[Senate Hearing 111-]
[From the U.S. Government Publishing Office]


 
  DEPARTMENTS OF LABOR, HEALTH AND HUMAN SERVICES, AND EDUCATION, AND 
          RELATED AGENCIES APPROPRIATIONS FOR FISCAL YEAR 2010 

                              ----------                              


                         THURSDAY, MAY 21, 2009

                                       U.S. Senate,
           Subcommittee of the Committee on Appropriations,
                                                    Washington, DC.
    The subcommittee met at 10:29 a.m., in room SD-138, Dirksen 
Senate Office Building, Hon. Tom Harkin (chairman) presiding.
    Present: Senators Harkin and Shelby.

                DEPARTMENT OF HEALTH AND HUMAN SERVICES

                     National Institutes of Health

STATEMENT OF RAYNARD S. KINGTON, M.D., PH.D., ACTING 
            DIRECTOR, NATIONAL INSTITUTES OF HEALTH
ACCOMPANIED BY:
        JOHN E. NIEDERHUBER, M.D., DIRECTOR, NATIONAL CANCER INSTITUTE
        ELIZABETH G. NABEL, M.D., NATIONAL HEART, LUNG, AND BLOOD 
            INSTITUTE
        ANTHONY S. FAUCI, M.D., DIRECTOR, NATIONAL INSTITUTE OF ALLERGY 
            AND INFECTIOUS DISEASES


                    statement of senator tom harkin


    Senator Harkin. Good morning. The Subcommittee on Labor, 
Health, Human Services, and Education will come to order.
    This morning we will examine the President's proposed 
fiscal year 2010 budget for the National Institutes of Health 
(NIH). We'll also discuss the $10.4 billion that was provided 
for NIH in the Recovery Act.
    I would say at the outset these are exciting times for NIH. 
After several years of stagnant funding, the Recovery Act has 
breathed new life into the field of biomedical research. The 
new Challenge Grant Program alone has generated more than 
20,000 applications from researchers across the country, far 
more than anyone expected.
    The scientific advances that result from this funding will 
probably take some time to gauge but in the meantime, I expect 
it to have a tremendous impact on the economy. Every time a 
researcher gets a grant, it supports an average of six or seven 
jobs. That's not just one researcher by himself or herself. 
It's lab technicians, post-doc fellows and research assistants, 
and then there's the ripple effect of the research itself.
    Maybe this grant leads to a new compound that a 
pharmaceutical company wants to develop into a new drug and 
that means more money in our economy. Maybe an entrepreneur 
uses some breakthrough to form a spin-off company. That 
stimulates the economy, also.
    I just want to note for the record, I don't want any of you 
here at the table to take this wrongly, but all of this money 
won't just go to Bethesda. It goes to researchers in every 
State and it helps the entire country.
    But while there's a great deal of optimism about the next 2 
years, there's also a concern about what happens after the 
Recovery Act funding runs out in the year 2011. After 2 years 
of healthy budgets, will we then have a cliff effect where we 
just kind of fall again?
    That's one of the questions I will want to discuss with our 
witnesses today.
    At this point, I know Senator Cochran is also on our 
Defense Committee hearing mark-up and will probably be here 
later, but I'll leave the record open for his opening statement 
at this point and any other statements that any members of the 
subcommittee might have.
    This morning we have Dr. Raynard S. Kington who was named 
Acting Director of the National Institutes of Health on October 
31 of last year, before that he was Deputy Director for 5 years 
under Dr. Zerhouni.
    Dr. Kington received his B.S. and M.D. degrees from the 
University of Michigan and a Ph.D. from the University of 
Pennsylvania, and I just want to add that, Dr. Kington, I know 
you've served in this capacity probably longer than you thought 
you were going to have to serve. But by every account that I 
have seen, you have done a great job in running this agency and 
I just want to thank you for this period of service and for all 
the previous service, Dr. Kington.
    Also at the table is Dr. Anthony Fauci, the Director of the 
National Institute of Allergy and Infectious Diseases. Again, I 
don't know if you've ever kept count of how many times have you 
appeared before this subcommittee, Tony, going back all these 
years? But again, welcome.
    Dr. Fauci came to NIH in 1968, after completing his 
residency at the New York Hospital, Cornell Medical Center. He 
received his M.D. degree from Cornell University Medical 
College.
    Dr. Elizabeth Nabel is the Director of the National Heart, 
Lung, and Blood Institute, appointed to that position in 2005, 
received her M.D. from Cornell University Medical College, and 
prior to coming to NIH, Dr. Nabel was the Chief of Cardiology 
and Director of the Cardiovascular Research Center at the 
University of Michigan.
    Dr. John Niederhuber is the Director of the National Cancer 
Institute, a graduate of Bethany College in West Virginia, 
received his medical degree from Ohio State, and prior to 
coming to NIH, Dr. Niederhuber was a Professor of Surgery and 
Oncology at the University of Wisconsin School of Medicine.
    I know other Directors are here this morning. Dr. Lawrence 
Tabak at the National Institute of Dental and Craniofacial 
Research is here. Dr. Tabak is here.
    Dr. John Ruffin from the National Center on Minority Health 
and Health Disparities.
    Dr. Steven Katz, the National Institute of Arthritis and 
Musculoskeletal and Skin Diseases, Dr. Katz is here, yes.
    Dr. Story Landis of the National Institute of Neurological 
Diseases and Stroke, Dr. Landis.
    Dr. Richard Hodes, National Institute of Aging. Nice to see 
you again.
    Dr. Griffin Rodgers from the National Institute of Diabetes 
and Digestive and Kidney Diseases, NIDDK.
    And Dr. Thomas Insel, National Institute of Mental Health, 
also here, too.
    Thank you all for being here.
    Now, I had a series of really wonderful hearings last year 
where we brought down something like three directors at a time, 
and I wanted to do that this year, but because of healthcare 
reform that we're working on and I also wear another hat, we're 
trying to get the reauthorization of the Child Nutrition bill 
through, so there's just a lot of things piled up on us right 
now, so I don't have that luxury.
    I think it's very important that we hear from the Directors 
of these Institutes in a more indepth session. I will just say, 
Dr. Kington, it's my intent, consistent with what we have to do 
here in the Senate this year, that maybe we can catch up on 
this later on. I'm still hopeful that maybe this fall some 
time, if we get our healthcare reform bill through and we have 
a little bit more time I would come back and hopefully revisit 
that and reprise what we did again last year.
    I just don't have the time to do it now, but sometime this 
fall. So I say to you and the other directors it is my intent 
to do that. Okay?
    Well, with that, Dr. Kington, we'll turn to you for your 
statement. I just would say that all of your statements will be 
made a part of the record in their entirety and if you'd just 
summarize them in 5 minutes or so, I'd certainly appreciate it.
    Dr. Kington.


              summary statement of dr. raynard s. kington


    Dr. Kington. Thank you. Mr. Chairman, it's a privilege to 
appear before you today to present the National Institutes of 
Health budget request and to discuss the priorities of NIH for 
fiscal year 2010 and beyond.
    Again, I would like to thank all of my colleagues whom 
you've noted who are here joining me today and we would welcome 
the opportunity to come back and have further discussions 
whenever it is convenient.
    First, I want to express my gratitude to Congress and the 
president for the support reflected in the recent appropriation 
of $10.4 billion in the American Recovery and Reinvestment Act 
(ARRA) for NIH expenditure and the 3.2 percent increase in the 
annual fiscal year 2009 appropriations for NIH.
    The continued trust that you place in the NIH to make the 
discoveries that will lead to better health for everyone is 
appreciated.
    I thank you on behalf of the many scientists who we are 
able to support and more than 3,000 research institutions 
throughout the United States and on behalf of the public who 
count on our research to help detect, treat and prevent 
hundreds of diseases and conditions.
    As noted, I have submitted my testimony for the record and 
will just highlight key points for you now.


                    fiscal year 2010 budget request


    The budget request embodies the President's fundamental 
goal of increasing overall Federal investment in biomedical 
research as well as the President's particular emphasis on 
accelerating research in the areas of cancer and autism in 
fiscal year 2010.
    The budget request provides $31 billion, an increase of 
$443 million or 1.4 percent over fiscal year 2009, to help fill 
in gaps in our fundamental understanding of health and disease. 
This request will increase funding for research project grants 
by $243 million.
    The request supports an estimated 9,849 new and competing 
research project grants, about the same level as in fiscal year 
2009, which will provide a success rate in 2010 of about 20 
percent.
    The fiscal year 2010 President's budget request includes 
the following priorities. For cancer research, an increase of 
investment across the NIH to over $6 billion reflecting the 
first year of an 8-year strategy to double cancer research by 
fiscal year 2017. This request represents an increase of $268 
million or 5 percent over an estimated fiscal year 2009.
    For autism research, the NIH will contribute $141 million 
of the $211 million department-wide initiative on autism. 
Working with the Centers for Disease Control and Prevention and 
the Health Resources Service Administration, we will use these 
funds to support research into the causes of and treatment for 
autism spectrum disorders. For NIH this represents an increase 
of $19 million or about 16 percent above the estimated fiscal 
year 2009 level.


                economic and scientific benefits of arra


    I expressed earlier my gratitude to the President and 
Congress for their support of the NIH with ARRA. It is time 
that the ARRA funds be provided to NIH to stimulate the economy 
and advance biomedical and behavioral research. The biomedical 
research community is not spared from the recent downturn in 
the economy. This is worrisome not only because it means fewer 
jobs but also because innovation and a constant influx of young 
talent are crucial to the Nation's economic success and a 
robust biomedical research enterprise.
    We are moving quickly to identify the best science and 
support it with an additional $10.4 billion provided by ARRA to 
NIH and to obligate it within the next 2 years. We have already 
started selecting projects to receive the funding. To date NIH 
has begun obligating more than $375 million worth of ARRA 
support to a wide array of important projects. We expect the 
number of actions to increase exponentially over the coming 
weeks and months.
    For example, NIH ARRA funding is already supporting 
research to construct a reference sequence dataset for the 
Human Microbiome Project. This genomic survey project promises 
to lay the foundation for future advances to understand the 
impact that microbes in the human body have on health and 
disease.
    Another funded project seeks to develop molecular targeting 
to improve the delivery and efficacy of treatments for deadly 
brain tumors known as glial blastomas.
    Still another ARRA grant will support a Pittsburgh lab that 
has been developing a minimally invasive surgical approach for 
removing intracerebral hematomas, deadly bruises on the brain. 
In this case ARRA funds have allowed the lab to reopen and the 
staff newly returned to their benches to continue their 
potentially life-saving studies.
    Furthermore, your funding decisions sent a strong message 
to scientists in the field and to bright young people who may 
one day choose a career as scientists that the United States is 
working to support outstanding research and outstanding 
scientists.
    Just yesterday the Baltimore Sun published a story on the 
impact of ARRA funding and here's a quote from the article.

    ``There are a lot of really good ideas that were dying on 
the vine because they weren't getting funding,'' said James 
Hughes, Vice President for Research and Development at the 
University of Maryland, Baltimore, ``but with the stimulus 
money, Hughes estimates that his medical, pharmacy, dental, and 
nursing schools could see as much as an additional $100 million 
over the next 2 years, money that will not only further 
research but would create hundreds of good jobs.''

    I am certain that similar scenarios are occurring 
throughout the country and will continue to do so over the next 
2 years as we implement this act. Here's only a sampling of the 
important work that we will support with the ARRA funds.
    For example, we will expand our current understanding of a 
wide array of diseases and conditions, including diabetes, 
various forms of cancer, addiction, glaucoma, infectious 
diseases, heart and lung diseases, arthritis, kidney disease 
and mental disorders.
    In addition, we will expand our efforts in community-based 
research with special focus on minority and under-served 
populations, and make further investments into the potential 
applications of nano technology.
    Just to review briefly, the ARRA funding to NIH will be 
used in the following ways. The legislation allocated $1.3 
billion for the National Center for Research Resources with $1 
billion identified for extramural construction and renovation 
and $300 million targeted for shared instrumentation and other 
large capital research equipment.
    The positive impact of the support for institutions and 
researchers will be extraordinary, providing broader access to 
the state of our equipment. Funding for extramural construction 
and renovation will result in jobs in construction and a number 
of trades in the building industry.
    Shared instrumentation will improve the quality and even 
the speed of work that is done and build collaboration in ways 
that will accelerate discovery. Shared scientific 
instrumentation, including such resources as advanced real-time 
imaging tools, will allow scientists to image the brain in 
action in ways that have not been possible before.
    You appropriated $8.2 billion to NIH, of which $7.4 billion 
was distributed through the Office of the Director to 
Institutes and Centers of NIH and to the common fund for the 
direct support of biomedical research. The remaining $800 
million was distributed by the Office of the Director to fund 
specific research challenges of scientific priorities at the 
Institutes and Centers.
    Our current projections are that NIH activities with these 
funds will support more than 7,000 new awards, most of which 
will be for 2 years of scientific research.
    In addition, $400 million transferred to NIH from the 
Agency for Healthcare Research and Quality as directed under 
ARRA and will be used to support comparative effectiveness 
research. The remaining $500 million will be used to fund high-
priority repairs, improvements, and construction on the NIH 
Bethesda campus to enable the highest-quality research to be 
conducted.
    Let me review how NIH will be using ARRA dollars in direct 
support of science.
    NIH developed a nimble approach to investing the money 
quickly and with the greatest impact. For example, we are in 
the process of scrutinizing approximately 14,000 grant 
applications we received in our last round of review, 
applications that were already highly meritorious and approved 
by advisory councils at each Institute and Center, applications 
that despite their merit we could not fund before.
    We are now identifying and planning to fund some of these 
scientifically meritorious applications for 2 years where the 
scientific plan is appropriate for a 2-year award instead of 
the usual 4-year award.
    NIH has already issued a number of new funding 
announcements. In particular, we've made targeted grant 
announcements to stimulate research in high-priority exempt 
areas. An excellent example is research funding opportunities 
related to autism, a disease that affects so many families 
across the United States.
    NIH has committed $60 million of research funding, in 
addition to a $141 million in the base budget request, to 
address the differences across autism spectrum disorders. 
Resources will help develop and test diagnostic screening 
tools, assess risk for exposures, test early interventions and 
adapt existing pediatric treatments for older groups with 
autism spectrum disorders.
    While few trials can be completed in 2 years, the ARRA 
funds will be important for jumpstarting projects and building 
the foundation for longer-term autism research.
    NIH has created a number of new programs that will spur new 
areas of research and trigger an almost immediate influx of 
research dollars into communities across the Nation.
    For example, we've introduced the Challenge Grants, the 
Grant Opportunity or GO Grants, Signature Initiatives, a 
program to encourage the recruitment of new faculty to conduct 
research, and a program to hire students and science teachers 
to work in research laboratories.
    For the Challenge Grants, we issued the largest request for 
applications in NIH history, which is saying something, to 
initiate the program. The 220-page solicitation lists 237 
scientific topics in 15 broad scientific areas. As noted, we 
initially expected to devote approximately $200 million to this 
effort, funding the best proposals from a pool of around 
15,000, we initially estimated. However, upon receiving well 
over 20,000 applications, we now anticipate devoting 
substantially more than that.
    The magnitude of the response demonstrates the breadth and 
depth of the scientific capacity that exists across the United 
States, capacity awaiting only financial support to be 
actualized. It is inspiring to witness the scope and creativity 
of American scientists.
    Here are only a few examples of Challenge Grant topics. New 
advances in biosensors and lab on a chip technology to create 
novel ways to measure the health effects of contaminants in the 
environment and develop high-tech blood and tissue analysis 
techniques, new approaches to better understand persistent HIV-
1 infections in patients receiving antiretroviral therapy, and 
enhancing research in the bioethics field.
    Another new program is the Grant Opportunity Program or GO 
Grants. The GO Grant Program which was designed to complement 
the Challenge Grants will support large-scale research 
projects. These large-scale projects will accelerate critical 
breakthroughs early in applied research on cutting edge 
technologies and new approaches to improve the interactions 
among multidisciplinary, interdisciplinary research teams. The 
applications are due on May 29th of this year and I know that 
we've received already more than 2,400 letters of intent from 
potential applicants.
    NIH is also identifying a number of Signature Initiatives 
that will support exceptionally creative and innovative 
projects and programs to address major challenges in biomedical 
research in public health. The initiatives will cover new 
scientific opportunities in nano technology, genome-wide 
association studies, health disparities, arthritis, diabetes, 
autism, genetic risk for Alzheimer's disease, regenerative 
medicine, oral fluids as biomarkers, and HIV vaccine research.
    In addition to direct support from the Institutes and 
Centers ARRA funds, the Office of The Director will also 
support at least $30 million from its ARRA funds for these 
signature projects.
    We've also announced a new program to support newly trained 
faculty to conduct research. This will help address the need to 
support early career scientists who are one of NIH's top 
priorities. Funding will be provided to hire, provide 
appropriate start-up packages, and develop pilot research 
projects for newly independent investigators. The applications 
for this program are due to NIH May 29, as well.
    We are particularly delighted to tell you about our 
expanded summer program for teachers and students from all 50 
States and the District of Columbia. NIH will use $35 million 
of ARRA dollars to support short-term jobs over 2 summers for 
over 3,700 individuals. Most of these will be high school and 
undergraduate students, though the number also includes several 
hundred elementary, middle, high school, and community college 
science educators.
    This laboratory experience around the country will provide 
several thousand Americans with the opportunity to experience 
the extraordinary world of research. We hope this experience 
will spark the desire of many of these students to become 
scientists.
    We are mindful that a top priority for the use of ARRA 
funds by NIH is to create and preserve jobs as well as to 
increase purchasing power in all corners of the country. We 
firmly believe that we can do this while carrying out the core 
NIH mission and without compromising our commitment to fund the 
very best scientific research ideas.
    We will fulfill ARRA's comprehensive reporting 
requirements, including jobs created and preserved, tracking of 
all projects and activities and trend analysis. To track all of 
the NIH ARRA-related activities, I invite you to go to our Web 
site, www.nih.gov, which we will update regularly.
    In summary, groundbreaking discoveries are most often built 
on the foundation of many incremental advances that bring us 
closer to early diagnoses, better treatments and other public 
health improvements expected by Congress and the American 
public.
    Because of the ARRA funds, there will be more discoveries 
across the country next year and many years thereafter. These 
findings will yield better understanding of the major diseases 
and disorders, including those I touched on today, and hundreds 
more, as well as providing keys to living healthier lives.
    As I said in my opening comments, we are grateful for the 
commitment to biomedical research and all the promise it brings 
to the people here in the United States and around the world. 
We have employed a number of innovative strategies to quickly 
and wisely invest ARRA funds. We still stimulate the economy, 
create jobs and advance science.
    Most importantly, however, ARRA will help contribute to our 
principal mission: to make scientific discoveries that will 
improve people's health.


                          prepared statements


    I will be pleased to answer any questions that you might 
have.
    [The statements follow:]
                Prepared Statement of Raynard S. Kington
    Good morning, Mr. Chairman and distinguished members of the 
subcommittee.
    It is a privilege for me to appear before you today to present the 
National Institutes of Health (NIH) budget request and to discuss the 
priorities of NIH for fiscal year 2010 and beyond.
    First, I want to express our gratitude for your and the President's 
support as reflected in the recent appropriation of $10.4 billion in 
the American Recovery and Reinvestment Act (ARRA) for NIH expenditure 
and the 3.2 percent increase in annual fiscal year 2009 appropriations 
for NIH. The continued trust that you place in NIH to make the 
discoveries that will lead to better health for everyone is 
appreciated.
    I thank you on behalf of the many scientists we are able to support 
at more than 3,000 research institutions throughout the 50 States and 
United States territories; and on behalf of the public, who count on 
our research to help detect, treat, or prevent hundreds of diseases and 
conditions.
    As you well know, research conducted and supported by the NIH 
touches people's lives every day. NIH is the largest single engine for 
outstanding biomedical research in this country--and the world. Not 
only does NIH have an impact globally, it also has a lasting impact at 
the community level, bringing intellectual and economic growth to towns 
and cities across America.
Fiscal Year 2010 Budget Request
    The budget request embodies the President's fundamental goal of 
increasing overall Federal investment in basic research and development 
as well as particular emphasis on accelerating research in the areas of 
cancer and autism in fiscal year 2010.
    The budget request provides $31 billion, an increase of $443 
million or 1.4 percent over fiscal year 2009, to help fill gaps in our 
fundamental understanding of health and disease. NIH Research Project 
Grants (RPGs) support scientists to discover the fundamental 
underpinnings of complex human biology through investigator-initiated 
research, the mainstay of creativity in science. This request will 
increase funding for RPGs by $243 million. The request supports an 
estimated 9,849 new and competing RPGs, about the same level as fiscal 
year 2009.
    The fiscal year 2010 President's budget request includes the 
following priorities:
    Cancer Research.--Increases the investment across NIH to over $6 
billion for cancer research across NIH, reflecting the first year of an 
8-year strategy to double cancer research by fiscal year 2017. The 
fiscal year 2010 request represents an increase of $268 million or 5 
percent over the estimated fiscal year 2009 level.
    Autism Research.--Invests $141 million of the $211 million 
Department-wide initiative on autism. This total amount includes the 
Centers for Disease Control and Prevention and Health Resources 
Services Administration for research into the causes of and treatments 
for autism spectrum disorders. For NIH, this represents an increase of 
$19 million or 16 percent above the estimated fiscal year 2009 level.
Economic and Scientific Benefits of ARRA
    I expressed earlier my gratitude to the President and Congress for 
their support of NIH with ARRA. It is timely that ARRA funds be 
provided to the NIH to stimulate the economy and advance biomedical and 
behavioral research. The biomedical research community has not been 
spared from the drastic downturn in the economy. This is worrisome not 
only because it means fewer jobs, but also because innovation and a 
constant influx of young talent are crucial to the Nation's economic 
success and a robust biomedical research enterprise.
    We are moving quickly to identify the best science and support it 
with the additional $10.4 billion provided by ARRA to the NIH, and 
obligate it within the next 2 years. Moreover, your decision sends a 
strong signal to the scientists in the field, and to bright young 
people who may one day choose science as a career, that the United 
States is working to support outstanding research and outstanding 
scientists.
    To demonstrate the impact ARRA will have at the individual level, I 
would like to share with you the following: One of our program 
directors received an email after enactment of ARRA in response to news 
that an applicant's grant application was being considered for funding 
with ARRA money.
    Here is an excerpt from the email (with names deleted):

    ``Forgot to say that we gave a termination letter last Friday to my 
longtime (5 years) postdoc. His job has been saved. He is going to be 
thrilled to hear about his change in fortune! I also would like to hire 
a technician with the new funds, since at present I do not have one.''

    Let me highlight some of the important work that we will support 
with ARRA funds. For example, we will rapidly expand our current 
understanding of the genetic changes associated with a wide range of 
diseases and conditions, including addiction, Alzheimer's disease, 
various forms of cancer, chronic pain, diabetes, glaucoma, heart and 
lung diseases, kidney disease, and mental disorders, through genetic 
analysis of existing, well characterized population cohorts. We will 
take steps toward using this genetic information to better inform the 
modification of disease for those patients most at risk, principally 
through lifestyle factors and personal health behaviors.
    In addition, our efforts to expand community-based research 
efforts, with special focus on minority and underserved patients, will 
be accelerated through catalytic grants designed to enhance 
interrelationships among academic health centers, community 
organizations, and community healthcare clinical centers. Evaluation of 
the health and safety risks of nanoscale products is critical as 
nanomaterials are being used in applications as diverse as medical 
devices, drug delivery, cosmetics, and textiles. Biological, physical, 
and chemical characterization of selected nanomaterials will be 
conducted to both inform the establishment of standards for health and 
safety and developing computational models for the prediction of long-
term secondary effects.
    Just to review briefly, the ARRA provided NIH funding in the 
following ways:
  --It allocated $1.3 billion for the National Center for Research 
        Resources, with $1 billion identified for extramural 
        construction and renovation, and $300 million targeted for 
        shared instrumentation and other large capital research 
        equipment. The positive impact of this support for institutions 
        and researchers will be extraordinary, providing broader access 
        to state-of-the-art equipment. Funding for extramural 
        construction and renovation will result in jobs in construction 
        and a number of trades in the building industry. Shared 
        instrumentation will improve the quality and even the speed of 
        the work that is done, and build collaboration in ways that 
        will accelerate discovery. Shared instrumentation, including 
        such resources as advanced real-time imaging tools, will allow 
        scientists to image the brain in action or enable them to see 
        separate proteins that play a role in health and disease.
  --It appropriated $8.2 billion to NIH, of which $7.4 billion will be 
        distributed through the NIH Office of the Director, to the 
        Institutes and Centers of NIH, and to the common fund for the 
        support of biomedical research. The remaining $800 million will 
        be distributed by the Office of the Director to fund specific 
        challenges and scientific priorities at the Institutes and 
        Centers.
  --In addition, $400 million transferred to NIH by the Agency for 
        Healthcare Research and Quality (AHRQ), as directed under ARRA, 
        will be used to support comparative effectiveness research.
  --The remaining $500 million will be used to fund high-priority 
        repairs, improvements, and construction on the NIH campus to 
        enable the highest quality research to be conducted.
How Will NIH Accomplish This Task
    NIH is determined to seize the opportunity afforded by the infusion 
of ARRA resources to develop a nimble approach to investing the money 
quickly with the greatest impact. This opportunity is too important for 
us to conduct ``business as usual.'' It demands that we employ the best 
possible approaches to ensure progress at in an accelerated pace, with 
the most efficient and effective use of resources. For example, we are 
scrutinizing the 14,000 grant applications we received in our last 
round of review--applications that were already deemed highly 
meritorious and approved by Advisory Councils at each Institute and 
Center--applications that, despite their merit, we could not fund 
before. We are now starting to fund those scientifically meritorious 
applications for 2 years, where the scientific plan is appropriate for 
a 2-year award instead of the usual 4-year award. Also, every Institute 
and Center is identifying scientific priorities that can be funded 
through administrative supplements. Administrative supplements will 
accelerate the progress of a promising grant, typically by adding 
support for postdoctoral scientists and graduate students and key 
pieces of equipment
    The NIH team is proud of the trust placed in it to be a part of the 
economic recovery process. NIH will work tirelessly to support the 
goals and intent of ARRA, with wise resource investments in science.
    NIH has created a number of new programs that will spur new areas 
of research and trigger an almost immediate influx of research dollars 
into communities across the Nation. For example, NIH created a new 
program called the Challenge Grant award. To jump start this program, 
we issued the largest Request for Applications in our history. This 
220-page document lists numerous scientific topics in 15 broad 
scientific areas, including: bioethics, translational science, 
genomics, health disparities, enhancing clinical trials, behavioral 
change and prevention, and regenerative medicine--areas that would 
benefit from a jumpstart or in which a scientific challenge needs to be 
overcome. The Office of the Director expects to devote at least $200 
million of these funds to this effort.
    I will highlight only a few examples of the Challenge Grant topics 
that could be further explored:
  --New advances in biosensors and lab-on-chip technology to create 
        novel ways to measure the body burden and sub-clinical health 
        effects of emerging contaminants in the environment in large 
        study populations. Additional research funds could support 
        field testing of the most promising sensors and analysis 
        techniques through collaboration with existing epidemiologic 
        studies taking advantage of both new and banked tissue 
        specimens.
  --There is increasing evidence that suggests that HIV-1 infected 
        individuals experience similar immunologic changes as the 
        uninfected elderly. This may be due to persistent stimulation 
        of the immune cells. It is not clear whether antiretroviral 
        therapy can reverse this process. Research will aim to compare 
        the effectiveness of different treatment regimens in reversing 
        or preventing accelerated aging that appears in the immune and 
        other body systems.
  --Studies are needed to assess the impact and ethical considerations 
        of conducting biomedical and clinical research internationally 
        in resource-limited countries.
    Another new program is what we call the Grand Opportunity Program, 
or ``GO grants.'' The purpose of this program is to support high-impact 
ideas that require significant resources for a discrete period of time 
to lay the foundation for new fields of investigation. The GO program 
will support large-scale research projects that accelerate critical 
breakthroughs, early and applied research on cutting-edge technologies, 
and new approaches to improve the synergy and interactions among 
multidisciplinary and interdisciplinary research teams. Applicants may 
propose to address either a specific research question or propose the 
creation of a unique infrastructure/resource designed to accelerate 
scientific progress. For those projects that span the missions of 
multiple Institutes, Centers, and Offices (ICs), support may come from 
ARRA funds allocated to the Common Fund.
    NIH will identify a number of signature initiatives that will 
support exceptionally creative and innovative projects and programs--
and potentially transformative approaches to major challenges in 
biomedical research. The initiatives will cover new scientific 
opportunities in nanotechnology, genome-wide association studies, 
health disparities, arthritis, diabetes, autism, and the genetic risk 
for Alzheimer's disease, regenerative medicine, oral fluids as 
biomarkers, and HIV vaccine research.
    Each IC is developing at least one signature initiative, and a 
number will be done in partnership across ICs and/or the Office of the 
NIH Director. The areas being developed include an Office of the 
Director-led set of catalytic awards to enhance community-based 
research efforts to ensure that we are able to reach segments of our 
Nation that are too often overlooked in clinical research.
    In addition, considerable investment is expected to be made to 
understand the genetics of a wide range of specific diseases and 
conditions, as well as second generation ``deep DNA sequencing'' of 
very large and well-defined national patient cohorts to identify 
disease causing genetic variants. Using new technology developed with 
NIH-support, ``deep sequencing'' allows analysis of genome sequence 
from many individuals to provide greater insight about subtle genetic 
variations than could previous methods, and does so at lower cost.'' An 
initiative to modify disease risk-based on genome-wide association 
findings is also being planned. Complementing this will be initiatives 
to accelerate biomarker discovery and validation.
    Also, NIH will use other funding mechanisms, such as the Academic 
Research Enhancement Award, or AREA grants, that support small research 
projects in the biomedical and behavioral sciences conducted by faculty 
and students in health professional schools and other academic 
components that have not been major recipients of NIH research grant 
funds. A research program to support new faculty, called the ``Core 
Centers for Enhancing Research Capacity in U.S. Academic 
Institutions,'' will address the need for more bioethicists and provide 
opportunities for young scientists, who are one of NIH's top priorities 
for support. The Core Center grants are designed to establish 
innovative programs of excellence by providing scientific and 
programmatic support for research by promising investigators. They 
provide funding to hire, provide appropriate start-up packages, and 
develop pilot research projects for newly independent investigators, 
with the goal of augmenting and expanding the institution's biomedical 
research base. We must invest today to ensure tomorrow's scientific 
discoveries.
ARRA Funds for Administrative Supplements
    U.S. institutions and investigators with active NIH research grants 
may request administrative supplements for the purpose of accelerating 
the pace of scientific research through the programs and activities of 
their peer-reviewed projects. These supplements seek to promote job 
creation and retention, as well as scientific progress at NIH-funded 
institutions, by providing researchers with the means to employ, for 
example, postgraduate students or to enhance capacity for data 
analysis.
    We are particularly delighted to tell you about our expanded summer 
program for teachers and students across America. Funds will provide 
short-term summer jobs for high school and undergraduate students--as 
well as elementary, middle, high school and community college science 
educators in laboratories around the country--work that will not only 
provide summer income, but will also provide several thousand young 
people with the opportunity to experience the world of research, and I 
hope will spark their desire to become scientists.
    In addition to administrative supplements, U.S. research 
institutions and scientists with active NIH Research Grants may submit 
revision applications (so-called ``competitive supplements'') to 
support a significant expansion of the scope or research protocol of 
currently approved and funded projects.
The Economic Benefits
    We are mindful that a top priority for the use of ARRA funds by NIH 
is to create and preserve jobs, as well as increase purchasing power in 
all corners of the country. We firmly believe that we can do this while 
carrying out the core NIH mission, and without compromising our 
commitment to fund the best scientific research ideas. In keeping with 
the ARRA reporting requirements, we are asking recipients to document 
key economic benefits, such as jobs created and retained. A study 
indicates that, on average, every NIH grant supports 6 to 7 in-part or 
full scientific jobs.\1\ Another study suggests that every dollar spent 
by NIH in local communities around the Nation is leveraged on average 
three times its original amount, if you look at the national ``economic 
multiplier'' effect.\2\ These grants pay the salaries of scientists and 
technicians. The scientists and technicians, in turn, purchase goods 
and services in the communities in which they work and live.
---------------------------------------------------------------------------
    \1\ ``Estimating the Number of Senior/Key Personnel Engaged in NIH 
Supported Research,'' study issued October 2008. Study funded by the 
NIH Evaluation Set-Aside Program, 07-5002-OD-ORIS-OER, administered by 
the Evaluation Branch, Division of Evaluation and Systematic 
Assessment, OPASI, Office of the Director, National Institutes of 
Health.
    \2\ ``In Your Own Backyard: How NIH Funding Helps Your State's 
Economy,'' published by Family USA (A Global Health Initiative Report). 
June 2008.
---------------------------------------------------------------------------
ARRA: Risk Management
    NIH has implemented a risk management program in compliance with 
OMB guidelines that addresses the identification and assessment of 
proper controls over financial reporting and operations processes. In 
the financial arena, the risk program includes reviews of financial 
reporting at the transaction level that are conducted by both internal 
and external auditors. In the operations arena, the program includes 
internal assessments of systems and processes that support both 
intramural and extramural research.
The Scientific Benefits
    The advancement of science is a gradual process. Groundbreaking 
discoveries are most often built on the foundation of many gradual 
advances that bring us closer to diagnosis, treatments, and other 
public health improvements expected by Congress and the American 
public. Because of ARRA funds, there may be many such discoveries 
across the country next year and many years thereafter. These 
discoveries could yield better understanding of the major diseases and 
disorders such as heart disease, cancer, neurodegenerative illnesses, 
autism, arthritis, mental health, chronic, acute and rare diseases, and 
diseases related to addiction or behavior.
    We are committed to ensuring that ARRA funds will produce benefits 
to the economy, to scientific knowledge, and ultimately aid in 
improving the health of the Nation. As an agency, we are well-equipped 
to disburse these resources, to handle the increase in workload, and 
award grants expeditiously to the best scientists in the world.
    Again, NIH is grateful for your trust and commitment to biomedical 
research and all the promise it brings to people here in the United 
States and around the world. We have employed a number of innovative 
strategies to quickly and wisely invest ARRA funds. We will provide you 
and the public with regular updates and reports to ensure full 
transparency and accountability for how these funds are being spent. 
Americans deserve to know the impact of their tax dollars--on science, 
on the economy, and the Nation's health. In addition, we look forward 
to working with you on the fiscal year 2010 budget request.
    I would be pleased to answer any questions that you might have.
                                 ______
                                 
