowledge has accelerated over the 
past 5, 6 years with the completion of the human genome. We are 
continuing our efforts with the understanding of the genetic 
map and the continuing efforts and investments that NCI has put 
in understanding the genetics of cancer. That's the knowledge 
that allows us to do that.
    Senator Specter. On this subject, we have with us today Dr. 
Andrew von Eschenbach, who's the director of the National 
Cancer Institute. Dr. von Eschenbach, would you step forward?
    I might comment on the number of witnesses we had here 
because I had set at the outset that we have not followed the 
customary practice of having all of the directors where we 
couldn't possibly question more than 20 people who work in 
attendance. But Dr. Zerhouni and Dr. von Eschenbach are 
presidential appointees, and Dr. Zerhouni requested bringing 
Dr. Anthony Fauci and Dr. Allen Spiegel because of questions 
which might arise, and then we have added in, as I said 
earlier, Dr. James Battey because of the currency of an issue 
which has arisen on the application of the new ethics rules.
    Dr. von Eschenbach.
    Dr. von Eschenbach. Yes, sir.

                           THE WAR ON CANCER

    Senator Specter. You have the largest allocation in the 
National Institutes of Health, coming close to almost $5 
billion. President Nixon declared war on cancer in 1970. 
Thirty-five years have passed and we've won some wars, but not 
that one. What will it take to win that war?
    Dr. von Eschenbach. Well, Mr. Chairman, first of all, the 
wisdom and the support that we have received at the National 
Cancer Institute from the Congress in providing the resources 
has led us to a point where in 1971 when we began this effort 
we did not understand cancer. We didn't understand that it was 
a spectrum of diseases, and we certainly didn't understand the 
basis of that disease. But today----
    Senator Specter. A spectrum of diseases?
    Dr. von Eschenbach. Yes, sir.
    Senator Specter. How many roughly?
    Dr. von Eschenbach. Well, there are certainly a large 
number of cancers, but what we're learning even today is that 
even when we think of one cancer like breast cancer or 
lymphoma, or even colon cancer, there are subsets of those 
cancers because of the fact that there are unique, different 
changes in the genes and the molecules that cause and drive 
that cancer----

                                LYMPHOMA

    Senator Specter. How many subsets of lymphoma? I have a 
special interest.
    Dr. von Eschenbach. There are two major subsets of 
Hodgkin's and non-Hodgkin's lymphomas. But even within those 
groups, even as we speak, we are learning that there are 
subsets----
    Senator Specter. Subsets within Hodgkin's lymphoma?
    Dr. von Eschenbach. Correct, sir, and especially in non-
Hodgkin's lymphomas. For example----
    Senator Specter. But how about subsets in Hodgkin's 
lymphoma? You'll pardon my special interest.
    Dr. von Eschenbach. Yes, sir. If you allow me, one of the 
ways that we're beginning to understand even what we think is a 
single disease of Hodgkin's lymphoma is to recognize that in 
different patients that lymphoma may have different molecules 
or proteins on the surface of the cell that cause it to behave 
differently and respond differently to different therapies or 
interventions.
    For example, a recent drug that has been created is a drug 
that can attach itself to those proteins on the surface of the 
cell. One of those proteins is CD-20, an antibody. So if we can 
look at a Hodgkin's tumor and determine whether the antibody is 
present or not, we can then design and apply specific therapy 
for that specific patient.

                          RETURN ON INVESTMENT

    To follow up on the question of the return on investment, 
this investment in cancer research that has led us to a point 
today where we're beginning to understand cancers at the 
molecular and genetic and cellular level is influencing our 
selection of therapy and moving us to personalized medicine and 
personalized oncology.
    We're sparing patients unnecessary treatments that we can 
predict will not help them, while at the same time making 
certain we're giving patients the specific and exact therapy 
that we can predict and know at the molecular level will help 
them.
    This drug I alluded to that's recently been released, 
Bexxar, combines the knowledge of that antibody, of CD-20, in a 
group of other lymphomas, non-Hodgkin's lymphomas, called 
follicular lymphoma. By identifying that antibody and coupling 
to it a radioactive material, we can target those lymphoma 
cells, and patients who were previously considered incurable 
now have a 75 percent complete response rate in elimination of 
their tumor.
    Senator Specter. Before yielding to Senator Cochran, the 
distinguished chairman of the full committee I want to ask you 
one more question, Dr. Zerhouni, and you one more question, Dr. 
von Eschenbach. If we have a flat-level funding for NIH this 
year, how many grants will you have to reduce because of 
inflationary factors and other factors, contrasted with what 
you could do if we were able to get the extra $1.5 billion 
which is in the budget resolution?

                             SUCCESS RATES

    Dr. Zerhouni. The total number of grants will decrease by 
about 400 total. As I said, we were going to make a special 
effort to increase the number of grants for new investigators 
or what we call competing investigators so that----
    Senator Specter. With the extra $1.5 billion, then what?
    Dr. Zerhouni. We could reestablish--you know, one of the 
things you said that is very important that we hear a lot is 
NIH has too much money, it cannot spend any more money. The 
best statistics I can give you is we are getting more and more 
ideas we cannot fund, and our success rate is actually 
dropping. I'll show you some statistics here that you can see, 
and we were at about 32 percent a few years back to 30 percent 
to 25, 22, and eventually we will reach 21 percent in 2006. 
With----
    Senator Specter. Of grants on applications, percentage that 
you grant?
    [The information follows:]

    
    
    Dr. Zerhouni. By those number of scientists we can fund 
when they apply, one in five, or a little bit above that. So 
clearly anything we could do to reestablish the ability of 
fulfill and satisfy the scientific demand would be helpful. 
However, we recognize as you did the very, very difficult 
fiscal times we're in.

                       FUNDING THE WAR ON CANCER

    Senator Specter. Dr. von Eschenbach.
    Dr. von Eschenbach. Yes, sir.
    Senator Specter. With sufficient funding, can we win the 
war on cancer in the reasonably near future?
    Dr. von Eschenbach. Senator, we have made a commitment at 
the National Cancer Institute to eliminate the suffering and 
death that results from cancer, to eliminate the outcome of 
cancer, and to bring that about as early as 2015 in this 
Nation. We have made that commitment because we believe that 
this investment that has been made in cancer research has led 
us to a point today where we can build on our understanding of 
cancer and use that knowledge to develop new and more effective 
interventions that can in fact achieve the goal----
    Senator Specter. Do you have sufficient funding to reach 
that goal by 2015?
    Dr. von Eschenbach. The funding that we have we are 
applying as effectively and as efficiently as possible to 
achieve that trajectory. Obviously, with increase resources we 
have increasing opportunities to even further accelerate that 
pace of progress.
    Senator Specter. If your funding were increased, could you 
reduce that date to 2010?
    Dr. von Eschenbach. We certainly could accelerate the pace 
of progress, and how quickly and how soon we could bring that 
about, I could not absolutely predict.
    Senator Specter. I would like you to give that some thought 
and provide the subcommittee with a projection as to what kind 
of funding you would require to reduce the figure to 2010. A 
lot of people are going to have a lot of suffering in those 
other 5 years.
    Dr. von Eschenbach. Yes, sir.
    Senator Specter. Really in the 5 years from now until 2010.
    [The information follows:]

                       National Cancer Institute

    What would it take to accelerate the achievement of the NCI's 2015 
goal to eliminate suffering and death due to cancer from 2015 to 2010?
    You have requested information on the amount of money necessary for 
the National Cancer Institute (NCI) to achieve its 2015 goal by 2010. 
It should be noted, though, that these funding estimates for additional 
resources were developed without taking into consideration overall 
fiscal constraints and other competing priorities of NIH, HHS, or the 
rest of the Federal government over this five-year time period. The 
current annual NCI budget is nearly $5 billion, and the resources 
discussed below would be in addition to this base.
    NCI has established an ambitious goal of eliminating the suffering 
and death due to cancer by 2015 by sustaining and integrating progress 
in the discovery, development, and delivery of more effective 
interventions based on molecular mechanisms of cancer. We estimate that 
expenditure of an additional $4.2 billion above the NCI base of nearly 
$5 billion over the next five years could accelerate progress. While 
the elimination of suffering and death due to cancer may not be fully 
achievable by 2010, there would be significant progress toward 
narrowing the gap between 2015 and 2010.
    This $4.2 billion estimate reflects an additional up front 
allocation of $2.5 billion to be expended over five years for a 
National Advanced Technology Initiative for cancer (NATIc) to 
accelerate the emerging disciplines of molecular oncology, 
nanotechnology, and bioinformatics for use in creating a pipeline of 
new personalized cancer diagnostics and therapeutics. This would also 
reflect an annual increase of $171 million over current base NCI levels 
for five years to deploy a modern integrated cancer clinical trials 
infrastructure and an annual increase of $164 million for five years to 
expand and integrate the NCI-designated Cancer Centers program from 60 
existing centers to 75. In addition to resources, additional 
legislative authorities related to exemptions from specific parts of 
current procurement, grant review and processing, and licensing and 
patenting rules would also help speed progress toward an accelerated 
cancer goal.
    Three decades ago there were 3 million U.S. cancer survivors; today 
that number has increased to over 10 million. Today, each minute of 
every hour of every day, one American dies from cancer: 570,280 lives 
will be lost this year due to this disease. Despite this fact, there 
has been remarkable progress in understanding the cancer process and 
applying that knowledge. Today, 65 percent of patients diagnosed with 
cancer can expect to survive. If we had the ability to apply what we 
know today to every cancer patient, we could have an immediate impact 
on survival, largely through the NCI Cancer Centers. Incremental 
improvements in survival will continue toward our 2015 goal, but we can 
accelerate these gains. Even improving the overall survival rate to 90 
percent by 2010 could mean an additional 850,000 lives saved. The 
impact of this strategy could produce annual changes in the first two 
years of around 2-3 percent, with larger increases occurring in 2008-
10.
    For most cancer patients, survival is greatly influenced by early 
detection. The rapid deployment of advanced imaging, nanotechnology 
supported early detection platforms and targeted therapies will change 
the face of diseases such as ovarian cancer, lung, colon and breast 
cancers; where survival is low because we can not currently detect them 
before they spread. Ovarian cancer, which is very difficult to detect 
and diagnose in its early stages, has over 25,000 new cases diagnosed 
annually and over 14,000 deaths; the mortality rate is nearly 85 
percent. Imaging and detection techniques presently under development 
and broadly applied could reverse that mortality rate to be an 85 
percent survival rate. Lung cancer, with approximately 170,000 expected 
deaths this year, would see a significant reduction in the number of 
deaths if the application of new technologies combined with other 
interventions could be universally applied in an accelerated manner.
    The challenge to achieving the goal of eliminating the suffering 
and death due to cancer by 2010 is daunting, but with the authorities 
and appropriations commensurate with the task, the pace of progress 
could be accelerated, and the gap between 2015 and 2010 narrowed. The 
following reflects a brief overview of how such funds, if available, 
could be applied.
  --Rapid Deployment of a National Advanced Technology Initiative for 
        cancer--$2.5 billion one time appropriation with commensurate 
        authorities.
  --Deployment of a Modern Integrated Clinical Trials Infrastructure--
        $171 million addition to the NCI base budget.
  --Expansion and Integration of the Cancer Centers Program--$164 
        million addition to the NCI base budget.
  --Mechanisms and Flexibilities--streamlined procurement and review 
        processes to acquire materials and services; coordination of 
        licensing and patenting activities.
    A National Advanced Technology Initiative for cancer (NATIc) could 
provide a linkage between the National Cancer Program and R&D 
initiatives being developed in selected National Laboratories and 
advanced technology facilities located in more than 40 states and 
regions. Connected in real time through a common bioinformatics grid, 
NATIc as a ``network of networks'' of science, technology, and 
treatment, could serve to accelerate the emerging discipline of 
molecular oncology to create a pipeline of new personalized cancer 
diagnostics and therapeutics from bench concept to bedside and 
community delivery. In the next few years, such an initiative could:
  --Accelerate the implementation of a nationwide high-end information 
        technology grid for bioinformatics that could be uniquely 
        adapted for real time data sharing. NCI's pilot version, called 
        caBIG, is currently being implemented among 50 cancer centers, 
        the Food and Drug Administration (FDA), and other 
        organizations.
  --Develop a comprehensive biomarker discovery and validation program.
  --Foster the application of emerging technologies, such as 
        nanotechnology, and integrate molecular agents with advanced 
        imaging devices.
  --Accelerate a nationwide ``real time'' medical information 
        electronic system for research and medical data sharing using 
        technologies and devices currently employed by the banking 
        industry and large-scale commercial enterprises.
  --Enhance the discovery and validation of new targets of genes and 
        proteins critical to cancer development.
    NCI could deploy a more modem and integrated infrastructure for 
cancer clinical trials. This clinical research infrastructure could:
  --Strengthen collaborations with industry, FDA, Centers for Medicare 
        and Medicaid Services, and other public, private, academic, and 
        patient advocacy organizations to oversee the conduct of cancer 
        clinical trials.
  --Develop new infrastructure and procedures to standardize, 
        coordinate, and track clinical trials development and accrual 
        across all NCI-supported clinical trials.
  --Increase utilization of imaging tools in screening and therapy 
        trials, evaluate new imaging probes and methodologies, enable 
        access to the imaging data from trials in an electronic format, 
        and facilitate evaluation of image-guided interventions.
  --Expand access and improve the timeliness for completion of the 
        highest priority clinical studies.
  --Foster the development of a cadre of established clinical 
        investigators who could work between bench and bedside.
  --Pilot new approaches and develop prototypes for clinical trials 
        networks that could improve the efficiency, coordination, and 
        integration of our national efforts.
  --Develop a common clinical trials informatics platform that could be 
        made available to the full range of investigators working 
        within the cancer clinical trials system.
    NCI could accelerate the expansion and integration of the NCI 
designated Cancer Centers program, including the addition of 15 new 
cancer centers, increasing the number of centers from the current 60 to 
75. The Cancer Centers program could:
  --Implement progressive bioinformatics and communication systems to 
        achieve horizontal integration.
  --Fund additive programs in collaborative, multidisciplinary 
        research, and require integration and sharing of results.
  --Broaden the geographic impact of the centers, networks, and 
        consortia and vertically integrate them with community and 
        regional health care delivery systems.
  --Improve the access of minority and underserved populations to 
        state-of-the-art research and resources.
  --Create and strengthen partnerships with government agencies and 
        community organizations.
  --Broadly provide expertise, and other resources to caregivers, 
        patients and families, and appropriate health agencies.
    In addition to appropriations, flexible legislative authorities 
related to exemptions from specific parts of current procurement, grant 
review and processing, and licensing and patenting rules could also 
help accelerate progress. A streamlined procurement process could 
facilitate the acquisition of materials and services to support the R&D 
activities. Technology development could also be enhanced by sufficient 
flexibility and integration to enable interactions among a wide array 
of laboratories and other entities. Expedited review procedures and 
workflow processing could help to award funds in sequence as needed. 
This might include direct solicitation from known laboratories or other 
sources of technology, and capability to terminate funding instruments 
at the convenience of the government with limited appeal processes so 
that funds could be redirected from low performing consortia to the 
more productive venues.
    Coordination of the licensing and patenting activities among 
grantees, contractors and the intramural program could also be useful 
for many of the multi-component technology platforms that could be 
created through this effort. An accelerated process for Determination 
of Exceptional Circumstances (DEC) and deviations from appropriate 
Federal Acquisition Regulation (FAR) clauses, when deemed valuable to 
the broad research enterprise, could be utilized.

    Senator Specter. Senator Cochran, thank you for joining the 
subcommittee.

                   STATEMENT OF SENATOR THAD COCHRAN

    Senator Cochran. Mr. Chairman, thank you very much. We 
appreciate you chairing this hearing and also inviting Dr. 
Zerhouni and selected members of the National Institutes of 
Health staff who can help us understand the budget request and 
do our best to identify the areas that need emphasis in this 
budget. We appreciate your leadership on this subcommittee and 
on the full committee as well.
    I notice that the budget request is $144.5 million over 
last year's appropriate level for the National Institutes of 
Health. I'm hopeful that that will permit the NIH to continue 
its research into health disparities, examining why a 
disproportionate number of African-Americans, for example, 
suffer from heart disease than the rest of the population. I 
think taking the research to the underserved areas of our 
country is beneficial. I hope you can let us know what your 
reaction to that initiative is at this point and what you 
foresee in terms of the needs for funding will be.
    I think I'll stop at that point and let you respond, and I 
then have a couple of other questions.

                     STRATEGIC GOALS AND OBJECTIVES

    Dr. Zerhouni. Those points are absolutely on target, 
Senator. As you know, we have five major goals that we have 
outlined in our strategic plans. One is aging of the 
population, the change from acute to chronic diseases. The 
third one is health disparity, not in any particular order. 
Those are amongst the five. And then we have biodefense and 
emerging and re-emerging diseases, including, for example, 
obesity.
    We're acutely aware of the disparate impact of these 
conditions on the American population. As you know, we have the 
vanguard study in the Jackson heart study that in fact studies 
how to do this better. As part of the Roadmap for Medical 
Research, we are also developing the idea of a community-based 
corps of clinical researchers that will be included within the 
underserved areas of the country and connected through a better 
information system, so that more patients in those communities 
can participate.
    A good example of that, Senator, was the ALLHAT study, 
which was the study of hypertension conducted in over 600 
practices. A great majority of the practices were in African-
American communities and showing which drugs were the most 
effective in those populations.
    So we will continue that. I think the investment needs to 
be continued, Senator. This is not an easy problem to tackle, 
but we need to look forward to more activities that will 
integrate the main research that we do with the research that 
needs to be done in those communities.

                COMPLEMENTARY AND ALTERNATIVE MEDICINES

    Senator Cochran. One other interesting new area of inquiry 
for the National Institutes of Health is in the area of dietary 
supplements and herbal products. There is a growing number of 
Americans using these supplements and products. The National 
Center for Complementary and Alternative Medicines is playing a 
role in helping us understand the effects of that activity and 
the use of those products.
    What are the current research needs or priorities in terms 
of this budget request that we need to consider when we are 
reviewing the request and deciding on the amounts to 
appropriate?
    Dr. Zerhouni. First and foremost is your statement about 
the increasing use of dietary supplements across our population 
is real. Herbal products are becoming very popular. One of the 
things we need to do as scientists is to figure out whether or 
not these products are of equal effectiveness across their 
compositions. So we need to have more research done in exactly 
how to make these herbal products reliable and safe.
    We are doing that at NCCAM. We verify the purity of these 
herbal products. We also have trials verifying their 
effectiveness. This year NCCAM and the Office of Dietary 
Supplements are going to fund five new botanical research 
centers across the country. There is a request for applications 
that has gone out. We've received the applications. So we'll 
have at least an infrastructure now of five centers that will 
look exactly at these issues of how do you really make sure 
that when you buy a particular product it's effective for what 
you think it is effective for.
    Senator Cochran. My final question has to do with the role 
for new technologies in the detection and treatment of disease. 
For example, the National Institute for Biomedical Imaging and 
Bioengineering was created specifically to enhance research on 
these technologies across the NIH Institutes. What budget 
levels are needed for this work to be done and to improve the 
rate of discovery in biomedical research across the Institutes 
and increase the development of new tools for diagnosis and 
treatment in clinical practice?

      NATIONAL INSTITUTE FOR BIOMEDICAL IMAGING AND BIOENGINEERING

    Dr. Zerhouni. This is newest Institute, as you all know, 
that is essentially going through its strategic first steps. It 
is the only Institute that has for a mission the interaction of 
technologies, physical sciences, biological sciences, in the 
context of bioengineering or biomedical imaging. In that 
regard, it is very important to continue to invest, because as 
we see, you know, when we look at detection, for example, of 
new diseases, new technologies to do research, it's becoming 
very apparent that we need to make specific investments in 
those areas if we are going to make progress in both detection 
and therapy.
    For example, nanotechnology is a good example whereby you 
can through nanotechnology techniques concentrate energy inside 
a tumor and treat a tumor in a way that you couldn't otherwise. 
NIBIB is key to that interface. It's taken a role, a lead role, 
in matching physical sciences and biological sciences at NIH, 
works with the National Institute of General Medical Sciences.
    Obviously, the budgetary environment is such that they have 
to make very tough choices in terms of prioritization. But from 
my standpoint, Senator, emerging research technologies, I see 
that and we've identified in the Roadmap for Medical Research, 
as a major area of investment. In the past, biomedical 
researchers tended to wait for technology to be developed and 
then used it off the shelf, whether it be computers or robotics 
or other technologies.
    In the future, as we are going to areas of research that 
are only specific to medical research, no one in the free 
market is going to develop an off-the-shelf technology that 
will have just application to medicine. And therefore, NIBIB's 
strategic role has to increase over time, and all of NIH's 
investment in that area.
    Senator Cochran. Thank you very much. I appreciate your 
leadership in these areas that I've touched on and generally at 
NIH. I think you're doing a great job and we appreciate your 
service.
    Dr. Zerhouni. Thank you, Senator.
    Senator Specter. Thank you very much, Senator Cochran. I'm 
now going to yield to the distinguished ranking member, Senator 
Harkin. I'm going to go vote and I will return promptly so we 
can maintain the continuity of the hearing.
    Senator Harkin [presiding]. Thank you very much, Dr. 
Zerhouni.
    Dr. Zerhouni. Good morning.
    Senator Harkin. I apologize for being a little late for 
your presentation. Obviously we all have a lot of committees we 
have to go to. But I just wanted to make a brief opening 
statement and welcome you back and the others back.
    As you know, Dr. Zerhouni, both Senator Specter and I have 
been very strong supporters of NIH and funding. We've partnered 
in doubling the funding for NIH over 5 years. We got that job 
done. It was one of my proudest moments as a Senator to 
actually get that accomplished.
    Yet as I look at the President's budget for 2006, it's with 
a sense of disappointment. We didn't double the funding for NIH 
to then have the bones cut out of the funding. But that's what 
it seems is happening. This budget would provide the smallest 
percentage increase since 1970, .5 percent. The total number of 
grants would drop by 402. Most importantly, the success rate 
for new and competing grants would fall to 21 percent. I have 
the table here. I guess you put it up here. I missed it, but my 
staff told me you put it up here. Twenty-one percent, that's 
the lowest since 1970, and that's as far back as our records 
go, 21 percent. This is very disturbing.
    Our scientists have just mapped the human genome. We should 
be entering a golden age of medical research. Scientists should 
be flocking to this field. It's the wrong time to hold this 
budget flat.
    I'm also troubled by other developments. Top researchers 
are leaving NIH. Recruitment is suffering because of new 
conflict of interest regulations. While I strongly support 
restrictions on outside compensation, I am concerned that the 
new regulations go too far, Dr. Zerhouni, especially when it 
comes to requiring employees to divest stocks that they've had 
for many years.
    I just, as an aside, ran into a woman yesterday, just 
yesterday afternoon. The AACI group had a reception yesterday 
and I was just talking to a woman. I mentioned this hearing and 
she mentioned how it was her sister, I believe, was a 
researcher at the National Institute of Environmental Health 
Sciences in North Carolina, had been there for a long time, is 
leaving because through the years she said the most income she 
and her husband ever had was $125,000 a year. Lately, because 
she's worked all these years, she bought some stock early on, 
that's her retirement, that's for her kids going to college, 
and according to her--I don't know, I'm just telling you what 
she told me--she has zero input to any kind of drugs or drug 
companies or anything. Yet she's told she's got to divest that 
stock. You know what? She's leaving. That's wrong. That's 
wrong. We've got to change this, Dr. Zerhouni. We've got to 
change this.
    I look forward to working with you and I'll have some more 
questions about that.
    Jim Battey, who's leaving, has been a great researcher, 
great leader. I've worked with him on deafness and 
communication disorders. As I understand it--I don't mean to 
get into all this personal stuff--but I understand there's a 
family trust set up that he has to administer and stuff like 
that, and he has to leave because of this. This isn't right. We 
have to have a change and we have to have a change soon, 
immediately.
    Now, let me just switch to something else, and that's the 
whole issue of stem cell research. The administration's 
outdated policy on stem cells is making NIH increasingly 
irrelevant in one of the most exciting areas of research today. 
We know about California putting in $300 million a year. NIH is 
spending less than one-tenth of that amount, NIH one-tenth the 
amount of one State. Inevitably, researchers are going to look 
to individual States for direction on stem cell research 
instead of the NIH.
    What's happening to NIH? Is it just a shell of its former 
self? It's supposed to be the greatest biomedical research 
institution in the world. I'm beginning to wonder.
    Our federally funded scientists are on the front lines in 
the war against cancer and heart disease, diabetes, on down the 
line. To me there is no higher priority in this appropriations 
bill than funding NIH at an adequate level.
    So that's my opening statement and I just want to return to 
the conflict of interest rules. Now, you know I have the 
greatest personal admiration for you and friendship. I think 
you're doing a great job in leading the institution. But I must 
chastise you. These are too onerous. They've got to be redone, 
and they've got to be redone soon before you start losing more 
people out of there. I mean, you know, sometimes we tend to see 
a conflict of interest and we go overboard, and I think we've 
gone overboard here.
    So I'm just asking, are you prepared to recommend to HHS 
that the Department issue new revised regulations that won't 
hurt NIH's ability to retain and attract top scientists?