               Prepared Statement of John E. Niederhuber
    Mr. Chairman and Members of the subcommittee: Thank you for the 
opportunity to offer testimony on behalf of the National Cancer 
Institute (NCI) and the National Cancer Program.
    I am pleased to present the President's fiscal year 2010 budget 
request for the NCI of the National Institutes of Health (NIH). The 
fiscal year 2010 budget includes $5,150,170,000, which is $181,197,000 
more than the fiscal year 2009 appropriation of $4,968,973,000.
                        doubling cancer research
    The fiscal year 2010 budget reflects the President's prioritization 
of biomedical research supported by NIH. The budget is the first year 
of an 8-year strategy to double the NIH-wide cancer research budget and 
includes over $6 billion for this purpose. The budget balances the 
President's commitment to cancer research with that of research in 
other areas.
    NIH's fiscal year 2010 budget will build upon the unprecedented $10 
billion provided in the American Recovery and Reinvestment Act of 2009, 
which will support new NIH research on a wide array of diseases, 
condition, and disorders in 2009 and 2010.
    Because cancer research involves the dissection and understanding 
of perhaps the most basic functions of human cell growth and 
differentiation, cancer research will always produce many serendipitous 
discoveries. Such discoveries involving the most basic properties of 
human cells have historically contributed to our understanding of the 
basic biology underlying almost all diseases.
    In addition, cancer research also involves technology development 
that will benefit research in a number of disease areas. For example, 
cancer research includes a major effort to understand the complete 
genetic alterations that result in abnormal cell growth. This effort in 
whole genome sequencing is a major driver in the development of 
sequencing technology that we believe will lead to our ability in the 
next 2-3 years to perform whole genome sequencing in a matter of hours 
for less than $1,000.
    Numerous other Institutes and Centers contribute their expertise to 
fundamental research on biological processes, technologies and tools, 
and work collaboratively with NCI to fund important research in cancer. 
For example, much of what has been learned at NCI in controlling 
tobacco usage is now being applied to study and address the growing 
health burden of obesity. NIH will work to ensure that cancer research 
resources are allocated responsibly, effectively, in accordance with 
peer review principles, and on the basis of sound science and cancer 
relevance.
                      moving past a legacy of fear
    One of the great American voices on behalf of biomedical research 
was Mary Lasker. A well-known figure in Washington politics and 
government, Mrs. Lasker was a driving force behind the creation of 
several Institutes of the NIH and a key player in the formulation and 
passage of the National Cancer Act of 1971. Among her towering 
accomplishments, however, one stands out, perhaps because of its 
simplicity. In the years after World War II, cancer, she once remarked, 
remained ``a word you simply could not say out loud.'' Mary Lasker 
changed that. She persuaded David Sarnoff, the powerful head of the 
Radio Corporation of America--RCA--to allow the utterance on the 
airwaves of that single, chilling word.
    Today, we feel no compulsion to avoid speaking its name; yet few 
would argue that we fear cancer less in 2009 than we did 50 or 100 
years ago. Cancer will befall approximately 1 of 2 American men and 1 
of 3 American women. Its diagnosis engenders thoughts of mortality, of 
debilitating treatments, of diminished quality of life, of lingering 
burdens on loved ones, of personal financial peril.
    This major health problem is fueled by an aging, more heterogeneous 
population. A study published in April 2009 by the University of Texas 
M.D. Anderson Cancer Center estimated that the number of new cancer 
cases in the United States each year will increase by 45 percent over 
the next two decades, to 2.3 million per year by 2030.
    It is thus quite understandable when the public and those 
responsible for health care ask if we are investing enough to advance 
the science needed to avert such predictions. Since 1971, the Federal 
Government, private foundations, and companies have spent approximately 
$200 billion on cancer research. This investment has led to our 
understanding of many of cancer's numerous complexities; has resulted 
in a steady decline in the annual overall cancer mortality--and has 
increased the number of cancer survivors to more than 12 million 
Americans. NCI's budget request and its research projects are 
consistent with the President's multi-year commitment for cancer and 
autism. Aggressive programs in screening and prevention have greatly 
reduced the incidence of a number of cancers. For example, NCI led 
efforts to eliminate the use of tobacco has resulted in a 1.9 percent 
decrease per year from 1992 to 2003 in male lung cancer incidence 
rates. This has accelerated to a 3.3 percent decline per year over the 
period from 2003 to 2006. Despite these advances, it is evident that a 
greater investment than ever is needed to continue the dissection of 
the fundamental biology underlying the initiation of abnormal cell 
growth and its progression to invasive and metastatic disease.
                        the power of the genome
    Cancer is an extremely complex disease of altered genes. These 
changes within the cells of our body take many forms--and are both 
inherited and acquired, as we live out our lives. Since the completion 
of the Human Genome Project in 2003, the knowledge of the genetic 
alterations associated with cancer has grown exponentially. Vastly 
improved technologies are making it possible to study the genomes of 
thousands of individuals, in the search for common abnormalities that 
point to risk of cancer. Likewise, one of NCI's signature projects, The 
Cancer Genome Atlas (TCGA), is studying the genetic changes associated 
with the development of several cancer types, including lung, ovarian, 
and brain cancers. The success of this pilot program is leading NCI to 
expand TCGA's scope to the sequencing of 20 to 25 tumor types. 
Sequencing these tumors in more than 200 patients per tumor type, 
coupled with whole genome scans of large population cohorts, is 
uncovering important information about cancer risk and patient-specific 
profiles unique to disease. Within just 5 years, some have suggested, 
whole genome deep sequencing will be part of virtually every laboratory 
cancer experiment, and within a decade, such deep genomic sequencing 
will be commonplace for patients.
    At this moment, the results of this deep probing of the genetic 
basis of cancer remain, in most cases, fascinatingly powerful 
information. How we turn that information--sometimes referred to as 
code--into new methods of prevention, early detection, and treatment of 
cancer will require a major infusion of new resources. We must convert 
this coded information, which is stored in large data sets, into a 
clear interpretation and understanding of the functional biological 
alterations these genetic changes impart. NCI is working to fill this 
large gap in our knowledge, through a well-considered, coordinated 
blueprint appropriate for a new era of medicine. It begins with new 
discoveries at the level of the gene and ends at the patient's bedside.
    NCI is preparing to bring together a network of investigators, 
whose work will begin after genomic sequencing is completed, taking 
information generated by TCGA and allied projects and turning that data 
into new knowledge of biologic function. The goal will be to identify 
potential new therapeutic targets in molecular pathways and physical 
processes that are, today, considered ``undruggable.'' This network 
will be virtual: a consortium of researchers primarily at research 
universities who will be offered the chance to participate in 
collaborative projects, often partnering between institutions. These 
projects will be prioritized on the basis of potential patient impact 
and technical feasibility--assigned to investigator sites on a 
competitive basis, each with a project manager.
    The targets that will come forward from this functional biology 
consortium will be somewhat akin to a key piece of a jigsaw puzzle. It 
will be necessary to find the adjoining pieces--the new drugs, 
biologics, and other therapeutics--that connect. When potential new 
targets emerge, NCI will then employ its state-of-the art, high-
throughput capacity to screen thousands of previously identified 
compounds, both natural and synthetic, to identify the exact piece to 
complete the puzzle.
    In many cases, new therapies will require refinement, for example, 
to make them water soluble, or to create mass-producible versions of a 
natural product. Another virtual network, the Chemical Biology 
Consortium, will provide the necessary chemistry and chemists to 
optimize further development of these new anti-cancer agents. NCI will 
then be able to have those new agents produced in small batches for 
refinement and testing--using best manufacturing principles--and move 
them into pre-clinical testing, including toxicology screening.
    Early phase clinical trials will follow. NCI has conducted the 
first of a new kind of trial called Phase 0, which uses a small number 
of carefully selected patients who, after receiving small doses of new 
drugs, are studied, in real time, at the molecular level, to see if the 
new medication is reaching and affecting its target. Phase 0 trials 
will allow for significantly earlier decisions on whether to move 
forward with Phase 1 trials.
    It is not only Phase 0 trials that will require well characterized 
patients. As genomic characterization of the populace comes closer to 
becoming standard medical practice, NCI is taking steps on the leading 
edge of that transition, creating the first of a national network of 
patient characterization centers that will centrally conduct genomic 
and genetic characterization. Always employing the latest technologies 
and standardized protocols, these facilities will serve wide geographic 
areas, bringing together genomics and genetics, proteins and 
proteomics, all in the interest of matching a genetically characterized 
patient and his or her characterized tumor to appropriate and optimal 
therapeutic solutions.
    The NIH Clinical Center; NCI's Specialized Programs of Research 
Excellence; the NCI Community Cancer Centers Program; Cooperative 
Groups; the Community Clinical Oncology Program; and the NCI-designated 
Cancer Centers network will all be key players in establishing a highly 
characterized national cohort of patients who can be easily matched 
with potential new agents.
                  developing electronic health records
    Creating an integrated, 21st century translational science program 
will require data integration and a national commitment for the cancer 
electronic health record. NCI's cancer Biomedical Informatics Grid, 
better known as caBIGT, and its companion BIG Health Consortium, are 
leaders in this Federal effort, working to develop a unified biomedical 
information infrastructure, along with data standards and protocols for 
electronic medical records that are consistent with the Federal 
Government's national health IT efforts. Through caBIG, NCI is helping 
both large facilities from the NCI-designated Cancer Centers network 
and local facilities in the NCI Community Cancer Centers Program 
develop electronic records.
    In addition, accomplishing the scale-up of TCGA and the genetic 
characterization of our patients--with data integration through caBIG--
will require biospecimens collected using standardized protocols, 
tissue characterization, cataloging, and analysis, all coordinated by 
NCI's caHUB initiative.
                         a wide-ranging effort
    This plan will require the contributions of biologists, chemists, 
informaticians, and clinical scientists devoted to a clear path from 
discovery to patient. This is not only the nature of translation; it 
will be a model for the study of many diseases and, ultimately, a model 
of 21st century healthcare. This platform is a vision for a new way of 
thinking. But it is not an unrealistic concept. It is an action plan: a 
roadmap for what we have begun to assemble this year, making the 
optimal use of every new resource.
    In 2008, NCI began a series of meetings with theoretical physicists 
and mathematicians, designed to bring unique perspectives to the 
problem of cancer. The result is a new network of physical sciences--
oncology centers, soon to launch, which will study physical forces--
heat, stress, and cellular evolution, just to name a few--in cancer. 
This network is an exciting frontier in cancer research, which we 
fervently believe will be further proof that scientific collaboration 
pays great dividends.
    NCI's goal is to make cancer a chronic condition one can live with, 
and not die from. We will continue to find better ways to prevent 
cancer's development and for the earliest detection, when a tumor is 
limited to a very small number of cells. We will continue to develop 
new therapies with fewer side-effects and greater quality of life. We 
will continue to study environmental causes of cancer. We will continue 
efforts to better understand the behaviors that increase cancer risk, 
and we will continue to follow those who have survived cancer, to 
understand the reasons why they are so often at risk for subsequent 
malignancies. These efforts will require coordinated programs and the 
continued work of a remarkable national cadre of individual laboratory 
investigators.
    NCI is committed to paying dividends on behalf of every American. 
We no longer fear speaking the word cancer. Yet, our work is far from 
finished, and NCI remains committed to making every effort to advance a 
vastly different medical future.
    Thank you for the opportunity to provide you this testimony. I look 
forward to the opportunity to take your questions.
                                 ______
                                 
                Prepared Statement of Elizabeth G. Nabel
    Mr. Chairman and members of the subcommittee: I am pleased to 
present the President's fiscal year 2010 budget request for the 
National Heart, Lung, and Blood Institute (NHLBI) of the National 
Institutes of Health (NIH). The fiscal year 2010 budget of 
$3,050,356,000 includes an increase of $34,667,000 over the fiscal year 
2009 appropriated level of $3,015,689,000.
    The NHLBI provides global leadership for a research and education 
program to promote prevention and treatment of heart, lung, and blood 
diseases. The vision is to enhance the health of all individuals and 
thereby enable them to lead longer and happier lives. The work of 
Institute is guided by the goals and approaches outlined in its 
strategic plan, which was completed and published in September 2007 and 
submits that its research projects re consistent with the President's 
multi-year commitment for cancer and autism.
    This statement describes several initiatives that are being 
undertaken during the current fiscal year and outlines a number of 
opportunities to be addressed in fiscal year 2010.
                          stem cell consortium
    Recent advances in knowledge, coupled with development of new 
technologies and reagents, have set the stage for rapid progress in the 
field of regenerative biology and medicine. The NHLBI is capitalizing 
on this extraordinary opportunity through formation of a Progenitor 
Stem Cell Biology Consortium that includes leading scientists in the 
fields of cardiovascular, pulmonary, and hematopoietic cell biology 
working closely with experts in the general field of progenitor cell 
biology. Its goal is to identify and characterize progenitor cell 
lineages, to direct the differentiation of stem and progenitor cells to 
desired cell fates, and to develop strategies to address the challenges 
presented by the transplantation of such cells. The Institute will fund 
6 research hubs and 1 administrative coordinating center in fiscal year 
2009, with plans for a total support period of 7 years.
          clinical trial of hypertension management strategies
    A new clinical trial, the Systolic Blood Pressure Intervention 
Trial (SPRINT), was launched in fiscal year 2009. The health benefits 
of lowering blood pressure in individuals with hypertension have been 
well demonstrated, and current practice strives to achieve a systolic 
blood pressure (SBP) level below 140 mmHg for most patients. However, 
epidemiological evidence suggests that the optimal SBP goal may be even 
lower. SPRINT will enroll about 7,500 individuals with hypertension or 
pre-hypertension, randomly assign them to a SBP goal of <120 mmHg or 
<140 mmHg, and assess cardiovascular disease outcomes. The potential 
public health impact of this work is substantial, given the multi-
millions of people in this country and worldwide who suffer from high 
blood pressure.
                             asthma network
    The NHLBI has for many years supported highly successful clinical 
research networks designed to fill gaps in science and address emerging 
areas of concern in the management of asthma. Upon the anticipated end 
of the current funding period for the asthma networks, the Institute 
convened a workshop to obtain advice from key scientific leaders on a 
network structure that would sustain the past success and meet future 
clinical research needs. As a result of its recommendations, the 
Institute is establishing AsthmaNet, a clinical research network that 
will develop and conduct clinical trials of new treatment and 
management approaches in pediatric and adult populations. Launched in 
fiscal year 2009, AsthmaNet will include multiple clinical centers and 
one data coordinating center. The NHLBI's plans for promoting use of 
shared resources and promoting programmatic and scientific efficiency 
in the network coincide with the expansion of the NIH Roadmap 
initiative to Re-engineer the Clinical Research Enterprise through the 
Clinical and Translational Science Award program.
                     hemoglobinopathies data system
    The NHLBI is developing and implementing a national data system and 
biospecimen repository on people with sickle cell disease, thalassemia, 
and hemoglobin E disease. It will be designed to collect, analyze, 
interpret, and disseminate State-specific data on the epidemiology, 
clinical characteristics, healthcare utilization, and community 
resources of patients with these conditions. The system will support 
research, information dissemination, policy decisions, healthcare 
planning, and provider training at the social, State, and national 
levels. This fiscal year 2009 initiative is being conducted via an 
interagency agreement with the CDC.
     cardiac translational research implementation program (c-trip)
    A new program has been designed to accelerate the movement of 
laboratory discoveries to the bedside of patients with heart failure or 
arrhythmias. C-TRIP is a two-stage project to speed translation of 
promising new therapeutic interventions derived from basic research 
through well-designed clinical trials to demonstrate safety and 
efficacy. Two-year stage 1 exploratory planning grants, to be awarded 
in fiscal year 2010, will support feasibility studies, analysis of 
existing data, preparation for regulatory clearances, team-building, 
development of clinical management tools and recruitment strategies, 
and finalization of protocols. Subsequently, stage 2 grant applications 
will be considered for the conduct of the safety and efficacy trials.
          new programs to prevent and treat childhood obesity
    Obesity is a major cause of morbidity and mortality, and effective 
interventions are urgently needed to address this increasingly 
prevalent public health menace. A new research consortium will test the 
efficacy of innovative approaches to prevent weight gain among normal-
weight young children and to prevent additional weight gain or 
facilitate weight loss among obese adolescents.
    A second fiscal year 2010 initiative will examine outcomes 
associated with existing community programs designed to reduce 
childhood obesity by improving children's diet and physical activity. 
One research unit will be funded to serve as a study coordinating 
center, which will work with the National Collaborative on Childhood 
Obesity Research to design and implement the research. The study will 
establish common metrics for evaluation of the programs and examine 
outcomes associated with program policies, environments, educational 
activities, dietary and physical activity regimens, and other factors. 
The goal is to inform national and local policy for control of 
childhood obesity.
            resuscitation outcomes consortium (roc) renewal
    In 2004 the NHLBI, the American Heart Association, the U.S. 
Department of Defense, and several Canadian health agencies established 
the ROC to design and conduct studies of promising experimental 
strategies to resuscitate patients who experience out-of-hospital 
cardiac arrest or life-threatening trauma. The ROC brings together 
investigators, hospitals, emergency medical services (EMS), and local 
communities to address the unique characteristics of this research and 
ensure the efficient translation of proven strategies into clinical 
practice. In addition to supporting new trial protocols, the 2010 
renewal will develop information to define and improve pre-hospital 
best practices, facilitate public health efforts for the prevention of 
emergency life-threatening conditions, and improve EMS delivery and 
training.
          prematurity and respiratory outcomes program (prop)
    The new PROP will promote collaborative, innovative research to 
identify mechanisms, and associated biomarkers of respiratory disease 
risk of premature infants who are ready for discharge from the neonatal 
intensive care unit. Increased survival of very premature infants is 
leading to increasing numbers of children with chronic lung disease 
that often results in multiple readmissions. Currently no objective 
measures exist that can be used to predict which premature newborns 
will have persistent respiratory problems after discharge from the 
hospital. This cooperative, multidisciplinary scientific group will 
investigate hypotheses on the molecular mechanisms that make certain 
premature newborns prone to develop recurrent respiratory disease, with 
the long-term goal of improving outcomes in the first year of life.
                      nhlbi proteomics initiative
    The Institute will continue to invest substantial resources in the 
use of proteomic approaches and technologies to develop a greater 
understanding of pathway and interactions that influence heart, lung, 
and blood diseases. Planned for fiscal year 2010 is a combined renewal 
of the NHLBI Proteomic Centers and the NHLBI Clinical Proteomic 
Program, both of which terminate in September 2009. Each of seven 
centers will focus on proteomic technology development and molecular 
mechanistic and functional studies related to a specific clinical need, 
problem, or disease. The ultimate goal of this work is to bring greater 
precision, reliability, and sensitivity to detection, diagnosis, 
treatment, and prevention strategies for the individual patient.
    We are delighted to have the opportunity to pursue these exciting 
new research avenues. I would be pleased to answer any questions the 
subcommittee may have.
                                 ______
                                 
                 Prepared Statement of Anthony S. Fauci
    Mr. Chairman and members of the subcommittee: I am pleased to 
present the President's fiscal year 2010 budget request for the 
National Institute of Allergy and Infectious Diseases (NIAID), of the 
National Institutes of Health (NIH). The fiscal year 2010 budget 
includes $4,760,295,000, which is $57,723,000 more than the fiscal year 
2009 appropriation of $4,702,572,000.
    NIAID conducts and supports biomedical research to understand, 
treat, and prevent infectious and immune-mediated diseases of domestic 
and global concern, including HIV/AIDS, tuberculosis, malaria, 
neglected tropical diseases, emerging and re-emerging infectious 
diseases. NIAID's budget request and its research projects are 
consistent with the President's multi-year commitment for cancer and 
autism. As economies and societies around the world have become 
increasingly interdependent, responding to emerging infectious 
diseases, such as the 2009-H1N1 influenza virus, as well as to long-
established health challenges such as neglected tropical diseases, has 
taken on new urgency. As we address infectious diseases in a global 
context, we have the added benefit of contributing to preparedness 
against the threat of bioterrorism and naturally occurring disease 
outbreaks. Meanwhile, our ongoing research on domestic health 
challenges such as HIV/AIDS, influenza, and asthma, allergies, and 
other immune-mediated diseases continues to yield important advances. 
Using a multidisciplinary approach that engages academic, industry, 
governmental, and nongovernmental partners, NIAID remains committed 
both to basic immunology and infectious disease research and the 
application of this knowledge to the development of strategies to 
detect, prevent, and treat these diseases.
    The research activities of NIAID will become more important than 
ever, as current and as-yet unrecognized health threats, particularly 
in the context of the inevitability of emerging and re-emerging 
infectious diseases, will require new diagnostic, preventive, and 
therapeutic interventions. These new tools promise to have a great 
impact on the public health over the next two decades.
    We have long known that the threats posed by infectious microbes do 
not remain static, but change over time as new microbes emerge and 
familiar ones re-emerge with new properties or in new settings. This 
will not change in the coming decades. Addressing these global threats 
requires that we consider infectious diseases not through the lens of 
individual diseases, infections, or microbes in a vacuum, but by 
understanding how diseases interact in people with multiple health 
issues. Only then can we develop the tools for a comprehensive and 
practical approach to global health.
    Tuberculosis (TB) is a prototypic example of a re-emerging threat 
as an increase in the prevalence of drug-resistant forms of TB presents 
major challenges to the control of this disease. TB also is an example 
of a disease that often occurs with other infectious diseases such as 
HIV/AIDS--people co-infected with TB and HIV appear to have a more 
rapid and deadly disease course. Recently, NIAID-supported clinical 
trials have shown that mortality among TB patients co-infected with HIV 
is remarkably reduced when antiretroviral (ARV) therapy is provided at 
the same time as TB therapy. Additional studies are under way to 
determine optimal strategies for the prevention, treatment, and 
diagnosis of TB in the setting of HIV infection. NIAID continues to 
conduct and support research to create a foundation of knowledge for 
the discovery of new diagnostics, drugs and vaccines for TB, including 
drug-resistant TB. The Institute's support for public-private 
partnerships has been instrumental in linking research across sectors 
to build a robust pipeline of tools to combat TB.
    Malaria continues to exact a devastating toll on individuals 
worldwide, mostly among children in sub-Saharan Africa. Compounding the 
problem is the emergence of drug-resistant malaria parasites and 
insecticide-resistant mosquito vectors. In 2008, the Institute released 
the NIAID Strategic Plan for Malaria Research and the NIAID Research 
Agenda for Malaria. The Plan and Agenda outline our efforts to 
accelerate control and move toward eradication of malaria through 
biomedical research, including the development of prevention 
modalities, promising drugs and vaccine candidates. Accomplishing these 
goals will require the support and cooperation of malaria researchers 
and other organizations to build on the foundation of NIAID's basic 
research program in malaria. Over the next two decades, we hope to have 
a major impact on global TB and malaria burden through the development 
of vaccines that protect against these infectious killers.
    Seasonal influenza, which changes slightly every year, is the 
classic example of a re-emerging infectious disease. Influenza viruses 
also can undergo more drastic genetic changes that periodically enable 
them to evade pre-existing immunity and cause a pandemic, such as the 
deadly influenza pandemic in 1918 that killed more than 50 million 
people worldwide. NIAID has seen significant progress in its influenza 
research program, particularly in the area of pandemic influenza 
preparedness. This progress has prepared the Institute to respond 
rapidly to the newly identified 2009-H1N1 influenza virus, which has 
emerged as a public health threat in the United States, Mexico, and 
throughout the world. NIAID-funded researchers have responded quickly 
to this new threat, characterizing the virus and preparing for the 
development of a vaccine and other countermeasures.
    Nearly 28 years since the first cases of AIDS were documented, the 
terrible burden of HIV/AIDS continues to grow. The 2.7 million new 
infections worldwide in 2007 underscore the continuing urgency of the 
global AIDS pandemic, and sobering HIV/AIDS statistics in the District 
of Columbia remind us that the AIDS epidemic here in the United States 
demands our strongest efforts. Over the past two decades, NIH and 
NIAID--supported by Congress and by this subcommittee--have devoted 
substantial resources to the fight against HIV/AIDS.
    Worldwide, for every two people who receive ARV treatment, five 
others are newly infected. Therefore, our first priority in the fight 
against HIV/AIDS is prevention. NIAID-supported investigators have made 
great strides in advancing our understanding of the modalities of 
effective prevention, including those that prevent mother-to-child 
transmission of HIV. NIAID-supported research recently determined that 
medically supervised circumcision of adult males markedly reduces the 
risk of HIV acquisition through heterosexual intercourse for at least 
3.5 years after the procedure, demonstrating long-term efficacy of male 
circumcision as a prevention tool. Research conducted by our 
Microbicide Trials Network found the microbicide gel PRO 2000 to be 
safe and showed the first suggestion of potential efficacy among 
several clinical trials with other products. Of course, the most 
powerful prevention tool would be a safe and effective HIV vaccine. In 
response to the significant challenges that United States and 
international vaccine investigators have experienced in HIV vaccine 
development, NIAID has expanded our basic vaccine discovery research 
portfolio to provide the knowledge necessary to identify a viable HIV 
vaccine candidate. Our hope is that these advances in HIV prevention 
research will become part of a comprehensive HIV prevention ``toolkit'' 
that will markedly decrease new infections over the next two decades.
    In addition to these prevention modalities, NIAID is boldly 
advancing three new approaches to HIV prevention. Together with 
Government and nongovernmental partners, the Institute is investigating 
the feasibility of pre-exposure prophylaxis (PrEP) for HIV prevention, 
which involves providing ARVs to HIV-negative individuals who are at 
high risk of HIV infection. Second, recent modeling data have shown 
that aggressive HIV testing and treatment potentially could reduce the 
number of new HIV cases by 95 percent in the next decade; NIAID is 
evaluating critical research questions that underpin the validity of 
this voluntary ``test and treat'' approach. Finally, NIAID is expanding 
its efforts to find a cure for HIV/AIDS. Through research to improve 
our basic understanding of HIV viral latency, we hope to achieve long-
term HIV remission following discontinuation of effective therapy--a 
``functional'' cure--or, ultimately, a complete eradication of residual 
virus.
    Since the acceleration of our biodefense research program in fiscal 
year 2003, NIAID has achieved major successes in the development of 
countermeasures against significant bioterrorism threats. Some 
countermeasures have been fully developed and are stockpiled or 
available for use in an emergency; others in the pipeline have been 
transferred to the HHS Biomedical Advanced Research and Development 
Authority for advanced development. Promising candidate countermeasures 
in development include ST-246, a smallpox drug candidate that has 
protected animals from an otherwise lethal exposure to live poxviruses.
    Equally important, NIAID has developed a physical and intellectual 
research infrastructure that has been critical to our ability to 
respond to new and re-emerging infectious diseases. This year, the 
Institute recompeted the Regional Centers of Excellence for Biodefense 
and Emerging Infectious Diseases, which comprise a network of 11 
regionally based, multi-institutional centers engaged in 
interdisciplinary research to develop vaccines, therapeutics, adjuvants 
and diagnostics for biodefense and emerging infectious diseases.
    Autoimmune diseases, allergic diseases, asthma, rejection of 
transplanted organs, and other immune-mediated disorders are 
significant causes of chronic disease and disability in the United 
States and throughout the world. NIAID-supported research in immunology 
and immune-mediated diseases has led to significant advances in our 
understanding of the mechanisms underlying these diseases and in the 
development of strategies to detect, prevent, and treat them.
    For example, food allergies affect the health and quality of life 
of many Americans, particularly young children. NIAID remains committed 
to basic research and clinical studies to advance the understanding of 
food allergy and food allergy-associated anaphylaxis. In June 2008, 
NIAID awarded twelve 2-year grants, totaling $2.5 million, to 
investigators to lead high-impact, innovative studies of food allergy 
under the Exploratory Investigations in Food Allergy initiative. 
Cosponsored with the Food Allergy and Anaphylaxis Network, the Food 
Allergy Project, and the U.S. Environmental Protection Agency, this 
program supports innovative pilot studies on the mechanisms of food 
allergy, with a goal of attracting new investigators to the field of 
food allergy research. We plan to renew this program in fiscal year 
2010.
    NIAID also continues to support clinical trials to prevent the 
development of food allergies and to reverse established allergy to 
milk, eggs, and peanuts. Lastly, NIAID, in collaboration with 
professional societies, advocacy groups, and other Federal agencies, is 
developing clinical guidelines to provide guidance to medical 
practitioners on the diagnosis, management, and treatment of food 
allergies.
    For more than six decades, NIAID has conducted and supported basic 
research on infectious and immune-mediated diseases that has 
underpinned the development of vaccines, therapeutics, and diagnostics. 
These, in turn, have improved health and saved millions of lives in the 
United States and around the world. Through partnerships with academic, 
industry, governmental, and nongovernmental partners, the Institute 
will continue to leverage these fundamental discoveries into the tools 
needed to achieve a healthy world.
                                 ______
                                 
      Prepared Statement of Dr. Roger I. Glass, Director, Fogarty 
                          International Center
    Mr. Chairman and members of the subcommittee: I am pleased to 
present the President's budget for the Fogarty International Center 
(FIC) of the National Institutes of Health (NIH). The fiscal year 2010 
budget of $69,227,000 includes an increase of $536,000 more than the 
fiscal year 2009 appropriated level of $68,691,000.
    Over the past year, Congress has renewed its commitment to 
confronting global health issues, recognizing that these investments 
will not only improve the health and well-being of all, but also 
enhance U.S. stature abroad, economic development, and U.S. 
competitiveness. As the recent H1N1 virus outbreak illustrates, solving 
health problems in an interconnected world requires greater 
international collaboration than ever before. To effectively confront 
complex health issues that transcend national boundaries, scientific 
collaborations must be continually developed and nurtured. Research 
advances are more likely to occur when investigators study diseases on-
site, and U.S. scientists partner with international scientists to 
develop health interventions that are responsive to local and 
international needs and priorities. This model requires a critical mass 
of trained, in-country scientists and capable institutions that are 
uniquely positioned to address local study populations and to support 
sustainable collaborations with U.S. and other investigators.
    Since its inception, the Fogarty International Center (FIC) has 
been the focal point for global health at the NIH. FIC supports and 
facilitates global health research conducted by U.S. and foreign 
investigators, builds collaborations between U.S. and health research 
institutions worldwide, and trains the next generation of scientists to 
address global health needs. FIC-supported research and research 
training programs address a wide range of diseases and needs, including 
HIV/AIDS, malaria, Tuberculosis and other infectious diseases; 
noncommunicable diseases, such as brain disorders and cancer; and 
cross-cutting areas that foster sustainable research environments, 
including research ethics and informatics for health research. In 2008, 
FIC launched a strategic plan that addresses emerging areas of science 
and shifting disease burdens, and strengthens the global health 
research workforce in the United States and around the world.
        addressing the rising burden of noncommunicable disease
    Rapidly developing countries like India, Brazil, Mexico, China, and 
Bangladesh have seen life expectancies grow for the past 40 years. 
Population forecasts now predict that by 2030, 1 out of 8 people will 
be 65 or more than 1 billion adults. In addition, poorly balanced 
nutrition, less physical activity, and tobacco use are all on the rise 
in developing countries as a result of poverty, industrialization, 
urbanization and global marketing of goods and products. With 
increasing longevity, convergence of risk factors and diseases blurs 
the distinction between disease burdens in developing and developed 
countries, and calls for a common health research agenda. International 
research collaborations to study these diseases in highly endemic areas 
accelerate scientific advances on how to prevent and treat them. In 
response to this trend, FIC established the new Millennium Promise 
Awards in Non-Communicable Disease Program in partnership with several 
other NIH Institutes, designed to support research training in low- and 
middle-income countries in fields related to cancer, stroke, lung 
diseases, obesity, and environmental factors.
    According to the World Health Organization, tobacco use kills 5.4 
million people every year--an average of 1 person every 6 seconds. 
Almost half the world's children breathe air polluted by 8 causes of 
death in the world. If current smoking patterns continue, this number 
will rise to 8 million in 2030, with approximately 80 percent of the 
deaths occurring in developing countries. FIC, in partnership with the 
National Cancer Institute and the National Institute on Drug Abuse, is 
helping to address this rising epidemic through its International 
Tobacco and Health Research and Capacity Building Program. This program 
enhances the ability of scientists in low- and middle-income nations to 
understand risk factors for smoking uptake, particularly in youth, to 
develop effective prevention and mitigation programs, and to identify 
the most effective implementation and communications strategies to 
reduce the negative impacts of smoking on populations. The knowledge 
gained and effective interventions developed abroad through the Tobacco 
Program will also benefit U.S. populations who share common risk 
factors with low-resource communities in developing countries.
    The continuing burden of infectious disease in low-income 
populations, as well as the rapid rate at which microbial agents can 
evolve, adapt and develop resistance to antibiotics, demand that FIC 
continue to invest in infectious disease research and training. In 
particular, FIC will continue to support interdisciplinary research 
that develops predictive models and principles governing the 
transmission dynamics of infectious disease agents. This will result in 
increased capacity to forecast outbreaks and improved understanding of 
how diseases like the H1N1 flu emerge and re-emerge, and strategies to 
control them.
                    advancing implementation science
    Unprecedented resources are being invested in interventions that 
have been proven safe and effective, although many have not been 
implemented on a wide scale due to logistical, cultural, financial, and 
other barriers. Bridging the gap between effective interventions and 
improved health outcomes will in large part depend on a cadre of local 
scientists who can ask and answer questions regarding what works, what 
does not, and why, in particular settings. To advance this area of 
science FIC supports research training for scientists who can generate 
knowledge to improve scale-up of interventions and help identify the 
most effective ways to translate research findings into clinical and 
public health practice.
    For example, FIC's International Clinical, Operational, and Health 
Services AIDS/TB Research Training Program is developing a network of 
researchers who are studying how to best apply research knowledge and 
new technologies related to HIV/AIDS and TB in clinical and community 
settings. With support from this program, scientists in Haiti have 
developed a new masters degree in public health program at a Haitian 
university and are training the personnel needed to monitor and 
evaluate the implementation of a new country-wide program to provide a 
standardized package of HIV care and prevention to 300,000 people per 
year.
         maintaining u.s. leadership in global health research
    If we are to continue to lead in biomedical research, then U.S. 
researchers must be supported to effectively participate in 
international science. Biomedical research has always been an 
inherently international enterprise. Many significant scientific 
advances have resulted from research conducted by teams of scientists 
working across international borders. For example, U.S. and local 
scientists together pioneered the development of oral rehydration 
therapy (ORT) for treatment of cholera. ORT is now the first line 
treatment for childhood dehydration worldwide and recommended for 
treatment of every American child with diarrhea. In this era of 
globalization, this trend will not only continue, but will likely 
become stronger. It will also require a well-trained cadre of U.S. 
health scientists who are able to work seamlessly in diverse settings.
    To this end, FIC support strengthens the ability of U.S. academic 
institutions to engage in the global scientific marketplace. The vast 
majority of FIC awards support scientists in U.S. institutions, who in 
turn collaborate with colleagues in foreign institutions. Additionally, 
FIC is capitalizing on the burgeoning interest in global health on U.S. 
university campuses through two innovative programs. First, we are 
providing a launching pad for American health sciences students and 
junior researchers to build relationships abroad and to address 
critical global health research questions through the Fogarty 
International Clinical Research Scholars Program (FICRS). This program 
responds to the acute need for future clinical investigators who can 
help translate basic research advances into clinical practice on a 
global scale. This next generation of clinical researchers will require 
hands-on experience in conducting clinical trials and clinical research 
in countries where the disease burdens are highest. The FICRS provides 
highly motivated U.S. graduate students in the health sciences and 
medical residents or fellows 1 year of mentored clinical research 
training at distinguished low- and middle-income country research 
institutions. Each U.S. student is paired with a foreign student, who 
also receives training as an equal partner, thus strengthening 
scientific capacity in the United States and abroad simultaneously. 
Several NIH Institutes partner with FIC in the effort, and therefore, 
the program includes a wide breadth of research areas, including 
cancer, maternal and child health, and extensively drug-resistant TB.
    An increasing number of U.S. and foreign academic research 
institutions are welcoming the opportunity to use their substantial 
creative resources to make a significant and lasting difference in 
global health. As scientific problems become more complex, there is a 
need for team and systems approaches to tackle important health 
challenges. To help catalyze this approach in academic research 
institutions, Fogarty's Framework Programs for Global Health support 
the development of multidisciplinary global health programs on campuses 
in the United States and in low- and middle-income countries. This 
innovative program develops new curricula and degree programs that cut 
across departments and schools to create a pipeline for a new 
generation of researchers schooled in multiple fields to address global 
health challenges. Schools representing more than 17 different 
disciplines participate in the program including, engineering, 
environmental sciences, journalism, business, law, medicine and public 
health.
    Congressman Fogarty was prescient in arguing that the needs and 
rewards of global health research will benefit the United States as 
well as the global community. FIC is extending his vision, given that 
international trade, travel and communications have created a truly 
interdependent world. As we look to the next two decades, we envision a 
world in which a global scientific workforce is equipped with the 
knowledge and the skills to better prevent and treat disease as a 
result of rigorous global research. This workforce will form the 
backbone of research institutions in the United States and abroad, 
which will be effectively linked with each other through years of 
sustained productive research and training collaborations. Working 
towards this vision moves us closer to the ideal of global health--one 
that reflects the aspiration of all people to live long and healthy 
lives.
                                 ______
                                 
   Prepared Statement of Dr. Josephine P. Briggs, Director, National 
           Center for Complementary and Alternative Medicine
    Mr. Chairman and members of the subcommittee: I am pleased to 
present the President's fiscal year 2010 budget request for the 
National Center for Complementary and Alternative Medicine (NCCAM) of 
the National Institutes of Health (NIH). The fiscal year 2010 budget 
includes $127,241,000, which is $1,770,000 more than the comparable 
fiscal year 2009 appropriation of $125,471,000.
    In December 2008, the NCCAM, in conjunction with the National 
Center for Health Statistics, released data from the 2007 National 
Health Interview Survey (NHIS).\1\ The survey is the most comprehensive 
and reliable information to date on the use of complementary and 
alternative medicine (CAM) in the United States. The 2007 NHIS data 
confirm that millions of Americans--38 percent of U.S. adults and 1 in 
9 children--use CAM to promote health and wellness and to address 
specific conditions such as chronic pain.
---------------------------------------------------------------------------
    \1\ Barnes PM, Bloom B, Nahin R. CDC National Health Statistics 
Report#12. Complementary and Alternative Medicine Use Among Adults and 
Children: United States, 2007. December 10, 2008.
---------------------------------------------------------------------------
    The NHIS data affirm the public health importance of NCCAM's 
mission to develop an evidence base for the integration of CAM with 
conventional healthcare and to disseminate research results to the 
public and healthcare professionals. Since its founding 10 years ago, 
NCCAM has created a nationwide CAM research enterprise, built on sound 
scientific principles, that enables the rigorous study of CAM. Among 
NCCAM's accomplishments are a Centers of Excellence program at leading 
biomedical research institutions; standards for quality and stability 
for the natural products used in research; and the development of tools 
and methodologies to discover the potential benefits and risks of CAM 
modalities. Today, under NCCAM's leadership, partnerships between 
biomedical research institutions and CAM institutions and practitioners 
are engaged in state-of-the-art scientific research. NCCAM-supported 
CAM research has resulted in more than 3,300 peer-reviewed 
publications. Professional associations, such as the American College 
of Physicians and the American Academy of Orthopedic Surgeons are now 
able to use CAM research findings to inform their practice guidelines. 
NCCAM will continue to meet the challenges of building the evidence 
base for CAM interventions through its rigorous research, research 
training, and outreach endeavors. NCCAM's budget request and its 
research projects are consistent with the President's multi-year 
commitment for cancer and autism.
            a structured approach to answering key questions
    CAM research is a promising scientific endeavor that requires 
multidisciplinary basic, translational, and clinical trial 
collaborations. In fiscal year 2010, NCCAM will fund awards under a new 
initiative, Partnerships for Complementary and Alternative Medicine 
Clinical Translational Research. This initiative, which replaces the 
NCCAM Developmental Centers for Research on CAM program, will foster 
such collaborations at CAM institutions and create tools and 
methodologies for research.
    NCCAM investigations span the continuum of research areas: basic 
(How does the therapy affect the body?); translational (Do we have the 
methods and tools to detect and measure the modality's effects?); 
efficacy (Is there evidence of safety and benefit under optimal 
research conditions?); and effectiveness (How well does the CAM 
practice work in the ``real world'' and in comparison to other 
treatments?). NCCAM has strong programs in all four of these areas; its 
current research strategy places particular emphasis on strengthening 
effectiveness research.
         area of promise and investment: managing chronic pain
    The 2007 NHIS data indicate that chronic pain is, by far, the most 
common health problem for which Americans turn to CAM. NCCAM-supported 
basic, translational, and clinical research is using state-of-the-art 
neuroscience, brain imaging, and novel study designs to demonstrate 
that mind-body medicine approaches, such as massage, chiropractic, and 
acupuncture, affect pain perception and to understand how patient 
expectancy and practitioner reassurance may have an impact on pain 
management. For example, using functional magnetic resonance imaging 
(fMRI) and positron emission tomography (PET), basic researchers are 
developing important insights into how acupuncture affects specific 
pain networks in the brain. In addition, emerging data, such as the 
recent report in the Annals of Internal Medicine that massage therapy 
and simple touch may provide pain relief for advanced cancer patients, 
point to the promise of mind-body practices. NCCAM is focusing on 
developing the evidence base for the use of nonpharmacologic CAM 
practices for pain management.
    Chronic back pain is a problem for millions of Americans, and costs 
associated with it total at least $50 billion annually. \2\ It is often 
difficult to treat, and medications used to address it can have 
troubling side effects. Certain CAM therapies, such as acupuncture, 
chiropractic, massage, and yoga, show promise in treating chronic back 
pain. In May 2009, NCCAM is sponsoring, with other NIH Institutes and 
Centers, a workshop on nonpharmacologic interventions for the treatment 
of chronic back pain, bringing together experts to identify gaps in the 
CAM evidence base and opportunities for future research. NCCAM plans to 
fund awards in fiscal year 2010 under a new initiative, Effectiveness 
Research--CAM Interventions and Chronic Back Pain. This initiative will 
support studies of CAM approaches to address a range of outcomes for 
back pain, such as reduced dependency on narcotics.
---------------------------------------------------------------------------
    \2\ Low Back Pain Fact Sheet; National Institute of Neurological 
Disorders and Stroke, National Institutes of Health, Department of 
Health and Human Services, July 2003.
---------------------------------------------------------------------------
          area of promise and investment: translational tools
    Basic and translational (i.e., ``bench-to-bedside'') research is 
especially challenging for CAM mind-body practices, acupuncture, and 
body-based and manipulative therapies, because current scientific 
methods may not adequately capture and measure the effects of these 
therapies. To decipher these practices' potential physiological effects 
and enable scientists to study them in clinical trials, better 
scientific tools, metrics, and methodologies must be developed. In 
fiscal year 2010, NCCAM will fund awards under its initiative, Program 
for Translational Tools for CAM Clinical Research. The research 
supported under this initiative will improve the quality and 
reproducibility of CAM clinical investigations.
            area of promise and investment: natural products
    According to the 2007 NHIS, almost 40 million U.S. adults and 2.850 
million children use natural products to manage their health and 
wellness. Given the widespread use of dietary supplements, NCCAM's 
research into the safety and efficacy of natural products remains a 
public health priority.
    NCCAM-supported studies, including collaborations under the NIH 
Botanical Research Centers program, demonstrate the promise of natural 
products research. For natural products, basic and translational 
research remains critical precursors to large-scale clinical trials. A 
recent study by the University of Maryland and Rutgers University 
elucidated an immune system mechanism of action of green tea 
polyphenols on rheumatoid arthritis. In another study, Duke University 
researchers reported that bromelain, an enzyme derived from pineapple 
stems, reduced inflammation resulting from Crohn's disease and 
ulcerative colitis.
    Although natural products research shows great promise, product 
quality remains a significant issue. In July 2008, an NCCAM-funded 
study in the Journal of the American Medical Association reported that 
one-fifth of Internet-available Ayurvedic medicines contained 
detectable levels of lead, mercury, and arsenic. The authors also found 
evidence for benefit of industry-established standards for quality in 
reducing levels of toxic metals. NCCAM has led the scientific community 
in requiring that all natural products used in its research undergo 
quality and stability screening to ensure that the research is safe and 
reproducible. Ongoing collaborations with the dietary supplement 
industry are important to this effort. Equally important are NIH 
partnerships in the development of an evidence base for natural 
products.
                    making wise decisions: outreach
    Studies confirm that consumers do not tell their doctors that they 
use CAM, and doctors do not ask their patients about CAM use. To ensure 
safe, coordinated care NCCAM developed its time to talk patient and 
provider education program. NCCAM also partnered with the National 
Institute on Aging to develop a CAM section on NIH Senior Health, the 
NIH Web site especially for older adults.
    In fiscal year 2009, NCCAM will initiate a new educational section 
of its Web site (nccam.nih.gov) to provide health professionals with 
evidence-based information and clinical practice guidelines on CAM use. 
NCCAM also cosponsored the North American Research Conference on 
Complementary and Integrative Medicine, on May 12-15, 2009. This 
international meeting of scientists and CAM and conventional 
practitioners highlighted the emerging science on CAM and future 
directions for research.
                      nccam: looking to the future
    There are areas of considerable promise and potential for the field 
of CAM research, and NCCAM will focus its resources to ensure that they 
will be optimally directed. The Center has begun to develop its next 
strategic plan, seeking the input of the scientific community as well 
as its diverse community of stakeholders. As a first step in this 
process, the Center has convened a Blue Ribbon Panel to consider future 
directions for its intramural research program.
    Thank you for the opportunity to testify. I would be pleased to 
answer the subcommittee's questions.
                                 ______
                                 
Prepared Statement of Dr. Barbara M. Alving, Director, National Center 
                         for Research Resources
    Mr. Chairman and members of the subcommittee: It is a privilege to 
present to you the President's budget request for the National Center 
for Research Resources (NCRR) for fiscal year 2010. The fiscal year 
2010 budget of $1,252,044,000 includes an increase of $25,781,000 more 
than the fiscal year 2009 appropriated level of $1,226,263,000. NCRR's 
funding priorities for fiscal year 2010 include expansion of the 
Clinical and Translational Science Awards (CTSA) program. Additionally, 
NCRR will sustain the range of activities supported by the Center's 
other major programs, including the Research Centers in Minority 
Institutions, the Institutional Development Awards, the National 
Primate Research Centers, and the Biomedical Technology Research 
Centers.
    The mission of the NCRR, as one of the 27 Institutes and Centers of 
the National Institutes of Health (NIH), is to provide support and 
training for researchers that extend from the laboratory to clinical 
trials and into dissemination of prevention strategies and treatments 
that will impact communities as well as patients.
         appreciation for investment in research infrastructure
    On behalf of NCRR and the research community, I extend our 
appreciation to the President and the Congress for the $1.6 billion 
allocated to our Center as American Recovery and Reinvestment Act 
(ARRA) funding. We will ensure that the $1 billion for extramural 
construction funding and the $300 million in shared instrumentation 
funds are invested wisely at academic institutions throughout the 
Nation. The NCRR is using the additional ARRA funding to supplement 
awards in the Institutional Development Award (IDeA) program, the 
Research Centers in Minority Institutions (RCMI) program, the Clinical 
and Translational Science Award (CTSA) program, as well as other NCRR 
programs.
       building a matrix for clinical and translational research
    The NCRR, through its stewardship of the IDeA, RCMI, and CTSA 
programs, is linking investigators and communities by supporting and 
encouraging collaborations for training, sharing of data, accelerating 
advances in research and clinical informatics, and dissemination of 
best practices for community engagement. For example, the University of 
Washington CTSA is partnering with academic institutions in IDeA States 
to create greater opportunities to reach underserved populations. CTSAs 
are also connecting with RCMIs: Emory University (Atlanta) is 
partnering with Morehouse School of Medicine; Vanderbilt University 
(Nashville, Tennessee is partnering with Meharry Medical College; and 
Weill Cornell Medical College (New York) is partnering with Hunter 
College.
    Led by NCRR, the CTSA program is a partnership between the NIH and 
a national consortium of 39 academic health centers and research 
institutions to build academic homes for clinical and translational 
research. The CTSA program is designed to translate more efficiently 
the rapidly evolving knowledge developed in basic biomedical research 
into treatments to improve human health. Additionally, the CTSAs are 
training a new generation of clinical and translational researchers to 
excel in the interdisciplinary, team science environment.
    The momentum of the national CTSA consortium continues to build as 
new connections are rapidly emerging within, across, and beyond the 
consortium. In the last year, 15 new CTSAs joined the consortium, 
adding representation from 5 new States, additional pediatric 
expertise, and greater informatics capabilities. When the program is 
fully implemented, the NCRR expects to fund CTSA awards at 60 
institutions at a total cost of $500 million per year. As the CTSA 
program increases in complexity and size, institutions are forming 
regional consortia to focus on shared goals with greater efficiency.
    The CTSA institutions are using business principles and practices 
to improve the processes involved in translational research. 
Investigators and core facilities directors at the CTSA at Yale 
University are increasing efficiencies and reducing redundancies by 
using Web-based resources and systems to maximize the use of their core 
research facilities, which include imaging, informatics, and genomic. 
Thanks to this integration, researchers now have improved access to 
sophisticated technologies and valuable expertise with less 
administrative burden.
    The CTSA consortium has identified five strategic goals: (1) to 
develop strategies and resources to move laboratory discoveries into 
early clinical testing (T1 translation); (2) to reduce complexities and 
improve ways clinical and translational research is conducted; (3) to 
enhance training and career development of clinical and translational 
investigators; (4) to encourage consortium-wide collaborations; and (5) 
to improve the health of communities across the Nation.
                  fostering t1 translational research
    The potential to accelerate research discoveries from the bench 
into early clinical studies (T1) usually requires preclinical studies, 
those studies that involve the appropriate animal models. Currently, 
researchers with expertise in animal models (including mouse, rat, and 
nonhuman primate models) are working with CTSA investigators on pilot 
projects that focus on cardiovascular disease, ovarian cancer, and 
other diseases. NCRR and its National Primate Research Centers are 
working closely with National Institute of Allergies and Infectious 
Diseases and the NIH Office of AIDS Research to ensure that adequate 
numbers of animals and resources are available to meet the need for 
development of new AIDS vaccines.
    NCRR's Biomedical Technology Research Centers are cutting-edge 
interdisciplinary centers that create transformative technological and 
computational infrastructure for biomedical research. The CTSAs are 
leveraging the expertise of investigators in these centers to conduct a 
wide range of translational research, from cell biology to clinical 
imaging.
         leveraging partnerships to benefit biomedical science
    The CTSAs are realizing returns on their research discoveries by 
securing patents and licensing them. From 2006 to 2008, the CTSAs 
established more than 350 academic, public, and private partnerships. 
To achieve its overall mission to speed the translation of scientific 
discoveries to improve human health, the CTSAs are establishing 
innovative partnerships with industry to accelerate the development of 
treatments, diagnostics, and devices. For example, the CTSA at Scripps 
Research Institute is collaborating with Qualcomm to develop and 
clinically validate biosensors--tiny devices that measure body 
functions--and other wireless healthcare technologies. Similarly, the 
Oregon Health and Science University is partnering with Intel to apply 
wireless and mobile technology with various sensors to enable earlier 
detection and treatment of life-threatening events for diabetics and 
individuals at high risk of stroke.
    Ensuring that the public is actively engaged in research and 
benefiting from research findings is a key component of the CTSA 
program. One example of ways CTSAs are improving the health of their 
communities is a collaborative effort in Houston, which is helping 
children in two inner-city neighborhoods make healthier lifestyle 
choices and reduce their risk of obesity. CTSAs in Chicago have joined 
forces to ensure active participation from their communities throughout 
all stages of research--from project design to results dissemination. 
Similarly, connections between the CTSA consortium and NCRR's Science 
Education Partnership Award program are growing, helping to inspire the 
next generation of researchers. As an example, the University of 
Pittsburgh CTSA and Science Education Partnership Award investigators 
hosted an outreach event for middle school students, featuring a mobile 
science laboratory.
                     improving research informatics
    NCRR continues to support informatics tools and resources to 
enhance research collaboration. For example, NCRR is funding a 
Biomedical Informatics Research Network coordinating center at the 
University of Southern California to enhance data sharing among the 
network's research centers and other researchers. Through an ARRA-
funded initiative, NCRR will facilitate interdisciplinary collaboration 
and scientific exchange by developing tools and infrastructure that 
will help connect basic, clinical, and translational investigators and 
students with other researchers that share their interests or who could 
benefit from their expertise. NCRR also plans to support development of 
an animal models informatics resource to provide researchers with one-
stop access to information related to animal models of human disease.
                      expanding research capacity
    NCRR is enhancing the capabilities of RCMIs to conduct clinical and 
translational science through the RCMI Infrastructure for Clinical and 
Translational Research Awards. Funding may be used for out-patient 
clinical resources, biostatistical support, core laboratories, and 
patient-oriented research infrastructure. This award is a 
reorganization of previous RCMI programmatic activities and will 
enhance research capacity, improve collaboration between translational 
and clinical researchers, facilitate multidisciplinary training and 
career development and enable seamless interactions with CTSAs.
    The IDeA program fosters health-related research and increases the 
competitiveness of investigators in 23 States and Puerto Rico. NCRR's 
previous investments in developing research capacity through its IDeA 
program have resulted in additional funding opportunities for 
investigators. For example, the University of Kansas recently received 
$9.6 million in grants from non-Federal sources for drug development 
efforts; the expertise that provided the foundation for this award 
grew, in part, from funding for a center of excellence in the IDeA 
program.
    This snapshot of NCRR's programs and activities demonstrates our 
continuing commitment to advancing clinical and translational research. 
NCRR's budget request and its research projects are consistent with the 
President's multi-year commitment to finding cures for cancer and 
autism. By encouraging collaboration among our clinical and 
translational programs, NCRR is maximizing the Nation's investment to 
translate research discoveries into improved treatments for patients.
                                 ______
                                 
   Prepared Statement of Dr. Paul A. Sieving, Director, National Eye 
                               Institute
    Mr. Chairman and members of the subcommittee: I am pleased to 
present the President's budget request for the National Eye Institute 
(NEI). The fiscal year 2010 budget of $695,789,000 includes an increase 
of $7,309,000 more than the fiscal year 2009 appropriation level of 
$688,480,000.
                          ophthalmic genetics
    The loss of sight affects us in fundamental ways, threatening 
independence, mobility, and quality of life. Many eye diseases strike 
later in life. Thus, as life expectancy has increased, more Americans 
have become susceptible to vision loss and blindness. One such disease, 
age-related macular degeneration (AMD), is the leading cause of vision 
loss in the United States. AMD causes a progressive loss of light-
sensing cells in the macula, the center of the retina, making it 
difficult to read, recognize faces, drive a car, or perform even simple 
tasks that require hand-eye coordination. Based on published study 
data, 8 million older Americans are at risk to develop advanced AMD.
    Advanced AMD can take two distinct forms, either geographic atrophy 
or wet AMD. In geographic atrophy, large areas of the retina atrophy 
and die. In wet AMD, abnormal blood vessels grow into the retina, 
leaking blood and serum that damages the retina. Previous studies have 
found several gene variants, which regulate inflammation, are 
associated with the ``wet'' type of AMD. These variants are thought to 
lead to chronic, overactive inflammatory responses that damage retinal 
tissue and eventually lead to AMD. Most recently, the first gene 
associated exclusively with the geographic atrophy, namely the Toll-
like receptor 3 (TLR3) gene, was published. The TLR3 gene encodes a 
viral sensor which activates immune responses. When TLR3 activates in 
response to certain viruses, it induces cell death in the retina thus 
causing geographic atrophy. Alternatively, in humans, it appears that 
low activity of TLR3 confers protection against geographic atrophy, 
most likely by sparing the death of retinal cells. This is the first 
evidence that viral infection may contribute to the development of 
geographic atrophy. Ongoing work includes screening for viruses in 
affected individuals as well as developing methods to decrease TLR3 
activity in the retina.
    Glaucoma is a group of eye disorders that share a distinct type of 
optic nerve damage, which can lead to blindness. Elevated intraocular 
pressure is frequently, but not always, associated with glaucoma. 
Published study data find that approximately 2.2 million Americans have 
glaucoma and a similar number are unaware that they have developed the 
disease. Like AMD, glaucoma is a genetically complex disease likely 
involving many changes in many genes. NEI is committed to exploiting 
the latest genetic technologies in finding the genes that contribute to 
this common disorder. To this end, NEI initiated funding for genome-
wide association studies, a powerful approach that enables 
investigators to scan the entire human genome to detect multiple, 
subtle gene variants that increase the risk of developing this complex, 
blinding disease. Knowledge of the genetic basis of glaucoma is crucial 
to developing personalized therapies that target specific genes in 
order to prevent vision loss.
    Each genetic discovery has made it possible to study the implicated 
gene's function in health and disease. NEI investigators have made 
considerable progress in understanding the molecular mechanisms of 
genetic eye disorders and are developing rational therapies that 
address the molecular cause of the disease. The first success in this 
translational research effort are the reports of positive results from 
recent phase I clinical trials of gene transfer in a form of Leber 
congenital amaurosis, a severe, early onset retinal disease. In the 
effort to accelerate progress NEI established eyeGENE, a research 
program that offers genetic testing to patients through a national 
network of vision research laboratories in exchange for participation 
in a secure, confidential patient registry and DNA repository. DNA 
samples and corresponding diagnostic and clinical information are made 
available to the vision research community to recruit patients for 
clinical trials and to conduct genetic and molecular studies. eyeGENE 
represents a new paradigm to personalize medical care in the practice 
of ophthalmology. Knowledge of an individual's genomic profile will 
enable patients to make informed decisions about presymptomatic, 
preventive treatments or highly targeted molecular therapeutics.
                         translational medicine
    Neovascularization refers to the growth of new blood vessels. In 
some diseases, such as diabetic retinopathy and AMD, neovascularization 
is mistakenly activated and becomes a major pathologic consequence of 
the disease. Neovascularization can cause severe and irreversible 
vision loss due to abnormal vessel growth and consequent fluid leakage 
into the retina. Previous studies have established vascular endothelial 
growth factor (VEGF) spurs neovascularization and several therapies 
have been developed to prevent the abnormal activation of the VEGF 
protein. A recent National Institutes of Health (NIH) supported study 
reports on the discovery of a protein, Roundabout4 (Robo4), that 
stabilizes the existing vasculature and prevents neovascularization by 
inhibiting VEGF activity. Robo4 maintains vascular integrity by 
inhibiting VEGF-induced cell migration, vessel formation, and 
permeability. Vascular eye diseases are the most common cause of vision 
loss in the United States. This study suggests a new and promising 
therapeutic avenue to control neovascularization by regulating Robo4 
activity.
    RNA interference is a new approach that has been touted as having 
great potential for treating many diseases. This method harnesses a 
naturally occurring process that cells employ to control gene 
expression. By designing a small, interfering RNA sequence (siRNA), it 
is thought investigators can target and silence specific genes with 
specific siRNAs. Vision researchers have developed siRNA sequences to 
prevent the expression of VEGF in AMD and diabetic retinopathy that 
have been demonstrated to prevent neovascularization in animal models. 
However, a recent NEI-supported study suggests that siRNA may not 
always target the intended gene to initiate RNA interference. This 
study provides an important cautionary note to the entire field of 
siRNA that systemic administration of this treatment may have 
unintended consequences and side effects.
                          visual neuroscience
    Although the function of astrocytes, a cell type found in the brain 
and central nervous system, is not entirely understood, they have long 
been thought to maintain normal neuronal function. More recent evidence 
suggests that astrocytes may have some function in neural signaling and 
processing. Recently, NEI investigators found key evidence that 
astrocytes also act as a critical intermediary between neurons and 
local blood flow. In this study, inhibition of astrocyte activity 
decreased local blood flow. This finding explains why imaging devices, 
like functional MRI, detect blood flow changes that correspond to 
neuronal activity. Pathologic changes in astrocytes are implicated in 
Parkinson's, Alzheimer's, and other neurodegenerative diseases. The 
specific effect of astrocyte activity on the hemodynamic response 
provides a basis for the interpretation of functional MRI, adding 
qualitatively to the clinical and research utility of this powerful 
imaging tool across the broad spectrum of neurologic disease.
                    clinical trials and diagnostics
    Cataracts (clouding of the ocular lens) remain the primary cause of 
blindness in the world today. Researchers at NEI and NASA collaborated 
to develop a dynamic light scattering device which allows clinicians to 
detect and quantify the amount of unbound alpha crystallin proteins in 
an intact eye. With this device, it is now possible to safely and 
reproducibly measure the extent of lens damage and cataract formation 
caused by oxidative stress to a patient's eye (and perhaps the body) by 
measuring alpha crystallin reserves. This provides clinicians with the 
ability to monitor lens health, and may allow preventive or therapeutic 
actions that delay or eliminate cataract formation and blindness.
    Each year approximately 33,000 Americans undergo corneal 
transplants to replace diseased corneas, the normally transparent 
tissue that protects the eye and helps focus light on the retina. 
Corneal transplants are among the most common and successful 
transplantation procedures in medicine but sufficient donor is not 
available. Eye banks, the primary source of donor tissue, refrain from 
harvesting tissue from donors over age 65 because of uncertainty about 
the integrity of older corneas. However, the recently published Cornea 
Donor Study (CDS) found that corneal transplants using tissue from 
older donors, ages 66 to 75, have similar success rates as tissue from 
younger donors, ages 12 to 65. Based on these findings, the study 
authors recommend that the age limit for donor tissue should be 
expanded to 75. The CDS study gives eye banks, transplant surgeons, and 
patients confidence in the use of older donor tissue. This finding 
should help eye banks keep pace with the demand for corneal tissue.
                         medicine of the future
    Development of an artificial cornea will provide an abundant source 
of nonimmunogenic tissue for transplantation. Cell transplantation has 
prevented vision loss in rodent models of retinal disease. It is likely 
that these efforts will culminate in viable forms of regenerative 
medicine for eye disease. Genomic medicine will allow us to predict 
susceptibility to disease and pre-empt it with a variety of gene-based 
therapies. Gene transfer will likely become an option to treat many 
retinal degenerative diseases. We will have the opportunity to restore 
ambulatory vision to the blind through new prosthetic devices that 
reproduce vision electronically. Such devices will allow those with 
untreatable conditions to maintain independence and mobility. While 
there is much work ahead, current research efforts to treat and cure 
eye disease are very promising.
                       cancer research portfolio
    NEI funds basic research on cell biology, development and the 
regulation of blood vessel growth where findings could have relevance 
to our understanding and treatment of cancer. NEI also supports a phase 
III clinical trial on the treatment of retinoblastoma, a cancerous, 
blinding and potentially fatal eye disease. Consistent with the fiscal 
year 2010 NIH priority to expand cancer research funding, NEI will 
increase its fiscal year 2010 commitment to this portion of the 
portfolio by 4.4 percent.
                                 ______
                                 
Prepared Statement of Dr. Alan E. Guttmacher, Acting Director, National 
                    Human Genome Research Institute
    Mr. Chairman and members of the subcommittee: I am pleased to 
present the President's fiscal year 2010 budget request for the 
National Human Genome Research Institute (NHGRI) of the National 
Institutes of Health (NIH). The fiscal year 2010 budget includes 
$509,594,000, which is $7,227,000 more than the fiscal year 2009 
appropriation of $502,367,000.
    NHGRI's budget request and its research projects are consistent 
with the President's multi-year commitment for cancer.
        windfall of discoveries of the genetic basis of disease
    The Nation's previous investments in the Human Genome Project and 
the International HapMap Project have moved research forward into many 
diseases with unprecedented speed. HapMap-enabled genome-wide 
association studies (GWAS) identify a stunning number--more than 130 in 
2008 alone--of genetic factors associated with major causes of 
morbidity and mortality in the United States, such as autism, diabetes, 
cardiovascular disease, lung and prostate cancer, and inflammatory 
bowel disease. Identification of gene variants associated with disease 
raises the possibility of using genetic testing, in combination with 
family history information, to identify susceptible, pre-symptomatic 
subjects for screening and preventive therapies. It also provides key 
new understanding of the gene-environment interactions and biological 
pathways that lead to disease, thus providing new insights into 
treatment and prevention.
                        the cancer genome atlas
    Initiated in fiscal year 2007, the TCGA is a pilot project, jointly 
supported and led by the NHGRI and the National Cancer Institute (NCI) 
that applies a comprehensive, large-scale genomic analysis approach to 
cancer research. TCGA is designed to develop and test the complex 
scientific and technological approaches needed to identify the 
mutations and other genomic changes associated with various types of 
cancer. Three NHGRI-supported sequencing centers provide genomic 
sequencing capability for the TCGA. In fiscal year 2008, the first 
major results of this pilot project were obtained for the most common 
form of brain cancer, glioblastoma multiforme. Another very exciting 
result was an unexpected observation that points to a potential 
mechanism of resistance to a common chemotherapy drug used for brain 
cancer. These first results from the TCGA pilot project represent an 
exciting indication of the value of the multi-dimensional analysis of 
the molecular characteristics in human cancer. In the next 1 to 2 
years, the focus of TCGA will be on two other common cancers, squamous 
cell lung cancer and ovarian cancer, as well as further analysis of 
glioblastoma (brain cancer), as well as potential scale up to deal with 
many other forms of cancer.
                           medical sequencing
    The NHGRI's medical sequencing program aims to drive continued 
technology improvement (lowering the cost of genome sequencing) and to 
produce data useful to biomedical research. Seven studies are currently 
underway to identify the genes responsible for several relatively rare, 
``single-gene'' diseases and to survey the range of gene variants that 
contribute to certain common diseases. In fiscal year 2008, a number of 
medical sequencing projects were initiated: (1) Sequencing the genomic 
regions identified in genome-wide association studies as containing 
genetic components underlying common diseases, such as diabetes, breast 
cancer, schizophrenia, or Crohn's disease; (2) Sequencing the genomes 
of important human pathogens, such as those that cause malaria and 
sleeping sickness, and their invertebrate vectors (in collaboration 
with the National Institute of Allergy and Infectious Disease; and (3) 
the TCGA project.
                     personalized genomic medicine
    In addition to basic research underway to support medical 
applications of genomics, two clinical genomics initiatives launched in 
fiscal year 2007 are now in full stride. The first, ClinSeq, is a pilot 
study aimed at developing technological and procedural approaches to 
facilitate large-scale medical sequencing in a clinical research 
setting. The second, the Multiplex Initiative, is a study intended to 
provide genetic susceptibility testing for several common health 
conditions, such as cardiovascular disease and osteoporosis, to 
evaluate patients' reactions to the testing and receipt of results.
                        the 1000 genomes project
    The 1000 Genomes Project builds on the human haplotype map 
developed by the International HapMap Project to produce a much more 
comprehensive view of genomic variation. In fact, it aims to find 
almost all the variants in the genome, including those that contribute 
to disease risk. The 1000 Genomes Project will map not only the single-
letter differences in people's DNA, called single nucleotide 
polymorphisms, but also will produce a high-resolution map of larger 
differences in genome structure called structural variants, which are 
rearrangements, insertions, deletions, or duplications of DNA segments. 
The importance of these structural variants has become increasingly 
clear from surveys completed in the past 18 months that demonstrate 
that differences in genome structure may play a role in susceptibility 
to such conditions as mental retardation and autism.
    The project includes large-scale implementation of several new 
sequencing platforms to capitalize on the cost reductions emerging from 
evolving technologies, described in the journal Nature Biotechnology in 
October 2008. Using standard DNA sequencing strategies, the effort 
would likely cost more than $500 million. However, the cost of the 
project is expected to be far lower to the program--$30 million to $50 
million--due to the project's pioneering implementation of new 
technologies.
                         large-scale sequencing
    Currently, 197 genomes are either in the pipeline or have been 
completed by the NHGRI-supported large-scale sequencing centers, which 
are world leaders, renowned for their cost-effective and high-quality 
work. Completed in fiscal year 2009, the most recent study of a cow was 
an important development in agriculture that may lead to higher-quality 
beef and milk production and possibly lower carbon dioxide emissions. 
Ongoing sequencing targets include several nonhuman primates, mammals, 
fungi, and multiple strains of yeast.
                           the $1,000 genome
    The NHGRI's continuing commitment to the development of innovative 
sequencing technologies, which reduces the cost and increases the speed 
of DNA sequencing, fuels the swift pace of genomic discoveries. In the 
past year, several groups have demonstrated the ability to work with 
individual DNA strands and read individual DNA bases. These two 
breakthroughs are being combined to deliver the ability to sequence DNA 
isolated directly from cells without any processing apart from 
purification. This is one technology with promise to achieve the goal 
of sequencing a genome for $1,000 by 2014, NHGRI's original goal.
                            genomic function
    The NHGRI supports research to identify and characterize the 
function of all parts of our genome and to understand their biological 
relevance. Efforts to uncover functional elements are not limited to 
the human genome, since understanding the genomes of other, ``model,'' 
organisms also can give insight into the structure and function of the 
human genome.
    Following a successful pilot project, the NHGRI implemented a full-
scale ENCyclopedia of DNA Elements (ENCODE) Project in fiscal year 2007 
to examine the entire human genome for sequence-based functional 
elements. Concurrently, the NHGRI initiated modENCODE, which has 
similar goals for the analysis of the genomes of two important model 
organisms. This program will take advantage of the small, more 
manageable genomes of these organisms to unlock the function of the 
many genes they share with humans.
                ethical, legal, and social implications
    The NHGRI supports six Centers of Excellence in Ethical, Legal, and 
Social Implications (ELSI) Research. The Centers focus on issues 
surrounding large-scale genomics research and emerging genetic 
technologies. The NHGRI continues to support ELSI research as a core 
aspect of our research portfolio in an effort to anticipate and address 
the societal issues that will continue to arise as we learn ever more 
about the human genome and its contributions to human health and 
disease.
                             moving forward
    The NHGRI recently began two new programs to harness genomic 
knowledge and technology to help patients whose needs are not met by 
existing scientific and medical programs. Launched in 2008, the 
Undiagnosed Diseases Program (UDP), jointly led by the NHGRI, the NIH 
Clinical Center, and the Office of Rare Diseases Research, focuses on 
the most puzzling medical cases referred to the NIH by physicians 
across the Nation. The NIH Therapeutics for Rare and Neglected Diseases 
(TRND) Program, launched in fiscal year 2009, builds upon the 
technology and strategies of high-throughput genomics to identify and 
shepherd novel therapeutics for diseases where the risks of failure are 
currently too high for the private sector, but the human need is too 
great to ignore. These conditions by definition either occur in fewer 
than 200,000 Americans or in the developing world, limiting the profit 
motive for industry. UDP and TRND exemplify how the country can 
leverage the advances funded and developed by the NHGRI and the NIH to 
drive the development of more personalized, predictive, pre-emptive, 
and participatory diagnostic and therapeutic options, improving health 
outcomes for all Americans.
                                 ______
                                 