                   PENDING CONFLICT OF INTEREST RULES

    Dr. Zerhouni. Well, I'm glad you asked the question, 
because as you know, this has been a painful episode for NIH 
where we've looked at several hundred issues that came up 
through the activities of scientists for private pay with 
biotech and pharmaceutical companies, as you were concerned 
about. From my standpoint it was very important to take care of 
that issue, and we did.
    We proposed the moratorium because I think there were two 
reasons there that prompted me to do that. One was the fact 
that there were activities there that truly did not advance 
research. They were more into the marketing and product 
endorsement activities. I thought that we needed new 
guidelines. Second, I believed that our management system of 
ethics was not functional, and to establish a new one, to re-
centralize it, takes a while.
    Now, you should know that these rules and regulations are 
not under my direct authority.
    Senator Harkin. I understand.
    Dr. Zerhouni. They are those of----
    Senator Harkin. I misspoke. It's HHS.
    Dr. Zerhouni [continuing]. HHS and the Office of Government 
Ethics. We've consulted with them and indicated to them that 
some of the applications may need to be tested on the ground. 
That's why we insisted that these be called interim final 
regulations and they be subject to comments and evaluation and 
adjustments. I have to say that I'm as concerned as you are.
    Remember that at this point the most impact I have seen, 
because the rules have not been implemented in terms of stock 
divestiture, is the impact on families and the impact on all of 
the employees that would be required to divest of stock. That 
part of the rule frankly is the one that I think we need to 
reevaluate very quickly, as you said. I have requested a delay 
in the application of this rule from Secretary Leavitt, who's 
been extremely responsive and extremely concerned about any 
impact.
    In the preamble to the rule, as you may know, we have 
stated very clearly that the Department and NIH will carefully 
look at the impact on retention and recruitment and the impact 
on the activities of our scientists in terms of outside 
activities.
    So we are totally prepared to look at that, I am totally 
prepared to look at that, and request from those who have the 
authority--the Office of Government Ethics and the Department--
to consider changes. So far I would say that, number one, we've 
had a responsive interaction. Number one, we've had a 90-day 
delay, and no one has been asked to divest at this point.
    But nonetheless, the uncertainty itself can be damaging to 
morale and damaging to recruitment and retention. You've 
mentioned the example of Dr. Battey, who's a very good 
colleague of mine, an outstanding scientist, and I understand 
very much his predicament and I've made that known to the 
Secretary and to the Department.
    There's another case, as you know. I've taken a lot of time 
and effort in recruiting outstanding directors. When I became 
director there were six vacancies and two others. I was very 
proud of the fact that we've been able to recruit outstanding 
directors from outside of the NIH and inside of the NIH. The 
latest one was Dr. David Schwartz from Duke University, who 
last week sent me a letter saying that he was delaying his 
coming until this issue of stock divestiture is clarified.
    So I feel the same way you do in the sense that the 
philosophy of the interim regulation as promulgated by those 
who promulgated that with our consultation is in my view one 
that would be more appropriate for a regulatory agency rather 
than a scientific agency, and does require in my view more 
selective approaches rather than these approaches.
    I think the Department has been responsive. As you may 
know, the Department has excluded trainees from these rules. 
That's over 5,000 scientists who are not subject to these 
rules. However, we've also encouraged our scientists at NIH to 
come forward. I've had multiple meetings with scientists who 
are very concerned about this, and gotten their comments, and 
based on those comments we'll adjust accordingly.
    So I share your concern and I do believe that, as you will 
see, we will be adjusting accordingly to correct for that 
issue, which I think is the one that is at the core of the 
complaints that you've heard. But also I am concerned about any 
impediments that free academic exchange might incur because--
with trade associations--because of this over-regulatory 
interpretation of what NIH does. I don't think NIH has the 
influence of a regulatory agency, and I think as we go through 
the evaluation comment period, you will see improvements in 
that, Senator.
    Senator Harkin. I appreciate that and I apologize for 
misstating. Sometimes I look out there I just see HHS, and I 
said--I meant not you but the whole Department----
    Dr. Zerhouni. It's okay. I'm used to it.
    Senator Harkin. The whole Department for what they did. But 
we----
    Dr. Zerhouni. I'll take responsibility for----
    Senator Harkin. We've got to settle this. I'm sorry. I've 
got to go vote, and I assume Senator Specter will be right 
back, and so the committee will stand in recess until the chair 
gets back.
    Dr. Zerhouni. Thank you.
    Senator Specter [presiding]. The hearing of the 
Appropriations Subcommittee on Labor, Health, Human Services, 
and Education will now proceed.
    Dr. Zerhouni, at the outset I thanked you for the 
assistance which NIH has provided on an arrangement with the 
Institute of Medicine to fund an examination of certain areas 
of asbestos-related injuries. We are trying to put through an 
asbestos bill and there is a question as to whether there is a 
causal connection between asbestos and certain ailments, and 
the Institute of Medicine has agreed to expedite a study in the 
course of 1 year. I worked with Dr. Raynard Kington in your 
absence and we were able to work that out expeditiously, and I 
thank you for that.
    Dr. Zerhouni, let's turn to the issue of the guidelines on 
ethics and the concerns which have been expressed by some. And 
I'm going to want to hear from--we're going to want to hear 
from Dr. James Battey in a few moments as to the range of the 
restrictions which have been imposed and the reaction and 
whether you think there might be some justification for a 
review of the standards and practices.

                          GUIDELINES ON ETHICS

    Dr. Zerhouni. Senator, first and foremost, the rules as we 
have--as they have been promulgated by the Department of Health 
and Human Services and the Office of Government Ethics are 
interim final regulations. In that process we made it very 
clear that those rules will be subject to an impact analysis 
and a comment period, especially when it comes to recruitment 
and retention areas and the maintaining of the excellence of 
the science at NIH.
    Now, as you know, when we developed the rules there was a 
component of the rules that was related to consulting with 
industry. I believe that the rules that we have put in place do 
establish and re-establish public trust and maintain public 
trust in that we will ban those until we are completely certain 
that we have an oversight system that is more functional than 
the one we had before.
    Senator Specter. Do they go too far?
    Dr. Zerhouni. In that context--in the consulting area, I 
think this is something that we need to do because we do not 
have, I believe, at this point an ethics oversight management 
system that can assure you and assure myself that those 
interactions are----
    Senator Specter. How about in areas other than consulting?
    Dr. Zerhouni. In areas such as stock divestiture, as you 
know, the rules require that all employees and their spouses 
divest of stock in either directly or indirectly related 
industries of NIH. As I looked at that rule over the past 2 
months, I've had extensive consultation with our scientists, 
with outside entities, directors of the Institutes, and it is 
clear to me that in the short 2 months, where these rules have 
not been implemented by the way, no one has been asked to 
divest, that this would have a deleterious impact. Best 
example, as you mentioned, is Dr. Battey, who really cannot 
disentangle himself from his family obligations; Dr. Schwartz, 
who's the new director that I just appointed and recruited from 
Duke University, who was to take his job on April 11, who has 
delayed his coming until we can understand these rules a little 
bit better.
    Senator Specter. How about the issue raised that someone 
couldn't accept train fare to travel to a distant city to give 
a lecture?
    Dr. Zerhouni. That is not correct. I've heard that. That, 
Senator, that is not correct. People can accept train fares, 
hotel reimbursement when they go to do an academic lecture at 
some other points.
    Senator Specter. Is there any other area besides consulting 
and divestment on a broad category?
    Dr. Zerhouni. I think the interaction between our 
scientists and trade associations, scientific associations, 
should not be hampered to the extent that we have seen them 
being hampered over the past two months. We need to work on 
that.
    I have to tell you, Senator, that Secretary Leavitt has 
been very responsive and receptive. We've requested a delay in 
the implementation of the stock divestiture rule of 90 days so 
we can understand it better. We have also asked that all of our 
scientist trainees, 5,000 of them, be exempted from these 
rules.
    So, again, I think we do believe that through this process 
of comments and evaluation that we have put in place in the 
interim final regulations, that we will be able to adjust 
accordingly.
    Senator Specter. How about on the trade association issue?
    Dr. Zerhouni. Right.
    Senator Specter. How about on the trade association issue?
    Dr. Zerhouni. Again, I think, Senator, from my standpoint, 
if you look at the framing of these interim final regulations, 
they make an assumption that NIH has the same influence as a 
regulatory agency. In that context obviously these interactions 
have to be scrutinized, but I don't at this point have a final 
opinion, but it seems to me that they may restrict areas of 
academic interchange----
    Senator Specter. So you do not have a final opinion, so 
you're still looking at that?
    Dr. Zerhouni. We're still looking at that, but I do believe 
that we should not as a policy goal restrict interactions that 
are purely scientific or academic in any way, shape or form.

                           STOCK DIVESTITURE

    Senator Specter. Let us hear from Dr. James Battey, if we 
may. Dr. Battey, thank you for joining us. We know that there 
has been an issue as to divestment which has been problemsome 
for you with retention at NIH. Would you tell the subcommittee 
your situation?
    Dr. Battey. Absolutely. But let me preface my remarks by 
wishing you Godspeed in recovering from your illness, Senator 
Specter.
    Senator Specter. Well, thank you. Thank you.
    Dr. Battey. I have the greatest job in the world as far as 
I'm concerned right now. I've been the Director of the National 
Institute on Deafness and Other Communication Disorders for 8 
years, and I have enjoyed every single minute of it for 8 
years. But I manage a family trust on behalf of my mother and 
father, it's their sole source of income, as well as my two 
sisters, as well as educating my father's seven grandchildren. 
That is a responsibility that I must put before even the 
greatest job in the world. I cannot divest the stocks in that 
trust. The cost to my family would be very, very substantial, 
and that is not something that I am willing to entertain on 
behalf of my sisters, my father's seven grandchildren, and my 
mother and my father.
    Dr. Zerhouni. I should point out, Senator, that Dr. Battey 
at no time had any consulting activity with industry during his 
entire career. He's been one of the outstanding citizens of 
NIH.
    Senator Specter. Well, Dr. Zerhouni, did Dr. Battey's 
situation run afoul of the ethical guidelines which have 
recently been established?
    Dr. Zerhouni. Not all of them obviously. It really relates 
specifically to the obligation to divest, forced divestiture of 
all holdings related to the industries that relate to NIH.
    Senator Specter. Well, is that rule----
    Dr. Zerhouni. That's really what the issue is.
    Senator Specter [continuing]. In effect at NIH?
    Dr. Zerhouni. This rule is not in effect. It is proposed to 
be implemented by July 3. We have asked the Secretary and 
received a delay of 90 days. It was supposed to be activated 2 
months after the beginning of the rule on February 3. It was 
clearly obvious to us at NIH that this would have a deleterious 
impact. We've been requesting and informing the Department, I 
believe that the Secretary by delaying the implementation of 
this part of the rule, the forced divestiture, by 90 days, is 
giving us the opportunity to adjust accordingly.
    Senator Specter. If, Dr. Battey, if this rule is not 
promulgated and become final, can we save you from California?
    Dr. Battey. There are a set of circumstances under which I 
would entertain remaining with the National Institutes of 
Health. As I said before, I love this job, I think it's the 
greatest job in the world.
    Senator Specter. Well, we will leave to Dr. Zerhouni the 
exploration of those set of circumstances. But my telephone 
number is in the book.
    Dr. Battey. Senator, I very much appreciate your support.
    Senator Specter. Because as I had said earlier, very much 
concerned about the impact and I'm not faulting anyone. This is 
a tough area to move in, and there are bound to be unintended 
consequences. But with your record and your reputation, it 
would be very unwise, not helpful, to have the NIH lose you on 
this issue. I'm glad to see that Dr. Zerhouni and the others 
who are promulgating the rules are having a delay and will take 
these issues into account.
    Dr. Battey. Thank you. Let me just add that I agree 100 
percent with Dr. Zerhouni that it is absolutely essential that 
the Agency maintain the public trust and be a neutral broker in 
the eyes of all those who consult with us and ask us to give 
opinions in the area of biomedical research.
    Senator Specter. Well, I'm pleased to hear you say that, 
and let's see if we can't get it to work out to retain Dr. 
Battey and move ahead with the ethical guidelines in ways which 
are really meaningful and necessary.

                           STEM CELL RESEARCH

    Before Senator Harkin returns, Dr. Zerhouni, just a 
question or two about stem cells. Where are we heading? Are we 
going to be losing all of our stem cell geniuses to Europe, to 
California, to Massachusetts?
    Dr. Zerhouni. California right now is probably the State 
that has the most wide-ranging policy allowing research in the 
field of regenerative medicine. Clearly, when you look at the 
scientific evolution of this field, and as I've said before, 
from the purely scientific standpoint, there's no doubt that 
access to more cells is seen by scientists as very important to 
their progress.
    Much can be done with the cells available through NIH and 
they're federally funded through the current policy. However, 
it is clear that when you look forward, NIH is funding about 
$30 million worth of human embryonic stem cells and over $390 
million total in regenerative medicine. The California 
investment is about $300 million total, not just in embryonic 
stem cells. So it's not fair to say that the Federal investment 
is one-tenth of the California investment. That relates to the 
human embryonic stem cells. The California investment is not 
specific to just human embryonic stem cells.
    Senator Specter. Dr. Zerhouni, why shouldn't we utilize the 
stem cells which are frozen, several hundred thousand created 
for in vitro fertilization? They have the potential to save 
lives. Why shouldn't we use them for scientific research?
    Dr. Zerhouni. From the purely scientific standpoint, 
scientists will tell you, I will tell you that there are areas 
of research that could be advanced, especially when you look at 
the 22 cell lines that we have. There is mounting evidence that 
we have contamination issues that may prevent their use for 
clinical applications, other issues of genetic stability are 
also emerging.
    Clearly from the purely scientific standpoint, more cell 
lines may well be very helpful. The issue is not a scientific 
issue, as you well know. The issue is the policy is predicated 
on a moral and ethical line that says that we could not use 
Federal funds to remove the potential for life of these 
embryos.
    Senator Specter. Well, what is the moral and ethical line 
if they're going to be destroyed? If they could create life--
Senator Harkin and I took the lead in appropriating funds for 
embryo adoption. People would take the embryos and utilize them 
to produce children, people. But if they're going to be 
destroyed, where is the moral issue?
    Dr. Zerhouni. I think you'll have to ask that from those 
who hold that view. I mean, obviously there are--there is a 
polarization of views on this issue. Some believe very strongly 
that an embryo is the beginning of life, and therefore, any use 
of that is inappropriate. Others obviously see the good on the 
other side. Every ethical issue is a balance between a social 
good and something that is seen by some as destructive.
    I think that debate needs to go on, needs to occur. It is 
occurring, I think, amongst yourselves as legislators. From a 
purely scientific standpoint we believe, and we've said so, 
that more lines may well be helpful to this research.
    Senator Specter. The legislation which Senator Harkin and 
Senator Feinstein, Senator Hatch, Senator Kennedy, and I have 
introduced bans cloning. We have the issue of nuclear 
transplantation, which does not come near the question of 
cloning. There are reportedly remarkable opportunities on 
nuclear transplantation to provide cures for the individual 
himself, herself, whose bodily substance is satisfied. Why not, 
Dr. Zerhouni?
    Dr. Zerhouni. Well, again, the issue here is Federal 
funding being used on the one hand to use discarded embryos, as 
you mentioned. Then the other is somatic cell nuclear transfer 
where you create an embryo. The issue here is fundamentally the 
use of Federal funds for this kind of research. It's not a 
scientific issue.
    Senator Specter. Well, I know the issue. The President's 
policy permits the use of some lines developed up to August 9, 
2001. But there is growing evidence that the stem cell lines 
available on the NIH registry are showing epigenetic and 
genetic changes in small regions of the chromosomes. This is a 
prepared statement, Dr. Zerhouni, so I'm reading. Deputy 
Senator Taylor just made this available to me and I want to ask 
you the question.
    I've been instructed to ask you this, Dr. Battey. When I 
get an instruction from Bettilou Taylor, I take it.
    Dr. Battey. I think that's very well-advised, Senator.

                 FEDERAL FUNDING FOR STEM CELL RESEARCH

    Senator Specter. Well, this is a joint question from Ellen 
and Bettilou and Tom and Arlen. All of those lines are being 
used to study basic biology of stem cells. Their use in 
clinical applications is questionable. There is confusion among 
scientists and administrators at universities where scientists 
have both Federal and non-federal funding for stem cell 
research about exactly what research infrastructure or core 
facilities developed with NIH funds in the past can be used in 
studies involving stem cells not eligible for Federal funding.
    Dr. Battey, in addition to the position which you 
identified, and until last week you were chair of the NIH Stem 
Cell Task Force, what is your view of the current limitations 
of Federal funding?
    Dr. Battey. Senator, the state of the science is moving 
very, very rapidly here, and we have learned many things since 
the last time I had an opportunity to testify before this 
subcommittee. For example, scientists at the University--or in 
the city of Chicago have now made stem cell lines from embryos 
that were identified in pre-implantation genetic diagnosis to 
harbor mutations that cause disease.
    These stem cell lines could potentially be used to create 
cellular model systems that would allow the development of 
drugs to treat these diseases. I'm talking about diseases like 
muscular dystrophy and Huntington's disease. These cell lines, 
however, were all created after August 9, 2001, and are 
therefore ineligible for Federal funding.
    The issue you mentioned about funding streams, it's a real 
issue. Let me give you an example. Imagine for the sake of 
argument an investigator who has a cell line he got from Doug 
Melton, it's not eligible for funding, and a cell line from 
Wisconsin that is. That investigator extracts messenger RNA 
from those two cells and then wants to go to his core facility 
for doing a study of what's been expressed in terms of gene 
expression that was funded initially by support from the 
National Institutes of Health. Can that investigator analyze 
that sample in that facility?
    These are the sorts of complex issues that are now arising 
on a daily basis in places where there are substantial amounts 
of funding for stem cell research that is outside the confines 
of that which can be funded using Federal dollars.
    Senator Specter. Well, thank you very much, Dr. Battey. 
Senator Harkin has this on his agenda, and I'm going to excuse 
myself at this point and turn the hearing over to my 
distinguished colleague, Senator Harkin. We often say that when 
the gavel changes hands, it's seamless. Show them, Tom. We have 
had a unique partnership in this contentious Senate and 
Congress to put aside party differences in the interests of 
moving ahead on a factual basis. I think the American people 
are really sick and tired of the bickering, and Senator Harkin 
and I have, I think, established the kind of a relationship 
which is in the public interest. It's all yours, Tom.
    Senator Harkin [presiding]. The only follow-up I had with 
Senator Specter's question for you, Dr. Battey, was on the 
scientific basis of this. Now, I don't know what all these 
words mean, but your statement says: ``there's growing evidence 
that the HESC lines available on the NIH human embryonic stem 
cell registry are showing epigenetic and genetic changes in 
small regions of the chromosomes.'' Please explain what that 
means.

             EXPLANATION OF EPIGENETIC AND GENETIC CHANGES

    Dr. Battey. I'll try to explain as best as I can. A genetic 
change, Senator, is an actual change in the order of bases in 
the DNA sequence itself. An epigenetic change is a change that 
involves marking on those DNA bases that have implications for 
which genes get expressed and under what circumstances. What is 
becoming increasingly apparent is that as the cells are 
cultured for prolonged periods of time, we are observing both 
small genetic changes as well as epigenetic changes. This does 
not come as any great surprise to a cell biologist, and in fact 
is observed almost any time you culture cells for prolonged 
periods of time.
    The reason for that is, although all the words are 
complicated, the reason is very simple and easy to grasp, and 
that's that when you grow cells in culture, you are continually 
selecting for a more rapidly growing cell. That is intrinsic to 
the process of passaging and growing cells.
    So it is inconceivable to me that you would not evolve 
changes that would confer a growth advantage as you culture 
cells over prolonged periods of time. In fact, what is 
remarkable is how stable these embryonic stem cell lines are 
over time. The fact--but nevertheless, these changes will 
evolve if you culture the cells for maybe 50, 75, or 100 
passages.
    Senator Harkin. To my layman's mind, it seems what you're 
saying is that somehow this would affect their use in any kind 
of further down-the-road treatment in humans?
    Dr. Battey. That we don't know. That is not clear yet. If 
the changes, however, move the cell towards a more rapidly 
growing state, it is possible that you would have a cell that 
would evolve a genetic change that would take it one step 
closer to becoming a tumor of the stem cells, which is a 
teratoma. I think that's the major concern.
    Dr. Zerhouni. Senator, the best analogy--sorry.
    Senator Harkin. No, go ahead. Yes, please.
    Dr. Zerhouni. The best analogy to this is the one I had to 
come up with to explain this in layman's terms. That is that 
if, suppose you have an original document and you want to make 
Xerox copies of that document, and you make billions of copies 
each generation from the previous document. What may happen is 
that after the 150th generation, after making billions of 
copies of the DNA, you'll have errors, and you'll have a poorer 
copy and a poorer copy and a poorer copy as you go forward.
    At the onset of this field, 5 or 6 years ago, everyone 
thought that stem cells were renewable in a perfect state, as 
if you had a perfect copy each time. Well, as the science has 
advanced and our methods of measurements have become more 
accurate, we are finding that in fact there are errors that 
occur over the transmission of information through that copying 
process. That may, in fact, have profound implications as to 
the viability of an experiment and the viability of the use of 
these over a long period of time.
    Senator Harkin. Again, in my layman's mind, it sounds like 
that argues for getting as many stem cell lines as possible.
    Dr. Zerhouni. From a scientific standpoint, I think there 
are lots to be learned. In addition to the new science that has 
occurred recently, in terms of disease-specific cell lines that 
could be used such as the lines that Dr. Battey mentioned that 
have specific diseases in them, so that you could use that to 
study that disease process in a laboratory. From the scientific 
standpoint, this might be helpful.
    Senator Harkin. I just had a couple of other questions that 
I really wanted to go over here. Dr. Zerhouni, one of them had 
to do with, again, the success rate down to 21 percent overall. 
I noticed that at NCI, National Cancer Institute, it's 19 
percent. At NCCAM it's 8 percent. I'm concerned about, again, 
what message this sends to young investigators who have a 
particularly hard time winning grants when money gets tight.
    If a young med school student with huge loans to pay knows 
he faces only a 1-in-5 or a 1-in-10 chance of getting a grant, 
he or she may want to think twice about whether they want to 
enter this career. Would you just speak if you can for a little 
bit on the impact that you might see that a 21 percent success 
rate would have on your ability to attract young scientists to 
medical research?