    Prepared Statement of Dr. Richard J. Hodes, Director, National 
                           Institute on Aging
    Mr. Chairman and members of the subcommittee: I am pleased to 
present the President's fiscal year 2010 budget request for the 
National Institute on Aging (NIA) of the National Institutes of Health 
(NIH). The fiscal year 2010 budget includes $1,093,143,000, which is 
$12,347,000 more than the fiscal year 2009 appropriation of 
$1,080,796,000.
    Our Nation is currently in the midst of an unprecedented 
demographic shift. The number of Americans ages 65 and older is 
expected to double within 25 years. In less than 50 years, the number 
of ``oldest old''--people ages 85 and older--will more than quadruple. 
As record numbers of Americans reach retirement age and beyond, 
profound changes will occur in our economic, healthcare, and social 
systems.
    The NIA leads a national effort to understand the nature of aging 
and the diseases and conditions that are more common among older adults 
and to develop interventions that will help older adults enjoy robust 
health and independence, remain physically active, and continue to make 
positive contributions to their families and communities. We support 
and conduct a comprehensive and integrated portfolio of genetic, 
biological, clinical, behavioral, and social research related to the 
aging process, healthy aging, and diseases and conditions that often 
increase with age.
         understanding healthy aging and disease and disability
    Modern medicine and new insights into lifestyle and other 
environmental influences are allowing a growing number of people to 
remain healthy and socially and emotionally vital into advanced ages, 
and NIA remains at the forefront of the Nation's efforts to identify 
the genetic, physical, emotional, and environmental factors that 
contribute to healthy old age. For example, researchers on the NIA-
supported Long Life Family Study are analyzing data from families with 
two or more siblings over age 79 to identify factors that may 
contribute to long and healthy life, and the Longevity Consortium 
brings together leading researchers to facilitate the discovery, 
confirmation, and understanding of genetic determinants of longevity. 
NIA intramural investigators are continuing the SardiNIA Project to 
search for genes associated with nearly 100 traits in a small, 
genetically homogeneous population and the Age, Gene/Environment 
Susceptibility (AGES) Study to explore genetic susceptibility and gene/
environment interactions that contribute to various health outcomes in 
old age.
    NIA's biology programs are wide ranging and address organs, 
systems, and processes throughout the body. For example, the Institute 
supports research on long-term weight maintenance, diet composition, 
and energy balance as well as the role of nutrition in the prevention 
of common age-related conditions such as heart disease and cancer. NIA 
is also collaborating with the National Institute of Allergy and 
Infectious Diseases to support research to better understand the 
mechanisms underlying age-related decline of the thymus, an organ that 
produces white blood cells known as T cells, a critical component of 
the body's ability to launch a robust immune response against 
infections. Studies on basic bone biology have led to the surprising 
finding that the protein Lrp5, an important factor in the process 
through which new bone is created, regulates bone mass formation 
through serotonin synthesis in the intestine, and not by acting 
directly on the bone, as was previously believed. This finding broadens 
our understanding of bone remodeling and suggests new therapeutic 
approaches to increase bone mass. Research initiatives to help us 
better understand mechanisms of anemia, chronic kidney disease, and 
thyroid dysfunction in the elderly have also been established at NIA, 
and an advisory ``summit'' meeting was held in September 2008 to 
identify areas of scientific opportunity and facilitate the formulation 
of future plans for research on the underlying biology of aging-related 
changes.
    Cognitive aging is a high-priority research area for NIA. A new 
focus on brain health, as opposed to the study of specific causes of 
brain disease and dysfunction, has emerged in recent years and has 
become an increasingly important paradigm in neuroscience research. NIA 
is continuing its involvement with the trans-NIH Cognitive and 
Emotional Health Project to coordinate and accelerate research leading 
to interventions for neurological health, as well as with the NIH 
Neuroscience Blueprint Toolbox initiative on the development of 
assessment tools for cognitive and behavioral health. NIA also 
continues to support studies of age-related changes in cognition, 
including grants funded under two new and related research 
initiatives--one to develop neural and behavioral profiles of normal 
cognitive aging and one to develop interventions to remediate age-
related cognitive decline as distinct from Alzheimer's disease (AD) or 
related conditions.
    promoting healthy aging and preventing age-related disease and 
                               disability
    NIA is continuing to support the development of interventions to 
maintain health and prevent age-related disease and disability. For 
example, NIA-supported researchers are conducting a number of studies 
aimed at reducing the incidence and severity of falls, the leading 
cause of both fatal and nonfatal injury among older adults in the 
United States. Ongoing studies are exploring the association between 
vitamin D insufficiency and fall risk; examining the effects of 
neighborhood environmental characteristics on risk of outdoor falls; 
and focusing on development of strategies to improve strength, balance, 
and gait in the elderly.
    The NIA-supported Advanced Cognitive Training for Independent and 
Vital Elderly Study was the first randomized, controlled trial to 
demonstrate long-lasting, positive effects of brief cognitive training 
to forestall cognitive decline in older adults. However, the training 
did not improve the participants' ability to tackle everyday tasks. 
More research is needed to translate the findings from the laboratory 
into interventions that are effective at home. In 2008, NIA solicited 
research to convert insights from previous work in cognitive aging into 
feasible intervention strategies, including cognitive training, 
lifestyle interventions, dietary interventions, or behavioral change 
that can be tested in randomized clinical trials. Investigators are 
encouraged to develop interventions addressing the role of individual 
differences in cognition, personality, and sociocultural factors in 
mediating or moderating adherence and outcomes. This research will be 
active in 2010.
    The development of interventions that will extend life span as well 
as health span is another emerging area of study. Through the 
innovative Interventions Testing Program, NIA-supported researchers are 
investigating promising treatments, including diets, pharmaceuticals, 
and nutritional supplements, that have the potential to extend the life 
span and delay disease and dysfunction in mice, with the long-term goal 
of identifying those interventions most likely to have a beneficial 
effect in humans. Fourteen compounds are currently under study, with 3 
more slated to be added in 2009. Testing on these compounds will 
continue through 2010.
    early detection, diagnosis, and treatment of age-related disease
    Improved technologies as well as advances in our understanding of 
the mechanisms of disease are allowing for the development of 
interventions to predict, detect, diagnose, and treat age-related 
disease and disability. Scientists in NIA's groundbreaking Alzheimer's 
Disease Neuroimaging Initiative have made a significant step forward in 
developing a test to diagnose the early stages of AD earlier and more 
accurately by measuring two biomarkers--tau and beta-amyloid proteins--
in cerebrospinal fluid. The investigators found that certain changes in 
biomarker levels in cerebrospinal fluid may signal the onset of AD. 
They also established a method and standard for testing of these 
biomarkers.
    NIA currently supports more than 30 clinical trials of 
interventions to prevent, slow, or treat AD. Interventions under study 
include a highly promising immune approach; hormonal treatments, 
including testosterone and raloxifene; diabetes drugs such as metformin 
and insulin; antioxidants; physical and mental exercise; commonly used 
psychiatric drugs; and many others. The identification of imaging and 
biological markers as well as the development of improved clinical and 
neuropsychological evaluation methods will enable us to perform less 
expensive, shorter, and more efficient intervention trials.
    In addition, NIA supports studies of treatments for a variety of 
other conditions including new therapies for menopausal hot flashes; 
hormone supplementation in men with symptoms related to low levels of 
testosterone; and cognitive behavioral therapy for older adults with 
arthritis pain and insomnia. A follow-up study to the ground-breaking 
Diabetes Prevention Program established the efficacy of a lifestyle 
intervention and drug treatment that can sharply decrease the risk of 
type 2 diabetes in overweight individuals, which was most pronounced 
for individuals age 60 or over.
      addressing the societal implications of an aging population
    The social and economic implications of aging are multi-faceted. 
NIA supports long-term studies of older Americans covering a wide range 
of topics, including retirement and economic status, care giving, 
behavioral medicine, the dynamics of health and functional change at 
older ages, cognition, and long-term care. These studies include the 
ongoing Health and Retirement Study, the leading source of combined 
data on health and financial circumstances of Americans over age 50 and 
a valuable resource to follow and predict trends and help inform health 
policy. NIA also supports studies on the social, emotional, cognitive, 
and motivational processes and neurobiological mechanisms of economic 
behavior as these influence social, financial, and health-related 
decisions of middle-aged and older adults.
    One of NIA's most urgent priorities is to improve our ability to 
reduce health disparities and eliminate health inequities among older 
adults. NIA works to identify ways to reduce health disparities through 
its Resource Centers for Minority Aging Research, and the Institute has 
compiled a Web-based toolkit on outreach, recruitment, and retention of 
minority populations in clinical research on aging. Through the Healthy 
Aging in Neighborhoods of Diversity Across the Life Span Study, NIA 
intramural researchers are continuing their efforts to disentangle the 
complex relationships among race, socioeconomic status, and health 
outcomes. Other programs, notably the NIA Alzheimer's Disease Centers, 
have a strong focus on minority health and health disparities in both 
research and outreach.
    Once again, thank you. I welcome your questions.
                                 ______
                                 
    Prepared Statement of Dr. Kenneth R. Warren, Director, National 
               Institute on Alcohol Abuse and Alcoholism
    Mr. Chairman and members of the subcommittee: I am pleased to 
present the President's fiscal year 2010 budget request for the 
National Institute on Alcohol Abuse and Alcoholism (NIAAA), of the 
National Institutes of Health (NIH). The fiscal year 2010 budget 
includes $455,149,000, which is $4,919,000 more than the fiscal year 
2009 appropriation of $450,230,000.
    NIAAA's long-range vision for medicine with respect to alcohol-
related health issues is that research on the health effects of alcohol 
will reduce the burden of illness attributable to excessive alcohol 
consumption thereby enhancing the well-being of individuals at risk, 
their families, and society-at-large. Through translation of NIAAA 
supported research findings, we have an unparalleled opportunity to 
significantly reduce the burden of illness due to alcohol-related 
problems. We are especially appreciative of the American Recovery and 
Reinvestment Act funds which will accelerate our progress. NIAAA's 
budget request and its research projects are consistent with the 
President's multi-year commitment for cancer and autism.
               current scope of the problem and research
    According to the Centers for Disease Control and Prevention, 
alcohol is the third leading cause of preventable death in the United 
States. Even more important from a public health perspective, alcohol 
misuse negatively affects the quality of life for millions of 
Americans. According to the World Health Organization, alcohol is one 
of the top 10 causes of Disability Adjusted Life Years in the United 
States and contributes to a number of the other leading causes. Alcohol 
problems cost the United States an estimated $185 billion annually, 
with almost half the cost resulting from lost productivity due to 
alcohol-related disabilities.\1\ According to NIAAA's National 
Epidemiological Survey on Alcohol and Related Conditions, more than 18 
million people ages 18 and older suffer from alcohol abuse or 
dependence and only 7 percent of them receive any form of treatment. 
Furthermore, heavy drinkers, who are not dependent, but nevertheless at 
risk for adverse health and psychosocial outcomes, are seldom 
identified. The consequences of alcohol misuse can affect both drinkers 
and those around them at all stages of life, from damage due to alcohol 
exposure of the developing embryo, to injuries, to tissue and organ 
damage resulting from chronic, heavy alcohol use. Therefore, to achieve 
its goal of reducing the heavy burden of illness from alcohol misuse, 
NIAAA's research focus must be broader than simply reducing alcohol-
related mortality; it must encompass reducing the risk for all adverse 
alcohol-related outcomes at all stages of life.
---------------------------------------------------------------------------
    \1\ Harwood, H. Updating Estimates of the Economic Costs of Alcohol 
Abuse in the United States: Estimates, Update Methods and Data (2000).
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    Research supported by NIAAA has reframed our understanding of 
alcohol dependence in several ways by demonstrating that: (1) it is a 
developmental disorder that often has its roots in childhood and 
adolescence; (2) the highest prevalence of alcohol dependence in the 
U.S. general population occurs in 18-24 year olds; (3) there is 
substantial variation in the severity and chronicity of dependence 
among individuals; and (4) a large percentage of individuals with 
alcohol dependence are highly functional in society, and therefore go 
largely unnoticed by the healthcare system.
    These findings underscore the opportunity to: (1) be able to better 
predict which individuals are at risk for future dependence by 
understanding the complex interplay between genetic, environmental, and 
developmental factors; (2) pre-empt future problems through research-
based prevention efforts for children and adolescents as well as 
screening and guidance for people of all ages about how drinking 
patterns, especially binge drinking, relate to adverse health outcomes; 
(3) conduct research to develop treatment options that are personalized 
to individual needs and lifestyles; and (4) engage individuals, 
communities, and professional groups to be actively participatory in 
shaping the future of healthcare as it relates to alcohol misuse.
                         outlook for the future
    NIAAA is revolutionizing alcohol treatment by providing evidence-
based options for addressing the full range of alcohol- related 
problems. For example, research has shown the value of alcohol 
screening in primary care and mental health settings to help patients 
understand the risks associated with different drinking patterns. NIAAA 
has developed tools that clinicians can use to screen and intervene in 
these settings. Moving treatment of less severe forms of alcohol 
dependence into mainstream medical care will decrease stigma, improve 
availability, accessibility, and appeal of treatment options, and 
ultimately reduce the number of people who suffer with dependence. 
Alcohol-dependent patients will benefit from NIAAA's research focusing 
on the development of new treatments including behavioral therapies and 
medications that will shorten the duration, number, and severity of 
episodes of dependence and prevent, for most, the development of 
chronic, relapsing dependence. Studies suggest that as a result of 
these types of intervention, most people with mild to moderate 
dependence will recover.
    Patients with more severe and/or relapsing dependence, are more 
complex to treat and often need multi-faceted, personalized addiction 
services that may include medications, counseling, psychotherapy, and 
case management. These patients often have other health (infectious 
diseases, mental illness, and liver disease) and psychosocial (family, 
marital, and workplace) problems, some that are the direct result of 
their alcohol misuse. Comprehensive treatment must take all of these 
into account. NIAAA-supported research will continue to develop and 
refine treatment options for these individuals, both for their alcohol 
dependence as well as the many adverse health consequences that may 
result. Collectively, these changes in the approach to treatment of 
alcohol problems will substantially reduce the public health burden of 
heavy drinking and alcohol use disorders.
    Ensuring that appropriate research-based guidance about alcohol use 
for special populations, including pregnant women, is available and 
will result in a dramatic reduction in the incidence of fetal alcohol 
spectrum disorders, the most severe forms of which produce lifelong 
disability, and may also decrease the incidence of Sudden Infant Death 
Syndrome. NIAAA research will continue to inform this guidance, 
including information about the risks of alcohol exposure to the 
developing embryo and fetus, and will make it accessible to primary 
healthcare providers and obstetricians. For pregnant women who drink 
despite the best advice, research is focused on developing nutritional 
and/or pharmacological agents that may lessen the negative effects of 
alcohol exposure.
    Biomarkers, stemming from NIAAA-supported genetic and epigenetic 
research, will be available that: (1) predict individual risk for 
future alcohol dependence; (2) assess progression of at risk drinking 
through dependence; and (3) track damage to tissue and organs. These 
tools will enhance the ability of healthcare providers to offer 
guidance to patients about their drinking patterns and determine 
appropriate healthcare based on individual risk factors. A repertoire 
of medications will facilitate treatment tailored to the needs of the 
patient. Personalized treatment including medications and behavioral 
therapies will be based on individual genetic make-up, desired drinking 
outcomes, attention to co-occurring disorders, ease of compliance, and 
other factors.
                             moving forward
    NIAAA supported biomedical and behavioral research is supporting 
the research that will contribute to realizing the vision outlined 
above. Ongoing studies, as well as new initiatives, will provide the 
scientific knowledge and tools, to improve our ability to predict which 
individuals are at increased risk for alcohol-related problems 
including dependence, pre-empt the harm from alcohol misuse, and 
provide personalized treatment.
    The integration of routine alcohol screening, and where 
appropriate, brief intervention and/or referral to specialty treatment 
into primary healthcare for all ages is central to reducing 
consequences of alcohol misuse. NIAAA will continue to develop teaching 
and training tools to increase the usage of A Clinician's Guide: 
Helping Patients Who Drink Too Much. NIAAA has also recently launched 
Rethinking Drinking, a new Web site, and booklet that provides 
information and tools to help individuals change harmful drinking 
patterns, either on their own or by helping them reach the decision to 
seek help. NIAAA is also developing guidance on screening and brief 
intervention for children and adolescents, recognizing that criteria 
developed for adults may not fit the needs or behaviors of youth.
    Medications development remains a central focus of the Institute. 
Emerging data are changing the way we look at alcohol dependence, 
guiding us to be more strategic about the medications we test, the way 
we test and design them, and how we determine the subpopulations of 
patients most likely to benefit from them. For example, new 
understanding of the relationship between withdrawal induced anxiety 
and relapse has provided additional targets for drug development to 
minimize relapse. Broadening the desired treatment outcome, from 
targeting only abstinence to including reduction in heavy drinking, is 
also influencing the medications that are being tested as well as how 
they are tested. Other compounds that may mitigate tissue and organ 
damage are under study.
    Most individuals with alcohol dependence do not access treatment 
yet many of them recover without the benefit of professional care or 
facilitated self-help. NIAAA continues to investigate the process 
leading to a decision to stop drinking or to seek help. In concert with 
a broader NIH Roadmap Initiative, NIAAA is currently supporting studies 
to understand mechanisms of change away from harmful health behaviors.
    Given our current state of knowledge and what we are learning from 
ongoing studies, we are optimistic that we can substantially reduce the 
burden of illness for alcohol-related problems and the suffering it 
brings to individuals, their families and society at large.
                                 ______
                                 
Prepared Statement of Dr. Stephen I. Katz, Director, National Institute 
           of Arthritis and Musculoskeletal and Skin Diseases
    Mr. Chairman and members of the subcommittee: I am pleased to 
present the President's fiscal year 2010 budget for the National 
Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) of 
the National Institutes of Health (NIH). The fiscal year 2010 budget 
includes $530,825,000, which is $5,953,000 more than the fiscal year 
2009 appropriation of $524,872,000.
                              introduction
    As the primary Federal agency for supporting medical research on 
diseases of the bones, joints, muscles, and skin, the NIAMS touches the 
lives of nearly every American. For example, the U.S. Bone and Joint 
Decade notes that 1 in 2 people will experience back pain each year, 
and 1 in 5 will have pain that affects their ability to work. The 
National Arthritis Data Working Group estimates that 21 percent of 
adults have arthritis in at least one joint, a figure that is likely to 
grow as the population ages. Likewise, 1 of every 2 women and 1 in 4 
men aged 50 years and older suffer fractures each year because of 
osteoporosis; researchers project that the number of osteoporotic 
fractures in the United States will grow from 2 million to more than 3 
million in the next two decades. The NIAMS is committed to preventing 
disabilities and reducing costs associated with these and other 
conditions through balanced basic, translational, and clinical research 
investments.
    As the Institute sets priorities, it is considering how recent 
advances have positioned its research community for discoveries to 
prevent disease and improve each American's life. It is soliciting 
input from researchers, healthcare providers, patients, and the public 
on promising areas of inquiry; pressing scientific needs; programs to 
ensure a continuing supply of well-trained researchers; and strategies 
to eliminate health disparities. An important consideration is how 
investigators can engage in multidisciplinary opportunities. Chronic 
pain, for example, is an aspect of many diseases that are part of the 
NIAMS portfolio; staff are exploring partnerships through the Trans-NIH 
Pain Consortium. Prospects for stem cell research are growing rapidly 
as researchers isolate stem cells from skin and other organs, and as 
more lines become available under the Nation's policy for Federal 
support of embryonic stem cell research.
    Consistent with the Federal commitment to double NIH-wide cancer 
research spending, the NIAMS will continue to pursue collaborations 
with the National Cancer Institute in support of high-quality projects 
that relate directly to diseases and organ systems within the NIAMS 
mission, particularly the bones and the skin. Already, the NIAMS 
supports research on mechanisms underlying skin cancers, and 
investigators have uncovered a strategy that kills tumor cells with 
less damage to healthy skin.
                          preventive medicine
    Research to identify susceptibilities to and initial symptoms of 
disease, and to develop strategies to slow disease progression, is a 
NIAMS priority. Building on findings that early, aggressive therapy 
alters the course of rheumatoid arthritis (RA), NIAMS is comparing 
treatments against a related disease-juvenile idiopathic arthritis.
    The NIAMS and the National Institute on Aging lead the 
Osteoarthritis Initiative (OAI), a public-private partnership to 
identify and evaluate biomarkers of osteoarthritis (OA). NIH and its 
partners, with input from the Food and Drug Administration, launched 
the OAI in 2001. More than 1,100 researchers worldwide have accessed 
OAI data to explore issues such as differences in OA progression, or 
why only some people with X-ray evidence of OA develop pain. In 2010, 
the NIH will extend the OAI for 6 years. It expects the OAI to suggest 
approaches for slowing joint damage, facilitate clinical testing of 
interventions and allow clinicians to identify risk factors for OA 
development, predict severity, and personalize treatments for their 
patients.
                        complex genetic diseases
    The NIAMS community is benefiting from another public-private 
partnership, the Genetic Association Information Network (GAIN). Since 
GAIN's inception, NIAMS investigators have been involved in its 
Collaborative Association Study of Psoriasis, an ambitious effort to 
combine genetic and clinical information from people affected by 
psoriatic skin disease and psoriatic arthritis. The project has yielded 
a wealth of data that researchers are using to develop diagnosis, 
treatment, and prevention strategies.
    NIAMS-funded investigators have uncovered genetic susceptibility 
markers of alopecia areata and other autoimmune or auto-inflammatory 
skin and joint diseases, including lupus. Collaboration among United 
States and European researchers recently linked a component of the 
immune system and RA. At the NIH Clinical Center, sample collection has 
begun for a genomic analysis of Behcet's disease, a complex disorder of 
inflammation affecting skin, eyes, gastrointestinal tract, lungs, 
vasculature, and joints.
                    collaborations and team science
    Behcet's disease is one of many conditions researchers are studying 
through the new NIH-wide Center for Human Immunology, Autoimmunity, and 
Inflammation. NIAMS' intramural program is taking a leadership role in 
the Center. Collaborations among scientists from several NIH Institutes 
who are studying related disease systems will facilitate studies about 
conditions associated with defective immune or inflammatory responses, 
and will allow them to apply their results to the development of 
interventions and, ultimately, disease prevention strategies.
    In collaboration with orthopaedic surgeons at the Walter Reed Army 
Medical Center, NIAMS researchers recently discovered that tissue 
commonly discarded as waste contains special cells that feature many of 
the same properties as adult stem cells. The cells can be used for 
regenerative medicine, such as treating war-traumatized muscle, without 
subjecting patients to additional surgeries and related complications.
    The NIAMS participates in the multi-Institute Senator Paul D. 
Wellstone Muscular Dystrophy Cooperative Research Centers program. In 
addition to conducting research, scientists at the Centers maintain 
core resources that all who are studying muscular dystrophy can use. A 
group of NIAMS-funded muscle researchers showed that defects in blood 
vessel constriction are associated with the severe fatigue that people 
with muscular dystrophy experience; mouse experiments suggest that 
compounds with FDA-approval for other conditions may improve symptoms. 
Other scientists uncovered molecules that confer many of the benefits 
of exercise, at least in mice; the findings might lead to treatments 
for conditions that leave patients unable to exercise.
    The scale and complexity of today's research problems and their 
solutions demand that the NIH explore new models for team science. In 
fiscal year 2008, the NIAMS started a program, Building 
Interdisciplinary Research Teams (BIRT), to promote partnerships among 
fields that share interests, but historically do not interact. Because 
collaborations proposed in the first round of applications suggested 
that modest investments in the program will provide great dividends, 
the NIAMS opened BIRT up to additional communities and expects to make 
another set of awards at the end of fiscal year 2009.
    In the past year, the NIAMS has made considerable progress in 
leading a trans-NIH partnership with the National Aeronautics and Space 
Administration. By designating the U.S. portion of the International 
Space Station (ISS) as a National Laboratory, Congress underscored the 
significance that Americans place on the ISS' research potential. The 
NIH shares this belief and, for the next 3 years, will accept 
applications for studies that use the ISS for experiments directly 
related to the NIH goals of understanding human physiology and 
promoting the public's health.
                            clinical studies
    One element of improving the Nation's health is to support clinical 
studies on which physicians can rely when discussing treatment options 
with patients. Before the Spine Patient Outcomes Research Trial 
(SPORT), many who had low back pain were conflicted about surgery. Now, 
patients can be assured that surgery relieves pain from herniated 
disks, but--if the pain is tolerable and not worsening--it will likely 
subside without surgery. Similarly, people who have pain due to spinal 
stenosis (a narrowing of the spinal column that occurs with age) are 
likely to benefit more from surgery than from noninvasive treatments 
such as physical therapy; but, they are not causing more damage if they 
adopt a ``wait-and-see'' approach before committing to an operation. 
Recently, SPORT offered guidance to help people who suffer from 
herniated disks personalize their treatment decisions by reporting that 
study participants who had surgery on an upper lumbar disk improved 
more than those with damage further down.
    For decades, the NIAMS has invested heavily in efforts to 
understand fracture risk and to uncover strategies to prevent and treat 
bone loss. Although physicians now have an array of medications for 
people who are at risk of osteoporosis, many patients fail to benefit 
fully because they do not follow the treatment regimens. Because a 
method to improve compliance could immediately slow the growing health 
and economic burden that osteoporosis places on society, the NIAMS is 
funding research in this area.
                               conclusion
    The discoveries and activities highlighted above are just a few 
examples of research that will continue to benefit Americans from all 
walks of life. In partnership with Government and private entities, the 
NIAMS also develops and distributes science-based health information 
directly to patients, healthcare providers, and the public. The 
Institute will continue outreach to diverse populations through 
research, training, and information dissemination. Collectively, NIAMS 
programs have spurred understanding of many common, chronic, and costly 
diseases. Looking forward to the next decades, this progress provides a 
foundation for an era in which the burden of these debilitating 
conditions is reduced and--with time, continued support from the 
American public, and the dedication of our Nation's researchers--
eliminated for millions of affected adults, children, and families.
                                 ______
                                 
  Prepared Statement of Dr. Roderic I. Pettigrew, Director, National 
           Institute of Biomedical Imaging and Bioengineering
    Mr. Chairman and members of the subcommittee: I am pleased to 
present the President's fiscal year 2010 budget request for the 
National Institute of Biomedical Imaging and Bioengineering (NIBIB) of 
the National Institutes of Health. The fiscal year 2010 budget includes 
$312,687,000, which is $4,479,000 more than the fiscal year 2009 
appropriation of $308,208,000.
    The NIBIB is leading the development of revolutionary technologies 
that will help transform medicine in the United States and around the 
world. It has primary responsibility for uniting the engineering and 
physical sciences with the life sciences to bring about new ways of 
thinking that will accelerate discovery and technology development. 
With a global vision and a public health mission, the Institute is 
working to develop technologies that enable personalized healthcare, 
early detection of disease, and treatments that are minimally invasive, 
cost-effective and widely accessible.
                  translating technology into practice
    Ultimately, NIBIB seeks to expand the translation of technological 
advances into solutions that improve human health by reducing disease 
and enhancing quality of life. To accomplish this goal, NIBIB continues 
to fund bold and far-reaching projects that facilitate discovery and 
translate discovery to clinical practice. NIBIB-supported scientists in 
the innovative Quantum Grants Program are making extraordinary progress 
to develop new technologies and modalities for the diagnosis, 
treatment, or prevention of disease that will result in practical 
healthcare benefits for the Nation.
 changing healthcare delivery through point-of-care (poc) technologies
    Testing at the point of initial contact, or ``point-of-care,'' 
rather than at specialized centers or hospitals utilizes state-of-the-
art diagnostics and information systems that can be used in the 
doctor's office or even at home. Consequently, the use of POC devices 
can also help patients monitor their wellness in preventive medicine. 
The POC approach to health care delivery can significantly improve the 
quality and reduce the cost of health care by: providing earlier 
diagnosis of disease when treatment is more effective and less costly; 
making modern medicine available to those who lack access to regular 
care, such as people in rural settings or developing countries; 
combining cutting-edge diagnostic and communication technologies to 
bring patients into more frequent and regular contact with health care 
providers; and enabling a patient-centered process with home-based 
monitoring.
    The NIBIB currently funds a network of four POC Technologies 
Research Centers that target the development of new POC technologies 
for early and rapid detection of strokes, detection of sexually 
transmitted diseases, rapid multi-pathogen detection for national 
disaster readiness, and diagnosis of infections that can be used in 
low-resource settings among underserved populations. Additionally, the 
NIBIB and the Department of Biotechnology (DBT) of the Ministry of 
Science and Technology of the Republic of India held a joint workshop 
on Low-Cost Diagnostic and Therapeutic Medical Technologies in November 
2008 in Hyderabad, India. The workshop was a result of a bilateral 
agreement between the NIBIB and DBT to develop low-cost technologies to 
improve the quality of healthcare for underserved populations. Point-
of-care testing is becoming a vital part of the world's healthcare 
delivery system, and is a key to reducing healthcare costs while 
maximizing accessibility for everyone.
                     health information technology
    Health information technology research that enables the integration 
of clinical data, medical image diagnostic and treatment data with the 
patient's medical history in a comprehensive electronic medical record 
will improve clinical decisionmaking. The ability to connect and 
exchange diagnostic information and medical images between healthcare 
providers, clinics, and hospitals will help provide the timely 
information that is needed for effective healthcare and will help 
reduce unnecessary, excessive, and duplicative procedures. A patient-
centered approach to comprehensive electronic health records will allow 
patients access to their health information. This will enable patients 
to play an active role in their own wellness by enabling them to ask 
knowledgeable questions about treatment options. Additionally, patients 
are also empowered to provide this information to any and all 
healthcare providers as needed, independent of their location or where 
the medical data was created or stored. The NIBIB supports research in 
new technologies to address issues such as: interoperability of data 
systems, compatibility of computer software across medical 
institutions; security of data during transmission; HIPPA compliance; 
and availability of affordable data systems for patient care providers.
           microchip captures early circulating cancer cells
    NBIB's budget request and its research projects are consistent with 
the President's multi-year commitment for Cancer. Malignant cancers 
shed cells that enter the circulation, travel to other areas of the 
body, and often grow into secondary tumors, or metastases. Indeed, 
metastases are responsible for the great majority of cancer deaths. It 
is estimated that 70,000 men per year are diagnosed with recurrent 
prostate cancer after prostatectomy, as shown by rising prostate 
surface antigens. For these men, the ability to detect and characterize 
the malignant cells in the blood may enable personalized therapy. 
Researchers are developing a technology to facilitate quantitative 
detection of circulating tumor cells (CTCs). They have engineered a 
microchip with a large surface area of an adhesion molecule that binds 
CTCs from whole blood, making detection of CTCs more reliable than 
previous approaches. They are analyzing molecular and genomic 
information in the CTC's to identify new biomarkers to customize 
treatments that are personalized for the patients and to predict 
treatment outcomes. The NIBIB-supported research has the potential to 
eliminate or greatly reduce cancer deaths due to metastases.
          regenerating brain tissue to promote stroke recovery
    Brain cells can be irreversibly damaged in a matter of minutes when 
the blood supply carrying oxygen and glucose is interrupted in a 
stroke. Individuals who have had a stroke may experience partial 
paralysis or problems with awareness, attention, learning, judgment, 
memory, or speech. An international team of researchers from Baylor 
College of Medicine, Rice University, London's National Institute of 
Medical Research, King's College of London, and Edinburgh University is 
integrating cutting-edge imaging, biological, and engineering 
techniques to map and understand normal brain regions that are 
responsible for generation of new neurons in the adult. The ultimate 
goal is to bioengineer a cellular system mimicking these brain regions 
that can eventually be used to replace and/or drive repair of stroke-
damaged tissue.
       miniature artificial kidney replaces traditional dialysis
    Nearly one-half of a million people in the United States suffer 
from end-stage renal disease (ESRD), and the incidence rate of this 
disease has been steadily increasing for over 25 years. Kidney 
transplantation provides the best option for ESRD patients, but a 
shortage of donors means that most patients never make it to the top of 
a waiting list. The alternative is dialysis, which is expensive, 
inconvenient, far less effective, and significantly lowers the 
patient's quality of life. An interdisciplinary group of researchers 
has envisioned a way to improve management of ESRD by developing an 
implantable, self-regulating, bioartificial kidney capable of filtering 
toxins from the blood as well as replacing some of the metabolic 
functions of a healthy kidney. Such an implantable bioartificial kidney 
could substitute for transplantation and will truly be a quantum leap 
in healthcare, giving hope, independence, and mobility to the 350,000 
patients presently tethered to thrice-weekly in-center dialysis.
 insulin-producing cells from amniotic fluid stem cells treat diabetes
    More than 1 million people in the United States suffer from type 1 
diabetes, which is caused by the destruction of insulin-producing 
pancreatic islet cells. Currently available insulin therapy by itself 
does not cure the disease or prevent many of its long-term 
complications. Transplantation of islet cells has shown promise, but 
there is a shortage of donors, and the process is expensive, 
inefficient, and requires life-long immunosuppression. Researchers from 
Wake Forest University and the University of Miami have combined their 
expertise in stem cell differentiation and in vivo islet cell 
transplant studies to explore a new approach using amniotic fluid stem 
cells. The team has successfully isolated amniotic fluid stem cells and 
generated insulin-producing, islet-like cells in vitro. Future work 
will determine whether these cells are able to function and survive in 
animal models of diabetes. If successful, this approach could 
potentially provide a curative treatment for type 1 diabetes through 
transplantation using cells produced from amniotic stem cells.
    molecular theranostics: new technologies for the diagnosis and 
                         treatment of diseases
    The concept of combining a therapeutic with a diagnostic agent is 
rapidly evolving and goes beyond traditional diagnostic tests that 
screen or confirm the presence of a disease. With specialized molecular 
imaging techniques and biomarkers, theranostics might predict risks of 
disease, diagnose disease, and monitor therapeutic response leading to 
real-time, cost-effective treatment. NIBIB supports a number of teams 
that are developing novel theranostics and approaches that can be 
applied in clinical studies of human patients. A team of chemists and 
neurosurgeons at the University of Michigan is developing highly 
specific, dye-loaded nanoparticles capable of delivering targeted 
photosensitizers to improve the survival of brain tumor patients. This 
technique will allow neurosurgeons to visualize the brain tumors for 
surgical resection of the main tumor mass while eradicating remaining 
tumor cells through a process known as photodynamic therapy. These 
particles also contain imaging contrasting agents to visualize response 
to therapy.
                                 ______
                                 
Prepared Statement of Dr. Nora D. Volkow, Director, National Institute 
                             on Drug Abuse
    Mr. Chairman and members of the subcommittee: I am pleased to 
present the President's fiscal year 2010 budget request for the 
National Institute on Drug Abuse (NIDA) of the National Institutes of 
Health (NIH). The fiscal year 2010 budget includes $1,045,384,000, 
which is $12,625,000 more than the fiscal year 2009 appropriation of 
$1,032,759,000.
    Drug abuse and addictions are preventable conditions, yet continue 
to cause immeasurable human suffering, with associated societal costs 
estimated to exceed one-half a trillion dollars annually in the United 
States. Tobacco use alone is responsible for more than 400,000 deaths 
per year, and is the leading cause of preventable death in the United 
States. NIDA's budget request and its research projects are consistent 
with the President's multi-year commitment for cancer. For example, 
NIDA has active programs to hasten the development of new, more 
effective treatments for nicotine addiction that can dramatically 
reduce the prevalence of diseases like lung cancer and emphysema, which 
mean an early death for many smokers. Other NIDA-supported research 
advances have contributed to steady declines in both licit and illicit 
drug use over the years, particularly among our Nation's youth. Our 
latest Monitoring the Future (MTF) survey of drug use patterns and 
trends among 8th, 10th, and 12th graders reveals, for example, that 
tobacco use has declined continuously since its peak in the mid-1990s, 
and is presently at its lowest level since the first MTF survey in 
1975. However, if we are to fully eradicate drug abuse and addictions, 
we must find novel approaches to prevent drug abuse (including smoking) 
among the significant fraction of youth who, because of strong genetic 
and/or environmental propensity, appear refractory to current efforts. 
Additional challenges include the growing abuse of prescription 
medications, including opioid analgesics (e.g., painkillers), 
stimulants (e.g., ADHD medications), and CNS depressants (sleep and 
anxiety medications). NIDA is committed to closely monitoring these 
trends and to furthering the development of innovative strategies to 
counter them, including the widespread dissemination of screening and 
early intervention tools for medical settings to increase the medical 
community's participation in identifying and treating substance abuse 
disorders.
        addiction medications: changing the culture of treatment
    NIDA's accelerating rate of discovery is beginning to spur the 
advent of better medications and behavioral interventions to counteract 
drug-induced changes in brain function. Among the strategies NIDA 
supports for medications development are those to: counter stress 
responses, which frequently trigger relapse to drug use; strengthen 
executive function and inhibitory control so that drug abusers can 
better control their urge to take drugs; and interfere with drug-
conditioned memories to prevent relapse when drug abusers are exposed 
to environments they associate with drug use. Other research includes 
development of vaccines, or antibody-based approaches, which can block 
both illicit and licit drugs (e.g., nicotine) from ever reaching the 
brain, thereby inhibiting their rewarding effects. In the context of 
nicotine addiction, this approach may help prevent smokers from 
escalating to addiction and/or facilitate abstinence in those who seek 
to quit. It also complements ongoing efforts to discover new, more 
effective medications through conducting screens of novel compounds and 
chemical libraries and applying promising findings to help people 
achieve abstinence from tobacco and other addictive substances.
    To accelerate progress in combating substance use disorders, there 
must also be social change to recognize that people who suffer from 
addiction require medical treatment. Presently, addiction treatment 
occurs largely outside of mainstream medicine, even though drugs 
undermine overall health, frequently appearing alongside other medical 
and psychiatric conditions. To help change this culture, NIDA is 
providing knowledge of associated brain dysfunctions and developing and 
deploying effective addiction medications. As these efforts succeed, 
the consequent medicalization of drug abuse and addiction will allow 
(1) clinicians to respond to their patients' needs more effectively and 
in a more personalized fashion; (2) insurance companies to become 
increasingly responsible for the coverage of treatments that can 
dramatically improve overall health; and (3) pharmaceutical companies 
to be incentivized to develop novel addiction medications. As the 
stigma of addiction wanes, the dissemination of proven treatments will 
expand to include the populations that need them the most, such as 
those involved in the criminal justice system, half of whom meet the 
criteria for drug abuse or dependence, according to estimates from the 
Department of Justice. Broader treatment access for drug-addicted 
offenders will help them to successfully transition back into society, 
dramatically reducing not just drug abuse, but also criminal 
recidivism.
              genes and environment: high pay-off research
    A steady flow of genetic discoveries is uncovering previously 
unsuspected genes whose products may be involved in the addiction 
process and therefore present good candidates for medication 
development. They also herald the advent of more personalized 
interventions based on a patient's genetic profile. And, because genes 
influence both vulnerability and resilience to substance abuse and 
other mental disorders, genetic data will further our understanding of 
the basic mechanisms underlying the disease of addiction, as well as 
its frequently associated comorbid conditions.
    But genes do not act in isolation; rather, they work in tandem with 
developmental and environmental factors to determine a person's drug 
abuse vulnerability. Therefore, NIDA is encouraging more research to 
understand how genes might mitigate or amplify social influences that 
affect individual choices and behaviors related to substance abuse. 
Conversely, environmental elements, such as parenting quality, home 
conditions, stress, diet, pollutants, and, of course, exposure to drugs 
of abuse, can regulate gene expression. Uncovering the mechanisms 
behind these so called epigenetic effects, offers a path to alleviate 
and perhaps even override a genetic predisposition by adjusting 
environmental variables.
    One approach NIDA is pursuing is the merging of genomic and brain 
morphology (i.e., brain structure) data in order to understand how 
genes influence human brain development. Such data would be invaluable 
as a basis for understanding the contribution of specific genes to 
neuropsychiatric disorders and how exposure to certain environmental 
factors can trigger disease in those who are genetically vulnerable. 
This research would, in turn, open the door to next-generation 
pharmaceuticals that could target and perhaps even prevent or reverse 
disease processes. The recent discovery of histone demethylases--a new 
family of genome modifying enzymes--is just one example of a set of 
proteins that could be targeted for medications development.
    Also critical to substance abuse prevention and treatment is the 
development of reliable assays for drug exposure and addiction 
vulnerability. Although tests of bodily fluids or hair and surveys 
using self-report questionnaires are used routinely, their value is 
compromised by their limited reliability, low sensitivity, and narrow 
scope. NIDA will encourage research to find reliable biomarkers--or 
indicators of a biological response/vulnerability to drug exposure--for 
assay development. The ability to quantify thousands of biomarkers in a 
consistent, expeditious, and affordable manner will yield revolutionary 
new approaches to the prevention and personalized treatment of 
substance abuse.
            the relevance and impact of comorbid conditions
    NIDA research has demonstrated that drug abuse cannot be treated in 
isolation from associated concerns, such as criminal behavior, mental 
and physical health status, social functioning, and HIV/AIDS. A robust 
and consistent effort to tap into and integrate different sources of 
knowledge will be needed to design and implement effective 
interventions in the future. This will be particularly important for 
members of the military and their families, who may be facing difficult 
challenges related to substance abuse in the coming years. Many are 
returning from active duty with post-traumatic stress disorder (PTSD) 
and/or chronic pain conditions, both of which can be comorbid with drug 
abuse and require comprehensive treatment interventions. In response to 
these projections NIDA will increase our research investment in this 
area and collaborate with the Veteran's Administration, the Substance 
Abuse and Mental Health Administration (SAMHSA), and other NIH 
Institutes--NIMH, NCI, NIAAA, and NHLBI--in developing a responsive and 
forward-looking research agenda.
            understanding the dynamics of drug abuse and hiv
    NIDA's recent revamping of its HIV/AIDS research strategy better 
addresses the critical need for new therapies for drug abusers with HIV 
and for research designed to uncover more about the complex medical 
consequences, such as neuroAIDS. Initiatives in this area will help 
elucidate the effects of genetic variations on disease progression, and 
on how drugs of abuse and medications (for drug addiction and HIV) 
interact with both host and viral genes. To further such innovations, 
NIDA has established the Avant-Garde Award for exceptionally creative 
researchers offering transformative approaches to major challenges in 
biomedical and behavioral research on drug abuse and HIV/AIDS. Awardees 
are undertaking diverse approaches, such as evaluating the 
effectiveness of expanded access to highly active antiretroviral 
therapy in decreasing new cases of HIV infection among injection drug 
users. Evidence to date suggests the utility of this approach for 
injection drug users and their partners; if widely adopted, it could 
also help stem the HIV epidemic around the world. In addition, NIDA is 
promoting research on HIV screening and on how to best integrate 
testing and counseling into drug abuse treatment settings, among 
criminal justice populations, and in other countries that have been hit 
especially hard by the epidemic. Learning one's HIV-positive status 
reduces risk behaviors and, when linked to HAART, makes the person a 
less efficient vector for spreading the disease.
    In sum, the health of our Nation and its leadership role in 
bringing science to bear on drug abuse and addiction depend on our 
ability to continue to support promising biomedical research that can 
bring with it enduring and transformative public health changes not 
just to this country but to the rest of the world. Thank you for this 
opportunity, and I will be pleased to answer any questions you may 
have.
                                 ______
                                 
  Prepared Statement of Dr. James F. Battey, Jr., Director, National 
        Institute on Deafness and Other Communication Disorders
    Mr. Chairman and members of the subcommittee: I am pleased to 
present the President's fiscal year 2010 budget request for the 
National Institute on Deafness and Other Communication Disorders 
(NIDCD) of the National Institutes of Health (NIH). The fiscal year 
2010 budget includes $413,026,000, which is $5,767,000 more than the 
fiscal year 2009 appropriation of $407,259,000.
    The NIDCD conducts and supports research and research training in 
the normal and disordered processes of hearing, balance, smell, taste, 
voice, speech, and language. Last year, NIDCD celebrated its 20th 
anniversary. Over the past two decades, extraordinary research 
opportunities have led to scientific breakthroughs in the study of 
genes, proteins, sensory and supporting cells, and molecular processes 
that directly affect our understanding of communication disorders. 
NIDCD-supported scientists have also made substantial progress in 
behavioral studies that increase our understanding of how communication 
processes impact health. NIDCD's budget request and its research 
projects are consistent with the President's multi-year commitments to 
cancer and autism research. The following are notable research 
highlights built upon two decades of NIDCD support.
                         hair cell regeneration
    Our ability to hear relies on sensory cells in the inner ear, 
called hair cells. Hair cells can be damaged by disease, injury, aging, 
or exposure to certain drugs. When enough hair cells are damaged, an 
individual experiences hearing loss. Although fish, amphibians, and 
birds can spontaneously regenerate new hair cells to replace damaged 
ones, mammals (including humans) cannot. NIDCD-supported research into 
the development of the mammalian inner ear has led to a better 
understanding of which cells in a developing embryo become hair cells, 
and which become supporting cells that help maintain the hair cells. 
These basic studies have provided the foundations for more recent 
advances. For example, NIDCD-supported scientists have identified 
specific genes that determine an inner ear hair cell's fate. Building 
on these studies,
    NIDCD-supported scientists were able to regenerate new hair cells 
in laboratory mammalian animal models, and restore hearing in some 
cases. These promising results provide hope that we might someday be 
able to regenerate functioning hair cells in humans.
                 preventing noise-induced hearing loss
    Prevention of noise-induced hearing loss is another important goal 
for the NIDCD. Approximately 15 percent of Americans between the ages 
of 20 and 69--an estimated 26 million American adults--have high-
frequency hearing loss caused by exposure to loud sounds or noise at 
work or during leisure activities. Since the sensory hair cells of the 
inner ear do not spontaneously regenerate in humans, preventing noise 
damage to these cells is critical for long-term health. In October 
2008, NIDCD launched a new public education campaign called ``It's a 
Noisy Planet. Protect Their Hearing.'' The campaign is designed to 
increase awareness among parents of children ages 8 to 12--or 
``tweens''--about the causes and prevention of noise-induced hearing 
loss. With this information, parents and other adults can encourage 
children to adopt healthy habits that will help them protect their 
hearing for life.
   improving technologies to treat hearing loss and balance disorders
    The NIDCD supports many research efforts to develop or improve 
technologies for the treatment of hearing loss and balance disorders. 
The cochlear implant is an electronic device that provides a sense of 
sound to individuals who are profoundly deaf or severely hard-of-
hearing. Cochlear implants process sounds from the environment by 
directly stimulating the auditory nerve, bypassing the malfunctioning 
cells in the inner ear. Sustained NIH support has greatly improved this 
technology so that, with the appropriate training and support, deaf and 
severely hard-of-hearing individuals who receive a cochlear implant can 
enjoy an enhanced quality of life by participating more fully in 
society. Currently, cochlear implants are most successful in children 
who receive them at a young age, when the brain is still in an active 
phase of language development. NIDCD-supported scientists are 
investigating the benefits of bilateral cochlear implantation, in which 
a cochlear implant is fitted into both ears. Results show that 
individuals receiving two cochlear implants are significantly better at 
localizing sounds and hearing speech in a noisy room compared to 
individuals with one implant. In addition, within 1 to 2 years after 
implantation, children with two cochlear implants will have learned how 
to locate sounds, and most will be able to localize sounds better than 
children with only one implant.
    Much like hearing, our sense of balance relies on hair cells 
arranged in specialized structures within the inner ear, which together 
make up our vestibular system. Vestibular hair cells are susceptible to 
damage by the same mechanisms as hearing hair cells--drugs, trauma, and 
infection--and their dysfunction can lead to dizziness or balance 
problems. Building on lessons learned from cochlear implant research 
and technology, NIDCD-supported scientists are now working to develop 
an implanted device to help partially restore a person's sense of 
balance. Although the prototype vestibular implant is still being used 
in animal studies, it has the potential to benefit more than 90 million 
Americans who experience dizziness or balance problems in the future.
    NIDCD also actively supports research to improve hearing aid 
technology. Improving hearing in noisy environments is a major 
challenge for hearing aid users. Of the currently available 
technologies, directional microphones that focus on nearby sounds and 
filter out sounds further away show the most promise for addressing 
this problem. NIDCD-supported scientists have successfully completed a 
prototype of a low-power, highly directional microphone that is modeled 
on the acute directional hearing of a parasitic fly and is small enough 
to fit into a hearing aid. The device could offer hearing aid users 
significant improvement in their ability to listen to conversations 
amidst background noise. NIDCD's goal is for this research is to lead 
to the development of hearing aids that are more personalized and 
better able to restore normal hearing.
       identifying genes responsible for communication disorders
    NIDCD-supported scientists are identifying and describing genes 
involved in many communication disorders, including autism, dyslexia, 
stuttering, speech-sound disorders, and hearing loss. Currently, 
scientists have mapped more than 80 genes responsible for inherited 
hearing loss. Starting in fiscal year 2009, NIDCD is serving as the 
lead Institute for an NIH Government Performance and Results Act (GPRA) 
goal to ``identify or study additional genes involved in communication 
disorders in human and animal models by 2011.'' To achieve this goal, 
NIDCD- and other NIH-supported scientists are using the knowledge 
gained from the Human Genome Project to identify genes that play a role 
in communication disorders. These efforts will inform scientists as 
they develop genetic tests to predict communication disorders and 
personalize treatment plans for individuals affected by them. In a 
recent study, NIH-supported scientists scanned the human genome for 
genetic differences between individuals with and without autism. They 
identified both common and rare genetic factors that affect the risk 
for developing autism spectrum disorders (ASD). The results suggest 
that there are specific inherited genes that can cause abnormal 
connectivity between nerve cells in the brains of people with an ASD. 
These abnormal connections may be, in part, responsible for their 
communication difficulties.
                          autism and language
    According to the American Psychiatric Association, approximately 
20-40 percent of individuals with autism spectrum disorders have 
apparently normal intellectual abilities and relatively intact language 
skills, but they still have difficulty with the social aspects of 
communication. These individuals are categorized as having high-
functioning ASD. In order to develop useful and appropriate treatment 
programs for them, scientists need to know what specific aspects of 
communication are most impacted. NIDCD-supported scientists have used 
standardized conversational tests to compare individuals with high-
functioning ASD to age-matched individuals without ASD. These 
comparisons enabled them to identify three main areas of conversational 
difficulty for individuals with high-functioning ASD: (1) Managing 
topics--responding in a way that is pertinent to the topic and 
identifying topics of interest to both parties; (2) Managing 
information--understanding how much information is enough and knowing 
what type of information to provide; and (3) Establishing reciprocity--
participating in a balanced back-and-forth exchange. Researchers can 
now use these results to develop personalized treatment programs 
targeted to improve existing conversational skills and build new skills 
in the areas of communication that are most affected in individuals 
with high-functioning ASD.
                        vocal fold regeneration
    The vocal folds--also referred to as vocal cords--are two elastic 
bands of tissue located in the larynx, or voice box, directly above the 
trachea, or windpipe. The vocal folds produce voice when air held in 
the lungs is released and passed through the partially closed vocal 
folds, causing them to vibrate. Vocal fold scars can result from injury 
or inflammation, or because of surgery to remove vocal fold nodules or 
polyps. The scars increase vocal fold stiffness and reduce their 
ability to vibrate. An individual with scarred vocal folds may have a 
hoarse, breathy, or low-pitched voice. NIDCD-supported scientists have 
developed a new class of soft gel material to serve as a scaffold to 
encourage regeneration of vocal fold tissue. Specific particles within 
the material can also be modified to bind and slowly release 
therapeutic drugs within the vocal folds as a way to further encourage 
regeneration of the tissue. This new material is currently being tested 
to learn what types of changes, such as particle size, distribution, 
and so on, will optimize tissue regeneration. Once the gel is optimized 
in laboratory tests, it may offer a potential future personalized 
treatment for individuals whose vocal folds have been damaged due to 
scarring.
    Mr. Chairman, I would like to thank you and members of this 
subcommittee for giving me the opportunity today to present examples of 
scientific advances made with the support of the NIDCD. I am pleased to 
try to answer your questions.
                                 ______
                                 
    Prepared Statement of Dr. Lawrence A. Tabak, Director, National 
             Institute of Dental and Craniofacial Research
    Mr. Chairman and members of the subcommittee: I am pleased to 
present the President's fiscal year 2010 budget request for the 
National Institute of Dental and Craniofacial Research (NIDCR) of the 
National Institutes of Health. The fiscal year 2010 budget includes 
$408,037,000 which is $5,385,000 more than the fiscal year 2009 
appropriation of $402,652,000.
                           facing the future
    Extraordinary advances have been made in recent years at the 
interface of traditional scientific disciplines. Multidisciplinary 
teams of scientists, engineers and clinicians have combined advances in 
biochemistry, cell and molecular biology, engineering, genetics, and 
neuroscience to gain a deeper understanding of the mechanisms 
underlying disease pathogenesis. This has yielded clues for the 
prediction of those most at risk for disease, approaches to 
personalized interventions, and strategies to prevent disease 
progression.
    For example, who has not marveled at the complexity of a face? Or 
how nature designed the mouth and its unique soft and hard tissues as a 
gateway to the body and, in some creatures, a first line of defense? 
Among Nature's greatest miracles of design and engineering is the 
craniofacial complex. Utilizing the many powerful research techniques 
and tools now available, teams of NIDCR-supported scientists are 
creating a publicly accessible informatics platform, termed FaceBase, 
that will enable multiscale analysis of all aspects of craniofacial 
development. This basic understanding is key to one day preventing and 
more effectively managing craniofacial defects and disorders. Each year 
thousands of infants are born with a variety of craniofacial 
dysmorphologies. While many of these conditions, such as cleft lip and/
or palate can be managed surgically and with supportive therapies, 
others are more challenging to treat. For example, children born with 
ectodermal dysplasias must deal with either malformed or multiple 
missing teeth.
    The NIDCR's new strategic plan captures the communal spirit 
required to address complex oral and craniofacial diseases and 
conditions. It lays out the challenges of the immediate road ahead for 
dental, oral, and craniofacial research--challenges that our 2010 
budget positions us to meet. But above all, our plan lays out the great 
promise that awaits scientists and the American public in the years 
ahead.
                       widen the scope of inquiry
    As the volume of biological information has grown, so, too, have 
the questions that scientists can ask. No longer must the human body be 
neatly subdivided into its constituent parts and studied in strict 
isolation, one organ from another. Biological clues in one part of the 
body often have application elsewhere in the body.
    An excellent example is oral cancer which results in more than 
7,500 deaths each year in this Nation. Unlike cancers that arise in the 
internal organs, tumors of the oral cavity are often readily accessible 
for biopsy and prompt study. This has allowed a dedicated corps of 
scientists to make tremendous inroads into defining the molecular 
errors that trigger the disease. For example, a key signaling pathway, 
termed Akt-mTOR, is frequently dysregulated in head and neck 
carcinomas. Their research efforts not only will improve the diagnosis 
and treatment of oral cancer, it also will provide comparative data and 
possible new leads for scientists who study other less accessible 
tumors.
    The same is true of research on the microbial biofilm that forms on 
the hard and soft tissues of the mouth. Oral health researchers have 
defined more than 600 microbes that inhabit the mouth and have spent 
generations studying the communal dynamics that contributes to common 
diseases, such as periodontal disease and tooth decay. This decades-
long head start will help to guide research now under way on the other 
biofilms that form throughout the body. This line of study emerges from 
the growing recognition that subtle shifts in the composition of the 
body's biofilms may play a major contributory role in myriad human 
diseases. Advances are being enabled by powerful new technologies that 
allow for the more facile sequencing and analysis of microbial genomes. 
Indeed, microbes that have not yet been cultivated are now amenable to 
study, in silico, which helps describe the lifestyle of each organism.
    NIDCR intends to make considerable investments in genome wide 
association studies of diseases and conditions affecting the 
craniofacial complex that will also inform pathology in other regions 
of the body. For example, an analysis of genes associated with 
Sjogren's syndrome, an autoimmune disease affecting 1 million or more 
Americans, will likely provide clues for other diseases such as 
rheumatoid arthritis or systemic lupus erythematosus. Chronic facial 
pain, including temporomandibular joint and muscle disorders, has begun 
to yield its secrets to the efforts of geneticists and neuroscientists. 
Particularly important are efforts to better understand the transition 
of acute to chronic pain. Compelling evidence suggests this may be 
related to neural plasticity, in a manner not dissimilar to mechanisms 
that underlie memory.
    These are but a few of the cross-cutting issues that are now on 
NIDCR's research agenda. To investigate them vigorously, the NIDCR must 
continue to encourage innovation and bring to bear the best science 
possible. But therein lays another challenge.
                        keep the pipeline strong
    For the Nation's oral health community to tackle NIDCR's ambitious 
research agenda successfully, it needs tight integration among 
research, practice, and education. This synergy holds the key to 
solving the many disorders that affect the oral and craniofacial 
complex. During 2010, the Institute will continue to emphasize training 
and career development for oral health professionals, to ensure that we 
increase a thriving community of dentist-scientists ready to capitalize 
on the rapid and significant advances occurring in biomedical and 
behavioral research. At the same time, the Institute must continue to 
attract scientists from outside its traditional research arenas. We 
will need to cover all of the scientific bases, from chemists and 
computer scientists to molecular biologists and mathematicians. All 
play critical roles and will be invaluable in ensuring that the best 
science moves rapidly into clinical studies. In an effort to strengthen 
the pipeline at every stage, the NIDCR is determined to maintain its 
high level of commitment in 2010 to funding new and early-stage 
investigators in a wide range of scientific fields.
                      promote clinical innovation
    Moving forward in the clinical realm will require a great deal of 
innovative thinking. In 2010, NIDCR will continue to lay the foundation 
for the next great revolution in oral healthcare: biology-based dental 
care. As the name suggests, dentistry will launch molecular-based 
healthcare over the next several decades. Using salivary-based 
diagnostics, this new oral health paradigm will provide patients with 
more precise diagnoses and a greater opportunity to practice 
prevention. Greater understanding of disease pathogenesis and the 
variation in individual susceptibility will yield targeted and 
personalized therapies to treat their conditions more efficiently. This 
will provide a better chance to maintain their teeth and supporting 
bone ultimately leading to a lifetime of high-quality health.
    To catalyze adoption of these advances, and to further the evidence 
base of the dental profession, in 2010, the NIDCR will continue to 
support its Practice Based Research Networks initiative, which now 
engages hundreds of dentists nationwide in scientific studies.
                       address health disparities
    As beneficial as biology-based dental care will be one day in 
improving the oral health of Americans, every effort must be made, now 
and in the future, to combat oral health disparities. Millions of 
primarily low-income Americans have yet to benefit fully from advances 
in dental care, including countless children and their families.
    The fiscal year 2010 budget request will allow the NIDCR to 
maintain strong support for its Centers for Research to Reduce Health 
Disparities. These Centers continue to demonstrate the value of 
partnering with communities throughout the research process in order to 
gain a complete understanding of the factors contributing to dental 
disease in each community and to develop appropriate intervention 
strategies. Emerging from this initiative will be a greater focus to 
identify the many complex factors that contribute to the disparities, 
targeted, multi-tiered research to address the problem, and coordinated 
efforts to promote greater awareness of oral disease.
    The Institute also plans to continue partnering with the Centers 
for Disease Control and Prevention to monitor the status of the 
Nation's oral health. As a part of this effort, the NIDCR will seek to 
validate new methods to measure and document oral, dental, and 
craniofacial diseases.
                       dental care in the future
    Biology-based dental care will transform the most fundamental 
principle of the profession: restoration of form and function. No 
longer will dentists rely as readily on mechanical instruments and 
ceramo-metallic materials to repair damaged tissue. They will 
regenerate form and function (a) using the precision of molecular 
information--or the underlying cause of the disease--as their 
operational guide and (b) employing the body's own cells and 
biochemistry as their engineering materials.
    Future dentists will possess more powerful optical instruments to 
visualize and accurately characterize whether near microscopic losses 
of mineral from a tooth surface will be self-correcting or whether they 
will progress to full blown decayed lesions. Advances in imaging, 
genomics and proteomics will allow a clinician to profile the circuitry 
of a tumor cell biopsied from the mouth. This diagnostic work-up will 
guide the choice of chemotherapy drugs to those that are most likely to 
target the internal wiring of the tumor cell and kill it. Targeted 
treatments will allow the removal of only the cancerous tissues.
    In closing, and as highlighted in our 2010 budget justification, 
the NIDCR will continue to invest in research and research training to 
meet emerging scientific opportunities and challenges. This budget 
request will enable us to work towards achieving the four goals 
outlined in our strategic plan. These goals are attainable, and in 
striving to meet them, we can realistically expect to improve the 
Nation's oral health for generations to come.
                                 ______
                                 
   Prepared Statement of Dr. Griffin P. Rodgers, Director, National 
        Institute of Diabetes and Digestive and Kidney Diseases
    Mr. Chairman and members of the subommittee: I am pleased to 
present the President's fiscal year 2010 budget request for the 
National Institute of Diabetes and Digestive and Kidney Diseases 
(NIDDK) of the National Institutes of Health (NIH). The fiscal year 
2010 budget includes $1,781,494,000, which is $20,156,000 more than the 
fiscal year 2009 appropriation of $1,761,338,000. Complementing these 
funds is an additional $150,000,000 also available in fiscal year 2010 
from the special statutory Type I Diabetes Research Program for NIDDK.
    Our Institute supports research on a wide range of common, chronic, 
costly, and consequential health problems that affect millions of 
Americans. These include diabetes and other endocrine and metabolic 
diseases; digestive and liver diseases; kidney and urologic diseases; 
blood diseases; obesity; and nutrition research. Additionally, 
consistent with the President's commitment to increase funding for 
cancer research, and with the HHS-wide initiatives on autism, NIDDK 
will support research relevant to these diseases.
                  genetic factors in complex diseases
    Many complex diseases within the NIDDK mission result from 
interactions amongst multiple genetic and environmental factors. 
Building upon the wealth of genetic information from the Human Genome 
Project, basic research on genetic contributors to these diseases lays 
the foundation for translation of knowledge into clinical settings, 
where it can be used to better predict and pre-empt disease 
development, as well as provide more personalized medical care.
    For example, the NIDDK supported recent research uncovering six new 
genetic variants involved in type 2 diabetes. Combined with previous 
genetic findings, this new knowledge can help to determine who is at 
risk for this disease and how it might best be treated and prevented. 
NIDDK research has also recently shown how a genetic variant associated 
with type 1 diabetes works to alter immune function, enhancing 
understanding of this disease and highlighting potential targets for 
therapy. NIDDK also contributed to international research efforts 
yielding an explosion of new genes or gene regions associated with the 
inflammatory bowel disease known as Crohn's disease. The total number 
of known susceptibility genes currently stands at more than 30, each of 
which promises fresh insights into this disease and its management. 
Genetic analyses have also identified contributors to other diseases 
within the NIDDK mission, including nonalcoholic fatty liver disease, 
liver cancer, and diabetes-related kidney disease. Some of this 
research addresses populations disproportionately affected by certain 
diseases. For example, genetic variants were identified that account 
for much of the burden of nondiabetic kidney disease in African 
Americans. These studies may lead to future screening strategies and 
more personalized therapies.
    The NIDDK also participates in trans-NIH efforts exploring how 
genetic factors impact disease. Data from an NIDDK-sponsored study of 
the genetics of diabetic kidney disease are being analyzed by the Gene 
Association Information Network to inform disease prevention, 
diagnosis, and treatment. The NIDDK leads two projects within the 
Genes, Environment, and Health Initiative, which studies effects of 
genetic variants on disease risk in response to environmental 
exposures. The NIH Roadmap Epigenomics Program is researching how 
epigenetics--or biochemical changes to DNA--can control genes during 
different stages of development, such as fetal epigenetic responses in 
the intrauterine environment and the risk of diabetes after birth.
                 clinical and population-based research
    Clinical and population-based research generates important 
information not only for developing more effective therapies, but also 
for identifying strategies to pre-empt disease development--both 
essential for the future of medical care. NIDDK-sponsored research 
informs screening efforts to detect early signs of susceptibility and 
prevent full-blown disease. For example, recent studies have proven the 
potential of intensive early colonoscopy screening for precancerous 
polyps in African Americans to reduce their disproportionate colon 
cancer burden.
    NIDDK-sponsored efforts are also testing interventions to address 
type 2 diabetes related to overweight in both adults and children. 
Researchers are studying obese adults with type 2 diabetes to observe 
the effects of lifestyle changes to lower risk of diabetes 
complications. Similarly, in children, a study is determining if 
healthier food choices in schools, increased physical activity, and 
improved awareness of healthy behaviors can reduce weight and lower 
risk factors for type 2 diabetes--a disease that was once seen only in 
adults, but has been increasing in American youth.
    Obesity continues to be one of our Nation's most pressing health 
problems. The NIDDK supports a multi-pronged obesity research effort 
that includes studies of molecular and environmental contributors to 
feeding behavior and metabolism, processes such as inflammation in 
metabolic tissues, bariatric surgery and other potential treatments for 
obesity, and lifestyle interventions to prevent or reverse obesity. For 
example, a recent study showed that modest reductions in time spent by 
children watching TV or using the computer have beneficial effects on 
their weight.
    Clinical research is also yielding new insights into the 
development and management of kidney, urologic, and liver diseases. 
Recent clinical studies showed the limited effectiveness of drugs to 
enable vascular access during hemodialysis for kidney failure and for 
treating chronic kidney disease due to high blood pressure in African-
American patients. A multi-center network is investigating causes of 
the two most common urologic pelvic pain disorders-interstitial 
cystitis/painful bladder syndrome and chronic prostatitis/chronic 
pelvic pain syndrome--which may yield new targets for managing these 
diseases. A new clinical research network conducting translational 
research on chronic hepatitis B is focused on understanding disease 
processes and applying this knowledge to more effective treatment and 
control strategies.
                    enhancing future health research
    The biomedical research enterprise will depend heavily on the next 
generation of investigators, innovative ideas of individual scientists, 
and the synergy of public-private partnerships. The NIDDK, along with 
the wider NIH, will continue its commitment to helping new 
investigators realize their potential through such efforts as special 
funding consideration, small grant and career awards, and mentoring 
workshops. The Institute also remains firmly committed to supporting 
investigator-initiated research. Public private partnerships through 
such entities as the foundation for the NIH will continue to expand the 
reach of NIDDK research.
    Strategic planning, analyses of disease burden, and research 
coordination are tools utilized by the NIDDK to advance research. 
Recently, the National Commission on Digestive Diseases--for which 
NIDDK provided leadership and support--released its long-range research 
plan, identifying challenges and opportunities for digestive diseases 
research. A separate report on the burden of digestive diseases in the 
United States was prepared by the NIDDK to inform this research plan. 
The ``NIDDK Prostate Research Strategic Plan,'' released in 2008, 
provides recommendations for future research efforts targeting the 
causes, prevention, and treatment of benign prostate disease.
    NIH recently initiated an effort to update its 2004 ``Strategic 
Plan for NIH Obesity Research'' in order to review research progress 
and identify new opportunities. This strategic planning effort is 
overseen by the NIH Obesity Research Task Force, which I co-chair 
together with Dr. Elizabeth Nabel, Director of the National Heart, 
Lung, and Blood Institute.
    Coordination to enhance research efforts across the NIH and with 
research partners in other Federal agencies is also achieved through 
the work of coordinating committees. The Diabetes Mellitus Interagency 
Coordinating Committee (DMICC) coordinates diabetes activities across 
the Federal Government and fosters opportunities for agency 
collaboration. In its coordinating role, the DMICC encourages Federal 
research collaborations, minimizes overlap of agency research efforts, 
and enhances public awareness of diabetes research and health 
information provided by Federal agencies. The DMICC is the focal point 
for diabetes research planning efforts.
                       promoting health awareness
    In addition to supporting health research, the NIDDK remains 
committed to ensuring that knowledge gained from research is used to 
promote health awareness. Relevant activities include the National 
Diabetes Education Program, National Kidney Disease Education Program, 
Weight-control Information Network, Celiac Disease Awareness Campaign, 
and programs to promote prevention of obesity and overweight.
    Recently, the NIDDK expanded its health information materials with 
a new Awareness and Prevention series of fact sheets. These 
publications are designed to raise awareness of diseases such as 
diabetes, digestive diseases, and kidney and urologic diseases among 
people not yet diagnosed with these illnesses. Materials produced by 
the NIDDK are often translated into multiple languages. For example, 
the Institute is currently developing Asian language materials on 
hepatitis B to reach people whose origins place them at higher risk--a 
priority highlighted at the NIH Consensus Development Conference on 
Management of Hepatitis B in October 2008.
    Another resource for promoting health awareness in affected groups 
is a set of teaching tools for school-based diabetes education in 
American Indians, who have the highest rates of diabetes in the United 
States. Through educating American Indian youth about diabetes 
prevention, these tools aim to reduce the incidence of type 2 diabetes 
in these young people and their families, as well as encourage entry 
into health-related careers.
                            closing remarks
    A key goal of the NIDDK is to maximize the return on research 
investments to derive the greatest health and economic benefits. 
Embedded in the population-based projects I mentioned is a 
consideration of their cost-effectiveness. As areas of research 
converge around common disease mechanisms--such as microbial influences 
on health--and research tools--like genetics-based technologies--
opportunities exist to leverage resources and foster collaborations. 
Past investments in sample repositories and databases can be extended 
in ancillary and follow-up studies. In these ways, the intrinsic 
economic benefit of NIDDK-sponsored research can be fully realized.
    In closing, I thank the chairman and members of the subcommittee 
for this opportunity to highlight some of the NIDDK's research and 
outreach efforts to improve our Nation's health. I would be pleased to 
answer any questions you may have.
                                 ______
                                 