                        NATURE OF SUCCESS RATES

    Dr. Zerhouni. Again, the 21 percent success rate reflects 
two facts. One is the doubling has been very successful in 
attracting a larger number of excellent scientists to NIH. So 
the number of applications has in fact increased over time. I 
wanted to show you again the graphic there. The black line 
shows the number of applications rising all the way to 44,000. 
So we have more--go ahead.
    Senator Harkin. Now, are those applications or are those 
peer-reviewed applications that are----
    Dr. Zerhouni. Peer-reviewed applications.
    Senator Harkin. Peer-reviewed.
    Dr. Zerhouni. Right. The applications----
    Senator Harkin. Not the total. These are just the----
    Dr. Zerhouni. These are the ones that are peer-reviewed by 
NIH that are----
    Senator Harkin. Made it through.
    Dr. Zerhouni. Made it to review. Of those, we funded 32 
percent in 2001, 25 percent in 2004, and 22 and 21. Obviously 
if the number of applications had stayed level, our success 
rate would have been higher. But the fact is we have more areas 
of research that we are into today than we were 5 or 10 years 
ago.
    Now, your concern about young scientists is my concern as 
well. As you may know, I have requested a study from the 
Institute of Medicine. Two years ago we engaged our advisory 
councils about the issue of the lengthening of the time it 
takes for a young scientist today to be independent and to have 
their own research ideas worked on. Thirty years ago, 27 
percent of our NIH grantees were 35 years or younger. Today, 
less than 4 percent of our NIH grantees are 35 years or 
younger.
    That reflects two things--I'm sorry.
    Senator Harkin. What was that year cut-off?
    Dr. Zerhouni. 30 years ago.
    Senator Harkin. 30.
    Dr. Zerhouni. 27 percent of our scientists 30 years ago 
were younger than 35 years of age. Today it's 4 percent. On 
average when you look at the first grant, median is about 39, 
40 years of age. This to me is a little too long. I really 
believe that there is a lot of creativity that occurs early in 
a scientific career.
    The effect is twofold. One is the lengthening of the 
training period, but also the competitiveness of our grant 
process. That's why a 21 percent success rate, if not balanced 
by new grants, as I've done, and if not carefully managed, can 
lead to a loss of talent.
    Think about it this way, Senator. If you're a 25-year-old 
scientist and you look at your career and you have to wait 
until age 39 to have a chance to get a grant from NIH, you 
might consider other career tracks. That to me is the one thing 
that I worry the most about. We're going to consider very 
carefully the IOM recommendations and try to do the best we can 
within the fiscal constraints that we have.
    But I think it is a trend, Senator, that all of us have to 
be aware of, and that is the plight of the young scientist, not 
just in biomedical sciences, by the way, Senator. It affects 
science and technology in general.
    Senator Harkin. It seems to me in my memory bank someplace, 
that this has been a discussion point in the past. Do you have 
a fund in the Director's office or something like that where--
who was it termed it the ``ah-ha'' fund? Some young scientist 
says ah-ha, I got this idea, and you can kind of pick some of 
these young people and say, oh, they're on to something maybe, 
maybe, we don't know. But don't you have some fund like that? 
Is there something at NIH that allows that to happen under your 
direction?

                       VARIOUS SOURCES OF FUNDING

    Dr. Zerhouni. I do not have a fund for that. But through 
the Roadmap, we've established a Pioneer Award to try to in 
fact encourage that, to try to find out if there are scientists 
out there that we're not funding through the process.
    Institutes themselves, by the way, through loan repayment 
programs, career award developments, K-22 awards, all kinds of 
mechanisms are responsive to a different degree to this issue 
of the young scientists. We have Shannon awards, which provide 
a young scientist with transitional dollars.
    I think, as the IOM recommends, it's time for us to look at 
all of our policies across NIH and find out, especially in 
tougher times, what we need to do proactively to in my view 
protect the pipeline of talent that 20 years from now will be 
the discoverers of the new cures and new treatments and new 
knowledge that we need.
    We have a retreat with the NIH directors planned later this 
year to talk just about this as well. We have discussed this 
issue amongst ourselves quite a bit, as we are concerned about 
it.

                            AVIAN INFLUENZA

    Senator Harkin. I'll look at that some more myself, see if 
there's some way we can set something up like that. There were 
a couple of other areas I wanted to cover, one for Dr. Fauci 
and one for Dr. von Eschenbach. I'll start with Tony.
    A lot of stuff being written about avian flu. Why is the 
spread of this avian influenza so alarming? What steps is the 
Institute taking to address this issue?
    Dr. Fauci. Well, thank you for that question, Senator 
Harkin. It's a very important public health issue. The concern 
surrounding the avian flu threat that we are currently 
undergoing now relates to the fact that the situation in 
countries in Southeast Asia, particularly Thailand, Vietnam, 
and to a lesser degree Cambodia, is that there a virus called 
H5N1 circulating among chicken flocks. That is the way we 
designate influenzas by an H and an N, which are two of the 
proteins that are the important identification markers.
    The regular flu that's circulating around this winter was 
an H3N2, a totally human influenza virus. The H5N1 is a bird 
flu. It has been infecting and killing large numbers of 
chickens in Asia. But what has happened over a period starting 
from the first identification in 1997 in Hong Kong of H5N1, 
which infected 18 people by jumping from the chicken to the 
human, and killing six of those, over the past year-and-a-half, 
in 2003 and now in a very accelerated way in 2004 and 2005, 
we've now had larger numbers of chickens infected and larger 
numbers of people. As of last night's count, there were 79 
official cases confirmed and 49 official deaths confirmed.
    Now, that may seem like a small number, but first of all, 
the mortality is very high, and second, there's a transition of 
the viruses getting a greater efficiency of spreading from the 
chicken to the human. Then what we're very concerned about is 
human-to-human spread. That has not occurred efficiently up to 
this point. There is at least one documented case in Thailand 
of a mother who got it from her 11-year-old child who, the 
child got it from the chicken, but the mother actually got it 
from the child.
    If there is increased efficiency of spread from person to 
person, we have the possibility of what we call a pandemic. 
Now, that means that the society in general, our civilization, 
doesn't have any baseline immunity to H5N1, because unlike 
H3N2, where each year we get exposed to one variety or another 
of that strain, we get vaccinated or we get infected, so that 
our society has some degree of background immunity to an H3N2. 
We have zero background immunity to H5N1.
    So the possibility of there being rampant spread, 
particularly with the high mortality that we're seeing right 
now, is a very sobering prospect that we're looking at. What 
are we doing about it?
    Senator Harkin. So the flu shot I got does not protect me 
from----
    Dr. Fauci. Not even a little bit. Not even a little bit. 
So--but don't worry because there's not H5N1 right here now. 
But we're concerned about it.
    So what are we doing about it? The NIH component of the 
broader Department of Health and Human Services pandemic flu 
preparedness plan is the research limb. You know, the CDC does 
the surveillance, the identification, the public health 
measures. The FDA does the regulation of the vaccines and the 
drugs that we're screening for, and that's all done under the 
Office of Public Health Emergency Preparedness.
    What we're doing is fundamental basic research on the 
virus, understanding its virulence and pathogenesis, getting 
sequence data on all of the various strains so that we can make 
them available to investigators to do things like screening for 
drugs, targeting for drugs, and the development of vaccines.
    Probably the thing that's of most practical concern to you 
and the committee and the general public is that we have moved 
very rapidly in identifying the H5N1 using a particular 
molecular technique developed by one of our grantees to develop 
a seed virus. Two weeks ago, we started the screening for a 
trial. Last week we gave the first injections, and as of 
yesterday, we have over 150 people enrolled in a phase 1 trial 
of H5N1 in three centers in our network of vaccine centers in 
Rochester, New York, UCLA, and Baylor, I believe.
    We have now data that we're going to be collecting on the 
safety, what is the proper dose of the vaccine, and what is the 
difference in the immunogenicity in normal adults. That will be 
finished within a period of a couple of months, people from 18 
to 64. Then we're going to move on to people greater than 65, 
and then we're going to do it in children.
    In addition, finally, as part of the departmental program, 
we've purchased 2 million doses for the strategic national 
stockpile of H5N1 in anticipation of being able to scale this 
up in commercialized lots, not just thousands or millions, but 
tens of millions if we need it.
    Finally, the Department's plan is to stockpile Tamiflu, 
which is the antiviral to which this particular virus is 
susceptible.
    Senator Harkin. What did you say?
    Dr. Fauci. Tamiflu. The regular name for it is Oseltamivir. 
It's an anti-influenza drug.
    Senator Harkin. I'm glad you've cleared that up for me.

              TRAVEL RISKS ASSOCIATED WITH AVIAN INFLUENZA

    Well, now, the only follow-up question I have is--okay, so 
we're not exposed to avian influenza, but they are in Southeast 
Asia. How concerned should we be of people traveling back and 
forth, picking up the virus, bringing it back here, and 
transmitting it?
    Dr. Fauci. At this point not. But the CDC, together with 
WHO, is heightening in a very accelerated way their 
surveillance mechanism in Southeast Asia. Since the virus does 
not transmit efficiently at all from human to human, it is 
extraordinarily unlikely that you would have a situation where 
someone would be infected, that most likely would be a chicken 
farmer, who would then get on a plane and come to Washington.
    So the chance of that is extremely unlikely. For that 
reason, there are no public prohibitions on travel with regard 
to this.
    I just want to mention one thing, I just thought of it. I 
gave you--just because I want the record to be correct--the 
other center that's doing the trial is not Baylor. It's the 
University of Maryland in Baltimore.
    Senator Harkin. Thanks very much, Dr. Fauci.
    Dr. Fauci. You're welcome.

                      HUMAN CANCER GENOME PROJECT

    Senator Harkin. Dr. von Eschenbach, I want to ask something 
Dr. Jim Watson brought up to me a couple of times, and that has 
to do with the human cancer genome project.
    Dr. von Eschenbach. Yes, sir.
    Senator Harkin. About the need for that kind of effort. I 
understand that NCI and the Human Genome Research Institute, 
Dr. Collins, have teamed up on an effort called the human 
cancer genome project. Just what is this? What are you doing? 
Tell me about this.
    Dr. von Eschenbach. Well, thank you, Senator, for the 
question, and also thank you very much for your passion and 
concern for patients, especially cancer patients. This effort 
is intended to address much of our opportunity in understanding 
cancer. We know, though it is a series of complex diseases, it 
is also a disease process. There is a portion of that process 
that defines our susceptibility to cancer and then the 
development and progression of that cancer to the point where 
it causes the suffering and death that we see all around us.
    So we're trying to understand that cancer process. We're 
trying to understand it at the very fundamental genetic and 
molecular and cellular level as to why and how we're 
susceptible to different cancers, how and why they develop and 
then progress in some patients to the point that they actually 
take our life.
    We have a series of investigations to understand that 
process. We're trying to understand it at the genetic level and 
also understand it at the molecular and proteomic level. We've 
even launched recently an effort in nanotechnology to begin to 
utilize that field to understand the process.
    The specific project that you are referring to is one of 
those initiatives where we are teaming up with another NIH 
Agency, the National Human Genome Research Institute, to co-
partner in an effort to understand and to determine all the 
genetic changes and mutations that determine our susceptibility 
to cancer and define the development of cancer.
    We believe that if we understand those genes and those 
genetic changes, we'll be able to use that knowledge and that 
information to be able to select and screen patients to 
determine susceptibility, to be able to define the risk that 
one has for a particular type of cancer, so that we then have 
that knowledge and can use that to intervene earlier in a way 
to try to prevent that process from occurring. Also to be able 
to use the knowledge of those genetic changes so that we can 
find better methods to detect the development of cancer, 
because if we can pick up the development of those genetic 
changes and know that cancer is now starting in someone's body, 
we could then eliminate that cancer when it's still very early 
and do that much more safely and much more easily.
    If we can detect and eliminate cancer early, we could 
eliminate the outcome of cancer, the suffering and death that 
we see. So this is one initiative that we believe holds great 
promise for achieving the goal of 2015, the elimination of 
suffering and death due to cancer.
    Senator Harkin. So you've embarked on this and----
    Dr. von Eschenbach. It's in process of development, sir. 
And we have a pilot project that we are in the midst of 
planning and developing so that we can create the 
infrastructure for a broader application of this.
    Senator Harkin. So when we meet again here later on, you'll 
be able to keep us updated as to what the progress of this is?
    Dr. von Eschenbach. Absolutely, sir.
    Senator Harkin. I appreciate that very much. I really don't 
have any more time. Did anybody else have any--Dr. Zerhouni, 
did you have anything else you wanted to add for the record?
    Dr. Zerhouni. No. I really appreciate the questions you've 
posed today.
    Senator Harkin. Thank you. Again, I apologize for jumping 
on you on the conflict of interest, but I hope there's some 
people here from HHS, because that's really who I was directing 
it at.
    But I'll say, we need you in forefront of this too. This is 
your NIH.
    Dr. Zerhouni. I certainly am.
    Senator Harkin. I just don't think we can afford to 
continue to put this off. We've got to address it right away.
    Dr. Zerhouni. I think you've heard me, sir.
    Senator Harkin. I know, and I appreciate that. Thank you 
all very much for the great job you do. Hopefully we can get 
that .5 up, but I don't know. We'll try our best.
    Dr. Zerhouni. Thank you very much.

                     ADDITIONAL SUBMITTED STATEMENT

    Senator Harkin. Thank you all very much.
    The subcommittee has received a statement from The National 
Alliance for eye and Vision Research which will be placed in 
the record.
    [The statement follows:]

Prepared Statement of The National Alliance for Eye and Vision Research
    The National Alliance for Eye and Vision Research (NAEVR) is 
pleased to submit this written testimony to the file of the April 6, 
2005, hearings of the Labor, Health and Human Services, Education and 
Related Agencies Subcommittee of the Senate Appropriations Committee.

                              ABOUT NAEVR

    Founded in 1997, NAEVR is a non-profit advocacy organization 
comprised of 50 professional, consumer and industry organizations 
involved in eye and vision research. NAEVR's goal is to achieve the 
best vision for all Americans through advocacy and public education 
about the value and cost-effectiveness of eye and vision research 
sponsored by the National Institutes of Health (NIH), the National Eye 
Institute (NEI) and other federal research entities.

NAEVR REQUESTS FISCAL YEAR 2006 NIH FUNDING AT $30 BILLION TO MAINTAIN 
                       THE MOMENTUM OF DISCOVERY

    Although NAEVR realizes that Congress faces an expanding set of 
challenges at home and abroad, we join the community of support for 
medical research in requesting Congress to fund the NIH at $30 billion 
in fiscal year 2006, or a 6 percent increase over the fiscal year 2005 
level, to maintain the momentum of discovery. NAEVR believes that the 
NIH has made tremendous contributions that have served to improve the 
quality of lives for millions of Americans and contain healthcare 
costs.
    NAEVR commends Chairman Specter's leadership in introducing Senate 
Amendment 173 to the fiscal year 2006 Senate Budget Resolution that 
would add $1.5 billion to the NIH beyond that proposed in the 
administration's budget, to a level of approximately $30 billion. NAEVR 
also recognizes the leadership demonstrated by the full Senate in 
successfully passing the amendment and Senate Budget Resolution, and we 
strongly urge the Senate and House conferees to maintain this number in 
the conference bill.
    Congress' past bipartisan leadership in doubling the NIH budget 
from fiscal year 1998 to fiscal year 2003 has had a profound impact on 
the health care of all Americans, in terms of earlier, more accurate 
diagnosis of disease; more targeted, effective treatment options; more 
comprehensive, cost-effective prevention strategies; and the 
transformation of acute diseases to chronic, manageable diseases. With 
this basis, NIH has plans to further transform how basic and clinical 
research is conducted through initiatives such as the NIH Roadmap for 
Medical Research (the NEI is a lead Institute on the Nanomedicine 
project) and NIH Neuroscience Blueprint, in which 15 Institutes are 
engaged, including the NEI.
    NAEVR commends NIH Director Dr. Zerhouni for his leadership in 
eliminating roadblocks that prevent collaborative research and using 
NIH-directed dollars in a cost-effective manner. However, his efforts 
to maximize the return on medical research dollars can only go so far. 
For example, in the fiscal year 2006 funding process, NIH would need an 
increase of at least 3.5 percent just to keep pace with the Biomedical 
Research and Development Price Index (BRDPI). Since the fiscal year 
2006 funding level in the administration's budget proposal would 
represent the third year in which the NIH would not keep pace with 
inflation, the gains realized from the past investment in the NIH will 
be jeopardized.
    In summary, to ensure that NIH's momentum is not eroded further, 
and to continue the fight against diseases and disabilities that affect 
millions of Americans, NAEVR requests that Congress seek an NIH budget 
of at least $30 billion in fiscal year 2006.

 NAEVR REQUESTS FISCAL YEAR 2006 NEI FUNDING AT $711 MILLION AS VISION 
           HEALTH IS A ``TOP PRIORITY'' AMONG MANY PRIORITIES

    NAEVR requests that Congress fund the NEI at $711 million in fiscal 
year 2006, or a 6 percent increase over fiscal year 2005. This 
``Citizens Budget'' for the NEI represents the eye and vision research 
community's judgment as the level necessary to advance the 
breakthroughs resulting from NEI's basic and clinical research that 
will result in treatments and therapies to prevent eye disease and 
restore vision.
    In presenting this request, NAEVR asks Congress to make this 
nation's vision health a ``top priority'' among the many priorities it 
faces in the fiscal year 2006 funding cycle for the following reasons:
  --Eye and vision research responds to the nation's top public health 
        challenges and touches the lives of all Americans.
  --The eye is a unique biological system offering exceptional 
        experimental advantages in which to conduct genetic, 
        neuroscience and cellular mechanism research.
  --Vision impairment and eye disease is a major public health problem 
        that is growing and which disproportionately affects the aging 
        and minority populations.
  --The economic and societal costs of vision impairment and eye 
        disease are significant and growing; adequately funding the NEI 
        is a cost-effective investment in our nation's health.
  --Past NEI-funded basic and translational research is resulting in 
        treatments and therapies to slow the progression of vision loss 
        and restore vision.

  EYE AND VISION RESEARCH RESPONDS TO THE NATION'S TOP PUBLIC HEALTH 
           CHALLENGES AND TOUCHES THE LIVES OF ALL AMERICANS

    Dr. Zerhouni has identified the NIH's top public health challenges 
as an aging population; chronic diseases; health disparities; emerging 
diseases (primarily co-morbidities); and biodefense. NEI is responding 
to all of these challenges as they relate to eye and vision research:
  --Not only has the NEI sponsored studies to characterize the 
        incidence of age-related eye diseases such as age-related 
        macular degeneration (AMD), glaucoma, diabetic retinopathy and 
        cataracts, it sponsors extensive research into the cause and 
        potential prevention of and treatments for these chronic 
        diseases.
  --Working with the National Center on Minority Health and Health 
        Disparities (NCMHD), the NEI has sponsored studies to 
        characterize vision impairment and eye disease disparities to 
        direct further research--whether into the underlying 
        physiological cause and potential concomitant therapy, or to 
        the socio-economic or access issues that may enable it to focus 
        its public health education programs.
  --NEI has taken its basic research on diabetic retinopathy, a co-
        morbidity of diabetes, and tested treatments through a Clinical 
        Trials Network. This optimal example of translating basic 
        research ``from bench to bedside'' has resulted in treatments 
        that are more than 95 percent effective and save the United 
        States $1.6 billion annually.
  --Going beyond the traditional focus on battlefield visual acuity, 
        NEI's biodefense research has resulted in new therapies to 
        treat infectious eye diseases and promote corneal healing.
    While addressing the nation's top public health challenges, NEI 
research also touches all Americans, whether directly or through loved 
ones. NEI research has the potential to ensure the best vision health 
of individuals at all stages of life--from newborns to the most 
elderly?thereby ensuring their independence, productivity and quality 
of life.

THE EYE IS A UNIQUE BIOLOGICAL SYSTEM OFFERING EXCEPTIONAL EXPERIMENTAL 
   ADVANTAGES IN WHICH TO CONDUCT GENETIC, NEUROSCIENCE AND CELLULAR 
                           MECHANISM RESEARCH

    As the entire medical research community gains a better 
understanding of the genetic basis of disease, the eye emerges as a 
unique biological system in which to study cellular mechanisms and 
pathways. The eye and vision community is at the forefront of genetic 
research, as the eye offers accessibility and a system in which one can 
measure the potential effect from a treatment. For example, NEI-
sponsored researchers have recently announced the discovery of a gene 
strongly associated with a person's risk of developing AMD, which is 
the leading cause of vision loss in older Americans. This may enable 
researchers to develop tests for the disease before symptoms begin to 
appear and when drug therapies might help slow its progress.
    Since the retina is a direct outgrowth of the brain and nerve cells 
underlie the ability to process vision, the eye also serves as an 
important system in which to study neurodegenerative diseases. For 
example, NEI-funded researchers have recently announced the 
regeneration of the optic nerve in mice, which could potentially result 
in treatments for Americans blinded by glaucoma or other injuries that 
destroy the optic nerve, as well as for other Central Nervous System 
disorders.

VISION IMPAIRMENT AND EYE DISEASE IS A MAJOR PUBLIC HEALTH PROBLEM THAT 
     DISPROPORTIONATELY AFFECTS THE AGING AND MINORITY POPULATIONS

    Over the past 40 years, Americans have consistently identified fear 
of vision loss as second only to fear of cancer in public opinion 
polls. In recent NEI-sponsored research, patients with advanced AMD 
equated that condition to the gravest chronic diseases. These societal 
implications of vision impairment and eye disease are important since, 
as of the year 2000 census, there were more than 119 million Americans 
age 40+ who are most at risk from age-related eye disease such as AMD, 
glaucoma, diabetic retinopathy and cataracts.
    In 2004, an NEI-sponsored study reported that vision loss from eye 
diseases will increase as Americans age. Also in 2004, the NEI reported 
on an African American subset analysis in its Ocular Hypertension 
Treatment Study (OHTS) and initial findings from its Los Angeles Latino 
Eye Study (LALES), both of which were co-sponsored by the NCMHD. 
Combined, these three studies reported that:
  --Blindness or low vision currently affects 3.3 million Americans age 
        40+, or 1 in 28, and is projected to reach 5.5 million by year 
        2020.
  --Age-related eye diseases currently affect more than 35 million 
        Americans age 40+, and include intermediate-to-advanced AMD, 
        glaucoma, diabetic retinopathy and cataracts. This number is 
        projected to increase to about 50 million by the year 2020.
  --More than 1.8 million Americans currently have advanced AMD, and 
        this number is expected to grow to 3 million by the year 2020. 
        Another 7.3 million Americans currently have intermediate-stage 
        AMD. Currently, 200,000 Americans each year develop advanced 
        AMD, and this number is expected to double by 2020. Because AMD 
        affects the part of the eye called the macula, which is 
        necessary for central vision, it affects a person's ability to 
        read and drive. This has an enormous impact on quality of life 
        and independence for older Americans.
  --Glaucoma, a chronic potentially blinding disease that requires 
        life-long treatment to control it, currently affects 2.2 
        million Americans, with 3.3 million expected to develop it by 
        the year 2020. Glaucoma is now the leading cause of blindness 
        in the fast-growing Hispanic population age 65+. Glaucoma is 
        almost three times as common in African Americans as in White 
        Americans and is the leading cause of blindness in the African 
        American population.
  --Diabetic retinopathy is the leading cause of blindness in the 
        industrialized world in people between ages 25 and 74. It 
        currently affects 4.1 million Americans age 40+, or one out of 
        12 Americans with diabetes in that age group, and is expected 
        to increase to 7.2 million by the year 2020. Although 
        successfully treatable in more than 95 percent of cases, many 
        people do not know they are diabetic until symptoms, such as 
        vision loss, occur. And with estimates of 50 million Americans 
        having diabetes by the year 2020 at a yearly cost of $1 
        trillion, and one-third of all American children born in year 
        2000 developing it in their lifetimes, there will be increasing 
        demand for research into new treatments and prevention 
        therapies.
  --Cataracts, which are the leading cause of low vision, currently 
        affect nearly 20.5 million Americans age 65+, which is 
        projected to increase to 30.1 million Americans by the year 
        2020. In the United States, a cataract is widely treatable by 
        removing the natural lens and implanting an intraocular lens 
        (IOL). However, in the rest of the world, cataracts are the 
        leading cause of blindness due to lack of access to adequate 
        care.
    The past investment in the NEI's basic research has yielded 
breakthrough discoveries in the potential cellular mechanisms that 
result in these diseases, and its clinical research has resulted in an 
array of treatments for these conditions. However, the expanding 
population at risk for eye and vision disease will demand new and more 
effective therapies that restore vision or ultimately prevent the onset 
of these diseases. Adequately funding the NEI now ensures that its 
basic and clinical research ``in the pipeline'' comes to fruition and 
can be responsive to this growing public health problem.