Prepared Statement of Dr. Linda Birnbaum, Director, National Institute 
                    of Environmental Health Sciences
    Mr. Chairman and members of the subcommittee: I am pleased to 
present the President's fiscal year 2010 budget request for the 
National Institute of Environmental Health Sciences (NIEHS) of the 
National Institutes of Health. The fiscal year 2010 budget includes 
$684,257,000, which is $21,437,000 more than the fiscal year 2009 
appropriation of $662,820,000.
                              introduction
    NIEHS works at the forefront of public health to meet the 
challenges the field of environmental health sciences faces in the 21st 
century. Meeting these numerous and demanding challenges is vital to 
reducing and preventing disease burden across the Nation. As biological 
sciences generate a deeper understanding of the working of organisms at 
the molecular and systems levels, opportunities open to advance our 
knowledge of the effects of environmental exposures--not just the clear 
and obvious effects, but also the subtle, complex ways human health is 
affected by the environment. Tackling scientific questions with this 
level of complexity requires an ongoing evaluation of our ideas and 
approaches, and an emphasis on integration across disciplines--from 
computational and molecular, to clinical and public health, and 
everything in between. Our discoveries translate into improvements in 
environmental regulation, public health, and clinical practice.
    To improve our Nation's health, and to increase the benefits of our 
health care system, the use of medical interventions must go hand in 
hand with the adoption of behaviors aimed at disease prevention and 
wellness promotion. The goal of environmental health sciences is to 
remove human exposures to deleterious agents before disease processes 
and dysfunction begins. By advancing our understanding of the 
interactions of the environment with human health, and opening the door 
to new ways to prevent disease, NIEHS's investments serve to undergird 
a recovering economy and to support improvement of the health of our 
citizens, as well as our healthcare system. NIEHS budget request and 
research projects are also consistent with the President's multi-year 
commitment for cancer, autism, and nanotechnology.
               neurological disorders and the environment
    There is continued concern that neurological disorders such as 
autism, attention deficit hyperactivity disorder (ADHD), and adult 
onset diseases such as Parkinson's and Alzheimer's may be rooted in 
early exposures to environmental toxicants. NIEHS supports basic 
research to determine the mechanisms and pathways by which toxicants 
may bring about neural damage to the developing brain. Some of the key 
neurotoxicants being studied are metals such as lead, mercury, and 
manganese; pesticides; tobacco smoke; and polychlorinated biphenyls and 
polybromated diphenyl ethers used to make insulating and fire retardant 
products.
    With NIEHS support, the Children's Center at the University of 
California, Davis is conducting the first large-scale human population 
study of children with autism. These researchers are looking at a wide 
range of environmental exposures and their effects on early development 
in more than 1,000 California children. NIEHS researchers are also 
developing new and improved animal and cellular models for ADHD and 
autism--models that will help determine how neurotoxic substances may 
impact brain development and behavior, and may be useful in testing 
therapies.
            environmental health and safety of nanomaterials
    Engineered nanoscale materials display novel physical, chemical, 
and biological properties that contribute to new technologies useful 
for drug delivery systems, tissue engineering, biological and 
environmental sensor technology, and environmental remediation. By 
2015, the global nanotechnology market is projected to exceed $15 
billion. Nanotechnology, like all emerging technologies, should create 
innovation while minimizing risk of adverse health effects, and health 
effects of exposure should be assessed prior to extensive use. Safety 
assessment is challenging due to the diversity of materials used to 
synthesize nanoparticles, as well as the wide range of physical and 
chemical properties that emerge at the nanoscale. NIEHS and the 
National Toxicology Program (NTP), which is headquartered at NIEHS, 
support research on the impact of size and size-dependent properties of 
nanomaterials on biological response at the systemic, cellular, and 
molecular levels. This research has begun to demonstrate trends in the 
relationship of physical and chemical properties to biological 
response. NIEHS and NTP will continue to support research that 
increases the understanding of potential health impacts of these novel 
materials, as well as help to guide development of nano-enabled 
products to reduce adverse health impacts in our increasingly exposed 
population.
             environmental disruptors of endocrine systems
    Chemicals can mimic the hormones of our endocrine system and 
disrupt its functions, with potentially adverse effects on health and 
development. A consensus statement expressing concerns about the 
possible health effects of one such chemical, Bisphenol A (BPA), was 
issued by an expert panel as a result of a meeting organized by NIEHS 
in November 2006.
    NTP also recently completed an evaluation of BPA. BPA was selected 
for evaluation because of the volume produced, widespread human 
exposure, extensive animal data on reproductive and developmental 
effects, and growing public concern. BPA is used in plastic water 
bottles and containers, in some medical tubing, and in the plastic 
coating inside of food cans, among other uses. Data from the Centers 
for Disease Control and Prevention showed BPA in 93 percent of 2,517 
urine samples from people 6 years and older. The NTP evaluation graded 
various health concerns on a six-level scale: serious concern for 
adverse effects; concern; some concern; minimal concern; and negligible 
concern. NTP concluded there is ``some concern'' for effects on the 
development of the brain and behavior, and prostate gland development, 
in fetuses, infants, and children at current exposures, and ``minimal 
concern'' for effects on mammary gland and earlier age of female 
puberty in fetuses, infants and children at current levels of exposure. 
As a result of NTP's work, scientists at the Food and Drug 
Administration are reviewing their policies on BPA.
    In separate NIEHS-supported studies in rats, BPA exposure induced 
changes in the mammary gland that were time and dose specific, so that, 
for example, high-dose exposure resulted in architectural modifications 
in the number of undifferentiated epithelial structures of the breast 
tissue. High-dose exposures induced changes in genes related to cell 
differentiation suggesting alterations in the normal development of the 
gland. These studies are part of the larger NIEHS-National Cancer 
Institute program of Breast Cancer and Environmental Research Centers; 
NIEHS expects that these and other research findings will shed light on 
the ways in which environmental exposures can influence the risk of 
breast cancer in women.
                     hexavalent chromium and health
    Chromium compounds, such as hexavalent chromium, are widely used in 
electroplating, stainless steel production, leather tanning, textile 
manufacturing, and wood preservation. The United States is one of the 
world's leading producers of chromium compounds. Hexavalent chromium 
compounds have been shown to cause lung cancer in humans when inhaled, 
but it was not known whether these compounds could also cause cancer 
when ingested; hence they were nominated for NTP toxicity and 
carcinogenicity testing because of concerns over its presence in 
drinking water, its potential health effects, and the lack of adequate 
cancer studies on ingested hexavalent chromium.
    NTP studies showed that sodium dichromate dehydrate, a compound 
containing hexavalent chromium, causes cancer in laboratory animals 
following oral ingestion. Male and female rats developed malignant 
tumors in the oral cavity. In mice, the studies showed dose-related 
increases in the number of benign and malignant tumors in the small 
intestine. This is the first and only lifetime study that clearly 
demonstrates the carcinogenicity of hexavalent chromium in rodents 
after oral exposure.
    The results of these studies were closely monitored by many groups, 
including the affected industries and numerous national and 
international public health and regulatory agencies. The data will most 
certainly be used as the basis to develop State and Federal drinking 
water and soil cleanup standards, and will have significant public 
health impact on thousands of people exposed to hexavalent chromium in 
contaminated drinking water and soil.
                               conclusion
    These examples highlight important NIEHS and NTP research on the 
environmental connection to human disease and stand in for other vital 
research supported by the Institute. Research, such as the Sister 
Study, an epidemiological study following a cohort of 50,000 sisters of 
women diagnosed with breast cancer, promises to produce ground breaking 
information on the environment's role in the causation of breast 
cancer.
    The field of environmental health sciences is beginning a new 
chapter of scientific progress, with new and better tools at our 
disposal, an expanding understanding of the human genome and its 
relationship with the environment, and young scientists coming into the 
field who are well-prepared and eager to apply these tools and 
knowledge to our current scientific challenges. I am honored, as 
Director of NIEHS and NTP, to facilitate the challenges and 
opportunities ahead to alleviate suffering and improve human health.
                                 ______
                                 
Prepared Statement of Dr. Jeremy M. Berg, Director, National Institute 
                      of General Medical Sciences
    Mr. Chairman and members of the subcommittee: I am pleased to 
present the fiscal year 2010 President's budget request for the 
National Institute of General Medical Sciences (NIGMS). The fiscal year 
2010 budget includes $2,023,677,000, which is $25,876,000 more than the 
fiscal year 2009 appropriation of $1,997,801,000.
    Each year, NIGMS-supported scientists uncover new knowledge about 
fundamental life processes. While answering basic research questions, 
these scientists expand our awareness and understanding of how disease 
takes hold in the body. Institute grantees also develop important new 
tools and techniques that have research and medical applications. The 
payoffs from NIGMS research investments are impressive on many fronts. 
As just one example, 67 scientists have received Nobel Prizes in 
recognition of the scientific breakthroughs they made with NIGMS 
support.
                    genetic studies guide treatments
    The future of medicine will center on precise diagnosis and 
personalized treatments. This is a departure from most of today's 
medical approaches, which are based on studies of populations and one-
size-fits-all statistics derived from them. The ability to pre-
emptively tailor healthcare to individuals offers huge potential for 
increasing the efficiency and effectiveness of efforts to preserve 
health over the course of a lifetime.
    Americans are eager for information that will help them make 
intelligent, individualized choices about their health. Toward this 
end, in 2000 NIGMS partnered with a number of other National Institues 
of Health (NIH) components in launching an effort to determine how 
genes affect the way people respond to medicines, including 
antidepressants, chemotherapy agents, and drugs for asthma and heart 
disease. Since then, studies by this Pharmacogenetics Research Network 
(PGRN) have shown that genetic information can help predict how beta-
blockers, breast cancer medications, and nicotine patches will work in 
a specific person. In early 2009, PGRN researchers merged data sets 
from around the world to demonstrate that information about certain 
genetic variations could aid doctors in determining the proper, 
personalized dose of warfarin, a blood-thinning drug taken by millions 
of Americans. This work set the stage for a prospective clinical trial 
that will test if using such genomic information will make it quicker 
and easier to get the right dose and furthermore, whether doing so 
could prevent serious treatment complications like heart attacks, 
strokes, and internal bleeding.
    Other NIGMS-funded genetic studies have revealed surprising roles 
for RNA. Nobel laureates Andrew Fire and Craig Mello paved the way for 
this paradigm shift by showing that a process called RNA interference, 
or RNAi, silences the activity of targeted genes. RNAi is now being 
widely used both as a research tool and for the development of products 
that could combat diseases like cancer and HIV. In 2008, other NIGMS-
supported scientists won the prestigious Lasker Award for their 
groundbreaking discovery of microRNAs, short RNA molecules that 
regulate gene function using some of the same mechanisms central to 
RNAi. Our rapidly expanding understanding of RNA's many roles is 
already providing novel medical insights, such as the linkage of 
abnormal microRNA levels to cancer and other diseases.
                physical sciences shine light on biology
    The intersections between fields of science--such as those between 
the physical sciences of physics, chemistry, mathematics, and computer 
sciences and the biomedical and behavioral sciences--often yield 
particularly fruitful and high-impact lines of investigation. One 
timely example is the NIGMS-supported computational modeling tools 
being used to predict the spread of emerging infectious diseases and 
the results of possible interventions. These field-spanning approaches 
provide important insights to help policymakers and public health 
officials respond to outbreaks, including H1N1 flu.
    Further evidence of how basic physical science can greatly 
contribute to biomedical research is found in nuclear magnetic 
resonance (NMR). This technique, developed by physicists in the 1930s, 
underlies the well-known medical procedure of magnetic resonance 
imaging. But in the laboratory, NMR is the basis of some of the most 
powerful analytical methods in chemistry and biochemistry. In 2008, 
NIGMS-funded researchers used NMR to identify a contaminant in several 
batches of another widely used blood-thinning medicine, heparin. The 
scientists determined the chemical structure of the contaminant, which 
was only subtly different from heparin and therefore difficult to find 
by other methods, and showed how the contaminant could cause severe 
reactions and even death in humans. As a result of this work, NMR may 
now be used to screen additional drug preparations for contaminants 
that are difficult or impossible to detect by other means.
    A physics-based technique called X-ray crystallography is also key 
to understanding molecules that are central to health and disease. 
Using this approach along with NMR, scientists funded through a 
coordinated NIGMS effort called the Protein Structure Initiative (PSI), 
have produced a wealth of information about the shapes of proteins, 
which are essential to their functioning. Following successful pilot 
and production phases that included the development of critical tools 
and techniques, the Institute is now focusing the PSI on structures 
with specific biological roles and expanding its reach throughout the 
scientific community. This new direction, called PSI:Biology, will 
emphasize partnerships between biologists and high-throughput structure 
determination centers to address important biomedical problems and 
provide information that will aid the development of new medicines.
    Among the advances from chemistry studies are powerful imaging 
techniques that allow scientists to visualize life processes in 
unprecedented detail. The discovery and development of green 
fluorescent protein (GFP) is a case in point. GFP was first purified 
from jellyfish in 1962, and before long, NIGMS-funded American 
researchers were finding ways to use this new tool to monitor 
activities in living cells and organisms. These scientists, who won the 
2008 Nobel Prize in chemistry for their insights, put the GFP gene into 
a variety of organisms, including bacteria and worms. Today, GFP is an 
essential part of the fabric of biological research and is used, for 
example, as a key component of powerful drug development tools.
                     finding and funding innovation
    To keep knowledge streaming from the Nation's scientific 
laboratories, we must be agile in responding to the changing needs of 
researchers, both individuals and teams. The Institute has been a 
pioneer in novel funding programs that address the needs of the 
scientific community and encourage innovation. One good example is 
Konrad Hochedlinger, who received an NIH Director's New Innovator Award 
in 2007. This program, which NIGMS developed and administers, jump-
starts the careers of unusually creative early stage investigators. 
Since groundbreaking work in 2007 in which other NIGMS-funded 
scientists reprogrammed ordinary skin cells to become induced 
pluripotent stem cells (iPS) this area of inquiry has exploded. Dr. 
Hochedlinger's project aims to unravel the many details of how 
reprogramming works. He is currently working on creating 
``reprogrammable mice'' in which every cell can become an iPS cell 
capable of morphing into any cell type.
    Another New Innovator is explaining basic behavioral principles 
using animal models. Karin Pfennig is studying how different species of 
toads choose a mate, a decision that has costs and benefits and 
involves trade-offs. Understanding the fundamental drivers of such 
``context-specific'' behavior may help us treat behavioral disorders in 
people and address behavioral aspects of disease transmission and 
spread.
    Dr. Pfennig has contributed to the research enterprise in another 
important way. As part of its commitment to training the next 
generation of scientists and increasing the diversity of the scientific 
workforce, NIGMS developed the Institutional Research and Academic 
Career Development Award (IRACDA). This program gives postdoctoral 
scientists mentored teaching experiences at minority-serving 
institutions. Through IRACDA, Dr. Pfennig pursued her own cutting-edge 
research at the University of North Carolina, Chapel Hill, while also 
teaching at a historically Black college, North Carolina Central 
University. Dr. Pfennig, who grew up in a single-parent household with 
very limited resources, attributes her desire to ``give back'' to her 
own great teachers and mentors who challenged her to pursue her 
ambition to become a scientist. Programs like IRACDA pay lasting 
dividends on many levels, providing role models for students, preparing 
future teachers, and promoting partnerships between institutions.
                investing today for american prosperity
    In addition to building a solid foundation of knowledge for medical 
advances, basic biomedical and behavioral research yields tangible 
economic benefits. NIGMS grants support the salaries and laboratories 
of thousands of researchers throughout the United States. And NIGMS-
funded advances have played a significant role in the development of 
the multi-billion-dollar biotechnology industry, which is now its own 
engine of discovery as well as a critical partner to the pharmaceutical 
industry.
    I want to close by affirming the Institute's deep appreciation for 
the extraordinary opportunities provided by the American Recovery and 
Reinvestment Act of 2009. In addition to its impact on stimulating the 
Nation's economy, this legislation will enable scientists to uncover 
new knowledge that will lead to better health for everyone. We intend 
to use these funds to support highly meritorious research that could 
not be funded with our regular appropriations and to further accelerate 
the tempo of science through targeted supplements to existing grants. 
NIGMS is also addressing research projects which are consistent with 
the President's multi-year commitment for cancer and autism. We are 
also eager to fund creative studies sparked by the new NIH Challenge 
and Grand Opportunities grant programs, which are designed to focus on 
health and science problems where significant progress can be expected 
in 2 years.
    Thank you, Mr. Chairman. I would be pleased to answer any questions 
that the subcommittee may have.
                                 ______
                                 
Prepared Statement of Dr. Thomas R. Insel, Director, National Institute 
                            of Mental Health
    Mr. Chairman, and members of the subcommittee: I am pleased to 
present the President's fiscal year 2010 budget request for the 
National Institute of Mental Health (NIMH) of the National Institutes 
of Health (NIH). The fiscal year 2010 budget includes $1,474,676,00, 
which is $24,185,000 more than the fiscal year 2009 appropriation of 
$1,450,491,000.
                 public health burden of mental illness
    According to the most recent estimates, roughly 12.5 million 
American adults reported mental illness symptoms so severe as to cause 
them significant disability in the past year.\1\ \2\ According to the 
World Health Organization, mental disorders are the leading cause of 
medical disability in the United States and Canada for people under age 
45. In contrast to many other chronic medical conditions, mental 
disorders typically begin at an early age, usually before the age of 
30. Indeed, mental disorders, such as schizophrenia, depression, and 
bipolar disorder, are increasingly recognized as the chronic medical 
illnesses of young people. These illnesses also shorten people's lives. 
Americans with serious mental illness die, on average, 25 years earlier 
than the general population.\3\
---------------------------------------------------------------------------
    \1\ Kessler RC, Chiu WT, Demler O, Walters EE. Prevalence, 
severity, and comorbidity of twelve-month DSM-IV disorders in the 
National Comorbidity Survey Replication (NCS-R). Archives of General 
Psychiatry, 2005 Jun;62(6):617-27.
    \2\ U.S. Census Bureau. Population Estimates by Demographic 
Characteristics. Table 2: Annual Estimates of the Population by 
Selected Age Groups and Sex for the United States: April 1, 2000 to 
July 1, 2004 (NC-EST2004-02) Source: Population Division, U.S. Census 
Bureau Release Date: June 9, 2005. http://www.census.gov/popest/
national/asrh/
    \3\ Parks J, Svendsen D, Singer P, Foti ME (Eds.). Morbidity and 
mortality among people with serious mental illness. Alexandria, VA: 
Medical Director's Council, National Association of State Mental Health 
Directors (NASMHPD). October 2006. http://www.nasmhpd.org/
general_files/publications/med_directors_pubs/
Technical%20Report%20on%20Morbidity%20and%20 Mortaility%20-
%20Final%2011-06.pdf
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    The annual economic costs of mental illness in the United States 
are enormous. The direct costs of mental health treatment represent 6.2 
percent of all healthcare spending, \4\ which, according to the Centers 
for Medicare and Medicaid Services, totaled 15.8 percent of the gross 
domestic product in 2003. Indirect costs associated with mental 
illness, which include all nontreatment-related costs such as lost 
earnings, Social Security disability payments, homelessness, and 
incarceration, account for even greater expenses than the costs of 
direct mental healthcare. A recent study found that serious mental 
illnesses cost the United States at least $193 billion annually in lost 
earnings alone.\5\ A conservative estimate places the total direct and 
indirect annual costs of mental illness at well over $300 billion.\6\
---------------------------------------------------------------------------
    \4\ Mark TL, Levit KR, Coffey RM, McKusick DR, Harwood HJ, King EC, 
Bouchery E, Genuardi JS, Vandivort-Warren R, Buck JA, Ryan K. National 
Expenditures for Mental Health Services and Substance Abuse Treatment, 
1993-2003. SAMHSA Publication No. SMA 07-4227. Rockville, MD: Substance 
Abuse and Mental Health Services Administration, 2007. http://
www.samhsa.gov/spendingestimates/SAMHSAFINAL9303.pdf.
    \5\ Kessler, RC, Heeringa S, Lakoma MD, Petukhova M, Rupp AE, 
Schoenbaum M, Wang PS, Zaslavsky AM. The individual-level and societal-
level effects of mental disorders on earnings in the United States: 
Results from the National Comorbidity Survey Replication. Am J 
Psychiatry. 2008 Jun; 165(6):703-11.
    \6\ Insel TR. Assessing the economic cost of serious mental 
illness. Am J Psychiatry. 2008 Jun; 165(6):663-5.
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              mental disorders are chronic brain disorders
    NIMH's mission is to transform the understanding and treatment of 
mental illnesses through basic and clinical research, paving the way 
for prevention, recovery, and cure. These illnesses can now be studied 
as brain disorders, as they are becoming more accessible to medical 
science by using the tools of modern neuroscience. These disorders 
frequently begin in childhood and are chronic, affecting people of all 
races and ethnicities, in both rural and urban settings. To prevent a 
lifetime of disability for millions of Americans, NIMH research is 
directed toward identifying the biological basis of mental disorders, 
examining the psychological and social aspects that contribute to the 
disorders, and pinpointing targets for improved prevention, diagnosis, 
and treatment.
                    mental healthcare in the future
    In the future, the practice of medicine will be increasingly 
predictive, pre-emptive, personalized, and participatory. Genetics and 
clinical neuroscience will make this possible for mental illnesses. 
Clinical neuroscience seeks to discover fundamental knowledge about the 
brain and behavior and to use this knowledge to develop better tools 
for prevention, diagnosis, and treatment. For instance, biomarkers can 
detect risk to permit prevention, neuroimaging may facilitate 
diagnosis, and the discovery of new molecular targets should yield 
novel treatments. The study of pathophysiology is fundamental for 
NIMH's mission, which is to use science to transform care: not merely 
to reduce symptoms among persons with mental illness, but to promote 
recovery among this population and ultimately to discover pre-emptive 
interventions that can prevent psychosis, disability, and suicide.
    In pursuit of this mission, NIMH is in the process of implementing 
its new Strategic Plan, which details the scientific priorities that 
will direct and accelerate mental health research in the years to come. 
The American Recovery and Reinvestment Act of 2009 (the Recovery Act) 
directs part of the Nation's stimulus funding to support job creation 
and retention in the field of biomedical research. These supplemental 
funds present an exciting opportunity for NIMH, allowing us to 
jumpstart the groundbreaking science outlined in the Strategic Plan, as 
well as the strategic plans of the NIH Office of AIDS Research and the 
Interagency Autism Coordinating Committee (IACC). This commitment will 
expand our knowledge about the underlying biology of mental disorders 
and accelerate the development of improved diagnostic measures and 
treatments. The fiscal year 2010 budget continues support for the IACC. 
NIH will receive $1 million from the Office of the Secretary to support 
the Committee.
    Mental healthcare in the future will be based on the ability to 
predict those most at risk, prevent the onset of disorder, and, in 
cases where prevention is not possible, develop treatments tailored to 
the individual. This requires collaboration among the diversity of 
people affected, including mental healthcare providers, researchers, 
and people with mental illness and their families. An example of NIMH 
research taking this approach is our recent partnership with the U.S. 
Army to reduce suicide among soldiers. The high rates of mental health 
and behavioral adjustment problems among recent U.S. military combat 
veterans and the increasing rates of suicide among Army soldiers are of 
growing concern. To address this issue, NIMH and the U.S. Army are 
collaborating on a $50 million research project, which will be the 
largest single study NIMH has undertaken on the subject of suicide. The 
project seeks to strengthen the Army's efforts to reduce suicide among 
soldiers by identifying the risk and protective factors associated with 
suicidal thinking and behavior. While targeted for the Army, the 
study's findings will also inform our understanding of suicide in the 
other Armed Forces as well as the overall population, leading to more 
effective prevention and treatment for servicemembers and civilians 
alike.
    While we have long known that mental disorders are brain disorders, 
recent research has begun to reconceptualize these illnesses as 
disorders of brain development. Between infancy and adulthood dramatic 
changes are taking place in the brain, not only in size, but also in 
structure and function. Understanding these changes and how these 
trajectories can go off course provides unprecedented promise for the 
prediction and prevention of mental disorders, as well as opportunities 
to harness this knowledge to improve treatments for individuals who go 
on to develop a disorder, either in childhood or in early adulthood. As 
an example, research on brain development in children with attention-
deficit/hyperactivity disorder (ADHD) from the NIMH Intramural program 
recently reported a striking delay in cortical maturation. Between ages 
5 and 15, the maturation of the prefrontal cortex was found to be 
delayed by roughly 3 years in children with ADHD compared to age-
matched children without the disorder. Current studies are now 
exploring the effects of treatment on the rate of cortical maturation.
    The prototype neurodevelopmental disorder for NIMH is autism. 
Matching the increasing public health urgency of autism, NIMH research 
over the past year has yielded important discoveries on the 
pathophysiology of autism spectrum disorders (ASD). Research has shown 
that different cases of ASD could potentially be traceable to any of 50 
or more variations in the genome, alone or in combination, suggesting 
that ASD may be the final common path for many different genetic 
abnormalities. Most of the genes implicated are critical for brain 
development. For example, independent teams of researchers have linked 
inherited variations in a gene on Chromosome 7, called CNTNAP2, with 
ASD. CNTNAP2 is part of a family of genes that make proteins that play 
a key role in building the machinery by which brain cells communicate. 
One variation of this gene was found to influence the age at which 
children with ASD say their first word. Another variation was 
identified that increases the risk for ASD, but mainly when it is 
inherited from mothers. These studies provide evidence that CNTNAP2, 
when disrupted, may represent one path to the development of ASD. In 
addition to breakthroughs in the genetics of autism, recent research 
has provided new tools for diagnosing autism as early as the first 
birthday. Early diagnosis is critical because early intervention is 
associated with the best outcomes.
    In order to build upon these research advances, NIMH will be using 
Recovery Act funding as an opportunity to fuel further research on ASD, 
including its underlying biology, methods for earlier and more 
effective diagnosis, and improvements in treatment. The new IACC 
Strategic Plan for ASD Research provides the scientific goals and 
benchmarks for this endeavor (www.iacc.hhs.gov). NIMH, in collaboration 
with other NIH Institutes, has issued a series of funding opportunity 
announcements (FOA) to address the heterogeneity of ASD. This will be 
the largest single funding opportunity for ASD research in NIH's 
history. NIMH may contribute as much as $30 million of the total $60 
million of Recovery Act funds that NIH has set aside for this effort 
(actual expenditures will depend on the proposals received). These FOAs 
encourage applications for 2-year projects that address ASD 
measurement, identification of biomarkers and biological signatures, 
immune and central nervous systems interactions, genetics/genomics, 
environmental risk factors, and ASD intervention and treatment. 
Additionally, we will be supporting autism research with Recovery Act 
funding through NIH's new Challenge Grants in Health and Science 
Program. This program encourages applications on a diverse range of 
research topics, such as improving access to services by individuals 
with ASD and their families and expanding NIH's National Database for 
Autism Research in order to accelerate the availability of new data for 
the ASD research community. Finally, NIMH intends to continue to build 
its investment in autism research via its base budget, which supports a 
new intramural program for autism research, Autism Centers of 
Excellence, and a broad range of individual grants for research and 
training related to ASD.
    Understanding the pathophysiology underlying mental disorders will 
not only lead to the improved prevention, diagnosis, and treatment of 
the disorders themselves, but will also help to clarify the 
relationships that exist between mental disorders and other physical 
health problems, such as cancer. People with mental disorders smoke 
cigarettes at twice the rate of those without such a disorder, and they 
consume 44 percent of all cigarettes smoked in the United States.\7\ 
NIMH research is not only addressing this major public health problem 
through behavioral studies on smoking cessation techniques in these 
populations, but is also seeking to understand the underlying causes of 
smoking behavior. Several studies are examining the link between 
cognitive function, which is often disrupted in severe mental illness, 
and its improvement through nicotine use. By gaining better insight 
into how nicotine influences neural mechanisms, NIMH researchers are 
hoping to discover new ways of improving cognitive function among 
people with mental illness, ultimately reducing the severe health 
consequences associated with tobacco use.
---------------------------------------------------------------------------
    \7\ Ziedonis D., et al. Tobacco Use and Cessation in Psychiatric 
Disorders: National Institute of Mental Health Report. Nicotine Tob 
Res, 2008;10: 1-25.
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    In summary, we are well positioned to fulfill the promise of 
predictive, pre-emptive, personalized, and participatory medicine in 
the future. By using the best tools, funding the best science, 
listening to our partners, and engaging our communities, we continue to 
make progress toward our goal of transforming the understanding and 
treatment of mental illnesses through basic and clinical research, 
paving the way for prevention, recovery, and cure.
                                 ______
                                 
Prepared Statement of Dr. Story C. Landis, Director, National Institute 
                  of Neurological Disorders and Stroke
    Mr. Chairman and members of the subcommittee: I am pleased to 
present the President's fiscal year 2010 budget request for the 
National Institute of Neurological Disorders and Stroke (NINDS) of the 
National Institutes of Health (NIH). The fiscal year 2010 budget 
includes $1,612,745,000, which is $19,401,000 more than the fiscal year 
2009 appropriation of $1,593,344,000.
    The important and challenging mission of NINDS is to reduce the 
burden of neurological disorders through research. Hundreds of 
disorders of the brain, spinal cord, and the nerves of the body affect 
people of all ages. Collectively, they cause an enormous burden in lost 
life, disability, and suffering, and cost billions of dollars each year 
in medical expenses and reduced productivity. The causes of nervous 
system disorders are diverse; among them are physical forces of 
traumatic brain injury, slow degeneration of nerve cells in Parkinson's 
and Alzheimer's disease, gene mutations in brain tumors and inherited 
diseases, blood vessel block or bleeding in stroke, and toxic effects 
of treatments for cancer, HIV/AIDS, and other diseases. Compounding the 
challenge, the brain and spinal cord are intricate in structure, 
difficult to access, sensitive to intervention, and do not readily 
repair themselves following damage.
                        planning for the future
    Over the last 2 years, NINDS has engaged the scientific community 
and the public in strategic planning to meet these challenges. Planning 
took a ``blue sky'' look at the future, but also gave outside experts 
unprecedented access to data about NINDS programs to inform 
recommendations of practical steps to better carry out our mission. 
Even as we finalize the strategic plan and seek further public input, 
we are implementing recommendations. One major lesson from planning is 
the importance of program evaluation; based on the results we are 
reallocating resources to maximize public health impact. Perhaps the 
most important message for today, however, is not at the level of 
program details, but about where we stand with respect to the NINDS 
mission-treatments for neurological disorders are still far from 
adequate, but research is yielding remarkable progress, and the 
prospects for the future are very encouraging.
    NINDS's budget request and its research projects are consistent 
with the President's multi-year commitment for cancer and autism.
                                 stroke
    Stroke, the ``S'' in NINDS, shows how far we have come and how far 
we have to go. Stroke remains the third leading cause of death in the 
United States and a major cause of long-term disability. However, 
American Heart Association statistics show that the age-adjusted stroke 
death rate decreased by 29.7 percent from 1995 to 2005, and actual 
stroke deaths declined by 13.5 percent, resulting in thousands of lives 
saved. Many NIH research studies contributed to the decline by 
predicting who is at risk for stroke, who will do best on which drug, 
and whether surgery to clean a carotid artery or repair an aneurysm is 
worth the risk for a particular patient. Research on stroke prevention 
is continuing apace, including research on the geographic and racial 
disparities.
    About a decade ago, a NINDS clinical trial demonstrated that 
appropriate use of the clot buster tPA can restore blood flow to the 
brain and significantly improve outcome from stroke. New clinical 
trials are building on this first successful emergency treatment by 
testing whether ultrasound improves tPA's effectiveness to break up 
clots in large brain arteries and whether direct injection of tPA into 
a blocked brain artery or clot retrieval devices may help some 
patients. Despite its proven benefit, too few people now receive tPA, 
which must be administered after specialist assessment and within a few 
hours of a stroke. A trial this year showed that telemedicine can 
expand access to emergency stroke treatment to areas of the country 
without specialized stroke centers. A second trial is assessing whether 
emergency personnel in the field can rapidly deliver a therapy to 
protect the brain prior to reaching a hospital. Beyond prevention and 
emergency treatment, a major challenge for stroke, as for traumatic 
brain injury, is promoting recovery after brain damage has occurred. 
Rehabilitation that harnesses the brain's ``plasticity'' is showing 
promise in people, and trials are assessing the most effective 
strategies, but there is still a long way to go.
                        genes and brain diseases
    Although there are hundreds of neurological disorders, common 
themes unify research across diseases. One lesson of planning is the 
importance of engaging the insight and ingenuity of researchers 
throughout the United States to recognize shared disease mechanisms and 
common therapeutic strategies. Research on genes is one unifying theme 
that spans many areas of basic and clinical science.
    A first wave of progress identified single gene defects that cause 
more than 200 neurological disorders, and continues with new findings 
in inherited types of ALS and other diseases. Often, the most immediate 
benefit of gene findings is genetic tests, which can spare families 
expensive and frustrating diagnostic odysseys to find out what is wrong 
with their child. Even when a single gene defect is identified, major 
obstacles confront therapy to correct the defect, especially in the 
brain, but there is progress; this year, for example, a preliminary 
clinical trial established the feasibility of gene transfer to treat 
Batten disease. Genes can also provide the first foothold on 
understanding causes and developing drug treatments, leading to 
rational therapy development programs, as NINDS has underway for 
muscular dystrophy, spinal muscular atrophy, and other disorders. 
Although most brain tumors are not inherited, acquired gene defects 
drive tumor formation. Observing which genes are affected in 
glioblastoma and other brain tumors is suggesting which tumors respond 
to which cancer drugs and providing clues to developing more effective 
treatment.
    Recently, scientists have begun to crack the more complex ways that 
variations in multiple genes together contribute to common neurological 
disorders and shape individual differences in therapy response. Gene 
tests show promise for establishing the appropriate dose of the drug 
warfarin, which is commonly used to prevent stroke in people with 
certain risk factors. Warfarin now requires frequent blood tests to 
find the safe and effective dose because of variability among people, 
and people are at risk until the dose is set. Genome-Wide Association 
Studies (GWAS) are one method that has associated genes with multiple 
sclerosis, Parkinson's disease, stroke, and other common disorders. For 
example, understanding autism is an NIH-wide priority, and
    GWAS recently implicated molecules that have been studied in the 
development of connections among nerve cells, linking a dynamic area of 
basic research to this disease.
              translating scientific insights to therapies
    NINDS basic and clinical research yield understanding of disease 
and clinical tools that are essential for therapy development in the 
private sector. The Institute has also long pursued translational 
opportunities that are not likely to be targeted by others, whether 
because bold therapeutic strategies present uncertainty and long 
development horizons that are not tolerable to investors, rare diseases 
represent a small market, or developments in surgery and interventions 
using existing drugs may not recapture investments. The NINDS 
Intramural program developed the first successful enzyme therapy for 
inherited disease. Among applied NINDS extramural programs, the 
Anticonvulsant Screening Program has catalyzed the development of 
several epilepsy drugs now on the market, and the Neural Prosthesis 
Program successfully pioneered devices to restore lost nervous system 
functions. In 2003, NINDS moved from selective translational research 
in a few areas, to a broad effort to capitalize on opportunities across 
all neurological disorders by initiating the Cooperative Program in 
Translational Research. This program supports academic and small 
business investigator-initiated preclinical therapy development, using 
milestone driven funding and peer review expertise and criteria 
tailored to therapy development. Therapies from this program have 
received investigational approval from the FDA and are moving to 
clinical trials. Based on the advice of strategic planning advisory 
panels, which included industry experts, NINDS has created an Office of 
Translational Research and recruited a leader who has extensive drug 
development expertise. The new office will coordinate and focus NINDS 
applied programs more effectively on therapy development, without 
reducing NINDS commitment to basic and clinical research that is the 
foundation for progress. As new opportunities for therapy development 
emerge, we cannot let them languish in the ``valley of death'' between 
the idea and the success.
    Progress against two gene disorders that cause nervous system 
tumors illustrates how basic understanding of disease can drive 
research toward treatment. In people who have neurofibromatosis type 1, 
tumors grow within nerves and can cause disabling symptoms by 
compressing nerve, spinal cord, and other organs. Several years ago 
NIH-funded investigators discovered gene mutations that cause the 
disease and developed animal models that mimic the human disorder. 
After years of work, researchers discovered how the mutant gene causes 
cells associated with nerves to develop tumors, and then recruit other 
cell types and blood vessels to the tumor. Once researchers understood 
the molecular steps, they recognized that the cancer drug Gleevec acts 
on the same molecules. They are now testing the drug in people who have 
neurofibromatosis.
    Tuberous sclerosis complex is another disorder in which tumors, 
called tubers, can grow in nearly any tissue, including the brain. Many 
people with this disease also develop epilepsy or autism. Again, 
finding genes led to understanding of the molecular steps in disease, 
and scientists recognized that an available drug, rapamycin, which is 
used to prevent organ transplant rejection, affects a key molecule in 
the disease process. Studies in mice that mimic the human disorder were 
especially encouraging because the results suggest that the disease can 
be reversed in adults, countering pessimism that the disease produced 
irreversible affects on brain development. Researchers are exploring 
whether rapamycin or similar drugs are safe for long-term use, and may 
also be of benefit for epilepsy or autism from other causes.
                         the research workforce
    As science progresses, we recognize themes that bring together 
research on disparate diseases, whether shared disease mechanisms, as 
in neurodegeneration, therapeutic approaches, as stem cells, or program 
needs, as translational research. The American Recovery and 
Reinvestment Act reminds us of another common theme--research is labor 
intensive. Progress depends on the men and women who do research and 
their commitment to research that may take decades. To maintain the 
vigor of NIH and private research, NINDS is committed to making 
research an attractive and sustainable career for young people who are 
innovative, intelligent, dedicated, and diverse.
                                 ______
                                 