 THE ECONOMIC AND SOCIETAL COSTS OF VISION IMPAIRMENT AND EYE DISEASE 
      ARE SIGNIFICANT; FUNDING NEI IS A COST-EFFECTIVE INVESTMENT

    Although the NEI estimates that the current annual cost of vision 
impairment and eye disease to the United States is $68 billion, this 
number does not fully quantify the impact of lost productivity and 
diminished quality of life. And as noted above, this financial burden 
to both the public and private sector is expected to increase 
dramatically, primarily due to an aging population and the growing 
prevalence of eye diseases that result in vision loss.
    Adequately funding the NEI can delay, save and prevent 
expenditures, especially those associated with the Medicare and 
Medicaid programs, and is, therefore, a cost-effective investment. For 
example:
  --As previously cited, the NEI-sponsored Early Treatment Diabetic 
        Retinopathy and Diabetic Retinopathy studies have saved as much 
        as $1.6 billion per year in costs of blindness and vision 
        impairment and resulted in treatments that are more than 95 
        percent effective.
  --NEI-funded researchers have developed treatments for Retinopathy of 
        Prematurity (ROP), a blinding complication in premature babies. 
        As a result, more than 1,500 infants born this year with the 
        most serious form of this condition can experience sighted 
        lives, which would have cost the government $1 million in 
        benefits and lost taxes over the lifetime of each child.
  --Economists estimate that cataract surgery provided Americans over 
        $300 billion in benefits in 2003 alone.
    Funding the NEI at $711 million in fiscal year 2006 is a cost-
effective investment, as it will directly save healthcare expenses and 
return individuals to productive roles in society.

 PAST NEI-FUNDED RESEARCH IS RESULTING IN TREATMENTS AND THERAPIES TO 
         SLOW THE PROGRESSION OF VISION LOSS AND RESTORE VISION

    The NEI has an impressive record of accomplishment over the past 5 
years, as documented in its National Plan for Eye and Vision Research. 
Some of the most exciting developments that have widespread 
implications for Americans of all ages and races include:
  --NEI is conducting additional clinical trials on nutritional 
        supplements that may slow the progression of AMD, following 
        previous research demonstrating that zinc and three antioxidant 
        vitamins are effective in reducing vision loss in people at 
        high risk for developing advanced AMD.
  --An NEI-sponsored study has found that eye injections of bone-marrow 
        derived stem cells prevented vision loss in two rodent models 
        of Retinitis Pigmentosa (RP), a family of eye diseases that 
        cause vision loss. This study raises the possibility that 
        patients could receive an injection of their own bone marrow 
        stem cells to preserve central vision.
  --NEI-supported investigators are moving closer to human clinical 
        trials of a gene therapy to treat neurodegenerative eye 
        diseases, including Leber Congenital Amaurosis (LCA), which is 
        a rapid retinal degeneration that blinds infants in the first 
        year of life. Previous research has restored vision in dogs 
        with LCA. This gene therapy not only has direct implications 
        for the 9 million Americans affected by AMD, RP, Usher Syndrome 
        and the entire spectrum of retinal degenerative diseases, but 
        can potentially lead to therapies for glaucoma, diabetic 
        retinopathy and cataracts.

                               CONCLUSION

    NAEVR supports fiscal year 2006 NIH funding at $30 billion to 
ensure that our nation's medical research infrastructure can maintain 
its momentum of discovery. NAEVR also requests that Congress make our 
nation's vision health a ``top priority'' among many priorities by 
funding the NEI at $711 million in fiscal year 2006. NEI-funded 
research results in therapies that reduce health expenses and return 
individuals to productive lives. It is a cost-effective investment in 
maintaining the momentum of discovery and vision health for all 
Americans.

                     ADDITIONAL COMMITTEE QUESTIONS

    Senator Harkin. 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 Arlen Specter

                            OBESITY RESEARCH

    Questions. Last year, NIH announced release of a comprehensive 
Strategic Plan for Obesity Research. What initiatives have you 
undertaken, particularly to address the critical problem of childhood 
obesity, since release of this plan?
    Answer. The NIH is pursuing a broad spectrum of research avenues 
consistent with the recommendations in the Strategic Plan for NIH 
Obesity Research. An important area of focus of these efforts is 
childhood obesity, to address the serious impact obesity has on 
children--potentially leading to a lifetime of serious health problems. 
Highlights of such efforts include fostering new research on prevention 
and treatment of pediatric obesity in primary care settings and other 
site-specific settings, which may include the home, day-care, school, 
or other community venues. In another effort, the NIH is beginning a 
project to develop a rating system for youth obesity-related policies. 
The current effort involves developing, for use as a research resource, 
a system to rate factors associated with physical activity and 
nutrition that are addressed by such policies. Such factors may 
include, for example, aspects of physical education or recess in 
schools. Once developed, this research resource would then be made 
available to investigators as a tool to facilitate analysis of the 
relative impacts of these factors on behaviors relevant to obesity. 
This effort would encompass policies at both the state and local 
levels. In developing this research resource, the NIH is coordinating 
with the CDC and other organizations which are supporting related 
efforts.
    Other recently-launched NIH research would impact obesity in both 
adults and children. For example, the NIH is encouraging new studies to 
address the influence on obesity of factors in the ``built 
environment,'' such as aspects of community design that may hinder 
physical activity. An upcoming conference will focus on environmental 
factors and obesity in youth. Improved technologies would facilitate a 
wide range of investigations. Such improved technologies would 
encompass, for example, the areas of more accurately measuring calorie 
consumption (energy intake) and physical activity (energy expenditure), 
and monitoring whether a person's energy intake and expenditure match 
(a state of energy balance) or whether one is greater. Thus, the NIH 
released research solicitations to bring innovative bioengineering 
technology to address issues in energy balance, intake, and 
expenditure. Capitalizing on major ongoing NIH research investments, 
the NIH is continuing to solicit proposals for ancillary studies to 
several existing obesity-related clinical trials and networks; the NIH 
is also encouraging other productive partnerships between basic and 
clinical researchers. Interdisciplinary research focused on obesity is 
also being enhanced as a result of a recent NIH Roadmap initiative to 
support new Exploratory Centers for Interdisciplinary Research; several 
of these centers will focus on obesity. The NIH is also continuing to 
pursue genetic studies of obesity. Efforts are underway to develop an 
Intramural Obesity Clinical Research Center, on the NIH campus, to 
generate new knowledge regarding the prevention, treatment, and 
underlying molecular mechanisms of obesity and its associated diseases. 
Intramural-extramural collaboration will be a focus of these efforts.
    Examples of efforts currently being developed include a new 
initiative to study how factors such as maternal weight during 
pregnancy can lead to obesity in offspring. Another effort is being 
planned to support collaborative research on the neurobiological basis 
of human eating behavior, bridging the gap between understanding at the 
genetic and molecular level of neural pathways involved in food intake 
and the understanding of behavioral influences on human obesity.

                               INFLUENZA

    Question. Dr. Fauci, why is the spread of avian influenza so 
alarming?
    Answer. The spread of avian influenza is of great concern because 
in the past, highly virulent pandemic influenza strains have originated 
as avian influenza. Influenza pandemics are global outbreaks that 
emerge infrequently and unpredictably and involve strains of virus to 
which humans have little or no immunity. Three deadly influenza 
pandemics have occurred in the 20th century: in 1918, 1957, and 1968. 
The 1918-1919 pandemic was by far the most severe, killing 
approximately 500,000 people in the United States and 20-40 million 
people worldwide--almost two percent of the global population at that 
time. Worldwide, the pandemics that began in 1957 and 1968 killed 
approximately 2 million and 700,000 people, respectively.
    H9N2 and H5N1 influenza are two avian viruses that have jumped 
directly from birds to humans and have significant pandemic potential. 
In 1999 and 2003, H9N2 influenza caused illness in three people in Hong 
Kong and in five individuals elsewhere in China; fortunately, the virus 
did not acquire the ability to spread from human to human. Between 
January 28, 2004 and April 14, 2005, there were 88 confirmed cases of 
and 51 deaths from H5N1 avian influenza infection in humans in 
Cambodia, Thailand, and Vietnam, according to the World Health 
Organization. To date, there have been a small number of cases where 
human-to-human transmission of the virus may have occurred. However, 
public health experts fear that the longer and more widely the H5N1 
virus circulates in poultry, the greater the likelihood that the virus 
may evolve into one that is more easily transmitted between people. If 
this were to happen, a worldwide pandemic could follow.
    Question. What steps is your Institute taking to address this 
issue?
    Answer. The National Institute of Allergy and Infectious Diseases 
(NIAID) is using a multi-faceted approach to address the threat of 
avian influenza, including surveillance of animals, vaccine and 
antiviral development, basic research, and genome sequencing. Through a 
contract to St. Jude Children's Research Hospital, NIAID is supporting 
disease surveillance in wild birds, live bird markets, and pigs in Hong 
Kong, allowing scientists to track potential emergent influenza 
strains. In January 2005, the contract was expanded to include animal 
surveillance in Vietnam, Thailand, and Indonesia.
    The Institute has taken a number of steps to develop and clinically 
test vaccines against the two influenza viruses with the greatest 
pandemic potential. For example, under contract to NIAID, Chiron 
produced 40,000 doses of an H9N2 inactivated vaccine; a Phase I 
clinical trial of this vaccine in healthy adults began March 31, 2005. 
NIAID intramural scientists have also developed an attenuated H9N2 
vaccine candidate that will soon be evaluated in humans.
    NIAID has also initiated clinical testing of an H5N1 influenza 
candidate vaccine developed by NIAID-supported researchers at St. Jude 
Children's Research Hospital. In January 2004, these researchers 
obtained a clinical isolate of the highly virulent H5N1 virus that was 
fatal to humans in Vietnam in late 2003 and early 2004. They used a new 
technique called reverse genetics to create an H5N1 candidate vaccine 
from this strain. In May 2004, NIAID awarded contracts to Sanofi 
(formerly Aventis) Pasteur and Chiron for the manufacturing and 
production of inactivated vaccine against H5N1 influenza using this 
strain. Sanofi Pasteur delivered vaccine to NIAID in early March 2005; 
delivery of the Chiron vaccine is estimated to be in fall 2005. NIAID's 
Vaccine and Treatment Evaluation Units (VTEUs) currently are conducting 
a clinical trial of the Sanofi Pasteur vaccine in healthy adults. 
Following the review of the safety and immunogenicity data from the 
adult trial, NIAID plans to initiate trials of the H5N1 vaccine in 
healthy elderly and other populations. In addition, NIAID intramural 
researchers have developed three attenuated H5N1 vaccine candidates, 
which have been shown to be protective in mice; initial clinical trials 
of one of these vaccine candidates may begin as early as this year.
    Efforts also are underway to test and improve antiviral drugs to 
prevent or treat avian influenza. NIAID is supporting an animal study 
to determine if combination therapy with two classes of antiviral 
drugs--neuraminidase inhibitors and adamantanes--is more effective that 
a single antiviral in reducing viral replication and emergence of drug 
resistant strains. The Institute is also supporting the development and 
testing of a long-acting next generation neuraminidase inhibitor that 
can be administered once per week.
    NIAID supports a number of basic research projects that could lead 
to significant advances in pandemic influenza preparedness, including 
research that could lead to vaccine strategies that would provide 
broader protection against a wide range of influenza strains and 
strategies to allow rapid production of a vaccine against a newly 
emergent strain. In addition, the Influenza Genome Sequencing Project, 
launched in the fall of 2004, is a collaboration between NIAID, the 
Centers for Disease Control and Prevention (CDC) and other 
organizations. The complete genetic sequences of thousands of influenza 
virus isolates will be determined and made available to the scientific 
community; to date, approximately 120 viruses have been sequenced. This 
program will enable scientists to better understand the emergence of 
influenza epidemics and pandemics by observing how influenza viruses 
evolve as they spread through the population. Moreover, scientists will 
be able to match viral genetic characteristics with virulence, ease of 
transmissibility, and other properties; this knowledge could lead to 
improved methods of treatment and prevention, as well as guide the 
public health emergency response should an influenza pandemic emerge.

                           BIOTERROR THREATS

    Question. Dr. Fauci, please update us on the progress in the 
development of countermeasures against bioterror threats?
    Answer. Since the attacks of September 11, 2001, and the anthrax 
attacks the following month, the United States has made significant 
progress in developing countermeasures against bioterror threats. The 
National Institute of Allergy and Infectious Diseases (NIAID) supports 
a comprehensive biodefense research and development program, which 
includes the development of biodefense countermeasures to combat 
Categories A, B, and C biological agents, as well as the expansion of 
the national research infrastructure and resources available to 
biodefense researchers. Basic research on microbes and host immune 
defenses serves as the foundation for applied research to develop the 
vaccines, therapeutics and diagnostics that the United States will need 
in the event of a bioterror attack.
    The NIAID biodefense program has benefited from the passage of the 
Project BioShield Act of 2004, which granted the National Institutes of 
Health and NIAID authorities to expedite and simplify the solicitation, 
review, and award of grants and contracts for the development of 
critical medical countermeasures. NIAID used its new BioShield 
authorities to make recent grant awards for research aimed at the 
development of therapeutics for botulinum toxin, Ebola virus, anthrax, 
pneumonic plague, tularemia, and smallpox. Using BioShield authorities, 
the standard eighteen-month timeline from the conception of an 
initiative to grant award was reduced to approximately nine months. In 
fiscal year 2005, the Institute anticipates making additional awards 
using these BioShield authorities for research related to the 
protection of the immune system against damage by radiological or 
nuclear attacks.
    The following are a few specific examples of NIAID's progress in 
the research and development of biomedical countermeasures against 
Category A bioterror agents:

Anthrax
    In 2002 and 2003, NIAID initiated early and advanced product 
development and testing of the next-generation anthrax vaccine (rPA) by 
awarding contracts to two companies, Avecia and VaxGen. In November 
2004, DHHS used its own Project BioShield authorities to award a 
contract to VaxGen to supply 75 million doses of rPA anthrax vaccine to 
the SNS. In addition, NIAID-supported scientists are conducting 
research to identify new targets for therapeutics. Scientists supported 
by NIAID determined the structure of the anthrax toxin, providing a 
better understanding of how the toxin causes disease and giving 
scientists the opportunity to design drugs that will specifically 
inhibit the anthrax toxin.

Smallpox
    In 2003, NIAID initiated the advanced development of Modified 
Vaccinia Ankara (MVA) smallpox vaccine through contracts to Acambis and 
Bavarian Nordic. Contracts awarded in October 2004 are supporting 
larger scale manufacturing of the MVA vaccine as well as additional 
studies of safety and effectiveness in animals and humans. Though a 
vaccine is the only proven way to prevent smallpox infection, 
therapeutics to fight an infection are also an important component of 
the biodefense arsenal. NIAID-supported scientists have discovered a 
new way to block the ability of smallpox to spread from cell to cell, 
which may lead to the development of next-generation antiviral drugs to 
combat smallpox and other viral infections.

Plague
    NIAID is supporting the manufacture of a plague vaccine through a 
contract awarded to Avecia in October 2004; this award will also 
support preclinical testing in animals and initial human clinical 
trials.

Tularemia
    In collaboration with the Department of Defense (DOD), NIAID is 
conducting a Phase I clinical trial using the DOD's Live Vaccine Strain 
(LVS) tularemia vaccine. In October 2004, NIAID modified an existing 
contract with DynPort Vaccine Company to support the manufacture of 
additional LVS vaccine in anticipation of possible future clinical 
trials as well as for use in evaluation of the stability of the 
vaccine.

Botulinum toxin
    In March 2005, NIAID made its first contract award using Project 
BioShield authorities to XOMA LLC, for the production of botulinum 
toxin monoclonal antibodies (serotype A) for clinical evaluation. In 
fiscal year 2005, NIAID expects to use Project BioShield authorities to 
make an additional contract award for the production of a recombinant 
botulinum toxin vaccine (serotype E) for clinical evaluation.

Viral hemorrhagic fevers
    NIAID's Vaccine Research Center (VRC) is currently conducting the 
first human trial of a vaccine to prevent Ebola infection. In addition, 
NIAID grantees and scientists recently made a critical discovery 
related to how Ebola virus infects cells. These findings raise the 
possibility that a broad-spectrum antiviral therapeutic could be 
effective against multiple hemorrhagic fever viruses such as Ebola and 
Marburg.

                           BIODEFENSE FUNDING

    Question. Dr. Fauci, we have heard that members of the scientific 
community have criticized that increased biodefense funding at NIH has 
come at the expense of other important public health research. Can you 
comment on this?
    Answer. The terrorist attacks of September 11, 2001, and the 
dissemination of anthrax spores through the U.S. mail later that fall 
prompted the Administration, with bipartisan support from Congress, to 
dramatically increase spending on biodefense research, with the 
specific goal of developing medical countermeasures to protect the 
public against agents of bioterror. More than $1.5 billion was added to 
the National Institutes of Health (NIH) budget in fiscal year 2003 for 
biodefense research. These funds are additive to funds for other 
infectious diseases research; the biodefense funds did not and will not 
divert resources from other important infectious diseases research.
    The non-biodefense resources of the National Institute of Allergy 
and Infectious Diseases (NIAID) increased by more than 50 percent from 
fiscal year 2000 to fiscal year 2005, keeping pace with or exceeding 
the average annual increases received by NIH during this same period.

                    DEVELOPING ADVANCED TECHNOLOGIES

    Question. From everything being written in the media, there is 
reason to be optimistic that we are close to unraveling the mysteries 
of cancer. Much of the progress being made is a direct result of new 
technology that wasn't available even only a few years ago. If there 
are still gaps in available technology that are preventing researchers 
from having a complete understanding of the complexities of cancer, has 
NCI considered ways in which the necessary tools could be developed?
    Answer. Research over the past three decades has led to unimagined 
progress in our understanding of the cancer process at the genetic, 
molecular, and cellular levels. The combination of scientific talent, 
infrastructure, partnerships, and expertise coupled with an 
extraordinary array of advanced technologies is allowing us to 
understand cancer as a process--a process that begins with a single 
genetic alteration and proceeds through several stages to a lethal 
disease. Even now, as we stand an inflection point for progress in 
eliminating the suffering and death due to cancer, emerging 
technologies hold the key to accelerating our understanding of the 
complexities of cancer and how to prevent, diagnose, and treat cancer 
in its many forms. As we search for the most effective ways to harness 
the power of scientific discovery and to enhance our understanding of 
cancer's complexities, we know that the most direct path will be 
through the optimal integration of science and technology, specifically 
advanced technologies such as bioinformatics, cancer imaging, 
proteomics (the study of proteins), and nanotechnology (man-made 
devices minuscule enough to enter living cells).
    The National Cancer Institute (NCI) has already taken steps to 
achieve paradigm shifting technology advances through the launch of the 
cancer Bioinformatics Grid (caBIG), an unprecedented platform to be 
available to the entire cancer research community. NCI has also 
established the Alliance for Nanotechnology in Cancer to unite a broad 
array of programs to maximize the technology outputs. Initiatives in 
proteomics and cancer imaging are underway as well. As these 
technologies mature, we must also create the technology development 
resources and the seamless system needed to capitalize on their 
discoveries.

                         PERSONALIZED MEDICINE

    Question. Over the past year, there has been a great deal of 
discussion surrounding research areas such as genomics, proteomics, and 
metabolomics. Articles suggest that research in these areas will 
provide research breakthroughs that will translate into new forms of 
targeted therapies and a way to personalize the treatment that cancer 
patients will receive in the future. Is this a realistic expectation or 
just science fiction?
    Answer. Personalized medicine is not only a real possibility; it is 
critical to achieving NCI's goal to eliminate the suffering and death 
due to cancer by 2015. The Nation's investment in cancer research has 
led us to a point today where we're beginning to understand cancers at 
the molecular and genetic and cellular levels, and this understanding 
is influencing our selection of therapy and moving us to personalize 
medicine and personalize oncology. As our understanding of the cancer 
process increases, so does our ability to seek out and target key 
points in that process to disrupt and reverse the development of 
cancer. Part of our challenge is to understand how those targets differ 
from cancer type to cancer type and how each patient might react 
differently to potential therapies. Technologies such as molecular and 
genetic profiling and proteomics are opening the door to understanding 
these diseases and how they behave on an individual basis.
    Using molecular profiling, NCI scientists have been able to 
identify and predict mantle cell lymphoma patients' survival following 
diagnosis based on the each cancer's distinct signature. Knowing whose 
disease is slow-moving and whose is progressing rapidly should help 
determine who would do well with a watchful waiting approach and who 
may benefit from early and aggressive treatment, possibly with new 
therapeutic regimens. For chronic lymphocytic leukemia, scientists have 
known for several years that there were two types of this leukemia, but 
the means for telling the two apart and affecting treatment choices was 
complex and not available to most patients. The same NCI group recently 
showed that expression of a single gene, ZAP-70, is a surrogate for 
this distinction, paving the way for better treatment choices for more 
patients.
    Recent breakthroughs are also enabling scientists to identify 
patterns of protein markers associated with cancer initiation and 
progression and with particular cancers. Biomarkers (tumor indicators 
found in body fluids or tissues) hold promise for making personalized 
medicine a reality. They have many potential applications including 
early diagnostic testing, monitoring response to treatment, detecting 
metastatic disease, and building ``designer'' therapies. Already, 
information-rich blood sample proteins are being use to detect patients 
with ovarian cancer, effectively differentiating early-stage cancer 
patients from unaffected individuals. Similar methods potentially may 
be used to monitor a patient's response to molecularly targeted drugs, 
which could prove useful in designing patient-tailored therapies.

                   CANCER BIOMEDICAL INFORMATICS GRID

    Question. NCI has built an impressive network of cancer centers 
around the country. Have you developed any resources that would enable 
the cancer centers and the broader cancer research community to share 
data and information?
    Answer. By using the power of modern information technology, NCI is 
leading the way in developing a bioinformatics platform that promises 
to revolutionize the biomedical research enterprise. Scientists in 
various disciplines will have access to a common infrastructure for 
collaboration and integration of findings, and new ``plug and play'' 
tools developed by the researcher community will make it possible for 
investigators to greatly accelerate their research. For example, 
researchers at Cancer Centers across the country will be able to access 
data on the molecular characteristics of patients with a particular 
type of cancer who are being treated with a specific drug. Diverse data 
mounted on common platforms will permit researchers to use innovative 
analytic tools to mine the information in ways inconceivable a few 
years ago.
    Up to the present, bioinformatics resources have been developed in 
organizational isolation, with tremendous variability in rules, 
processes, vocabularies, data content, and analytical tools. NCI will 
address these concerns and strengthen the potential for bioinformatics 
integration with the cancer Biomedical Informatics Grid (caBIG). The 
caBIG will provide a unifying architecture to transparently connect 
information and tools much like a home entertainment system in which 
components are made by different manufacturers but built to common 
standards that allow users to combine them in various ways. Our long-
term goal for bioinformatics is to improve the sophistication of 
information technology use and surmount the barriers that limit 
interaction across research institutions. NCI is currently piloting a 
core infrastructure with the participation of 50 Cancer Centers.
    We are also fostering the development and use of new informatics 
technology to accelerate, better coordinate, and facilitate 
participation in NCI-supported clinical research. Currently, volumes of 
valuable raw data are not tapped, effective best practices are not 
widely distributed, and resources are wasted because of duplication of 
effort. With new bioinformatics tools and infrastructure, trials will 
be completed more quickly in multi-institutional settings with uniform 
electronic case report forms and data reporting systems. Databases and 
analytical tools will make information from all clinical trials 
available to NCI-supported researchers for efficient patient accrual, 
information retrieval, and data analysis. Informatics systems will 
assist the cancer community with priority setting and allow for fuller 
participation and a more transparent decision making process. Advocacy 
groups and individual patients will be empowered to participate in 
clinical research and to authorize use of materials for basic science 
investigations. Confidential clinical and proprietary information will 
be protected by controlled, secure access. Just as e-business models 
have transformed the American market place, the caBIG platform will 
overcome traditional institutional limitations. Community 
practitioners, clinical research organizations, and academic centers 
will be linked through this new model of clinical research. Healthcare 
providers will become full partners in the research enterprise and 
educated consumers of research findings.

                          CANCER SURVIVORSHIP

    Question. Recent statistics show that there are now nearly 10 
million cancer survivors in the United States. This is a dramatic 
change from the outcome that the majority of people diagnosed with 
cancer faced in the not too distant past. What have been the key 
advances in medicine that have provided so many more people with a 
healthy outcome after being diagnosed with cancer?
    Answer. Healthy outcomes for cancer can be primarily attributed to 
two key areas--early detection and prevention, and better treatment 
regimens. Newly aligned goals focused on preventing cancer from 
occurring and detecting it early when it is most curable are the keys 
to reducing the incidence of cancer. Dramatic developments in 
technology and a more complete understanding of the causes and 
mechanisms of cancer have given us more effective ways to prevent the 
disease. New evidence-based interventions encourage lifestyle 
improvements in diet and physical activity, discourage smoking, and 
promote the use of safe and fully tested chemoprevention approaches for 
people at risk. Pioneering proteomic and biomarker advances and the 
promise of nanotechnology give hope for the early detection and 
diagnosis of cancer and prediction of patient response to treatment. 
Advanced information systems and methods of evaluation maximize the 
impact of existing technologies. NCI is ramping up specimen 
repositories and widely accessible bioinformatics resources to support 
the development of these breakthroughs.
    Newer and better drugs are being developed every day, and 
combinations of many of these drugs are leading to longer survival 
times for many cancer patients. For example, the long-term outlook for 
breast cancer survivors improved significantly with news of a study 
that revealed the benefits of a drug that inhibits the synthesis of the 
hormone estrogen. The large, international study of the drug letrozole 
was specific to postmenopausal women who had been treated for early 
stage breast cancer that was estrogen-receptor positive and had just 
completed a five-year course of tamoxifen. Women who took letrozole 
(Femara) were 43 percent less likely to experience a recurrence 
compared to women who took a placebo. The study, begun in 1998, was 
stopped ahead of schedule in 2003 when the positive effects became 
clear so that the women taking a placebo could be offered the drug.
    Another example is the promising agent, iodine-131 tositumomab 
(Bexxar), which is easier to take and less toxic than standard 
chemotherapy and has significant impact in extending the lives of 
patients who took it. In a phase II trial that included 76 patients 
with advanced-stage follicular lymphoma, nearly all of the patients (95 
percent) responded to treatment, and three out of four were free of the 
disease after a single course of treatment. Five years later, most of 
the patients were in remission.

                           CANCER PREVENTION

    Question. The development of new ways to treat cancer seems to be 
highlighted in the press quite often. It makes more sense to find ways 
to prevent cancer--can you tell us about any progress NCI has made in 
cancer prevention?
    Answer. The prevention of cancer focuses on studying and modifying 
behaviors that increase risk, mitigating the influence of genetic and 
environmental risk factors, and interrupting the carcinogenesis process 
through early medical intervention. We can save many lives, for 
example, by continuing to advance understanding of the biological and 
behavioral basis of nicotine addiction and energy balance. Evidence 
from recent NCI-sponsored studies suggest specific gene variations can 
affect smokers' cravings and that bupropion, an antidepressant used to 
help smokers quit, may ease these cravings, especially in women. Other 
medications to help smokers quit are under development and current 
evidence suggests that information and referrals from quit lines, as 
well as behavioral counseling from healthcare providers, significantly 
increase abstinence rates.
    NCI is also supporting the development of prevention vaccines and 
chemopreventive agents for suppressing the carcinogenic process either 
at its inception or in pre-invasive stages. A new vaccine that targets 
the infectious agent human papilloma virus (HPV), implicated in 
cervical cancer, is being tested in clinical trials and is anticipated 
to be available to women at risk in the near term. Preclinical studies 
are beginning to identify prevention agents that impact cellular level 
targets to intervene in the cancer process, and clinical trials will 
test the value of these agents in preventing disease. NCI has 
established a new consortium of research centers to conduct early phase 
cancer prevention clinical trials. In 2004, NCI completed recruitment 
of 19,747 postmenopausal women at increased risk of breast cancer to 
participate in a clinical trial of the chemopreventive agent 
Raloxifene. Another prevention trial, the Prostate Cancer Prevention 
Trial, ended early after showing that men who took finasteride reduced 
their chances of getting prostate cancer by nearly 25 percent compared 
to men taking a placebo. A new proteomics technique has been used to 
successfully distinguish people who responded well to a drug that 
reduces colon polyps from those who did not. This technique increases 
our ability to target preventive agents to those who will most benefit. 
The impact preventative medicine and behavioral research have on 
reducing the cancer burden will continue to grow as similar techniques 
are developed and refined.
    As we make such breakthroughs, we must actively translate 
prevention research into improved outcomes and facilitate the role of 
public policy to see that all people have knowledge of and access to 
preventive medicine and approaches. NCI understands that the media are 
a critical component of health communication as it relates to cancer 
prevention and we are working to optimize dissemination to patients, 
caregivers, and at-risk populations. For example, inadequate nutrition 
and physical activity appear to contribute to a sizable proportion of 
cancers. Through NCI's 5 A Day for Better Health Program, we seek to 
increase public awareness of the importance of eating 5 to 9 servings 
of fruits and vegetables every day for better health and provide 
consumers with specific information about how to include more servings 
of fruits and vegetables into their daily routines. NCI has also 
established Centers of Excellence in Cancer Communication Research, two 
of which are examining how the media communicate about cancer 
prevention. Through efforts like these, NCI is seeking ways to better 
work within media constructs to raise the level of dissemination and 
understanding of evidence-based cancer prevention messages.

             CLINICAL RESEARCH AND ACADEMIC HEALTH CENTERS

    Question. Dr Zerhouni, as a result of the recent doubling of NIH by 
Congress we've seen a remarkable increase in fundamental knowledge 
about diseases like Alzheimer's, Parkinson's and diabetes. But I'm sure 
you understand that knowledge, in and of itself, is not enough unless 
it's put to use. Many of us are concerned that the next step in the 
process--the clinical research that translates into cures and improved 
treatments--isn't getting enough attention. Please tell us specifically 
what's being done to get science from the bench to the bedside, and 
whether you have enough legislative authority to put more emphasis on 
that side of the equation?
    Answer. In order to improve human health, scientific discoveries 
must be translated into practical applications. Such discoveries 
typically begin with a clinical observation in a single patient or 
group of patients, or at ``the bench'' with basic research--in which 
scientists study disease at a molecular or cellular level. However, the 
discovery must then be translated to the clinical level, or the 
patient's ``bedside.'' Translation is complicated, with input needed 
from a multidisciplinary team of scientists and other professionals.
    In recent years, NIH-supported studies have addressed important 
translational issues, which have had direct implications for patient 
care on the front lines of medicine. The Women's Health Initiative 
assessed whether hormone replacement therapy (HRT) in post-menopausal 
women reduced heart attack rates; results demonstrated that it did not, 
and in fact, increased health risks; the Antihypertensive and Lipid-
Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) compared the 
occurrence of heart attack and stroke in high-risk hypertensive 
patients treated with either newer classes of drugs or with long 
established, inexpensive diuretics, and found that the diuretics were 
at least as effective as the new, more expensive medications; the 
Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) tested whether 
an implantable cardiac defibrillator (ICD) or an antiarrythmic drug 
would help prevent sudden death in heart failure patients, and reported 
that the ICD significantly reduced deaths (while the drug was no better 
than placebo); the National Emphysema Treatment Trial (NETT) tested the 
effectiveness of bilateral lung volume reduction surgery (LVRS) in the 
treatment of emphysema, and established that that LVRS benefits some 
but is harmful to others. Results were used as the basis for CMS 
coverage decisions regarding LVRS.
    Despite these and other important findings, NIH recognizes that 
concerns have been raised about the status of clinical and 
translational research. The agency is accelerating and strengthening 
this focus through the ``Re-engineering the Clinical Research 
Enterprise'' initiative, which is part of the NIH Roadmap. By 
integrating clinical and translational resources--such as informatics, 
biostatistics, career development, regulatory support--into a unified 
program, the NIH aims to greatly enhance the efficiency and scope of 
clinical research. This will allow more rapid translation of basic 
research into studies that can be performed in human subjects and 
provide tools for the rapid and broad dissemination of the results of 
clinical trials.
    As a result of Roadmap initiatives, academic institutions are 
beginning to undergo transformative changes to break down 
organizational roadblocks and disciplinary silos and bring individuals 
with different types of expertise into newly collaborative, integrative 
structures focused on solving complex health problems. There are also 
experiments underway that will allow for the creation of enhanced 
training and career pathways for individuals in the translational and 
clinical sciences. Because there is broad heterogeneity among the 
individual cultures of the AHCs, NIH is encouraging flexibility in 
experimenting with different and innovative approaches to address the 
need for training the clinical and translational investigators of the 
21st century.
    Moreover, the NIH Clinical Roadmap is working to develop a cadre of 
community-based physicians trained to carry out clinical studies in the 
context of their own health care settings, and to be leaders in 
translating cutting edge research findings directly into clinical care. 
An ongoing study is evaluating the feasibility and mechanisms necessary 
to succeed in implementing such a program.
    Also under the aegis of the Roadmap, the NIH has established a new 
Clinical Research Policy Analysis and Coordination Program to stimulate 
the development of coordinated policies, practices, and tools to 
harmonize Federal regulatory policy and to ensure efficient oversight 
of clinical and translational research and of human subject 
protections.
    In addition, NIH is fostering intergovernmental relationships with 
the Centers for Medicare and Medicaid Services (CMS), the Agency for 
Healthcare Research and Quality (AHRQ), the Centers for Disease Control 
and Prevention (CDC) and other agencies and health care plans to help 
ensure that clinical research results are used to develop evidence-
based, cost-effective healthcare.
    In its efforts to address the bottlenecks in translating results 
from clinical research into improved treatments and other 
interventions, the NIH aims to create a coordinated and supportive new 
infrastructure that will facilitate the more rapid translation of 
discoveries from the laboratory to the healthcare setting.
    Question. On a related note, the academic health centers where 
clinical research is carried out--like Case Western Reserve, for 
example--are being squeezed. Part of the problem is the result of 
unfunded federal mandates like HIPAA. How does this affect NIH's 
ability to support clinical research, and ultimately help patients?
    Answer. NIH recognizes the many requirements to which institutions 
must respond as they conduct and oversee clinical research. While these 
requirements pertain to important matters like human subject 
protections and safety oversight, NIH believes that much can be done to 
streamline them, thereby enhancing their effectiveness and diminishing 
unnecessary burden. To promote specific initiatives in this regard, the 
NIH established as a key element of its Roadmap effort a new Clinical 
Research Policy Analysis and Coordination (CRpac) Program.
    CRpac's goal is to create a trans-government forum for stimulating 
the harmonization, streamlining, and optimization of policies and 
requirements pertaining to the conduct and oversight of clinical 
research. CRpac staff thus work closely with other Federal agencies and 
offices that have responsibilities related to the funding and oversight 
of clinical research, including the Office for Human Research 
Protections, the Food and Drug Administration, the Department of the 
Veterans Administration, the Department of Defense, and other Federal 
agencies that have adopted the ``Common Rule'' for human subjects 
protections. Ensuring the more effective protection of research 
participants, as well as promoting the more efficient translation of 
research findings into clinically useful products, are two major aims 
of this program.
    Some specific foci of the CRpac program include harmonizing diverse 
adverse event reporting requirements; clarifying policy where 
variability in the interpretation of the human subjects regulations 
exists; providing guidance on the use of IRBs and DSMBs; and 
stimulating a dialogue and consensus on clinical trial design issues to 
advance the science, safety, and ethics of translational research.
    Question. Again, what do you need in the way of legislative 
authority to meet the demands placed on these academic health centers?
    Answer. NIH has sufficient legislative authority and flexibility to 
meet the demands placed on academic health centers.

                          ALZHEIMER'S DISEASE

    Question. For the past several years this Subcommittee has 
consistently encouraged NIH to assign a high priority to research on 
Alzheimer's disease. In fiscal year 2002, the Subcommittee went so far 
as to encourage NIH to boost its investment in Alzheimer's disease 
research to $1 billion. But despite the steady increase in 
appropriations for the Aging Institute, I understand that your 
investment in Alzheimer research actually declined by nearly $20 
million between fiscal year 2003 and fiscal year 2004. Would you 
explain how that could possibly happen?
    Answer. It is true that NIH funding for Alzheimer's disease (AD) 
research--for which the National Institute on Aging (NIA) is the lead 
NIH institute, although several NIH Institutes support AD research--
decreased from fiscal year 2003 to fiscal year 2004. Since its 
inception in 1974, the NIA has placed a very high priority on 
Alzheimer's disease and AD-related research, such that AD has received 
by far more funding by NIA than any other aging-related disease 
research. In fiscal year 2004, despite the Institute's best efforts, 
which included the funding of a major new multi-million dollar 
initiative, the Alzheimer's Disease Neuroimaging Initiative, the NIA--
and to a lesser degree, the NIH as a whole--experienced its first-ever 
decrease in AD funding.
    In fiscal year 2004, the number of Research Project Grant (RPG) 
applications submitted across all NIA programs was unusually high, up 
40 percent from fiscal year 2003. This made fiscal year 2004 a very 
competitive year overall for RPG funding at NIA. Of the applications 
the Institute received that were judged highly meritorious in peer 
review, considerable more dealt with other diseases and conditions 
included in the NIA mandate, while far fewer were AD-related, than in 
the preceding year. This was highly unusual, and there is every 
expectation that it will not re-occur and that funding for AD-related 
research will increase in fiscal year 2005.
    Question. Can you give the Subcommittee some assurances that this 
will not occur again?
    Answer. An immediate assurance can be offered to the Subcommittee 
that Alzheimer's disease research continues to be a high priority for 
the NIA, and that the situation is being continually monitored and 
proactive steps have been taken that should prevent the re-occurrence 
of this unanticipated situation. So far during fiscal year 2005, AD 
research applications have been more competitive in peer review than 
this time last year, so that AD-related awards are outpacing non-
Alzheimer's disease awards. In addition, $8 million of approximately 
$10.2 million available for new NIA initiatives in fiscal year 2005 has 
been allocated for AD initiatives. Finally, the fiscal year 2005 
Centers allocation will provide an increase in the AD Centers program 
funding of at least 1.5 percent above fiscal year 2004.
    We are continuing to monitor the situation closely, but currently 
fiscal year 2005 AD funding is on track and consistent with application 
success rates seen in previous years. If this rate continues through 
the rest of the fiscal year, fiscal year 2005 AD funding will most 
assuredly be higher than fiscal year 2004.

                                            [In millions of dollars]
----------------------------------------------------------------------------------------------------------------
                                                                                Fiscal year
                                                         -------------------------------------------------------
                                                              2003          2004          2005          2006
----------------------------------------------------------------------------------------------------------------
Alzheimer's Total NIH...................................          658           633           647           649
Aging Institute share...................................         (502)         (483)         (496)         (498)
----------------------------------------------------------------------------------------------------------------

                       POLYCYSTIC KIDNEY DISEASE

    Question. The National Institutes of Health in general--and the 
National Institute of Diabetes and Digestive and Kidney Diseases 
[NIDDK], in particular, has--under your NIH Roadmap to the Future 
initiative--focused anew on translating basic research discoveries into 
therapeutic interventions to treat/cure some of the world's most 
prevalent life-threatening diseases, including polycystic kidney 
disease or PKD . . . the most common life-threatening genetic disease 
affecting 600,000 Americans. I would appreciate your comments about 
whether the discovery of the PKD genes in 1994/1995 culminating in the 
current clinical drug trial for PKD in humans--enabled by research 
partnerships between the Federal government (via NIDDK), private 
funding sources, and industry, combined with innovative technological 
advances such as provided from the CRISP study--is an example of what 
was envisioned in the development of the NIH Roadmap initiative, and--
if so, in what respects?
    Answer. The intent in developing the NIH Roadmap for Medical 
Research was to tackle very broad scientific challenges and thereby to 
generally move translational research forward for the benefit of all. 
Thus, NIH Roadmap initiatives are not specific to any particular 
diseases, but are expected to yield benefits for a wide range of 
diseases. While not directly funded under the Roadmap, the PKD research 
you cited--such as the Consortium for Radiologic Imaging Studies of 
Polycystic Kidney Disease (CRISP) study--is indeed consistent with the 
vision of the broader NIH Roadmap for Medical Research. The CRISP study 
has been a successful collaborative effort of imaging specialists and 
clinicians focused on PKD. The focus of the CRISP study is investment 
in the groundwork that will facilitate the development and eventual 
testing of clinically practical intervention strategies for PKD. The 
CRISP investigators have used state-of-the-art imaging techniques to 
develop new non-invasive methods that can reliably assess PKD 
progression. Such methods are important as they will facilitate design 
of future clinical trials of new therapies for PKD, which will likely 
require shorter follow-up periods and fewer patients than current 
trials of kidney disease. Similarly, it is hoped that NIH Roadmap 
initiatives will, among other things, provide technologies and other 
resources to facilitate discovery and characterization of disease 
genes; integrate expertise from multiple disciplines to more 
effectively attack problems in health and disease; enable more rapid 
testing of promising therapies in animal models of disease and in 
humans; and promote partnerships between the public and private 
sectors. By optimizing scientific tools and removing barriers to 
progress for researchers across all research fields, the NIH Roadmap 
should help pave the way to an accelerated pace of discovery from the 
bench-to-the-bedside for specific diseases such as PKD.
    Question. In testimony before Congress on April 22, 2004, Dr. Allen 
Spiegel, the Director of NIDDK, said that ``PKD represents an 
intersection of public health need, scientific opportunity and input 
from stakeholders regarding research directions, and that the NIDDK--
working in conjunction with patient groups, such as the PKD Foundation, 
and investigator groups, such as the American Society of Nephrology--
resulted in a strategic plan to exploit research opportunities, engage 
in expanded molecular research, develop new animal models and establish 
four PKD Research Centers.'' In sum, he said NIDDK is committed to 
moving the research agenda forward toward the goal of developing more 
effective diagnosis, treatment and prevention of disease. Therefore, 
considering these developments and the fact that the prime cause of 
death for PKD patients is chronic cardiovascular disease, that PKD 
patients suffer greatly from psychosocial problems like depression, 
anxiety and suicide due to PKD's chronic nature, and the recessive form 
of PKD has such a high rate of morbidity and mortality in neonates and 
infants, to what extent is NIH considering ``inter-institutional'' 
research involving NIDDK, NHLBI (the National Heart, Lung and Blood 
Institute), NICHD (National Institute of Child Health & Human 
Development) and the NIMH (the National Institute for Mental Health) as 
a means to uncover potential interventional methods which could address 
these significant co-morbidities?
    Answer. There are two major avenues through which the NIH is able 
to pursue collaborative research opportunities and initiatives on the 
co-morbidities of PKD and other chronic kidney diseases. First, the 
statutory Kidney, Urologic, and Hematologic Diseases Interagency 
Coordinating Committee (KUHICC)--chaired by the National Institute for 
Diabetes and Digestive and Kidney Diseases (NIDDK)--encourages 
cooperation, communication, and collaboration among all relevant 
Federal agencies. Meetings of the Kidney Diseases Subcommittee provide 
an important opportunity for the NIH Institutes and Centers to initiate 
collaborations on shared interests in kidney disease.
    Second, as the lead Institute for research on chronic kidney 
diseases, including PKD, the NIDDK has spearheaded collaborative 
efforts to address many of the comorbidities experienced by PKD and 
other chronic kidney disease patients. Let me provide a few examples. A 
major new collaborative study being led by NIDDK, with participation of 
the NICHD, the NHLBI and the NINDS, is the Pediatric Chronic Renal 
Insufficiency Cohort Study (``CKIDS''). This important new undertaking 
will address the impact of chronic kidney disease on cardiovascular 
morbidity as well as neurocognitive development and emotional health; 
it will include children with both the recessive and dominant forms of 
PKD. In a related area, an initiative on chronic illness self-
management in children is currently being supported by the NIDDK, 
NHLBI, NICHD, and the National Institute on Nursing Research. The NHLBI 
convened a working group, ``Cardio-Renal Connections in Heart Failure 
and Cardiovascular Disease,'' on August 20, 2004 to further 
understanding of the interaction of the heart and the kidney in 
cardiovascular disease. The NHLBI is also a cosponsor of a planned 
NIDDK program announcement ``Pilot and Feasibility Program Related to 
the Kidney'' to foster the development of high-risk pilot and 
feasibility research; it is anticipated that this PA will be issued in 
2005. In 2001, the NIDDK collaborated with the NIMH and the NIH Office 
of Behavioral and Social Sciences Research (OBSSR) in holding a major 
conference to determine the state of knowledge with regard to the co-
morbid condition of depression in patients with diabetes, kidney 
disease, and obesity/eating disorders, and to propose a research agenda 
for the future. Finally, NHLBI and NIDDK have created a working group 
to address the relationship between hypertension and kidney disease, 
and are working collaboratively to design new initiatives in this area. 
All of these collaborative activities complement NIDDK's continuing 
efforts to address comorbidities of chronic kidney disease, such as the 
Chronic Renal Insufficiency Cohort (CRIC) study, which is examining the 
relationship between cardiovascular disease and chronic kidney disease 
in adults, in order to try to find opportunities to prevent and better 
treat both. Another example is the Folic Acid for Vascular Outcome 
Reduction in Transplantation (FAVORIT) trial, which is testing whether 
treatment to lower total homocysteine levels using a high-dose 
combination of folic acid, vitamin B12, and vitamin B6 will reduce 
cardiovascular damage in kidney transplant recipients. Both of these 
large studies include substantial numbers of patients with PKD.