    Prepared Statement of Dr. Patricia A. Grady, Director, National 
                     Institute of Nursing Research
    Mr. Chairman and members of the subcommittee: I am pleased to 
present the President's fiscal year 2010 budget request for the 
National Institute of Nursing Research (NINR) of the National 
Institutes of Health (NIH). The fiscal year 2010 budget request 
includes $143,749,000, which is $1,870,000 more than the fiscal year 
2009 appropriation of $141,879,000.
    NINR's budget request and its research projects are consistent with 
the President's multi-year commitment for cancer and autism.
                              introduction
    NINR supports clinical and basic research to build the scientific 
foundation for clinical practice, prevent disease and disability, 
manage and eliminate symptoms caused by illness, and enhance end-of-
life and palliative care. The breadth and depth of NINR's research 
portfolio is ideally suited to explore some of the most important 
challenges affecting the health of the American people. An aging 
population, an increasing incidence of chronic illness, a shortage in 
the health workforce, and rapidly escalating costs necessitate profound 
changes in the ways in which we approach healthcare. These challenges 
require us to develop new strategies for treating, managing, and 
preventing illness that are person-centered rather than disease-
centered, that focus on pre-empting the development of chronic illness 
rather than treating it, and that feature the person as an active 
participant in managing his or her own healthcare. The research 
supported by NINR can significantly contribute to the evidence base for 
many of the changes that will occur in healthcare in the coming years 
and decades. NINR advances science to address current and future 
challenges through its research programs in health promotion and 
disease prevention; self-management, symptom management, and 
caregiving; and end-of-life and palliative care. In addition, NINR 
maintains a strong commitment to the elimination of health disparities 
faced by at-risk and underserved populations through continued work to 
develop culturally appropriate, evidence-based interventions. NINR also 
trains the next generation of scientists to ensure the development of 
the innovative research and faculty workforce of the future. The 
research goals in NINR's strategic plan, changing practice, changing 
lives, emphasize the areas of public health that demonstrate the 
greatest needs and in which NINR can have the greatest impact.
    Let me now describe our research programs and highlight some of our 
recent accomplishments.
                         ninr research programs
Health Promotion and Disease Prevention
    Healthcare professionals and policy leaders have stressed the 
importance of preventive care to the health of all Americans. NINR 
supports research to discover new ways to prevent disease and achieve 
long-term, positive health outcomes in individuals across the lifespan. 
NINR-supported scientists explore strategies to understand and promote 
behavioral changes in individuals, evaluate health risks in diverse 
communities, and assess issues of patient safety. In recent years, 
successful efforts in the areas of health promotion and disease 
prevention research have increasingly involved community members in the 
design and conduct of the study.
    NINR research has an impact on clinical practice. In one example, 
researchers designed, implemented and evaluated a program to address 
the health burden and costs associated with premature birth, a 
condition affecting more than 500,000 infants in the United States 
every year. The Creating Opportunities for Parent Empowerment program 
(COPE), for parents of premature infants, is an educational-behavioral 
intervention program that begins 2 to 4 days after admission to a 
neonatal intensive care unit (NICU) and teaches parents how to care for 
their premature infant. The researchers found that COPE implementation 
reduced the length of stay in the NICU by 4 days, for an estimated 
healthcare cost savings of at least $4,800 per infant. Thus, in 
addition to improving parent and child outcomes, routine implementation 
of COPE in NICU's across the United States could possibly save the 
healthcare system more than $2 billion per year. The results of this 
study have sparked interest among hospitals and insurers nationwide.
    NINR-supported researchers are developing more programs to promote 
healthy behaviors and prevent disease, including: an outreach 
intervention designed to reduce HIV-risk among adolescent girls 
receiving services through community-based health centers; a parent 
training program designed to promote positive parenting and mental 
health among low-income ethnic minority families with young children; 
and a lifestyle-modification program for prehypertensive, middle-aged 
rural women.
          self-management, symptom management, and caregiving
    Given the increasing numbers of people living with chronic illness, 
whether children with diabetes or elders with heart disease, NINR is 
developing new approaches to help individuals manage their own health 
conditions, to decrease the effects of adverse symptoms, and to reduce 
the burden on caregivers. NINR is improving the quality of life of 
individuals with chronic illness and their families by supporting 
research related to self-management, symptom management, and 
caregiving.
    Our self-management research explores strategies that help 
individuals to participate in their own health practices. In one recent 
example, community ``Lay Health Educators'' were trained to deliver a 
health promotion and asthma management program to children in 
elementary schools from rural towns and unincorporated communities. 
Children receiving this program demonstrated significant improvements 
in asthma knowledge, self-management scores, and use of metered dose 
inhalers. Results from this study suggest that using Lay Health 
Educators for delivery of an in-school education program may be an 
effective means for improving children's skills in asthma self-
management, especially in hard-to-reach communities.
    Our symptom management research focuses on the biological and 
behavioral aspects of symptoms such as pain and fatigue, with the goal 
of improving patient health and quality of life. A recent symptom 
management study aimed to define patient-determined success for 
treatment of chronic spine pain in four areas: pain, fatigue, emotional 
distress, and interference with daily activities. This study found that 
the patients for whom pain was reduced experienced significantly less 
fatigue, emotional distress, and interference with daily activities. 
The findings confirm that successful treatment for chronic pain is not 
viewed by patients exclusively in terms of pain reduction, but also 
involves a number of additional quality of life factors.
Research Capacity Development
    The increasing demand for nurse clinicians, faculty, and 
scientists, and the inadequate supply of new nurses to meet that need, 
continue to burden America's health system. NINR builds research 
capacity and fosters interdisciplinary training for the next generation 
of scientists in basic, translational, and clinical research through 
individual and institutional training and career development awards. 
NINR training strategies focus on the development of nurse scientists 
and earlier entry into research careers with special consideration 
given to underrepresented and disadvantaged populations. In addition, 
innovative training programs at the NIH, such as the NINR Summer 
Genetics Institute, the NINR Graduate Partnerships Program, and the new 
BNC fellowship (a joint venture between NINR, the NIH Clinical Center, 
and the Bravewell Collaborative), all serve to increase the knowledge 
and experience base of new scientists, and assist them in their 
transition to long-term research careers.
End-of-life
    Faced with a complexity of life-limiting and eventual terminal 
conditions--whether cancer, heart disease, stroke, or neurodegenerative 
disorders--the challenges experienced by patients and their families as 
life draws to a close have refocused attention to the end of life and 
necessitated a better understanding of the dying process, the 
associated decisions about treatment, and the quality of care patients 
receive. Focusing on these topics, NINR end-of-life research seeks 
through science to improve the understanding of the mechanisms 
underlying palliation, including pain, fatigue, depression, and related 
symptoms; enhances communication and decision-making processes between 
patients and family members; and develops effective strategies to 
optimize care across diverse settings, populations, and cultural 
contexts.
    One recent study explored the relationship between diagnosis and 
advance directives. As part of a longitudinal study, patients with an 
expected 2-year survival of less than 50 percent who had either cancer 
or amyotrophic lateral sclerosis (ALS) were interviewed with the goal 
of determining whether and how end-of-life discussions differed between 
clinicians and patients. Results showed that cancer patients were less 
likely than ALS patients to have had advanced care planning 
discussions. Although these results may reflect perceptions that ALS 
has a more predictable disease trajectory, that advanced cancer has a 
greater number of treatment options, or the presence of differing views 
about hope, this study highlighted that cancer patients may be less 
than adequately prepared for end-of-life decisionmaking.
    Another recent study examined the life support withdrawal process 
for patients who died in the intensive care unit (ICU) or within 24 
hours of discharge from the ICU, and surveyed family members on their 
perceptions of the care provided. The researchers discovered that for 
family members of patients who had an ICU stay of 8 days or more, 
families were more satisfied with care received when withdrawal of life 
support occurred in a staggered progression. The outcome of this study 
indicates that clinicians need to work with the family throughout the 
patient's ICU stay to provide them with accurate information on which 
to base decisions, and prepare them emotionally for the possible loss 
of their loved one.
          ninr and the american recovery and reinvestment act
    Funding for scientific research received through the American 
Recovery and Reinvestment Act of 2009 (ARRA) has provided NINR with an 
enormous opportunity, not only to assist with the Nation's economic 
recovery by creating and retaining jobs and enhancing infrastructure, 
but to advance biomedical and behavioral research in areas of critical 
importance to the NINR mission. NINR is using the funds from ARRA to 
support additional research projects, to accelerate ongoing research 
through supplements to current grants, and to create opportunities for 
introducing prospective scientists to a research career. The additional 
science supported by NINR through ARRA will, in the long-term, 
contribute to improving the health of the Nation through enhanced 
prevention and management of chronic illness and disease.
    Thank you, Mr. Chairman. I will be happy to answer any questions 
that the subcommittee might have.
                                 ______
                                 
  Prepared Statement of Dr. Donald A.B. Lindberg, Director, National 
                          Library of Medicine
    Mr. Chairman and members of the subcommittee: I am pleased to 
present the President's fiscal year 2010 budget request for the 
National Library of Medicine (NLM) of the National Institutes of Health 
(NIH). The fiscal year 2010 budget includes $334,347,000, which is 
$3,576,000 more than the comparable fiscal year 2009 appropriation of 
$330,771,000.
    NLM, the world's largest biomedical library and the developer of 
electronic information services, delivers trillions of bytes of data to 
millions of users daily. Every day 3.5 terabytes of data are downloaded 
to users. By making research results--from DNA sequences to clinical 
trials data to published scientific articles and consumer health 
information--readily available, the Library magnifies the positive 
impact of the NIH's investment in the creation of new knowledge. By 
organizing increasing amounts and types of biomedical and health 
information, the NLM fuels new research discoveries, informs patient 
care decisions, helps people exert control over their health and 
healthcare, and AIDS disaster preparedness and response.
    The NLM is a key enabler for important congressional, NIH, and 
Department of Health and Human Services (HHS) initiatives. NLM's budget 
request and its research projects are consistent with the President's 
multi-year commitment for cancer and autism. Current priorities 
include: increasing the transparency of clinical trials in 
ClinicalTrials.gov; enhancing public access to NIH-funded peer-reviewed 
manuscripts in the PubMed Central archive; making results of Genome-
Wide Association Studies (GWAS) available in dbGaP to improve the 
understanding of genetic and environmental factors underlying human 
disease; supporting and distributing standard terminologies for 
electronic health records and clinical research data, including genetic 
tests, within NLM's Unified Medical Language System; conducting 
biomedical informatics research on health applications of information 
technology; and developing specialized information resources for use in 
emergency and disaster response.
    To be useful, NLM's information services must be known and readily 
accessible. The Library's outreach program relies heavily on the 5,800-
member National Network of Libraries of Medicine (NN/LM) and on 
exhibitions, events, and varied media to bring the message about NLM's 
free, high-quality health information resources to communities across 
the Nation. The NN/LM comprises academic health sciences libraries, 
hospital libraries, public libraries, and community-based 
organizations. They form an efficient way to make the published output 
of biomedicine easily accessible by scientists, health professionals, 
and the public and to develop partnerships with community organizations 
and underserved populations.
                    scientific information resources
    The NLM's National Center for Biotechnology Information (NCBI) 
meets the challenge of collecting, organizing, storing, analyzing, and 
disseminating scientific data by designing, developing, and 
distributing the tools, databases and technologies that are enabling 
the genetic discoveries of the 21st century. Celebrating 20 years since 
its enactment, the Center is at the hub of international interchange of 
molecular biology and genomic information, with Web sites accessed 
several million times a day.
    In addition to the widely known GenBank and PubMed/MEDLINE 
databases, the NCBI provides a wide array of genomic resources and is a 
valued collaborator throughout the NIH. The recent discovery of a novel 
H1N1 influenza virus highlights the value of the specialized virus 
resource that NCBI developed with the National Institute of Allergy and 
Infectious Diseases. It links vaccine researchers to genomic data about 
the influenza virus. The PubChem repository fills a critical need in 
the Molecular Libraries Roadmap Initiative, with information on more 
than 40 million ``small molecules'' that are crucial in drug 
development. The dbGaP database, which links genotype data with 
phenotype information from clinical research studies to support 
identification of genetic factors that influence health, is the public 
repository for the trans-NIH GWAS project. NIH's mandatory Public 
Access Policy ensures scientific articles written by NIH-funded authors 
are deposited in PubMed Central and linked to other scientific 
information.
    The Lister Hill National Center for Biomedical Communications leads 
research to create and improve biomedical communications systems, 
technologies, and networks. The Center recently completed a major 
expansion of ClinicalTrials.gov, in response to the congressional 
mandate. The system now maintains a registry of clinical trials 
involving FDA-regulated drugs, biologics, and devices and starting last 
September, began collecting summary results of trials of FDA-approved 
products. ClinicalTrials.gov currently contains data on more than 
70,000 trials in 166 countries and is searched by more than 500,000 
people every month.
    The NLM's two research centers collaborate on improving standards 
for genetic and genomic testing. The NCBI provides a database of 
reference values to assist in quality control of genomic tests. The 
Lister Hill Center is helping to expand the Logical Observation 
Identifiers Names Codes standard to cover genetic and newborn screening 
tests already in routine clinical and public health use.
    Electronic health records with advanced decision-support 
capabilities--and connections to relevant health information--will be 
essential to achieving personalized medicine and will also help people 
manage their own health. NLM supported much of the seminal research 
work on electronic records, clinical decision support and health 
information exchange. NLM is the HHS coordinating body for clinical 
terminology standards and supports development and dissemination of key 
standards for U.S. health information exchange. The Lister Hill Center 
is actively engaged in research on next generation electronic health 
records to facilitate patient-centered care, clinical research, and 
public health. This work has already resulted in tools that are helping 
system developers, including some at the Centers for Medicare and 
Medicaid Services, to incorporate the use of standards into health 
information systems.
                  information services for the public
    In addition to providing researchers and health care providers with 
access to scientific information, the NLM also serves the public--from 
elementary school children to senior citizens. The Library's main 
consumer health portal is MedlinePlus, available in both English and 
Spanish. In fiscal year 2008, there were more than 750 million 
MedlinePlus pages viewed by more than 132 million unique visitors from 
229 countries. In addition to more than 725 ``health topics,'' 
MedlinePlus has interactive tutorials for persons with low literacy, 
medical dictionaries, a medical encyclopedia, directories of hospitals 
and providers, surgical videos and links to the scientific literature. 
A ``Go Local'' feature links users to information about services in 
their communities. Today, there is go local coverage for approximately 
44 percent of the U.S. population and expansion is an important goal 
for the Library in fiscal year 2010.
    In 2009, the NLM celebrated its second year of producing the NIH 
MedlinePlus magazine, an outreach effort made possible with NIH and 
Friends of the NLM support. The free magazine is widely distributed to 
the public via physician offices, libraries, and other locations, with 
a readership of up to 5 million nationwide. A Spanish/English version, 
NIH MedlinePlus Salud (the Spanish word for ``health''), was launched 
in January 2009 to address the specific health needs of the growing 
Hispanic population.
    NLM also produces an array of specialized consumer health Web 
resources. Genetics Home Reference provides understandable information 
about genetic conditions and related genes or chromosomes. The 
Household Products Database provides easy-to-understand data on 
potential health effects of more than 2,000 ingredients contained in 
more than 8,000 common household products. The Dietary Supplements 
Labels Database has information from labels of more than 3,000 brands 
of dietary supplements, with links to authoritative sources of 
information.
          ensuring access to information in times of disaster
    NLM is committed to ensuring uninterrupted access to critical 
information services in the event of disaster or emergency. NLM's new 
Disaster Information Management Research Center is building on proven 
emergency backup and response mechanisms within the NN/LM to promote 
effective use of libraries and specially trained librarians--disaster 
information specialists--in disaster management efforts. The Center 
also collaborates with the Navy National Medical Center, Suburban 
Hospital Healthcare System, and NIH Clinical Center in the Bethesda 
Hospital Emergency Preparedness Partnership. The Partnership will 
provide hospital surge capacity for the national capitol area and 
create a surge model for use across the Nation. Recent studies found 
such capabilities lacking in major metropolitan areas. NLM coordinates 
R&D for this model and investigates new methods for sharing health 
information for disaster preparedness and response.
    NLM also develops advanced information services and tools to assist 
emergency responders when disaster strikes. NLM's TOXNET, a cluster of 
databases covering toxicology, hazardous chemicals, and toxic releases, 
provides a foundation for services to first responders, such as 
Wireless Information System for Emergency Responders and Chemical 
Hazard Event Medical Management (CHEMM). CHEMM builds on the Library's 
successful collaboration with the HHS Office of Public Health 
Preparedness, the National Cancer Institute, and the centers for 
disease prevention and Control to develop the Radiation Event Medical 
Management (REMM) system. NLM is also developing a tool for 
identification of post traumatic stress disorder and mild traumatic 
brain injury.
    In summary, the NLM is well-positioned to contribute to the 
Nation's health--by making increasing amounts of scientific data 
available to researchers and health practitioners, by improving the 
Nation's healthcare information infrastructure, by providing the public 
with access to authoritative information to maintain their personal 
health, and by enabling health sciences libraries to make substantial 
contributions to disaster information management. All of these 
activities will depend on a strong and diverse workforce for biomedical 
informatics research, systems development, and innovative service 
delivery. To that end, the NLM will continue its longstanding support 
for postgraduate education and training of informatics researchers and 
health science librarians.
                                 ______
                                 
  Prepared Statement of Dr. Jack E. Whitescarver, Director, Office of 
                             AIDS Research
    Mr. Chairman and members of the subcommittee: I am pleased to 
present the President's fiscal year 2010 budget request for the trans-
National Institutes of Health (NIH) AIDS research program of the NIH. 
The fiscal year 2010 budget includes $3,055,494,000, which is 
$45,155,000 more than the fiscal year 2009 appropriation of 
$3,010,339,000.
                           the aids pandemic
    More than 33 million people around the world are estimated to be 
currently living with HIV/AIDS infection. More than 25 million men, 
women, and children have already died.
    The pandemic affects the future of families, communities, military 
preparedness, national security, political stability, national economic 
growth, agriculture, business, healthcare, child development, and 
education in countries around the globe. As a result of multilateral 
and bilateral programs in low- and middle-income countries, almost 3 
million people now have access to antiretroviral drug treatment. 
However, for every 1 person who starts taking antiretroviral drugs, 
another 3 become infected.
    In the United States, HIV/AIDS remains an unrelenting public health 
crisis. The Centers for Disease Control and Prevention (CDC) reports 
more than 1.1 million people are infected with the virus, with 
approximately 56,300 new infections each year. According to CDC 
statistics, African-American men and women and gay and bisexual men of 
all races and ethnicities are the most affected groups in the United 
States. It is estimated that 1 out of every 20 individuals in the 
District of Columbia is HIV infected--a vivid example of the impact of 
AIDS on minority populations in the United States.
                  the trans-nih aids research program
    The NIH AIDS research program is the largest in the world--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. AIDS research 
is carried out by nearly all of the NIH Institutes and Centers in 
accordance with their mission. This diverse research portfolio requires 
an unprecedented level of scientific coordination and management of 
research. The Office of AIDS Research (OAR) was authorized to plan, 
coordinate, evaluate, and budget all NIH AIDS research, functioning as 
an ``institute without walls,'' allowing NIH to pursue a unified 
research program to prevent and treat HIV infection and its associated 
complications. OAR has established comprehensive trans-NIH planning, 
portfolio analysis, and budgeting processes to identify the highest 
priority areas of scientific opportunity, enhance collaboration, 
minimize duplication, and ensure that precious research dollars are 
invested effectively and efficiently. The research priorities that 
frame this trans-NIH budget request were established through the annual 
OAR strategic planning process, involving scientists from NIH, other 
Government agencies, academia, industry, and nongovernmental 
organizations, as well as community representatives.
       fiscal year 2010 research priorities: prevention research
    Prevention of HIV infection is NIH's highest priority for HIV-
related research. Disappointing results from recent clinical studies of 
HIV vaccine and microbicide candidates underscore the need for 
additional discovery (basic) research on HIV and the host immune 
response. Biomedical and behavioral interventions are urgently needed 
to reach individuals at risk, particularly in racial and ethnic 
populations in the United States, in international settings, among 
women, and among men who have sex with men. Priority areas include:
  --Microbicides.--Microbicides, antimicrobial products that can be 
        applied topically for the prevention of HIV and other sexually 
        transmitted infections, may offer one of the most promising 
        primary preventive interventions. NIH supports a comprehensive 
        microbicide research program that includes the screening, 
        discovery, development, preclinical testing, and clinical 
        evaluation of microbicide candidates, as well as fundamental 
        research aimed at understanding how HIV transverses mucosal 
        membranes and infects cells. NIH supports behavioral and social 
        science research on the acceptability and use of microbicides 
        among different populations. In fiscal year 2010, NIH will 
        increase funding for the design, development, and evaluation of 
        microbicide candidates.
  --Vaccines.--The best long-term hope for controlling the AIDS 
        pandemic is the development of safe, effective, and affordable 
        AIDS vaccines. AIDS vaccine research remains a high priority to 
        ensure that new and innovative concepts continue to advance 
        through the pipeline. NIH supports a broad AIDS vaccine 
        research portfolio encompassing basic, preclinical, and 
        clinical research. The disappointing results from clinical 
        studies of the Merck HIV vaccine candidate indicate a critical 
        need to reinvest in basic research studies on the virus and 
        host immune responses that can inform the development of new 
        and innovative vaccine concepts; as well as the development of 
        improved animal models to conduct pre-clinical evaluations of 
        vaccine candidates. In fiscal year 2010, NIH will fund 
        additional basic research on HIV and host responses, as well as 
        the design and development of new vaccine concepts and the pre-
        clinical/clinical development of vaccine candidates in the 
        pipeline.
  --Behavioral Research.--NIH supports research to further our 
        understanding of how to change the behaviors that lead to HIV 
        acquisition, transmission, and disease progression--including 
        preventing their initiation--and how to maintain protective 
        behaviors once they are adopted. In addition, NIH supports 
        research aimed at better understanding the social and cultural 
        factors associated with HIV risk or protection, particularly in 
        communities at high risk of HIV acquisition. This research will 
        contribute to the implementation of a broader range of 
        preventive and/or therapeutic strategies.
           fiscal year 2010 priorities: therapeutics research
    Antiretroviral treatment has resulted in improved immune function 
in patients who are able to adhere to the treatment regimens and 
tolerate the toxicities associated with antiretroviral drugs; and it 
has delayed the progression of HIV disease, extending the time between 
initial infection and the development of AIDS. However, a growing 
proportion of patients receiving therapy are demonstrating treatment 
failure, experiencing serious drug toxicities and side effects, and 
developing drug resistance. A critical area of research is the use of 
antiretroviral therapy as prevention. This includes evaluating the use 
of therapeutic regimens after exposure to HIV (postexposure 
prophylaxis), as well as testing the concept of the use of 
antiretroviral therapy in high-risk individuals prior to HIV exposure 
(pre-exposure prophylaxis).
    Epidemiologic studies have revealed a number of co-infections and 
co-morbidities associated with long-term HIV disease, including 
tuberculosis, hepatitis C, malignancies, metabolic disorders, 
cardiovascular disease, and neurologic disorders. A better 
understanding of the underlying etiology of these HIV-associated 
conditions will lead to better prevention and treatment strategies. NIH 
supports a comprehensive therapeutics research program to design, 
develop, and test drugs and drug regimens to prevent and treat HIV 
infection and its associated co-infections and co-morbidities.
    Translational and clinical studies also are needed to transform 
fundamental research results into improved strategies for preventing 
and treating these HIV-associated complications, including research on 
drug resistance, drug toxicities, pharmacogenomics, adherence, and the 
interrelatedness of HIV and nutrition.
                discovery research: enabling innovation
    A renewed emphasis on discovery research is essential to enable 
innovation, address critical gaps, and capitalize on emerging 
scientific opportunities. Ground-breaking strides have been made 
towards understanding the fundamental steps in the lifecycle of HIV, 
the host-virus interactions, and the clinical manifestations associated 
with HIV infection and AIDS. However, additional research is needed to 
further the understanding of the virus and how it causes disease, 
including studies to delineate how gender, age, ethnicity, and race 
influence vulnerability to infection and HIV disease progression. NIH-
supported genomics studies and breakthroughs in sequencing the human 
genome provide new opportunities to apply these valuable tools to the 
search for new HIV prevention and therapeutics strategies. OAR proposes 
to capitalize on those opportunities by providing funds for new, 
exciting areas of investigation, including studies utilizing genomics 
tools to investigate the immune response to HIV infection.
                research training and community outreach
    NIH must continue to support training programs for United States 
and international researchers to build the critical capacity to conduct 
AIDS research both in racial and ethnic communities in the United 
States and in developing countries. NIH funded programs have increased 
the number of training positions for AIDS-related research, including 
programs specifically designed to recruit individuals from 
underrepresented populations into research careers and to build 
research infrastructure at minority-serving institutions in the United 
States. The changing pandemic and the increasing number of HIV 
infections among women and in racial and ethnic populations of the 
United States, particularly in African-American and Latino/Hispanic 
communities, also underscore the need to disseminate HIV research 
findings and other related information to communities at risk.
                                summary
    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. NIH will continue to focus on the need for 
comprehensive strategies to decrease HIV transmission and improve 
treatment options and treatment outcomes in affected vulnerable 
populations in the United States, and in international settings. These 
interventions will address the co-occurrence of other sexually 
transmitted diseases, hepatitis, drug abuse, and mental illness; and 
consider the role of culture, family, and other social factors in the 
transmission and prevention of these disorders.
    The NIH investment in AIDS research is reaping even greater 
dividends in unraveling the mysteries surrounding many other 
infectious, malignant, neurologic, autoimmune, and metabolic diseases. 
AIDS research has provided an entirely new paradigm for drug design, 
development, and clinical trials to treat viral infections. Drugs 
developed to prevent and treat AIDS-associated opportunistic infections 
also provide benefit to patients undergoing cancer chemotherapy or 
receiving anti-transplant rejection therapy. AIDS research also is 
providing a new understanding of the relationship between viruses and 
cancer. We are deeply grateful for the support the administration and 
this subcommittee have provided to our efforts.

    Senator Harkin. Dr. Kington, thank you very much for your 
opening statement, and I see we've been joined by Senator 
Shelby.
    Did you have an opening statement?

                 STATEMENT OF SENATOR RICHARD C. SHELBY

    Senator Shelby. Mr. Chairman, I'm glad to join you. I look 
forward to the hearing. I'll be in and out of here. We have 
some other Appropriations subcommittee hearings, but I do have 
a statement that I'd like to be made part of the record and I 
do have some questions that I'm going to have to leave and come 
back to ask those questions, unless you let me go.
    [The statement follows:]
            Prepared Statement of Senator Richard C. Shelby
    Mr. Chairman, thank you. I appreciate you having this hearing today 
to discuss the vital mission carried out by the National Institutes of 
Health (NIH).
    We live in a world where there are thousands of debilitating and 
life-threatening diseases--all that could use additional funding for 
research and clinical trials. We must continue to work towards the goal 
of increasing the overall Federal investment in basic research and 
development.
    I support additional funding for NIH research, but in particular, I 
would like to emphasize today the importance of accelerating research 
in the area of Cystic Fibrosis (CF).
    CF is a life-threatening genetic disease for which there is no 
cure.
    But there is promise for people with CF--and that promise is in 
research.
    Federal funding for medical research should accelerate the process 
of discovery and clinical development of new therapies for the 
treatment of disease. Yet, there is a significant discrepancy 
persisting between funding for clinical versus basic laboratory 
research.
    Support for clinical research is particularly important for rare 
diseases, which often suffer from a lack of start-up funding needed to 
overcome the initial discovery phase of drug development and move into 
advanced stages of research.
    Clinical research programs like the Cystic Fibrosis Foundation's 
Therapeutics Development Network have produced innovative new therapies 
for that disease. Led by research institutions including the University 
of Alabama at Birmingham, this national network allows multiple 
therapeutic approaches to be pursued simultaneously, accelerating the 
development of new treatments for the disease.
    Dr. Kington coordinated networks such as the Cystic Fibrosis 
Therapeutics Development Network provide special insights regarding the 
most efficient means of conducting clinical trials.

    Question: Will the NIH increase Federal funding for these 
types of research?  deg.
    Senator Harkin. I have some, but, I mean, if you have to go 
to another----
    Senator Shelby. Senator Mikulski and I have a NASA hearing.
    Senator Harkin. Well, why don't you go ahead then? I'll 
hold mine and you go ahead and ask your questions.

                            CYSTIC FIBROSIS

    Senator Shelby. Thank you, Mr. Chairman.
    Mr. Chairman, I thank you for the work you've done in 
chairing this subcommittee, and I continue to work with you.
    We live in a world where there are thousands, everybody 
knows this, especially our panelists, we live in a world where 
there are thousands of debilitating and life-threatening 
diseases and they all could use additional funding for research 
and clinical trials, and I believe we must work toward the goal 
of increasing the overall Federal investment in basic research 
and development, and I applaud Senator Harkin in his work in 
this regard.
    I personally, as a member of this subcommittee, support 
additional funding for NIH research, but in particular, today 
just for a few minutes, I would like to emphasize the 
importance of accelerating research in the area of cystic 
fibrosis.
    Cystic fibrosis, as the panel knows, is a life-threatening 
genetic disease for which there is no cure but there is promise 
for people and that promise is in research.
    Federal funding for medical research should accelerate the 
process of discovery and clinical development of new therapies 
for the treatment of this disease and others, yet there is a 
significant discrepancy existing between the funding for 
clinical research versus basic laboratory research.
    Support for clinical research, as I understand it, is 
particularly important for rare diseases which often suffer 
from a lack of start-up funding needed to overcome the initial 
discovery phase of drug development and move into advanced 
stages of research.
    Clinical research programs, like the Cystic Fibrosis 
Foundation's Therapeutics Development Network, have produced in 
the way of new therapies for that disease. Led by research 
institutions, including the University of Alabama at 
Birmingham, this national network allows multiple therapeutic 
approaches to be pursued simultaneously, accelerating the 
development of new treatments for the disease.
    Dr. Kington, coordinating networks, such as the Cystic 
Fibrosis Therapeutics Development Network, provide special 
insights regarding the most efficient means of conducting 
clinical trials.
    Under your leadership, will the NIH increase Federal 
funding for these types of research?
    Dr. Kington. Let me start off with a general answer and 
then I'll ask Dr. Nabel to comment, as well.
    Senator Shelby. Okay.
    Dr. Kington. I think, in general, we agree that there are a 
lot of opportunities for us to accelerate the translation of 
scientific advances in the basic level into real treatments and 
interventions and diagnostic strategies at the bedside. We know 
that there are particular challenges for less common diseases.
    In fact, we just announced yesterday a new initiative to 
help facilitate that translation and the Cystic Fibrosis 
community in many ways is held up as a good example of how a 
community affected by a disease can work collaboratively with 
the research community to facilitate translation and we're 
committed to helping that in any way we can.
    Dr. Nabel, would you like to comment, as well?
    Dr. Nabel. I appreciate your question. The NIH is very 
concerned about rare genetic disorders, like cystic fibrosis, 
and, indeed, I think if we can take a minute and really reflect 
upon the progress that's been made in cystic fibrosis, it's 
really been remarkable over the past decade.
    We've gone from discovering the gene which causes the 
majority of cystic fibrosis, particularly the mutation, the 
CFTR gene. We know now that that gene leads to a protein that 
doesn't unfold properly. This protein is responsible for 
clearing secretion in the airways and in other tissues and when 
that protein doesn't unfold it can't lead to the clearance of 
secretions, mucous builds up, that gets infected and the 
sequela start.
    What's very interesting is that the gene led to the 
understanding of what we call the molecular pathway that causes 
the disease. Understanding that molecular pathway then led to a 
search for new therapeutics that perhaps you're familiar with, 
and that search has now come up with two compounds, we call 
them small molecules, that are in clinical testing which 
directly affect the molecular pathway and, indeed, you probably 
saw Dr. Rootman's article in the New Yorker a couple of weeks 
ago and the remarkable report by several individuals who were 
enrolled in those trials saying how well they feel while taking 
these new drugs.
    So that is, I think, a terrific example of how gene 
discovery leads to understanding, the molecular pathway leads 
to the detection of new therapeutics that are now being tested.
    Can we do more in this area? Absolutely, absolutely. We're 
hoping to increasingly fund translational research and new 
clinical research in this area. The NHLBI currently has a 
specialized center for clinically oriented research in cystic 
fibrosis that's analogous to the CF Clinical Networks that you 
described and so many of those investigators are really the 
same community of folks.
    But we look forward to really building and augmenting this 
research effort going forward.
    Senator Shelby. Well, I appreciate this. I know you have to 
start in the lab, but then you've got to move from the lab to 
the clinics to prove what's going on. So we have to have both, 
do we not?
    Dr. Nabel. Absolutely.
    Senator Shelby. Well, I look forward to working with you, 
not just on cystic fibrosis, this is my attention for the 
moment, but in a lot of other diseases, and with Chairman 
Harkin in this regard.
    Mr. Chairman, thank you for taking me out of order, but you 
know from chairing the subcommittee and being on other 
subcommittees, we sometimes meet at the same time.
    Thank you, Mr. Chairman.