                       BASIC BEHAVIORAL RESEARCH

    Question. As a matter of some concern I would like to bring to your 
attention an item relating to the National Institute of General Medical 
Sciences. I would also like to include Dr. Berg, as Director of NIGMS, 
on this item.
    Dr. Zerhouni, for the past seven years, starting in fiscal year 
1999, the Committee has included report language urging NIGMS to fund 
basic behavioral research and training. two years ago, Senator Inouye, 
Senator Harkin, and I had a colloquy on the senate floor expressing the 
Committee's strong support for basic behavioral research and training. 
Following the colloquy, I know the NIH commissioned a Task Force to 
study the matter and report back to the Director's Advisory Committee. 
I understand that report was made available to you and your Advisory 
Committee last December and it, too, very strongly urged that NIH 
initiate such a program and create an Institutional presence for it in 
an Institute like NIGMS.
    Dr. Zerhouni, what are your plans to implement a basic behavioral 
research and training program at NIGMS?
    Answer. In keeping with the preferred approach of performing 
portfolio analysis across NIH rather than on an institute-by-institute 
basis, a working group of the Advisory Committee to the Director, NIH, 
was formed to examine basic behavioral research across NIH. The working 
group reported to the Advisory Committee on December 2, 2004. Their 
analysis revealed that the institutes and centers (including NIGMS) 
supported approximately $2.68 billion in behavioral research, including 
approximately $936 million in basic behavioral research, in fiscal year 
2003. In addition to this base, several components of the NIH Roadmap 
for Medical Research are directed toward basic behavioral research. In 
particular, several mechanisms are being used to stimulate 
interdisciplinary research at the interface of the behavioral/social 
and biological sciences, provide the interdisciplinary training 
necessary for postdoctoral investigators to work in these areas, and 
support development of innovative methods and technology that will 
facilitate research at the intersection of the behavioral, social and 
biomedical sciences.
    Following the submission of the working group report, NIGMS has 
taken several steps to more clearly articulate the basic behavioral 
research it supports, encourage the submission of more research 
applications in these areas, and increase the number of investigators 
who can work at the interface of the behavioral and biological 
sciences:
    Research Training at the Interface of the Behavioral and Biological 
Sciences.--Basic behavioral research is of critical importance to the 
mission of the NIH and can play a crucial role in understanding the 
etiology of disease and enhancing preventive and therapeutic 
inventions. Greater understanding of the molecular, genetic, and neural 
processes governing behavior, and the reciprocal effects of behaviors 
on physiological processes, is crucial for a complete understanding of 
human health and those diseases in which behavior is a risk factor, 
diagnostic indicator, or symptom. To advance our knowledge in these 
areas, researchers will need to integrate multiple disciplinary 
perspectives, methodologies, and levels of analysis. NIGMS has a strong 
background in developing and supporting such interdisciplinary research 
training. While some existing NIGMS training programs such as the 
Medical Scientist Training Program and the Systems and Integrative 
Biology program include elements of the behavioral sciences, there has 
not been a program dedicated to training at the basic behavioral 
science-biological science interface. NIGMS has developed a proposal 
for such a predoctoral program and is coordinating its further 
development with other NIH Institutes having an interest in this area.
    Collaborative Research on Basic Mechanisms of Behavior.--To 
encourage the multidisciplinary research that is needed for a fuller 
understanding of the basic mechanisms of behavior, NIGMS has proposed 
an initiative to facilitate collaborations between basic behavioral 
scientists and investigators with expertise in state-of-the-art 
genetics, molecular biology, and genomics. It is anticipated that this 
collaborative research, performed with model organisms, will either 
enhance existing models or lead to the development of new models of 
normal or abnormal human behavior. The concept for this solicitation is 
to be presented for approval at the May 2005 meeting of the National 
Advisory General Medical Sciences Council.
    Assessing Interactions Among Social, Behavioral, and Genetic 
Factors in Health.--NIGMS is a major contributor to an Institute of 
Medicine committee examining the state of the science on gene-
environment interactions that affect human health. The study will 
identify approaches and strategies to strengthen the integration of 
social, behavioral, and genetic research in this field as well as 
consider relevant training and infrastructure needs. The results of 
this study will be used by the NIH to guide its programs in these 
areas.

                          WORK WITH PUBLISHERS

    Question. I know that you are putting together an Advisory Working 
Group to provide advice on implementation of the NIH Public Access 
policy. I understand that the Working Group will not be able to convene 
prior to the May 2nd implementation date of the new policy.
    Publishers are eager to work with you as they formulate their own 
policies for accommodating the NIH policy. They are important to the 
success of the NIH plan and I urge you to consult with them before May 
2nd, as you finalize the details of the implementation policy.
    Do you plan to consult with stakeholders before finalizing the 
details for implementing the access policy?
    Answer. Throughout the implementation phase, we have had inquiries 
from and communicated with a number of publishers and members of the 
library community concerning the operation of the submission system. 
The initial submission system has been designed to enable individual 
investigators to submit their manuscripts in keeping with the basic 
goals of the Policy. We plan to seek feedback from users, and we will 
make system enhancements based on substantial input from all 
stakeholders, including publishers, to facilitate submissions in the 
future by others designated to do so for the authors.
    Question. Given that your policy is to take effect May 2, can you 
outline the process NIH is following to assure such representation, and 
whether you expect to have scientific publishers identified and cleared 
for membership by May 2?
    Answer. Invitations to Working Group members have been made. The 
following publishers have accepted and will be participating in the 
Working Group: Jeffrey M. Drazen, M.D., Editor-in-Chief, New England 
Journal of Medicine; Brian Nairn, Chief Executive Officer, Health 
Sciences; Elsevier Mark E. Sobel, M.D., Ph.D., Executive Officer, 
American Society for Investigative Pathology; and Annette Thomas, 
Ph.D., Managing Director, Nature Publishing Group

                        SPINAL MUSCULAR ATROPHY

    Question. It is my understanding that the new Spinal Muscular 
Atrophy ``model'' for preclinical research and development for 
candidate therapeutics is in place. Please outline the applicability of 
this model to Muscular Dystrophy.
    Answer. The SMA Project, which is now underway, represents a new 
and as yet untested approach for developing therapies for diseases that 
meet certain criteria essential to a highly targeted therapy 
development strategy. SMA is a consequence of inherited mutations in 
the SMN1 gene. The SMN2 gene product has a very similar function to 
that of SMN1; thus, increasing the expression of the intact SMN2 gene 
was both a rational and plausible mechanism for therapeutic 
development. Moreover, since research had already identified several 
chemical structures with the biologic activity of increasing SMN2 
protein expression, there was a consensus that development of drugs 
targeting SMN2 expression represented the best pathway for SMA 
treatment development. In sum, the key traits in the design of the SMA 
project were: (a) a consensus pathway to SMA treatment development, 
such that resources were not diverted away from other, potentially 
successful, strategies and (b) the availability of lead chemical 
compounds on which to base drug development. It remains to be seen 
whether the unique drug development strategy that was selected for the 
SMA pilot program will be sufficiently effective to warrant its 
consideration for other neurological disorders.
    The important question with respect to MD is not whether the SMA 
model could be applied to MD in some way, but whether it is the best 
possible approach to apply the resources available for MD therapy 
development. There were critical criteria used in the NINDS's design of 
the SMA project (consensus on strategy and availability of lead 
compounds) that do not currently apply to MD. In the area of MD, there 
are at least five or six potential strategies under active study, any 
of which may prove to be effective in the treatment of MD. These 
strategies range from those that have a relative high probability of 
success in delaying the loss of muscle mass and thereby augmenting 
quality of life, to those that have a higher risk of sort-term failure 
but in the long run may more dramatically increase both quality and 
length of life. At this point in time, there is no consensus on any one 
strategy for emphasis, since the potentially most successful strategy 
is not nearly as clear as it was for SMA. Instead of choosing to divert 
resources to any one of a number of plausible strategies in MD therapy 
development, the NIH is making parallel investments in all of the 
strategies. As research progresses along these multiple, parallel 
pathways, their relative potential for therapeutic development and 
availability of candidate lead compounds likely will change and the NIH 
would adjust its aggressive pursuit of an MD therapy accordingly. 
Unless an arbitrary choice was made to exclude potentially successful 
treatment strategies in order to provide the necessary focus, an SMA-
type program is not applicable to MD.
    Question. The committee understands that the SMA Model statement of 
work is based upon an NIH Strategic plan developed by a steering 
committee. How does this separate steering committee reconcile research 
priorities with the NIH Director's strategic vision?
    Answer. The formal statement of work for the Spinal Muscular 
Atrophy (SMA) Project was developed by the NINDS scientific and 
contract staff to specify what services the contractor for the SMA 
Project would provide. The NINDS recruited the scientists and 
physicians on the SMA Project steering committee from industry, 
academia, the FDA, and the NIH based on their expertise in drug 
development and areas relevant to SMA. NINDS scientists serve on this 
committee in an ex officio capacity. This committee is advisory to 
NINDS, and the recommendations of the committee are implemented by 
NINDS in the context of the Director's strategic vision for NIH, which 
emphasizes applying innovative approaches to translate basic science 
progress into the development of therapies.
    Question. Please outline NIH assessment of the technical and 
contractual risk associated with the SMA model.
    Answer. There are two major aspects of risk associated with the SMA 
Project, neither of which can be meaningfully quantified. First and 
foremost, the scientific challenges of developing a therapy for a 
neurogenetic disorder are enormous. Medical science, despite extensive 
efforts, has had few successes so far in this endeavor for many 
reasons, not the least of which is the complexity of the nervous system 
and its diseases. Thus, the goal of developing a therapy within four 
years to the point that it is ready for human testing is extremely 
ambitious. This is one of the reasons that the selection criteria for 
the first disease of focus were necessarily stringent, and explains why 
the project must focus on one basic therapeutic strategy in order to 
move quickly toward the goal. The second aspect of risk concerns the 
structure of the program itself. The program is intended to expedite 
therapy development, but several aspects of the project are novel and 
untested, so whether it will indeed be an efficient and effective use 
of resources remains to be seen. In effect, the SMA Project must 
develop de novo a virtual drug company and develop a drug. It has 
proven challenging to identify contractors who are willing and able to 
perform services in disease areas that are outside the normal scope of 
their operations, particularly with such a rapid and restricted time 
line. Once the contracts are in place, the coordination of the various 
efforts and the marshalling of the whole toward accomplishment of the 
goal present considerable organizational, as well as scientific 
challenges, as evidenced by the high failure rate among even 
established biotechnology and pharmaceutical companies in this type of 
endeavor. It is difficult to anticipate what hurdles might arise in 
such a novel undertaking.
    Question. The committee understands that the SMA model was chosen 
because of the state of scientific understanding of this disease. What 
are the specific metrics and measures of merit for this determination?
    Answer. The NINDS chose SMA as the focus of the SMA Project because 
this disease best met the criteria that are critical for success of a 
narrowly focused approach to therapy development. These criteria 
include: (1) severity of disease (2) scientific readiness--which 
includes a defined genetic cause (loss of the SMN1 gene), a consensus 
strategy for treatment (increasing the SMN2 gene product), and the 
availability of ``lead'' chemical compounds. The focus of the SMA 
Project is a type of translational research that is normally conducted 
only in industry settings, which is the chemical conversion of an 
active chemical compound into a drug that is safe enough for human 
testing. Applying this strategy relies on the availability of ``lead'' 
chemical compounds that have a desirable biological activity and have 
the potential to be chemically improved for human use. Most 
importantly, previous academic and privately funded efforts had applied 
this strategy and identified small drug-like molecules with the desired 
activity, and the SMA Project is optimizing the activity and 
pharmacology of these molecules to make them suitable for clinical 
testing.
    Question. What would be the comparable level of understanding in MD 
research that would justify an MD model for translational research?
    Answer. Like SMA, MD is a severe, debilitating disease, and for 
some of the forms of MD, there are defined causes. However, unlike SMA, 
there is no consensus strategy for treatment, there is no single 
biological activity to target for treatment, and there are no ``lead'' 
compounds identified as potential therapeutics.
    In the case of Duchenne MD, there are several quite different and 
equally promising approaches to develop therapies. These include 
strategies to replace the defective gene, to repair that gene, to alter 
gene splicing, to override premature gene stop codons, to upregulate 
potentially compensatory genes, to increase the regenerative capacity 
of muscle by providing various trophic substances or by blocking the 
effects of growth inhibiting substances, to reduce the rate of muscle 
degradation by blocking various components of that process, and to 
replace cells via stem cells or progenitor cells. Unfortunately, none 
of these approaches have yet yielded the drug-like molecules that could 
form the basis of a drug development program for MD to the same degree 
that these are available for SMA, and the goal of identifying promising 
leads in these approaches to therapy development for MD is better 
served by a more diverse and competitive approach. The narrow focus of 
optimization efforts applied in the SMA Project will only be relevant 
to MD once these leads have been identified.
    The NIH is aggressively investing resources in translational 
research for MD through other mechanisms. These include the Wellstone 
Muscular Dystrophy Centers, the NINDS Cooperative Program in 
Translational Research, and investigator initiated research grants. 
Given finite resources, undertaking an SMA Project for MD at this time 
would require the NIH to divert funds from these other programs. The 
broad-based approach that the NIH is currently pursuing is the more 
appropriate way to advance MD translational research at this time.

                       MUSCULAR DYSTROPHY CENTERS

    Question. Please outline for the committee how MD centers are 
promoting translational research from advancements in basic MD 
research.
    Answer. Several of the Senator Paul D. Wellstone Muscular Dystrophy 
Cooperative Research Centers are supporting projects on translational 
research, which is research designed to take basic research to the 
stage of clinical testing. For example, investigators at the University 
of Washington are doing translational research in dystrophic mice that 
is designed to lead to a phase I clinical trial of gene therapy for 
Duchenne MD (DMD). Researchers at the University of Pittsburgh are also 
exploring methods for improved gene delivery using an adeno-associated 
virus (AAV) in a canine model of MD. AAV is a viral vector (the 
``delivery vehicle'' for a gene) that has been designed to carry a 
mini-dystrophin gene to a specific muscle location. If successful, this 
technique could allow the muscle to become more resistant to injury and 
restore function. A second translational study at the University of 
Pittsburgh center is using a dystrophic mouse model to explore the 
delivery of normal muscle derived stem cells to diseased heart tissue. 
The newest center at the University of Iowa will study the use of stem 
cell and novel gene therapy strategies for MD. One project in 
particular will study the development of mouse embryonic stem cells as 
therapeutic tools for muscular dystrophy. This center will also 
emphasize study of muscle membrane repair mechanisms that could lead to 
an alternative strategy for treatment of MD.
    An essential component of the Wellstone Centers program are the 
research cores at each center, which are developing improved research 
resources for use by the entire MD research community to accelerate 
translational research. For example, the core modules at the University 
of Washington are developing research and clinical grade gene transfer 
vectors and these vectors will be studied for their utility in gene 
therapy for the muscular dystrophies. The Wellstone Center at the 
University of Rochester uses one of its core modules to serve as a 
repository of resources, including cell lines, animal models, small 
molecules, and autopsy tissue. Core modules at the University of 
Pittsburgh support translational and clinical studies in clinical 
vector production for gene therapy. One of the cores within the new 
University of Iowa center will develop new in vitro models by 
inactivating genes that cause the various types of MD in an existing 
human embryonic stem cell line.
    Collaboration and coordination among the Wellstone Centers is 
another important component of the Centers program, and the Centers are 
awarded funds to support these collaborative efforts. Currently, the 
Wellstone Centers are using these funds to support two dog colonies--
one at University of Missouri and one at the Fred Hutchinson Cancer 
Research Center--as a national resource for research in MD, and working 
to ensure that these colonies are maintained and available for 
translational research. The dog MD models appear to have a phenotype 
that is very similar to that of Duchenne MD patients. The dog model is 
also important for assessing immune problems that may be associated 
with vectors used for gene therapy; thus, testing in the dog is an 
important stage after initial work in mouse muscular dystrophy models. 
These dogs are currently being used by researchers at a number of the 
Wellstone centers, as well as other researchers in the MD field.

                           MUSCULAR DYSTROPHY

    Question. Muscular Dystrophy researchers are exploring various 
avenues for therapeutic solutions, which include small molecule 
compounds, gene therapy and stem cell research. Please outline for the 
committee efforts in integrating these research efforts and 
prioritizing research investment strategies.
    Answer. NIH-funded researchers are pursuing a number of strategies 
to develop treatments for the MDs. These encompass drug-based (such as 
small molecule compounds), gene-based (such as gene therapy) and cell-
based (such as stem cells) approaches. For example, several studies are 
aimed at developing drug-based therapies to protect muscle mass and 
slow muscle degeneration by blocking various components of the 
degenerative process. Compounds such as protease inhibitors and 
glycosylating enzymes are potentially promising in this area. Other 
studies are pursuing strategies to enhance muscle repair and 
regeneration mechanisms to slow, and possibly stabilize muscle 
degeneration by either providing various trophic substances or by 
blocking the effects of growth inhibiting substances. In addition, NIH-
funded researchers are optimizing cell-based muscle replacement 
strategies, particularly strategies using stem cells or progenitor 
cells to populate skeletal and cardiac muscles with muscle fibers that 
express the absent proteins. Scientists are also developing and testing 
strategies for gene replacement therapy, including both gene or drug 
therapy strategies to replace the defective gene or increase expression 
of functionally homologous or compensatory genes. Finally, genetic 
modification therapies are being studied to bypass inherited mutations, 
using, for example, drug and antisense oligonucleotide exon skipping 
strategies.
    NIH is taking steps to ensure integration and coordination of these 
research efforts. For example, coordination of research efforts at the 
Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research 
Centers is facilitated by a Steering Committee made up of 
representatives from the Centers and from the NIH institutes that fund 
them (NIAMS, NINDS, and NICHD). The steering committee's goal is to 
maximize collaborative utilization of the unique resources in 
infrastructure, expertise, and clinical recruitment created by the 
Wellstone Centers. This integration is particularly important in the 
areas of gene therapy and stem-cell based treatment strategies as a 
number of the Centers have projects and support cores focused on these 
two areas.
    Integration of research efforts and prioritization of strategies is 
also an important function of the Muscular Dystrophy Coordinating 
Committee (MDCC). This summer, a scientific working group will meet to 
develop and prioritize specific research aims based on broad research 
goals in the Muscular Dystrophy Research and Education Plan developed 
by the MDCC. Treatment strategies is one of the programmatic areas 
addressed in Plan and includes approaches such as developing effective 
gene therapy techniques, optimizing potential cell-based therapies, and 
pursuing pharmacological treatment approaches. The working group will 
not only prioritize research strategies, but will also identify 
additional obstacles and barriers to the progress of MD research and 
treatment, noting those that are likely to be addressed through ongoing 
research and programs, and those that might benefit from additional 
emphasis. At the next meeting of the MDCC (November 2005), the MD 
Scientific Working Group recommendations will be presented for 
discussion by MDCC member agencies.
    The MDCC also serves as a venue to coordinate research efforts 
among member agencies and organizations. The November 2005 MDCC meeting 
will have a specific focus on translational research, examining the 
relationship of current translational efforts by the NIH, the 
Department of Defense, the Muscular Dystrophy Association, and Parent 
Project Muscular Dystrophy. This meeting will identify the 
translational research strategies that are currently supported by 
federal agencies and advocacy groups and will reinforce efforts to 
minimize overlap and maximize utilization of resources available for 
MD.
    Question. Please outline for the committee the specific 
translational research efforts for MD; indicating their relative 
maturity. What percentage of research is investigator-initiated versus 
Institute generated?
    Answer. Translating scientific advances into therapies that can 
help people with muscular dystrophies is a very high priority for the 
NIH, and multiple strategies for therapeutic development are currently 
being pursued. The relative maturity for the most promising of these 
translational research approaches and some of the NIH-funded research 
and research initiatives in these areas are described below. These 
approaches are presented in ascending order of risk and projected 
development time, starting with the lowest risk and shortest time 
frame. The risk/development time assessments should be recognized as 
estimates, and those that are most easily achieved may dramatically 
improve quality of life for muscular dystrophy patients but are not the 
cures that may be possible from higher risk/longer time frame 
approaches.
    Blocking the loss of muscle mass.--Muscle fiber degeneration and 
the profound loss of muscle mass is the most visible consequence of MD 
and is directly responsible for progressive deterioration of muscle 
function in several types of MD. Strategies to block muscle fiber 
degeneration have shown promise. For example, several studies have 
shown that systemic treatment with a protease inhibitor reduces muscle 
membrane damage and ameliorates muscle degeneration in the mdx mouse 
model of DMD. Investigators in the NINDS intramural research program 
are currently pursuing the use of a protease inhibitor as a therapeutic 
strategy in MD patients.
    A project has also been approved for funding through the NINDS's 
``Cooperative Program in Translational Research'' for development of 
protease inhibitors that may be capable of delaying muscle degeneration 
in a variety of types of MD.
    Enhancing muscle regeneration mechanisms.--Muscle has an inherent 
repair capacity that allows it to overcome damage but this mechanism 
appears to be overwhelmed in MD. NIH-funded researchers have identified 
genes that regulate muscle regeneration; these represent potentially 
important therapeutic targets for MD. One of these genes, GDF8 or 
myostatin, inhibits muscle development and regeneration. Myostatin 
inhibition studies using molecular genetics or a specific blocking 
antibody suggest that the strategy can increase muscle mass in several 
types of MD. The very recent development of a strategy using an 
endogenous myostatin inhibitor may hold promise. Alternatively, growth 
factors that promote muscle growth and regeneration also have shown 
promise as a therapeutic strategy.
    Replacing degenerating muscle with new muscle derived from stem 
cells.--Muscle and other tissues contain stem cells that can be 
directed to form muscle fibers. There has been considerable progress in 
isolating and expanding stem cells, directing their fate, targeting 
them to dystrophic muscle, and using imaging technology to monitor the 
efficacy of stem cell transplantation. Overcoming the host immune 
response is one of the significant obstacles to the success of cell-
based therapy in MD.
    A project at the Wellstone Center at the University of Pittsburgh 
is focused on delivery of stem cells to diseased muscle, while the 
Center at the University of Iowa will use one of its cores as a stem 
cell resource for the MD community. In addition, a project funded as a 
result of an NIH program announcement entitled, ``Muscular Dystrophy: 
Pathogenesis and Therapies,'' as well as other NIH-supported studies, 
are exploring how to coax stem cells to become skeletal muscle cells 
with the ultimate goal of transplanting these differentiated cells.
    Gene therapy.--Gene targeting to replace a defective gene must 
overcome the problems of accessing the muscle tissues and avoiding an 
immune response to the delivery system. In addition, the large size of 
the dystrophin gene--in the case of Duchenne MD--has necessitated the 
development of novel vectors and mini-dystrophin and micro-dystrophin 
constructs. NIH-supported research has made considerable progress in 
these areas. Dystrophin constructs that are capable both of restoring 
muscle function and of being contained in the AAV vectors have been 
generated and tested in animal models. An additional obstacle in gene 
therapy is delivering the gene construct to sufficient numbers of 
muscle fibers such that muscle function is improved. Delivery systems 
are currently being tested for achieving the goal of treating MD 
patients.
    A number of projects at the Wellstone Centers are pursuing gene 
therapy strategies, and the research cores at two of the Centers are 
developing tools for use in gene therapy studies, as outlined earlier. 
The NINDS Cooperative Program in Translational Research also recently 
funded a major project that brings together a team of basic and 
clinical scientists to carry out the steps necessary to bring gene 
therapy for Duchenne MD to readiness for clinical trials. In addition, 
the program announcement, ``Muscular Dystrophy: Pathogenesis and 
Therapies,'' has resulted in a number of funded projects focused on 
developing novel or modified vectors, using mini-dystrophin constructs, 
and studying ways to effectively deliver the genes to muscle.
    Genetic strategies to bypass the mutations that cause MD.--Other 
approaches to correct a defective gene besides gene replacement are 
also being pursued. For example, antisense oligonucleotide (AO) 
technology may be used to skip, or splice out, those portions of the 
gene containing mutations and then produce a shortened, but still 
functional protein. Through research in cell culture and in animal 
models, AO administration has been shown to enhance expression of 
normal dystrophin protein. Studies supported by the NIH have made 
critical breakthroughs in AO technology and in demonstrating proof of 
principal in cell culture. While this technology is very promising, the 
delivery of AOs is subject to the many of the same obstacles as in the 
gene therapy studies described above. Other approaches include the use 
of drugs to produce ``read-through'' past the gene defect. An NINDS-
supported clinical trial for gentamicin-mediated read-through in DMD 
patients is underway.
    Both of these approaches--AO therapy and identification of 
compounds to promote read through--are being pursued in studies funded 
as a result of the program announcement, ``Muscular Dystrophy: 
Pathogenesis and Therapies.''
    It is difficult to estimate the percentage of MD translational 
research that is investigator-initiated versus institute generated, 
although the NIH MD portfolio contains a significant amount of both 
types. Investigators may submit a grant to the NIH as part of the 
regular submission process, or in response to a particular Institute-
generated initiative. The NIH Institutes, with considerable input from 
the research community, have been working to develop initiatives and 
programs to stimulate translational research in the MDs. For example, 
in April 2005, NIAMS announced a request for applications for Centers 
of Research Translation. Furthermore, NIH is currently developing a 
translational research initiative specific to MD, which will stress the 
milestone-driven approach to research and will include substantial 
project development and grant management interactions with NIH program 
staff.
    Question. Accelerated review of research proposals remains a 
concern for patient advocacy groups and the committee. Please outline 
for the committee all efforts NIH has undertaken with the Center for 
Scientific Review to expedite review decisions. Please provide 
supporting data regarding the length of time from RFP to award on MD 
related research.
    Answer. NIH's peer review process is widely recognized as the 
cornerstone of the remarkable success of the NIH extramural program. 
The NIH Center for Scientific Review (CSR) receives all grant 
applications submitted to NIH (approximately 75,000 per year), logs 
them in, refers these applications to a peer review panel to be 
evaluated on technical and scientific merit, and identifies a potential 
funding source at NIH. The majority of applications that come to NIH 
are reviewed by CSR, while the remaining ones are reviewed by specific 
institutes, in particular those that are received in response to a 
specific solicitation.
    Currently, the interval between NIH receiving an application and 
the application being considered for funding is typically 6-7 months. 
For example, in the case of the Senator Paul D. Wellstone MD 
Cooperative Research Centers, applications in response to the first 
Request for Applications (RFA) were received in February 2003, and 
awards were made in September 2003. NIH and CSR are considering ways to 
reduce this interval. However, it is essential that efforts to speed 
the process do not compromise the core values of NIH peer review 
system--a thorough and fair review of the application by a review panel 
with the appropriate scientific and technical expertise. One approach 
to accelerate the review cycle is the electronic receipt of 
applications. NIH is now accepting several types of grant applications 
electronically and will continue to introduce electronic receipt of 
other application types. When electronic receipt of grant applications 
is fully implemented at NIH, the system should offer considerable time 
savings because data, which in the past have been manually entered, 
will be automatically captured as soon as applications are submitted. 
In addition, it may be possible to automatically analyze some of the 
data initially captured during electronic receipt and streamline the 
referral process, thereby offering additional time savings.
    Expediting review of grant applications while maintaining review 
quality is a high priority for NIH. To underscore this, Dr. Zerhouni 
has recently created a new NIH Peer Review Advisory Committee to 
provide guidance on developing ways to advance NIH peer review and 
ensure its vitality. In addition, in March 2005, Dr. Zerhouni named a 
new CSR Director, Dr. Antonio Scarpa. When Dr. Scarpa begins work on 
July 1, 2005, he is expected to place a high priority on the goal of 
compressing the peer review cycle.

                   PEER REVIEW ON MUSCULAR DYSTROPHY

    Question. Continuity in Peer Review for Muscular Dystrophy research 
remains a concern. Please outline for the committee all efforts to 
ensure peer reviewers' areas of expertise encompass the full body of 
muscular research.
    Answer. The peer review of the majority of applications received by 
NIH is conducted at the Center for Scientific Review (CSR). In response 
to concerns expressed by the MD community, a working group of the 
Center for Scientific Review (CSR) Advisory Committee met in March 2001 
to evaluate the review of skeletal muscle biology research 
applications. The Skeletal Muscle Biology Working Group was composed of 
17 leading scientists in the field and several NIH staff. A particular 
concern of the working group was the locus of review for muscular 
dystrophy applications. Ultimately, the working group recommended the 
formation of a Skeletal Muscle Biology Special Emphasis Panel (SMB 
SEP). Nearly all muscular dystrophy related research applications 
reviewed by CSR were to be reviewed in this committee. The SMB SEP met 
for the first time in October 2001.
    The Skeletal Muscle Biology Working Group offered this 
recommendation as an interim solution pending recommendations to be 
made by the larger Musculoskeletal, Oral and Skin Sciences (MOSS) Study 
Section Boundaries Team (also a working group of the CSR Advisory 
Committee) that was scheduled to meet in July 2001 as part of a CSR-
wide reorganization process. The MOSS Team meeting in July 2001 drew 
heavily on and expanded the recommendations of the Skeletal Muscle 
Biology Working Group. The MOSS Team recommended elevating the status 
of the review group from a special emphasis panel to a permanent 
regular study section. This recommendation was accepted by the CSR 
Advisory Committee, and a new regular study section named Skeletal 
Muscle Biology and Exercise Physiology (SMEP) was implemented. The last 
meeting of the SMB SEP was in June 2003 and the first meeting of the 
SMEP study section, its successor, was in October 2003. The SMEP study 
section is now the primary locus of review for muscular dystrophy 
related research applications at CSR.
    The range of science in the applications reviewed by SMEP is 
extremely broad, spanning fundamental molecular biology to therapeutic 
interventions. To match this breadth, the committee is composed of a 
number of individuals with the expertise necessary to cover these 
varied topics. Eleven of the regular members assigned to review these 
applications are noted investigators who themselves conduct muscular 
dystrophy related research. As members rotate off the committee they 
are replaced by individuals with a similar background--five new members 
have been nominated for the coming year. In addition, to supplement 
this broad expertise, the committee has used twelve temporary members 
who also are involved in conducting muscular dystrophy related 
research.
    As stated above, the majority of applications received by NIH are 
reviewed by CSR. In contrast, applications that respond to specific 
initiatives are reviewed by individual NIH Institutes. Like CSR, the 
Institutes are also committed to ensuring that individuals with the 
appropriate expertise review applications, and continuously work to 
identify and invite scientists with specific knowledge and appropriate 
background to participate in the review of applications.
                                 ______
                                 
               Questions Submitted by Senator Judd Gregg

                    UMBILICAL CORD BLOOD STEM CELLS

    Question. Given that Umbilical Cord Blood Stem Cells are already 
being used to treat over 70 life threatening diseases, should the 
National Institutes of Health take steps to educate the public, and if 
so, how should education take place?
    Answer. The NIH scientists address questions from representatives 
of the news media and the public who directly contact the NIH. In 
addition, NIH scientists speak at conferences that are convened by 
professional and public interest organizations and they provide advice 
to the Health Resources and Services Administration in the development 
of a national cord blood bank program. Future directions for public 
education would involve convening a strategy development workshop of 
researchers and relevant stakeholder groups to determine what is 
currently being done to address education issues, identify major 
education gaps, and recommend and prioritize specific education 
outreach activities and areas requiring further research.
    In addition to these efforts, the NIH maintains a stem cell 
information website at http://stemcells.nih.gov. The NIH Stem Cell 
website is frequently visited by individuals seeking information on 
stem cell research, including cord blood stem cells. For example, the 
website has an NIH report entitled ``Stem Cells: Scientific Progress 
and Future Research Directions.'' This report has a chapter (http://
stemcells.nih.gov/info/scireport/chapter5.asp) on hematopoietic (blood-
forming) stem cells, including stem cells from the umbilical cord. 
Several stem cell literature databases that include cord blood stem 
cell research studies can also be found on the NIH website at http://
stemcells.nih.gov/research/literature.asp. There are also links to 
several organizations, including the National Marrow Donor Program and 
the International Cord Blood Society, that have informational sites on 
cord blood stem cells. The website also contains a ``Frequently Asked 
Questions'' section (http://stemcells.nih.gov/info/faqs.asp#umbilical) 
with information on ``Where can I donate umbilical cord stem cells?'' 
Overall, the NIH Stem Cell website provides useful scientific 
information to the public about stem cell science.
    Question. What research is currently being done regarding the use 
of Umbilical Cord Blood Stem Cells to treat disease?
    Answer. The NIH currently funds clinical research to evaluate the 
safety and effectiveness of matched sibling cord blood transplantation 
in children with sickle cell anemia and thalassemia (Cooley's anemia). 
The first multi-center, unrelated-donor cord blood banking and 
transplantation study (COBLT), which was funded by the NIH, was 
recently completed. The COBLT study evaluated the safety and 
effectiveness of cord blood transplantation in adult and pediatric 
patients with hematologic malignancies as well as pediatric patients 
with inborn errors of metabolism and immune deficiencies. Its results 
were shared with the Institute of Medicine for a recent report on Cord 
Blood: Establishing a National Hematopoietic Stem Cell Bank Program. 
Publication of the COBLT study results is in progress.
    A major obstacle to cord blood transplantation in adult recipients 
is the limited hematopoietic stem cell dose available in a single cord 
blood unit. The NIH currently funds research exploring alternative 
approaches to optimize transplant outcome. These approaches include the 
transplantation of two partially matched cord blood units from 
different cord blood donors, use of a less toxic (non-myeloablative) 
conditioning regimen prior to cord blood transplantation, and expansion 
of cord blood stem cells in culture and their use in conjunction with 
non-expanded cord blood for transplantation in patients with 
hematologic malignant diseases. These studies are in the early phase of 
clinical investigation. In addition, the NIH funds the Center for 
International Blood and Marrow Transplant Research, which conducts 
registry studies to evaluate the clinical outcomes of cord blood 
transplantation.
    The NIH also funds a variety of basic and pre-clinical research 
projects to examine the properties of cord blood stem cells, including 
the immune responses of cord blood cells during and after 
transplantation, the growth properties of cord blood stem cells, and 
conditions to improve the outcome of cord blood transplantation.
                                 ______
                                 
               Questions Submitted by Senator Tom Harkin

                    POLYCYSTIC KIDNEY DISEASE (PKD)

    Question. In testimony before Congress last year, Dr. Allen Spiegel 
said the NIDDK is committed to moving the PKD research agenda forward 
toward the goal of developing more effective diagnosis, treatment and 
prevention of the disease. Considering that the prime cause of death 
for PKD patients is chronic cardiovascular disease, PKD patients suffer 
greatly from psychosocial problems like depression, anxiety and suicide 
due to PKD's chronic nature, and the recessive form of PKD has such a 
high rate of morbidity and mortality in neonates and infants, to what 
extent is NIH considering ``inter-institutional'' research involving 
the NIDDK, NHLBI, NICHD, and the NIMH as a means to uncover potential 
interventional methods which could address these significant co-
morbidities?
    Answer. The NIH has two major avenues for pursuing collaborative 
research opportunities and initiatives on the co-morbidities of PKD and 
other chronic kidney diseases. The first avenue is the statutory 
Kidney, Urologic, and Hematologic Diseases Interagency Coordinating 
Committee (KUHICC). This Committee, which is chaired by the National 
Institute for Diabetes and Digestive and Kidney Diseases (NIDDK), 
encourages cooperation, communication, and collaboration among all 
relevant Federal agencies. Meetings of the Kidney Diseases Subcommittee 
provide an important opportunity for the NIH Institutes and Centers to 
initiate collaborations on shared interests in kidney disease.
    The second avenue is through the activities of the NIDDK, the lead 
NIH Institute for research on chronic kidney diseases, including PKD. 
In this capacity, the NIDDK has spearheaded collaborative efforts to 
address many of the comorbidities experienced by PKD and other chronic 
kidney disease patients. Let me provide a few examples. In 2001, the 
NIDDK collaborated with the National Institute of Mental Health (NIMH) 
and the NIH Office of Behavioral and Social Sciences Research (OBSSR) 
in holding a major conference to determine the state of knowledge with 
regard to the co-morbid condition of depression in patients with 
diabetes, kidney disease, and obesity/eating disorders, and to propose 
a research agenda for the future. A major new collaborative study being 
led by NIDDK, with participation of the National Institute for Child 
Health and Human Development (NICHD), the National Heart, Lung, and 
Blood Institute (NHLBI) and the National Institute of Neurological 
Disorders and Stroke (NINDS), is the Pediatric Chronic Renal 
Insufficiency Cohort Study (``CKIDS''). This important new undertaking 
will address the impact of chronic kidney disease on cardiovascular 
morbidity as well as neurocognitive development and emotional health; 
it will include children with both the recessive and dominant forms of 
PKD. The NHLBI convened a working group, ``Cardio-Renal Connections in 
Heart Failure and Cardiovascular Disease,'' on August 20, 2004 to 
further understanding of the interaction of the heart and the kidney in 
cardiovascular disease. The NHLBI is also a cosponsor of a planned 
NIDDK program announcement (PA), ``Pilot and Feasibility Program 
Related to the Kidney,'' to foster the development of high-risk pilot 
and feasibility research; it is anticipated that this PA will be issued 
in 2005. An initiative on chronic illness self-management in children 
is currently supported by NIDDK, NHLBI, NICHD, and the National 
Institute on Nursing Research. Finally, through a working group they 
created to address the relationship between hypertension and kidney 
disease, the NIDDK and NHLBI are working collaboratively to design new 
initiatives in this area. All of these collaborative activities 
complement the NIDDK's continuing efforts to address comorbidities of 
chronic kidney disease. Examples of these efforts include the Chronic 
Renal Insufficiency Cohort (CRIC) study, which is examining the 
relationship between cardiovascular disease and chronic kidney disease 
in adults, in order to try to find opportunities to prevent and better 
treat both, and the Folic Acid for Vascular Outcome Reduction in 
Transplantation (FAVORIT) trial, which is testing whether treatment to 
lower total homocysteine levels using a high-dose combination of folic 
acid, vitamin B12, and vitamin B6 will reduce cardiovascular damage in 
kidney transplant recipients. Both of these large studies include 
substantial numbers of patients with PKD.

                             PUBLIC ACCESS

    Dr. Zerhouni, I commend you for instituting a new policy that will 
increase public access to NIH-funded research. I'm hopeful that this 
policy will help speed the pace of scientific progress and give 
patients and taxpayers better access to research that they are, after 
all, paying for.
    Question. There's still some question, though, about how many 
researchers will voluntarily submit their papers to PubMed Central, and 
how much of an embargo time they'll require between the publication of 
a paper in a scientific journal and when the paper will be posted for 
public access. Have you considered, as a way of leading by example, 
requiring your own intramural researchers to deposit their final papers 
in PubMed Central and make those papers accessible immediately at the 
time of publication?
    Answer. We have provided NIH staff training about the Policy and 
intramural research managers are now actively encouraging authors to 
submit manuscripts and designate public release as soon as possible. 
The Policy-related submissions will directly benefit NIH-supported 
investigators because recent studies have shown that freely available 
articles get cited more in other research publications. An increase in 
the number of citations helps improve the professional standing of 
investigators. Due to these benefits we anticipate that intramural 
authors will choose the earliest release dates.
    I also believe that the voluntary nature of the final policy 
permits sufficient flexibility to accommodate the needs of different 
stakeholders and leaves the ultimate decision in the hands of 
scientific investigators who are in the best position to judge the 
circumstances and the time frame under which their work may be made 
accessible to the public at large. This flexibility allows authors to 
delay posting of manuscripts if there are concerns about the policy's 
adverse impact on their area of research. Therefore, we believe that by 
having a Policy that provides maximum flexibility, authors will respond 
with maximum participation.
    Question. I'm also concerned that the policy could place 
researchers in a difficult position. It's up to researchers to 
negotiate with publishers to get permission to post the articles in the 
NIH database. Since participation is voluntary, publishers might 
pressure researchers not to release their work at all, or to wait a 
full 12 months. Do you share this concern? How will you know if this 
pressure is taking place?
    Answer. We will be gathering statistics on grantee participation 
rates and their specified embargo periods. An NIH Public Access Working 
Group of the NLM Board of Regents has been established and includes 
representatives of various stakeholder groups that will advise the NLM 
Board of Regents on implementation and assess progress in meeting the 
goals of the NIH Public Access Policy. The above statistics will be 
presented to this Working Group and, if it appears necessary, the 
Working Group may suggest modifications of the policy to ensure that 
the public archive is sufficiently timely and comprehensive.
    Question. Finally, could you provide this subcommittee with a 
report, as soon as possible after December 1, 2005, on how many 
eligible articles were deposited in PubMed Central during the first six 
months of the policy and what the average embargo period was. 
Additionally, we would like to know how many articles are in the 
pipeline awaiting posting. Lastly, do you have any way of tracking 
through PubMed the number of articles supported with NIH funds but not 
submitted to PubMed Central? In other words, will you be able to 
provide both the numerator and the denominator of the equation that 
will demonstrate success of your policy?
    Answer. We estimated that the results of NIH-supported research 
were published in approximately 60,000 to 65,000 articles based on the 
number of articles published in the last several years that contained 
an NIH grant number within the text. We will estimate participation by 
comparing the actual number of papers deposited in the NIH Manuscript 
Submission (NIHMS) system for a given interval with the historical 
average. For example, 5,000 deposited articles per month would indicate 
approximately 100 percent participation. By the close of the calendar 
year sufficient data should be available to make an assessment of the 
degree of participation. Statistics for the distribution of the embargo 
periods requested by authors will be readily available from the 
submission system.
                                 ______
                                 
            Questions Submitted by Senator Daniel K. Inouye

                 CANCER COUNCIL OF THE PACIFIC ISLANDS

    Question. The Cancer Center in Hawaii continues to provide vital 
research that will benefit Native Hawaiians, Pacific Islanders, and the 
world community. Last year, the Senate requested that a task force 
review the continuing and unique needs of Native Hawaiians and Pacific 
Islanders, specifically as those findings relate to the higher 
incidence of some types of cancers in these populations. Please provide 
an update from the Director's task force on your findings.
    Answer. As recommended by the work of National Cancer Institute's 
(NCI) task force in the Pacific Rim, NCI has created the Cancer Council 
of the Pacific Islands (CCPI), a community-and region-based council 
comprised of representatives of the professional native physicians and 
other health professionals representing the six U.S.-associated 
jurisdictions of the Pacific to address the cancer health needs within 
each of these jurisdictions. NCI has supported the development of this 
task force and conducted needs assessments in all jurisdictions, and 
continues to support capacity building and to address high priority 
cancer needs in these communities. The CCPI provides a community-based 
forum through which all federal agencies conducting programs in these 
jurisdictions coordinate efforts.
    The accomplishments of the Cancer Council of the Pacific Islands 
are substantial. These accomplishments are also significant in that, 
for the first time, Island leaders are provided a controlling voice in 
the design, development, and implementation of their own survey 
instrument and subsequent activities. With the assistance of selected 
professors and students from the University of Hawaii, a comprehensive 
cancer assessment was administered in Kosarae, Chuuk, Pohnpei, Yap, 
Belau, Marshall Islands (Ebeye, Majuro), Northern Mariannas, American 
Samoa, and Guam. We are now implementing the prioritized listings of 
health needs identified as a result of those assessments.
    NCI recently awarded a 5-year Community Networks Cooperative 
Agreement to the Lyndon Baines Johnson Tropical Medical Center in 
American Samoa to directly address cancer disparities, train minority 
investigators, reduce access barriers, and provide research 
infrastructure to link American Samoa to NCI research--Cancer 
Information Service (NCI's cancer information helpline), innovated 
screening, and diagnostic technologies and clinical trials, in 
particular.
    Recently, the CCPI met with NCI, the Health Resources and Services 
Administration, the Centers for Disease Control and Prevention (CDC), 
and other federal partners, as well as C-Change (a coalition of the 
nation's key cancer researchers and policymakers), to work on 
developing Comprehensive Cancer Plans for each jurisdiction, and a 
regional plan for the Pacific Rim. NCI is providing technical 
assistance and administrative support to augment CDC's efforts in 
developing these plans. Once these plans are developed, each 
jurisdiction and the CCPI will be able to apply for CDC implementation 
funds. NCI is committed to this community-based effort in the Pacific 
Rim and continues to develop collaborative programs for the CCPI with 
federal agencies who can improve the health and well-being of the 
Pacific Island communities.

                          CANCER AND ETHNICITY

    Question. Additionally, I chaired hearings in Honolulu during which 
data was presented showing striking differences in the incidents of 
cancer among various ethnic groups. I am told the FDA now encourages 
clinical testing for new drugs in a variety of ethnic groups because 
the drugs themselves have a different effect on each group. Has NIH or 
NCI been pursuing additional research on the genetic or cultural causes 
of cancer and the efficacy of treatment by different ethnic groups?
    Answer. Two years ago, the National Cancer Institute (NCI) launched 
the Breast and Prostate Cancer and Hormone-related Gene Variants Cohort 
Consortium (BPC3 Study) to pool data and biospecimens from 6 large 
cohorts to conduct research on gene-environment interactions in cancer 
etiology. One of these cohorts, the Multiethnic Cohort (MEC) Study, is 
evaluating the genetic and biochemical determinants of cancer risk in 
traditionally understudied minority populations and consists of 215,251 
men and women (ages 45-75 years at baseline) from Hawaii (Asians, 
Whites, and Native Hawaiians) and California (African-Americans and 
Latinos). NCI has begun a Minority Accrual Initiative, whose goals 
include increasing the number of minority investigators and minority 
patients in cancer research. The University of Hawaii received funding 
to foster minority accrual to clinical trials through this initiative. 
Historically, the University of Hawaii and its affiliated hospitals 
have accrued large numbers of minority patients, both Asian-Americans 
and Native Hawaiians, to prevention and treatment trials.
    NCI has also encouraged collaborations between sites with 
relatively non-diverse populations (e.g., Rochester, Minnesota) and 
sites with large minority populations (e.g., Wayne State, Howard 
University) to increase minority accrual to early clinical trials where 
substantial data regarding variations in drug disposition can be 
acquired. Drug disposition data from all NCI's Cancer Therapy 
Evaluation Program trials is evaluated to determine whether any 
differences are evident for these subcategories of patients. In 
addition, Phase 3 clinical trials are analyzed for differences in 
outcome according to race and age among other factors and have resulted 
in publications in these areas and new research approaches to eliminate 
disparities. The bioinformatics infrastructure that supports these 
clinical trials will facilitate even greater data sharing across trials 
and more robust comparisons and data analysis in the future.
    In a public-private partnership, NCI has funded seven sites to 
explore approaches to improve accrual of minority and older patients to 
early clinical trials. In addition, for large clinical trials groups 
that accrue approximately 25,000 patients per year to NCI sponsored 
clinical trials, there are a number of specially funded programs that 
focus on increasing the accrual and evaluation of under-represented 
racial, ethnic, and demographic groups (elderly and rural) to clinical 
trials. These include supplements to specific programs in the NCI 
Clinical Cooperative Groups and the long-standing Minority-Based Cancer 
and Community Oncology Program. There is also a large program funded in 
collaboration with the National Institute of General Medical Sciences 
that supports a Pharmacogenetics Network. This Network evaluates 
pharmacogenomics in drug development which includes the study of the 
impact of race/ethnicity on drug efficacy.
    Question. How satisfied are you with the amount and quality of 
research done in this area?
    Answer. Preliminary findings from the Hawaii Tumor Registry show 
that foreign-born Asians, when compared to U.S.-born Asians and 
Caucasians, have a lower percentage of cancer diagnosed at an early 
stage, a higher percentage of cancer diagnosed at a late stage, and 
lower rates of cancer survival. In an effort to overcome these 
disparities, we have strengthened NCI community-based programs in 
Hawaii including the Community Network Program, Imi Hale Native 
Hawaiian Cancer Network, the American Samoa Community Cancer Network at 
the Lyndon B. Johnson Tropical Medical Center in American Samoa, and 
strengthening support for the Cancer Research Center of Hawaii, a NCI-
designated cancer research center whose mission is to bring together 
researchers who focus on understanding the etiology of cancer and on 
reducing its impact on the people of Hawaii.
    NCI expects to continue to expand research in cancer health 
disparities to increase our understanding of why some populations 
experience greater incidence, mortality, and lower survival from cancer 
than the majority of Americans. In the NCI report, Making Cancer Health 
Disparities History, published in March 2004, a Trans-HHS Cancer Health 
Disparities Progress Review Group (PRG) comprised of leading cancer 
experts, researchers, patients, cancer survivors, and advocates in 
cancer and health disparities reviewed the status of cancer health 
disparities in the United States and forged a set of 14 priority 
recommendations for Department of Health and Human Services (HHS) to 
lead the Nation in eliminating cancer health disparities. On March 28, 
2005, the HHS Health Disparities Council established a Subcommittee on 
Cancer with NCI as its chair. The subcommittee will focus on six of the 
PRG's 14 recommendations that will address needs ranging from the 
planning and coordination of program efforts to discovery, development, 
and delivery of research advances to all Americans.
    Communities, caregivers, and researchers must form strong alliances 
and explore creative solutions for developing culturally competent 
venues for service delivery. Community-based participation must be an 
integral part of the planning, development, and implementation of 
solutions to bring research advances to all populations. This cross 
fertilization will build synergism and ensure stronger, more dynamic 
alliances for overcoming cancer health disparities.

                          BEHAVIORAL RESEARCH

    Question. Since 1999, the Committee's report has urged the National 
Institute of General Medical Sciences (NIGMS) to fund basic behavioral 
research. The legislative mandate for NIGMS specifically includes 
behavioral science research, yet I am not satisfied basic behavioral 
research has been adequately or even minimally addressed. I understand 
a working group was established as part of the NIH Advisory Committee 
to the Director on Research Opportunities in the Basic Behavioral and 
Social Sciences. I feel we have been extremely patient and sufficient 
time has elapsed to review this issue. Please provide a report to the 
Committee outlining the recommendations of the working group and your 
timeline for implementation.
    Answer. In keeping with the preferred approach of performing 
portfolio analysis across NIH rather than on an institute-by-institute 
basis, a working group of the Advisory Committee to the Director, NIH, 
was formed to examine basic behavioral research across NIH. The working 
group reported to the Advisory Committee on December 2, 2004. Their 
analysis revealed that the institutes and centers (including NIGMS) 
supported approximately $2.68 billion in behavioral research, including 
approximately $936 million in basic behavioral research, in fiscal year 
2003. In addition to this base, several components of the NIH Roadmap 
for Medical Research are directed toward basic behavioral research. In 
particular, several mechanisms are being used to stimulate 
interdisciplinary research at the interface of the behavioral/social 
and biological sciences, provide the interdisciplinary training 
necessary for postdoctoral investigators to work in these areas, and 
support development of innovative methods and technology that will 
facilitate research at the intersection of the behavioral, social and 
biomedical sciences.
    Following the submission of the working group report, NIGMS has 
taken several steps to more clearly articulate the basic behavioral 
research it supports, encourage the submission of more research 
applications in these areas, and increase the number of investigators 
who can work at the interface of the behavioral and biological 
sciences:
    Research Training at the Interface of the Behavioral and Biological 
Sciences.--Basic behavioral research is of critical importance to the 
mission of the NIH and can play a crucial role in understanding the 
etiology of disease and enhancing preventive and therapeutic 
inventions. Greater understanding of the molecular, genetic, and neural 
processes governing behavior, and the reciprocal effects of behaviors 
on physiological processes, is crucial for a complete understanding of 
human health and those diseases in which behavior is a risk factor, 
diagnostic indicator, or symptom. To advance our knowledge in these 
areas, researchers will need to integrate multiple disciplinary 
perspectives, methodologies, and levels of analysis. NIGMS has a strong 
background in developing and supporting such interdisciplinary research 
training. While some existing NIGMS training programs such as the 
Medical Scientist Training Program and the Systems and Integrative 
Biology program include elements of the behavioral sciences, there has 
not been a program dedicated to training at the basic behavioral 
science-biological science interface. NIGMS has developed a proposal 
for such a predoctoral. program and is coordinating its further 
development with other NIH Institutes having an interest in this area.
    Collaborative Research on Basic Mechanisms of Behavior.--To 
encourage the multidisciplinary research that is needed for a fuller 
understanding of the basic mechanisms of behavior, NIGMS has proposed 
an initiative to facilitate collaborations between basic behavioral 
scientists and investigators with expertise in state-of-the-art 
genetics, molecular biology, and genomics. It is anticipated that this 
collaborative research, performed with model organisms, will either 
enhance existing models or lead to the development of new models of 
normal or abnormal human behavior. The concept for this solicitation is 
to be presented for approval at the May 2005 meeting of the National 
Advisory General Medical Sciences Council.
    Assessing Interactions Among Social, Behavioral, and Genetic 
Factors in Health.--NIGMS is a major contributor to an Institute of 
Medicine committee examining the state of the science on gene-
environment interactions that affect human health. The study will 
identify approaches and strategies to strengthen the integration of 
social, behavioral, and genetic research in this field as well as 
consider relevant training and infrastructure needs. The results of 
this study will be used by the NIH to guide its programs in these 
areas.
                                 ______
                                 
               Questions Submitted by Senator Harry Reid

                        CHRONIC FATIGUE SYNDROME

    Question. Funding for research on chronic fatigue syndrome (CFS) 
has fallen to less than $5 million per year, at the same time national 
prevalence estimates for this serious condition have risen to nearly 
one million American adults and adolescents. In June 2003, Dr. Vivian 
Pinn announced plans to issue a Request for Applications (RFA) for 
research on CFS following an NIH workshop on neuro-immune mechanisms in 
CFS. Almost two years later this RFA has not been issued. What are 
NIH's immediate plans to stimulate research into CFS, a condition that 
CDC reports costs the U.S. economy $9.1 billion a year in lost 
productivity?
    Answer. Funding levels for CFS have remained at approximately $5-$6 
million a year without a significant decline in dollars in years. NIH 
continues to encourage an increase in the number of CFS research 
proposals that are submitted for review and funding each year. 
Applications to PA-02-034, The Pathophysiology and Treatment of Chronic 
Fatigue Syndrome, based on recommendations from an October 2000 
symposium, tripled from its release in December 2001 through fiscal 
year 2004. This PA was revised and reissued under the same title as PA-
05-030 in December 2004 to include research ideas from the June 2003 
scientific workshop, Neuroimmune Mechanisms and Chronic Fatigue 
Syndrome: Will Understanding Central Mechanisms Enhance the Search for 
the Causes, Consequences, and Treatment of CFS? This program 
announcement specifically invites the submission of investigator-
initiated grant applications to support research on the epidemiology, 
diagnosis, pathophysiology, and treatment of CFS in diverse groups and 
across the life span. Applications that address gaps in the 
understanding of the environmental and biological risk factors, the 
determinants of heterogeneity among patient populations, and the common 
mediators influencing multiple body systems that are affected in CFS 
are encouraged.
    The proceedings of this June 2003 workshop were recently published 
(NIH Publication No. 04-5497) and posted on the ORWH/CFS website 
(http://www4.od.nih.gov/orwh/cfs-newhome.html). Seven new projects 
related to CFS were funded in fiscal year 2004 and address topics 
raised at this workshop. One of these is an intramural project which 
reflects the impact of a new Trans- NIH Intramural Interest Group on 
Scientific Integrative Medicine that resulted from the June 2003 CFS 
Workshop. Also based on this workshop, the ORWH and the Trans-NIH 
Working Group for Research on Chronic Fatigue Syndrome will be issuing 
a new interdisciplinary Request for Applications (RFA) later in fiscal 
year 2005. This new RFA on CFS has progressed through the usual steps 
following the workshop when the intent was announced. In addition, NIH 
continues to plan relevant scientific activities and efforts on which 
to base future CFS research initiatives.
    Question. Last fall, an analysis of NIH funding for chronic fatigue 
syndrome (CFS) was presented to the DHHS CFS Advisory Committee by the 
CFIDS Association of America. This report documented that NIH had 
overstated its funding of CFS research for fiscal year 1999-fiscal year 
2003 by 19.6 percent through the inclusion of studies unrelated to CFS. 
Total funding of CFS research for this five-year period is just $26 
million--a very small amount given magnitude of the condition and the 
generous increases Congress provided to NIH during these same years. 
What efforts are being taken to ensure that spending figures issued by 
NIH are accurate and reliable and what is NIH doing to expand support 
of research on CFS?
    Answer. The funding figures provided by the NIH on expenditures 
related to CFS are based upon the best scientific and budgetary 
deliberations and are consistent and accurate. As with all scientific 
and budgetary data collections, these funding figures reflect projects 
designated as CFS research by Institute and Center (IC) staff, each 
utilizing his/her best scientific judgment. These figures include 
funding for basic and laboratory studies that are pivotal in the 
development of clinical and translational research; although such 
studies may not seem specific for CFS, they deal with the basic 
biologic processes that are fundamental to developing a better 
understanding of CFS and are thus integral to CFS research. The NIH 
continues to implement efforts to increase CFS research through an 
increase in funded proposals.
                                 ______
                                 
                Questions Submitted by Senator Herb Kohl

                           EPILEPSY RESEARCH

    Question. As you know, epilepsy is a major public health problem, 
affecting 2.5 million Americans throughout their life spans. The impact 
of epilepsy--ranging from debilitating side-effects of treatment to 
brain damage and even death--has long been under-recognized. Epilepsy 
is a public health problem of major proportions.
    Because epilepsy may occur at any age and as a result of many 
different, poorly understood and complicated causes, Congress has 
encouraged the NIH to focus on this problem with a multi-disciplinary 
approach involving efforts by the NIMH, NIA, NICHD and NHGRI in 
coordination with the lead institute, NINDS.
    Epilepsy is the perfect model for a disease that will succumb to a 
coordinated, multi-disciplinary research effort such as you outlined in 
``The NIH Neuroscience Blueprint''. A few of the above-mentioned 
Institutes have begun to address epilepsy, but coordination and 
communication between them is a necessity if this multi-disciplinary 
approach is to prove fruitful.
    It seems critically important to establish a working group to 
coordinate research efforts, clinical trials and learn from the co-
morbidities which are so common in patients with epilepsy. Dr. 
Zerhouni, how do you intend to facilitate the coordination which needs 
to exist between these research efforts in order to reduce the burden 
of this all-too-common neurological disorder?
    Answer. The National Institute of Neurological Disorders and Stroke 
(NINDS) is the lead NIH Institute for epilepsy research and the primary 
funding source for studies of seizure disorders. Several other NIH 
Institutes and Centers also fund epilepsy related projects, including 
the National Institute of Child Health and Human Development (NICHD), 
the National Human Genome Research Institute (NHGRI), the National 
Institute of Mental Health (NIMH), and the National Institute on Aging 
(NIA). In order to better facilitate coordination of research efforts 
in this area, these Institutes formed an Interagency Epilepsy Working 
Group. Since its establishment in January 2003, several other NIH 
Institutes with an interest in epilepsy research have joined, including 
the National Institute of Biomedical Imaging and Bioengineering 
(NIBIB), the National Institute on Alcohol Abuse and Alcoholism 
(NIAAA), the NIH John E. Fogarty International Center (FIC), as well as 
a representative from the National Center for Chronic Disease 
Prevention and Health Promotion at the Centers for Disease Control and 
Prevention (CDC).
    The members of the Interagency Epilepsy Working Group are primarily 
extramural program staff who administer epilepsy research grants and 
develop program activities to facilitate research efforts. The purpose 
of this group is to increase communication among institutes and 
agencies supporting epilepsy related research and to explore 
opportunities for increased coordination. An example of these 
cooperative activities is a recent workshop sponsored by the NINDS and 
the NIMH on the treatment of non-epileptic seizures, held on May 1-3, 
2005. The goals of the workshop were to better define diagnostic 
criteria for non-epileptic seizures, develop outcome measures for 
clinical trials, and to discuss a research strategy for this condition.
    The Interagency Epilepsy Working Group meets on a regular basis, 
most recently in October 2004 and April 2005. The April Working Group 
meeting focused on the development of biomarkers for epilepsy related 
research. Working Group members presented examples of relevant 
Institute activities which could be adapted to epilepsy and discussed 
possible approaches to planning a workshop in this important area of 
research. In addition, members of the Working Group participated in the 
most recent meeting of the Epilepsy Benchmark Stewards in February 
2005. The Epilepsy Benchmarks are milestones developed by the epilepsy 
community in 2001 to measure progress in epilepsy research, and 
Stewards have been designated to monitor progress toward meeting each 
Benchmark goal. The purpose of the February meeting was to review 
Benchmark progress and to begin planning a large epilepsy conference 
for 2007 to assess and update the Epilepsy Benchmarks. Working Group 
members will continue to be involved as conference planning progresses.

                            K30 GRANT AWARDS

    Question. As you know, the K30 grant program supports the training 
of clinical researchers--health professionals who translate laboratory 
discoveries to improvements in the care of patients. It is my 
understanding that this year, funding was insufficient to accommodate a 
decision to increase the size of awards from $200,000 to $300,000, 
resulting in the University of Wisconsin losing their K30 award as of 
June. While I applaud your efforts to increase the award amount, I am 
concerned that programs like the one at Madison, who depend on K30 
grants, will be forced to close their doors.
    The shortage of clinical researchers trained to advance medical 
science and improve the care of patients has been well-documented in 
reports from the National Academy of Sciences and the NIH. The 
University of Wisconsin's program has trained 144 clinical researchers 
to date. What will you do to ensure the K30 grant program is funded at 
a level sufficient to restore and expand the program at the $300,000 
level?
    Answer. The NIH recognizes the need for clinical research training 
to ensure that the nation's needs for clinician researchers are met. As 
such we have a number of programs designed to create well-trained 
patient-oriented researchers. A major part of this effort is the 
Clinical Research Curriculum Award (K30). To help address the needs of 
this specific trans-NIH program, a decision was made to increase the 
total funds available from $10,958,000 in fiscal year 2004 to 
$14,700,000 in fiscal year 2005. Additionally, all Institutes and 
Centers funding clinical research will contribute to these awards and 
the size has been increased to $300,000. While we realize that we 
cannot fund all meritorious applications, we do expect to award 49 
grants out of the 81 applications received which is a 61 percent 
success rate.

                        IRRITABLE BOWEL SYNDROME

    Question. Dr. Zerhouni, for the last several years, my colleagues 
and I on the Appropriations Committee have asked NIDDK to develop a 
strategic plan for research into Irritable Bowel Syndrome (IBS), a 
chronic complex of disorders that malign the digestive system. Can you 
update this Committee on the timetable for development and 
implementation of a strategic plan for IBS at NIDDK?
    Answer. The NIH concurs that a strategic plan for IBS will identify 
areas of scientific opportunity and serve as a stimulus in the 
prevention, diagnosis, and management of this functional disorder. Due 
to recent Congressional interest, the NIH is in the early stages of 
creating a new Commission on digestive diseases, which will develop a 
long-range research plan for the entire spectrum of these diseases, 
including IBS.
    The congressional directive to establish the Commission is in the 
Senate report language accompanying the Labor/HHS appropriations bill 
(Senate Report 108-345, page 165). In documentation accompanying the 
President's Budget request for fiscal year 2006, the NIH has informed 
the Labor/HHS appropriations committees that it considers the 
establishment of the commission at this time to be both appropriate and 
useful (HHS fiscal year 2006 Justification of Estimates for 
Appropriations Committees, pp. OD 64-65).
    This Commission will perform an assessment of the state-of-the-
science in digestive diseases and develop a Long-Range Research Plan 
for Digestive Diseases--with broad stakeholder input from scientific 
and lay experts. A parallel effort, under the leadership of the 
National Institute of Diabetes and Digestive and Kidney Diseases 
(NIDDK), will compile current data on the burden of digestive diseases, 
which would also feed into the Commission's planning process. As noted 
in the draft charter for the Commission, the Long-Range Research Plan 
would focus solely on research--consistent with the NIH mission.
    The Commission is important because the Long-Range Research Plan it 
develops will serve as a beneficial scientific guidepost to both the 
NIH and the digestive diseases community, and would serve the public 
health. According to recent estimates, the total costs associated with 
major forms of digestive diseases approach $43 billion annually. The 
Plan will focus on research in specific diseases, including IBS, and 
will also address the training and education of researchers in 
digestive diseases research; programs for the collection, 
dissemination, and exchange of information and resources in health and 
disease relevant to digestive diseases research; and identification of 
cross cutting, innovative research disciplines and technologies and 
opportunities for synergy in both basic and clinical research within 
the Institutes and Centers of the NIH. The inclusion of IBS as a part 
of a larger strategic planning effort, instead of conducting a stand-
alone IBS planning effort, will provide greater opportunity to identify 
cross-cutting themes common to multiple digestive diseases and common 
hurdles shared by many.

                    AGE-RELATED MACULAR DEGENERATION

    Question. I understand that the rate of occurrence of age-related 
macular degeneration (AMD) will double over the next 15 years, robbing 
our seniors of their sight. Can you tell us about the research into 
this disease, and specifically, what therapies may be emerging to stop 
or reverse this trend?
    Answer. The National Institutes of Health strongly supports 
research for age-related macular degeneration (AMD) and has contributed 
greatly to the understanding of the disease and to the development of 
new therapies for the disease. Four recently published studies 
supported by the National Eye Institute report on the identification of 
inherited variations in a gene that greatly increase the risk of 
developing AMD. The gene, known as complement factor H, is involved in 
the body's immune defense system. These findings suggest a possible 
role for inflammation in the cascade of biological events that leads to 
AMD. This important discovery may lead to development of new approaches 
to preventing, diagnosing, and treating this disease.
    The National Eye Institute conducted Age-Related Eye Disease Study 
(AREDS) found that a daily high-dose specific formulation of 
antioxidants and zinc can slow the progression of AMD from intermediate 
to advances stages of the disease. Based on an analysis of prevalence 
data and the AREDS study findings, it is estimated that more than 
300,000 Americans could avoid developing advanced AMD and its 
associated vision loss over the next five years by taking this 
formulation.
    An advanced form of AMD called ``wet'' AMD develops as a result of 
new, abnormal blood vessels that grow beneath the retina, leak blood 
and fluid, and produce scar tissue. Left untreated, catastrophic loss 
of central vision may occur. The FDA has approved two new treatments, 
verteporfin and pegaptanib, for controlling ``wet'' AMD. These newly 
approved treatments were developed by industry, but benefited from 
early support for basic research that provided a better understanding 
of the underlying biology. A number of even newer treatments, also 
aimed at preventing or reducing this abnormal blood vessel growth in 
AMD, are being evaluated in ongoing clinical trials.
                                 ______
                                 
            Questions Submitted by Senator Richard J. Durbin

                     DRUG RESEARCH AND DEVELOPMENT

    Question. NIH has made tremendous contributions to the public good 
through investments in medical research and therapeutic clinical 
trials. I'm troubled, though, that U.S. citizens are paying twice for 
pharmaceuticals, once through taxpayer support for NIH-funded research 
and then again at the pharmacy when they purchase the drugs that NIH 
funding helped to develop.
    For example, I have a hard time believing that prices charged for 
drugs like Taxol, AZT, Gleevec, and others that are substantially 
funded by taxpayer money are fair.
    Is there anything NIH can do to retain or recoup some of the market 
value of these therapies that are developed based on NIH-funded 
research?
    Answer. Since 2003, NIH has executed 610 new licenses and has 
collected $112 million in royalty income from its intramural research 
program. This represents about two-thirds of the royalty income 
collected by all federal agencies. Most of NIH's licenses are executed 
for early-stage technologies with small companies that do not yet have 
product sales. NIH, however, carefully crafts its licensing terms so 
that it captures a reasonable share of the profits for those products 
that achieve commercialization. In addition, NIH has established a 
Monitoring and Enforcement Branch in the Office of Technology Transfer 
dedicated to monitoring the expeditious development of our licensed 
technologies and to ensuring that we receive the full return on our 
investment.
    In May 2000, the U.S. Congressional Joint Economic Committee issued 
The Benefits of Medical Research and the Role of NIH, which examined 
the role of federal funding for medical research and the benefits that 
derive from that research. The Committee report concluded that the 
benefit of increased life expectancy to the United States as a result 
of advances in health care from NIH-funded medical research results in 
a payoff of about 15 times the taxpayers' investment in NIH. Clearly, 
there are financial and public health related benefits of remarkable 
value that flow from NIH-funded biomedical research.
    The NIH contributes to affordability by conducting and funding 
research that leads to the development of a wider selection of drugs or 
new drugs, where no drugs were available. More alternatives can 
translate into more choices for the public, greater market competition, 
affordability and, ultimately, overall return to society by the 
improvement of the quality of life. Thus, as long as NIH continues to 
focus on its core mandate, namely conducting and funding broad-based 
research that could lead to the development of new drugs and therapies 
in the future, we believe that NIH is acting as a responsible partner 
in the national enterprise to improve the quality of life for the 
public and to make drugs more affordable.

                             PUBLIC ACCESS

    Question. Your first steps toward more readily accessible research 
information for the public are commendable and appropriate. As I 
understand the process, the results of NIH-funded research should be 
available 12 months after it is published.
    But why are you proposing that making research results accessible 
to the public is ``recommended?'' If this is such a good idea--and I 
think it is--why isn't it required?
    Answer. The voluntary nature of the Policy was established to 
encourage investigators to deposit their manuscripts in NIH's public 
archive. We believe this approach will ultimately result in broader 
participation. The Policy-related submissions will directly benefit 
NIH-supported investigators because recent studies have shown that 
freely available articles get cited more in other research 
publications. An increase in the number of citations helps improve the 
professional standing of investigators. Due to these benefits we 
anticipate that authors will decide to participate and to choose the 
earliest release dates.
    I also believe that the voluntary nature of the final policy 
permits sufficient flexibility to accommodate the needs of different 
stakeholders and leaves the ultimate decision in the hands of 
scientific investigators who are in the best position to judge the 
circumstances and the time frame under which their work may be made 
accessible to the public at large. Therefore, we believe that by having 
a Policy that provides maximum flexibility, authors will respond with 
maximum participation.
    Question. A year's delay after publication in a journal strikes me 
as a very long time, given the pace of biomedical developments today. 
How much time do you expect most participating researchers to let go by 
between publication and release of the study publicly?
    Answer. The Public Access Policy strongly encourages all NIH-funded 
researchers to make their peer-reviewed author's final manuscripts 
available to other researchers and to the public at the National 
Library of Medicine's (NLM) PubMed Central (PMC) immediately after the 
official date of final publication. At the time of submission, authors 
are also given the option to release their manuscripts at a later time, 
up to 12 months after publication. NIH expects that only in limited 
cases will authors deem it necessary to select the longest delay 
period.
    The Policy-related submissions will directly benefit NIH-supported 
investigators by offering an alternate means by which they can fulfill 
the existing requirement to provide publications as part of progress 
reports. It is anticipated that, in the future, investigators applying 
for new and competing renewal support from the NIH will also utilize 
this resource by providing links in their applications to their PubMed 
Central-archived information. Further, recent studies have shown that 
freely available articles get cited more in other research 
publications. Increased citations help improve the professional 
standing of investigators. Due to these benefits we anticipate authors 
will choose the earliest release dates.
    Question. What rates of participation and time delays would you 
consider a success?
    Answer. Our goal is to build a comprehensive archive of the results 
of research that NIH funds. Rather than specifying a particular target 
number, we will be looking for an increasing number of manuscripts to 
be submitted over time and a decreasing delay period. Issuance of this 
policy is the beginning of a process that will include refinements as 
experience develops, outcomes are evaluated, and public dialogue among 
all the stakeholders is continued. An NIH Public Access Working Group 
of the NLM Board of Regents has been established. The Working Group 
includes representatives of the various stakeholder groups and will 
advise the NLM Board of Regents on implementation and assess progress 
in meeting the goals of the NIH Public Access Policy. Once the system 
is operational, modifications and enhancements will be made as needed 
based on the recommendations of the Working Group, or a permanent 
subcommittee of the Board, providing ongoing advice on improvements.
    We hope that secondary effects of the Policy might also be viewed 
in terms of ``success.'' Since the Proposed Policy's release in 
September 2004, we have heard that an increasing number of publishers, 
within and outside of the United States, are considering changes to or 
adoption of Open Access publishing models. For example, in January the 
Nature Publishing Group altered its open access model to increase 
accessibility to its publications. We are optimistic that these changes 
will provide the public with free electronic access to Journal 
articles, through the publisher's web site, on a faster time scale or 
for the first time. This ``change in the landscape'' complements the 
benefits of the NIH Policy since the majority of articles in Journals 
(approximately 90 percent) do not result from NIH-funded research.

                          SUBCOMMITTEE RECESS

    Senator Harkin. Thank you very much.
    The subcommittee will stand in recess to reconvene at 9:30 
a.m., on Monday, July 11 in room SD-192. At that time we will 
hear testimony from the Honorable Patricia Harrison, President 
and CEO, Corporation for Public Broadcasting.
    [Whereupon, at 11:18 a.m., Wednesday, April 6, the 
subcommittee was recessed, to reconvene at 9:30 a.m., Monday, 
July 11.]
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