                          SUCCESS RATE OF ARRA

    Senator Harkin. Thank you, Senator Shelby, and thanks for 
all your involvement in this subcommittee over many, many years 
in research, medical research. So thank you very much for that.
    Well, Dr. Kington, I want to talk about the Recovery Act 
and that money, and our budget. The problem is that the flip 
side of having all these requests come in is that most of them 
will not be funded. I'm hearing that the success rate for the 
Challenge Grants could be less than 5 percent.
    So how do you keep up a high level of interest when so few 
researchers will actually get these grants? On the one hand 
it's a good thing. On the other hand do you discourage a lot of 
people when they don't get funded?
    Dr. Kington. This is definitely a concern of ours. It's 
been interesting to read some of the press coverage which 
reporters have gone out speaking to scientists and we were 
pretty clear early on that we had a floor for dollars and that 
suggested that we would not have our usual success rate because 
this was a special program.
    In spite of that, the scientists saw this as an 
extraordinary opportunity to actually get on paper interesting 
ideas in important areas. We believe that even with the 
substantial increase, I predict that we'll more than double 
that floor of $200 million, we still won't have a high success 
rate and there will be many good grants that we won't be able 
to fund, and there will be consequences for the agency and for 
the scientific community.
    We anticipate that many of the scientists will resubmit 
those applications within our usual funding sequence. We 
suspect that we'll be able to fund some of them but our ability 
to fund even the very best of those applications will depend 
upon what our budget is in future years.
    So it's a concern. I think at the very least it shows this 
extraordinary untapped supply of great ideas out there in the 
scientific community and I see that as a good thing.

                        ARRA AND FUTURE SUPPORT

    Senator Harkin. It seems to me that concerning the program 
you talked about, the Grant Opportunity Program, the GO Grants, 
it is my information that the purpose of this program is to 
support high-impact ideas that require significant resources 
for a discrete period of time to lay the foundation for new 
fields of investigation, Yet out of that $10.4 billion, $200 
million is designated to GO Grants.
    It seems to me that if you put most of the money in the RO1 
grants and you do it for 2 years rather than 4 years, what 
happens after 2 years? Are you just sort of betting out on the 
cow that we're going to be able to keep that funding up? 
Because I'm not certain that we can.
    I guess my question is, since this was a certain amount of 
money for a discrete period of time and you have these grants 
as I just defined them, why wouldn't I see more of that money 
going to that rather than RO1 grants for 2 years?
    Dr. Kington. First of all, I think you'll see across the 
Institutes and Centers wide variation in whether or not--in how 
the dollars are distributed across these mechanisms and the 
numbers that we put forth were a floor.
    I anticipate that the number will be higher because many 
Institutes, NHLBI and others, are increasing their commitments 
already to that stream of dollars and it will depend upon what 
ideas we see.
    This was again a grand experiment in many ways to put out a 
broad call to see what the best ideas were and not restrict it 
to dollars, $1 million which was the limit for the Challenge 
Grants.
    So the bottom line is that we think that we'll ultimately 
end up funding more than what we had initially planned. We 
believe that it's important to allow flexibility across 
Institutes and Centers. For some Institutes and Centers, these 
types of programs will be great opportunities. For others, 
scientifically it's a stronger case to fund more of the RO1s, 
but again even the RO1s, our estimate is that about, I think, 
one-third or so of the dollars probably will go to the existing 
pool of RO1s, but it varies from Institute to Institute.
    Our goal is to make the framework as flexible as possible, 
but if we have great ideas, we'll put more resources toward the 
GO Grants and we are anxiously awaiting the applications. We 
anticipate that we'll get probably--I anticipate probably 
around 2,000 or so applications when all is said and done and 
if they're great ideas, we'll do our best to fund them.
    Senator Harkin. That's the GO Grants? That's what you're 
talking about?
    Dr. Kington. Yes, the GO Grants, and again we suspect that 
many of these ideas that aren't funded but are still good will 
be resubmitted and our ability to fund those will depend upon 
what our budgets are in the out years.
    We'll make the best decisions we possibly can to have the 
maximum impact of these dollars for science and public health, 
but again I see this in a very positive light, that we have had 
this extraordinary energized response by the scientific 
community.
    It really is amazing, speaking to deans and faculty across 
the country, how excited the scientific community is both about 
the opportunities, the real opportunities to do work they 
otherwise couldn't have done, but perhaps even more 
importantly, about what these dollars said as a reflection of a 
commitment of the country to invest in biomedical research.
    Senator Harkin. Let me ask you this question. If, in the 
wisdom of Congress, it was decided that this money was to go 
out over 2 years, right?
    Dr. Kington. Yes.
    Senator Harkin. But that's not to say we can't change our 
minds and it happens.
    Dr. Kington. Congress can do whatever Congress wants.
    Senator Harkin. We can change our minds. It's occurred to 
me that, yes, we initially put that out there to be 2 years, 
but maybe we might want to think about making an exception for 
NIH, that maybe this money should be more than just a 2-year 
period of time.
    Is that something that you could live with? I mean, would 
that help in any way or is it so set now for 2 years that we 
ought to just leave it alone? Rather than thinking about maybe 
changing it to provide for a longer period of time, say 4 
years, to get that money out or something?
    Dr. Kington. Well, we certainly made all of our decisions 
based thus far on a 2-year time horizon, but I will concede 
that having more flexibility probably would be helpful, but we 
also recognize the unique intent of these dollars and that is 
to stimulate the economy in the short run, and we believe we 
can responsibly spend the money in 2 years.
    But some flexibility might help us as we sort of work 
through the process of spending. We might be able to have a 
benefit from more flexibility, but we will make good decisions 
even without that flexibility.
    Senator Harkin. Well, I might come back to you on that, not 
in this hearing but later on, to see if that flexibility might 
be the best course of action for us to take. Like I said, I 
don't know. It's just something I've thought about because 
again I just want to see how we judge the success of the 
Recovery Act funding.
    I mean $10.4 billion within 2 years, but a lot of the 
results of that won't be known for some time. So I assume that 
a lot of people say we can judge the success on how many jobs 
it's created perhaps, if we're looking at it stimulating the 
economy. That's why the amount of money you put out there for 
extramural construction is important and getting new equipment 
in our labs is important, but I think a lot of the success of 
this will be judged, not just on the immediate jobs created but 
what's the long-term effect of the money that we provided?
    So people say, ``Did we get our money's worth?'' Well, 
that's what's led me to think maybe--and I'm not saying this 
could happen--but maybe we ought to think about more 
flexibility in that 2-year time frame because I'm really 
worried. I say this to all of you. I'm really concerned about 
the cliff.
    What's going to happen in 2011? We've got 2010, what 1.4 
percent? 1.4 percent increase. You had it up there on the 
screen. But we funded $30.8 billion, but what happens in 2011 
when--if all these Recovery Act funds come out? I mean that's 
going to be a pretty hard landing, it seems to me, and, you 
know, I'm thinking about how do we soften that because I think 
we might be in a tough budget situation next year as we are 
this year and so since we've already appropriated this money 
for the Recovery Act, that we might think about trying to 
soften the landing a little bit. If you have any thoughts 
beyond that, of how we soften this a little bit, I'd like to 
know it, either today or maybe in writing or something later 
on.
    Dr. Kington. We'd be happy to do that, and actually I'd 
welcome any of my colleagues. Just as all politics is local, 
all science is sort of local, as well, and many of--all of the 
Institute and Center directors are struggling with this exact 
same issue of how to responsibly make decisions now, 
recognizing the uncertainty about the future streams of 
dollars.

             SUPPORT OF PROMISING RESEARCH AND FLEXIBILITY

    Senator Harkin. This is my chance to ask all of you here 
some questions. I'll start with Dr. Fauci.
    Can you point to anything that your Institute is able to do 
now or can start and finish in 2 years? Is there something that 
you're able to do now with this Recovery money that you weren't 
able to do?
    I'll ask each of you that. Dr. Fauci, any specific examples 
of research that you're able to fund that you otherwise might 
not have been able to?
    Dr. Fauci. Thank you for the question, Mr. Chairman. There 
are examples of things that we would not be able to fund if we 
didn't have it and there are examples of things that we can 
greatly accelerate and we would be able to use monies later on 
that we could continue it.
    The example that I give is one of about three or four, and 
I'll only give one, is the money that we're putting in to 
accelerate the process of much more aggressive control of the 
HIV pandemic related to some novel and important research 
questions that need to be answered, as bold as trying to 
develop a functional cure for HIV to accelerating the process 
of what we call pre-exposure prophylaxis where you actually 
treat individuals who are in high-risk groups before they get 
infected.
    There is a lot of research--it seems like a very 
interesting and important concept, but there are some very 
important research questions to be asked--Does it work? What is 
the relationship to adherence? Would it lead to resistance? If 
we can prove the concept, then that concept could transform how 
we prevent HIV infection.
    And the last part of that triad is something that we call 
test and treat which the money for 2 years will help us 
accelerate the research endeavor in that we would not be able 
to do as quickly and we're committed to seeing it to fruition 
and the test and treat is a very bold concept that was put 
forth by a group at the World Health Organization about a half 
a year ago and that is to essentially test everybody and those 
who are infected, to actually treat them, regardless of where 
they are in the stage of the disease, with the thought that if 
you get the viral load low enough, they will then not infect 
other people.
    That is a very bold concept that will require globally a 
lot of resources, but the world is looking to the NIH to prove 
the feasibility of that concept and we're going to do that in a 
much more rapid way by the money that we have decided to use 
from the ARRA allotment to get that jumpstarted.
    Senator Harkin. You can't complete that in 2 years, surely, 
though, can you?
    Dr. Fauci. I might echo what Dr. Kington said. Flexibility 
in my mind is always something that would be helpful to us, but 
we still can get a lot done in the 2 years, but if we had more 
flexibility that would be advantageous to the program.
    Senator Harkin. Okay. Dr. Nabel.
    Dr. Nabel. Thank you, Senator Harkin. I'm going to provide 
you one example of something that we couldn't do without the 
ARRA money and then another example of things that we can 
accelerate.
    We will use ARRA monies as one-time money to expand our 
understanding of the genetics of complex diseases. I think this 
will apply across many of the Institutes but it will certainly 
apply to Heart, Lung, and Blood.
    For example, over the years you've probably heard from 
NHLBI and ARRA, my predecessors, about the many large, what we 
call, cohort studies that the NHLBI has studied, the Framingham 
Heart Study, the Jackson Heart Study, our Hispanic Heart Study.
    We've gathered beautiful clinical data for decades, in the 
case of the Framingham Heart Study 60 years. We now can take 
that data and combine it with the genetic understanding of the 
disease to gain new insights into the causation of blood 
pressure, cholesterol, asthma, COPD, and that's what we intend 
to do through some of our GO Grants, is to conduct more 
extensive genetic analysis of these large cohorts which you 
have helped us to support over the years. That's a one-time 
activity that we probably could not have afforded to do without 
the ARRA monies.
    In terms of accelerating medical advances, I think Senator 
Shelby really hit the nail on the head. What we can do with the 
ARRA money is now begin to accelerate our translational 
research program. This infusion of money really helps us to 
focus on a number of mechanisms by which we can help our 
investigators speed, accelerate the basic advances into 
clinical trials and in fact, in terms of the Challenge Grants, 
I think our particular Institute, the last I heard, there was 
somewhere between 1,900 and 2,000 Challenge Grants just for the 
NHLBI.
    We will supplement what Dr. Kington will fund from the 
Office of the Director, but many of these are focused on 
translational research and so we see this as an opportunity now 
to jumpstart.
    We have one particular clinical trial, we call it SPRINT. 
For many years we thought the target for blood pressure 
lowering should be 140 over 80 but, you know, that might not be 
the right target. Maybe we should go a little lower. Maybe if 
we went lower, we could actually reduce some of the age-related 
effects of high blood pressure.
    So SPRINT is to look at lowering down to 120 over 70, even 
120 over 60 as the potential target. We want to look at this in 
adults and, importantly, we want to look at this in our 
adolescents and our children.
    You know one of the complications of obesity, many of our 
kids are becoming diabetic and hypertensive at a very young age 
and so this ARRA money will help us speed and accelerate the 
start of that clinical trial, extend it to a broader 
population, but yes, and then we'll need to fund the out years 
through appropriated dollars, but that's another example of a 
very important public health program that we can jumpstart, 
accelerate with ARRA monies.
    Thank you.
    Senator Harkin. Dr. Niederhuber----
    Dr. Niederhuber. Thank you, Senator Harkin.
    Senator Harkin [continuing]. Tell us about cancer.

                         CANCER AND ARRA FUNDS

    Dr. Niederhuber. I think I'll echo flexibility. I think 
that would be helpful to all of us.
    But we have some great opportunities, as you know, in terms 
of novel agents that have been developed but have not yet been 
able to move into the clinical trials arena, our early phase 
translational research, and so we're going to use a significant 
amount of these stimulus dollars, Recovery dollars to actually 
really jump into the clinic with early phase, first-in-man 
studies in a number of these new agents. I think that's going 
to have a significant impact.
    Perhaps even more importantly than that is we have had a 
very successful pilot project that you're aware of, we call it 
TCGA, in which we've been actually developing the 
infrastructure to do complete sequencing of cancer. We've had 
three cancers in that pilot program, glioblastoma, ovarian 
cancer, and small cell lung cancer.
    We've already found some extremely exciting discoveries in 
doing the sequencing, for example, of glioblastoma, genes that 
are related to that tumor that we didn't know were related to 
that tumor in the past.
    I have a group of scientists meeting as we speak, yesterday 
and today, in San Francisco, that are analyzing our data on 
ovarian cancer and they tell me by phone some very, very 
exciting discoveries are coming out of that sequencing project.
    So, clearly, this is telling us that the direction that we 
need to go in is to scale this up and that's what we're 
planning to do and the Recovery dollars will be a great help in 
our jumpstarting to do other tumors, to do them on a larger 
scale.
    Without question, if we're going to repair this problem, we 
need to catalog all the defects and the technology is moving so 
quickly now that we will be able to do that and do that quite 
effectively over the next few years.
    So these Recovery dollars are extremely important to our 
ability to really scale that up. It's true in cancer but it's 
true really in all of the diseases that you see here at the 
table and represented behind me.

                          RESEARCH PRIORITIES

    Senator Harkin. Okay. A couple of other areas I just wanted 
to cover with you today. Of the $442 million increase proposed 
for NIH, $268 million would go for cancer research, $19 million 
would go for autism research. That leaves $155 million for 
everything else, heart disease, Alzheimer's, diabetes, AIDS, 
stroke, Parkinson's, on and on and on. I want to know if that 
makes sense.
    You know, I know the statistics on cancer. I've fought as 
hard as anyone for more money for cancer research, but there 
are other devastating diseases, too, and we hear from these 
groups almost on a daily basis.
    So when we're looking at a small increase, just 1.5 
percent, should we put so much of that into just one disease 
rather than spreading it out more? So there you go.
    Dr. Niederhuber, I don't mean to pick on you, but you're on 
the point on this. I'm saying, you've got a lot of the Recovery 
monies, but apart from that $442 million, I just question 
whether so much of it ought to go to two entities.
    Dr. Kington. Why don't I start off?
    Senator Harkin. I'll leave that to Dr. Kington. Go ahead. 
Did you want to start off?
    Dr. Kington. I'll take this one. As you noted, both cancer 
and autism are important public health challenges. These were 
priorities of the administration and the President and they're 
important priorities, and it's also important to note, though, 
that science in cancer is funded by every single Institute and 
Center. So it's not just Dr. Niederhuber. Every Institute and 
Center of the agency funds research related to cancer and we've 
initiated a strategic planning process, co-chaired by Dr. 
Niederhuber and Dr. Katz, to bring together all of the agency 
to think about how to develop a plan for increasing this 
investment in cancer.
    It's also important to know that advances in cancer can 
help us learn more about basic biology in ways that would be 
useful for other diseases, as well.
    Senator Harkin. Well, that can be true of just about any 
disease.
    Dr. Kington. That's absolutely true. Your point is well 
taken.
    Senator Harkin. So again, I'm back to square one. Is this a 
fair allotment of money? Any other observations on that? Do we 
have to decide ourselves how to allocate this money up here?
    I just throw it out there because obviously we're trying to 
respond in a way to the legitimate interests of a lot of people 
out there suffering from these illnesses and we've made great 
advances in a lot of areas.
    For instance diabetes, we have made some tremendous 
advances in diabetes research and others that I mentioned and 
taxpayers obviously have a right to question that we're putting 
all of the money in one area.
    So I understand that, and I think that those of us here 
know that the administration proposed this, but we may have a 
different view on that. That's what I have to say about that.

                        OVERSIGHT OF OBJECTIVITY

    Now, there are a couple of other things I wanted to bring 
up.
    Last year my colleague, Senator Grassley from Iowa on the 
Finance Committee, requested some investigations into conflicts 
of interest. In fact, I just saw him this morning. We talked 
about it again, and he's still looking into that, his staff is 
looking into that, and we hear about it periodically. It comes 
up in the press or something like that, that some extramural 
researcher has gotten large payments from a private company 
that could be a potential conflict of interest.
    In the fiscal year 2009 omnibus appropriations bill, I 
included a provision that required HHS to issue ``an Advanced 
Notice of Proposed Rulemaking'' which will start the formal 
process of revising the guidelines. The public comment period 
for that process started earlier this month.
    So I was disturbed to see an article last week in The 
Chronicle of Higher Education in which an NIH official, I think 
unnamed, is quoted as saying, ``We can't say definitely we 
would change the regulations.''
    Well, I don't know. Is that an authoritative statement? I 
hope not. I don't think that the present situation is working 
very well right now. So something has got to be changed here on 
this, Dr. Kington.
    Dr. Kington. First of all, we absolutely share your 
commitment to having the agency playing a central role in 
assuring that there's objectivity in the science that we 
support which is the key issue here, assuring that first-rate 
science of the highest quality, objective science, is funded 
and produced.
    We also recognize that there have been a number of cases of 
investigators that we believe may not have complied with our 
regulations and as almost all of the associations that have 
looked into this, as well, have concluded, we think that there 
are opportunities to strengthen our system of oversight.
    The first step in that process is this Advanced Notice of 
Proposed Rulemaking and I think that the quote--well, I know 
the quote was taken out of context because, technically, the 
whole point of starting this process is to ask the question and 
for us to presume at the beginning the answer might raise 
serious questions about the whole process and so I think it was 
a technical response.
    I think we've said, I've said personally in a number of 
settings, as well, that we believe that there are opportunities 
to strengthen our system of oversight. There are things that 
we're doing within our current regulation to do just that--
increase training and education and strengthening our reporting 
system. There are lots of things that we're doing now to change 
fundamentally and improve the way we oversee management of 
conflicts of interest.
    We're committed to doing that in the future and we will 
take seriously all the comments that we anticipate receiving 
under this Advanced Notice of Proposed Rulemaking and we're 
committed to doing the right thing.
    Senator Harkin. Well, I appreciate that. I think we have to 
be more positive in our approach on this, and on looking at 
these potential conflicts of interest.
    I've been on this subcommittee a long time and I know how 
difficult it is sometimes because a lot of research is paid for 
by the private sector, by the private drug companies, and it's 
good, valid research, and so how do you divide a researcher 
that has an institute--not an nstitute, but has a lab and 
they're getting some private money in and--but then they also 
qualify for an NIH grant. How you separate that out sometimes 
is pretty darn difficult. So I understand that.
    I'm more interested in the conflict of interest in which a 
person receives monetary income for their own bank account. I'm 
not so much interested in the lab itself and that money. I'm 
interested in what an individual might get paid by a drug 
company or something like that and when they are looking at 
certain drugs, for which they then recommend certain courses of 
action.
    This has to do with, I think, anti-psychotic drugs mostly 
and that this individual had been involved in researching it 
but also--maybe this is a bad choice of words, but promoting 
the use of these anti-psychotic drugs.
    I bring this up because I know that my colleague, Senator 
Grassley, is going to continue to look at this, as he should, 
and we have to. We have to be cognizant of this issue and do 
our best to answer those problems.
    Dr. Kington. Yes.

                                H1N1 FLU

    Senator Harkin. The other thing I wanted to ask, Dr. Fauci, 
and it's sort of a replay of what we went over a couple weeks 
ago when you were up here, this H1N1.
    Where are we now? What are you seeing? Is it kind of 
dwindling now here?
    There was some talk that it might move to the Southern 
Hemisphere because of wintertime there, then it might come back 
here again this winter in a more virulent form. I keep 
wrestling with this problem of developing a vaccine because 
some of the money that we put in this was to develop a new 
vaccine. But again if we develop a new vaccine for the H1N1 
strain that we see now, but then it comes back this fall and 
it's different, how are we going to be certain that the vaccine 
we develop this summer is going to be effective against the 
strain of flu that might come back this fall?
    I'm still wrestling with that. I still don't understand 
that.
    Dr. Fauci. Okay. So three questions you asked me.
    Senator Harkin. Okay.
    Dr. Fauci. The status, vaccine, and does it change?
    Senator Harkin. There you go.
    Dr. Fauci. Okay. The status of the outbreak right now is 
that there's still considerable flu activity with H1N1 in the 
United States and worldwide. A recent outbreak that you read 
of, I know, in Japan. So there's considerable activity still 
going on.
    The CDC estimates that even though there are about 6,000 
reported cases that are confirmed or probable in the United 
States, it's likely that there are close to 100,000 people that 
have been infected. You don't pick them up because much of the 
illness is mild illness, yet there are some serious cases, 
which causes us to have an appropriate amount of attention to 
following this.
    As I mentioned to you a couple of weeks ago, this is a 
brand-new virus. It's an H1N1 but a different kind of an H1N1. 
It has swine origin as well as some avian and human origin. It 
is brand new. So the inherent unpredictability of influenza is 
compounded by the fact that we're dealing with a virus that 
we've never had any experience with before.
    Fortunately for us, we're going into a summer season when 
the conditions, the physical conditions for the spread of an 
influenza are minimized, but that doesn't mean that we still 
are not going to have some considerable problems.
    So the bottom line is that this outbreak is still in a 
dynamic stage and it's not over for us yet for the immediate 
period of time.
    What about the concern of what it might do? The fact that 
it's out there and it has already manifested its ability to 
spread from human to human here in the United States, Mexico, 
Canada, Europe, Japan, et cetera, that the concern is that we 
have to watch this very carefully from two standpoints.
    What happens in the Southern Hemisphere in the next month 
or two when they enter into their fall and winter, and we're 
going to watch that very closely because it will tell us what 
might happen to us next fall and winter for our seasonal flu 
vaccine time. The reason is that what usually happens, not 
always but usually is that the Southern Hemisphere flu activity 
is generally a good reflection of what might happen to us in 
the Northern Hemisphere in the following season. So we're 
looking at that very, very carefully.

                                VACCINES

    Vaccine. The process of developing a vaccine has already 
begun and as I mentioned to you before but just to reiterate it 
very briefly, it's a multistep process and there are points in 
that process where there's a decision point, a go or no go.
    The first thing you do is you isolate the virus. That's 
been done. You start to grow it up as a reference strain or 
seed virus. The CDC is very actively involved in this and 
should have seeds ready to go out within a reasonable period of 
time. The prediction is by the end of this month. Hopefully 
that will be on time.
    Once that goes to the pharmaceutical companies, then they 
make pilot lots for clinical trials which is where the NIH 
comes in because then we have to ask the question: is it safe, 
does it induce an immune response that would be predictive of 
being protective, and what's the right dosage and the number of 
doses? At the same time, the companies will then start to, were 
the decision to be a go decision, to start to scale up.
    Your concern that bothers you is that if we're starting to 
make a vaccine for a virus that's circulating now and would 
likely return again in the fall and winter, what happens if it 
changes?
    Senator Harkin. Yes.
    Dr. Fauci. That's always a possibility. The likelihood of 
it changing so much that a vaccine that we're making now would 
be essentially noneffective is small, not zero, but it's small. 
That's the reason why the way we set it up in the department 
with the CDC, FDA, and the NIH is for multiple decision points 
along the way whether to make it, how much to make and whether 
to administer it.
    I will point out to you that every year when we make a 
vaccine for seasonal flu, put aside the pandemic for a moment, 
there's always the risk that the vaccine that you decide to 
make, that what happens to you the next season, it will change 
enough not to make a vaccine as effective as you want.
    Historically, most of the time we get it right. So we are 
hoping that we will get it right. I think we will. I don't 
think there will be that much of a change, but as I mentioned, 
influenzas are characterized by their unpredictability, but 
you've got to go with the science that you have, and the 
science that we have now tells us that this virus that's out 
there hasn't really changed much over the months that we've 
been following it.
    It started off in Mexico, the first detection in Mexico. We 
don't know where it started, but the first detection was 
somewhere in March or so. So we're now a few months into it and 
the virus seems to be pretty much the same as it's been. It's 
stayed relatively stable. That doesn't mean it's going to stay 
that way over the next year, but it has not drifted a lot.
    Senator Harkin. I keep hearing that even the seasonal flu 
vaccine may offer some immunity.
    Dr. Fauci. No.
    Senator Harkin. No?
    Dr. Fauci. No. This is good news for you, Senator, and me, 
and that is, it doesn't have--the vaccines that have been used 
seasonally don't appear to induce antibodies that strongly 
cross-react at all with the H1N1 that's the new novel H1N1.
    But what we are observing is that in the community this 
virus seems to be selectively more preferentially affecting 
young people. So the question is, Do old people--older people--
have in their body some antibodies or cell-mediated immunity 
that they acquired from previous exposures to H1N1s over the 
previous years that are a bit below the radar screen, but that 
seem to be giving some protection? That's one of the prevailing 
theories, not proven yet, of why we're seeing it much more in 
young people.
    In fact, when you measure the antibodies in older 
individuals, a rather significant percentage of them have some 
cross-reactivity with the virus that's circulating now and the 
most obvious, though not necessarily proven, but the most 
logical reason for that is that they've been exposed over the 
last few decades to an H1N1 that has some similarity to the 
H1N1 that we're seeing now.

                           BARKER HYPOTHESIS

    Senator Harkin. Well, I'll have to correct some of the ways 
I've been saying things then because I've been led to believe 
maybe some of the immunities we have comes because we've gotten 
the seasonal flu shots over the last few years, but that's not 
it. It has to do with our exposures to the influenza virus some 
time in the past and we've developed antibodies to it. I'll 
have to correct the way I say that now.
    There's only one other area I just want to get into.
    First, you all know that we've been working very hard on 
healthcare reform and the area that I've been involved in, of 
course, and I've been harping on this for many years is getting 
into prevention and wellness and focusing on that. I think 
we're going to have some, I hope, great success in the health 
reform bill in moving in that direction, which leads me to this 
next question, and it has to do with some of the information my 
staff has given me and I've been reading about it, the so-
called Barker Hypothesis.
    Dr. Barker of Oregon Health and Science University, who did 
a study that was very interesting--no, sorry, he didn't do a 
study. He examined other studies and came to some interesting 
conclusions, that pre-natal care--how you're taken care of 
before you are born may have a great impact on what happens to 
you later in life.
    My first initial reaction when I read that was, of course, 
if you have a low birth weight baby that means you don't get 
the right kind of nutrients and support during pregnancy. This 
happens sometimes in poorer families. I can understand that.
    But then evidently Dr. Barker factored that in and had 
accounted for that in his studies. And even accounting for 
that, it shows up that if you have a low birth weight baby, 
there were certain twins they followed the one that had the low 
birth weight had the most problems later on in terms of 
diabetes, stroke, hypertension, all kinds of things.
    So I guess my question is to maybe any body sitting there 
is, are we doing research? I've just come across this in the 
last few months and I wonder, are we looking into this? Is NIH 
doing any research in this area?
    Dr. Kington. Yes, we are. David Barker is a British 
physician who in the 1980s began to notice patterns of tracking 
of looking geographically at mortality rates in England, 
patterns of mortality that tracked adult cardiovascular 
mortality with infant birth weight and that was the beginning 
of this long line of research that has been supported by the 
agency, including by NICHD, and there are a range of evidence, 
some--most supported but some not supported, of this hypothesis 
that has evolved into a more complicated discussion about 
potential ways in which the intrauterine environment sort of 
sets trajectories by turning on or off genes or somehow setting 
trajectories that actually are manifest in late life but start 
off this trajectory.
    The hypothesis is that there's something unique going on in 
these early stages and it has implications for this entire 
continuum of potential causal pathways, from smoking now all 
the way back to shortly after conception and what happens in 
the intrauterine environment.
    It's an interesting hypothesis and generated a great deal 
of discussion, both in Europe and in the United States, and we 
fund research related to it. I think it's still to be 
determined what the implications are for intervention and what 
we do clinically, the argument being that if we know more about 
what happens in the intrauterine environment, we might 
intervene in ways beyond the obvious of good nutrition and 
prevention and all the things that you noted, better social 
environments and all the things that we know are good for 
starting off children beginning healthy lives.
    So the jury is still out about what the implications are, 
if it's correct, and there's a growing evidence base both in 
humans and in animal models, and we're supporting research and 
looking forward to seeing more advances in this area and we'd 
be happy to sort of synthesize some of the findings that we've 
supported and get back to you about that, as well.
    [The information follows:]
                         The Barker Hypothesis
    David Barker, an English epidemiologist working at the University 
of Southampton, noted that the geographical regions of the British 
Isles reporting high rates of death from coronary heart disease were 
the same regions that reported high rates of low birth weights. In a 
landmark study published in the medical journal Lancet in 1989, Dr. 
Barker and his colleagues reported on an analysis of serial data 
collected on 5,654 men in Hertfordshire. They found that the men with 
the lowest weights at birth had the highest death rates from coronary 
artery disease. Those with the lowest birth weights had more than twice 
the mortality rate than those with the highest birth weights.
    In seeking to explain the remote outcomes of low birth weight, Dr. 
Barker developed the Barker Hypothesis, which states: environmental 
factors that impair growth and development during fetal life and early 
infancy are risk factors for hypertension, type 2 diabetes, stroke, and 
coronary disease later in life.
    A general explanation for these findings is that birth weight 
represents an integral of all events that affect development during 
gestation, including nutrient supply, vascular sufficiency, infection 
and stress. The key question is to determine mechanistically what 
happens to the fetus to alter permanently its physiology and metabolism 
throughout later life.
    Studies in animal models are useful in revealing the physiological 
connections between impaired intrauterine growth and chronic disease 
later in life. Dr. Lori Woods at the Oregon University of the Health 
Sciences has shown that reduced maternal protein intake in a rat model 
impairs the development of the kidney in the offspring, leading to 
hypertension later in life. In a baboon model Dr. Peter Nathanielsz at 
the University of Texas at San Antonio has shown that nutrient 
restriction during fetal life leads to impaired development of insulin 
manufacture by the beta cells of the pancreas, predisposing the animals 
to type 2 diabetes later in life.
    The most widely accepted mechanism that explains these 
relationships is the metabolic adaptation that the fetus makes to 
survive in an intrauterine environment impaired by nutrient 
insufficiency, such as an increased secretion of cortisol. The survival 
mechanisms that are useful in the uterus, however, are maladaptive in a 
plentiful nutritional environment after birth as reported by Barker and 
his colleagues in two articles in the New England Journal of Medicine 
in 2004 and 2005. The first showed that low birth weight babies in an 
East Indian population who gain weight rapidly after birth are at high 
risk of developing type 2 diabetes in their third decade of life. The 
second showed that Finnish boys and girls with low birth weight are at 
increased risk of coronary artery disease later in life, especially 
those whose tempo of weight gain is greatest in the first decade of 
life.
    The Barker Hypothesis has stimulated new fields of related research 
on the effects of inimical environmental influences on the development 
of the brain and body during fetal life and early childhood. One line 
of investigation suggests that over-nutrition during pregnancy also can 
have untoward effects on offspring later in life. The NIH Obesity 
Research Task Force has identified this area as a research priority in 
regard to the development of type 2 diabetes, lipid disorders, and 
other metabolic disease in offspring. Studies in nonhuman primates have 
shown that consumption of a high fat-high calorie diet during pregnancy 
results in extensive fatty liver disease in the offspring, a disorder 
being seen with increasing frequency in obese adolescents. Maternal 
obesity has been reported to increase the risk of congenital defects, 
particularly neural tube defects, in developing offspring.
    Other studies suggest that high levels of blood sugar during 
diabetic pregnancies affect an offspring's risk of obesity and type 2 
diabetes later in life. NIH intramural investigators have shown in the 
Pima population of Arizona that type 2 diabetes in the mother leads to 
increased risk for type 2 diabetes and obesity in the offspring. 
Adverse effects of intrauterine exposure to diabetes were also shown 
recently in a racially and ethnically diverse population of youth; the 
NIH- and CDC-supported SEARCH study found that children with type 2 
diabetes received their diagnosis at an earlier age if their mothers 
had been diagnosed with diabetes prior to pregnancy.
    Another interesting line of research stimulated by the Barker 
Hypothesis involves the influence of maternal infections and 
intrauterine exposure to environmental agents on the development of 
disease in the offspring later in life. Dr. Alan Brown and colleagues 
at Columbia University have shown that maternal infections with strains 
of influenza virus type A and B during the first trimester of pregnancy 
increase the risk of schizophrenia spectrum disorders in the offspring 
later in life. They also showed a similar effect of maternal infection 
with toxoplasmosis. Preliminary, unpublished studies by Cohn and 
colleagues of the Public Health Institute in Berkeley, California, show 
an association between maternal serum levels of dichlorodiphenyl-
trichloroethane and testicular cancer in male offspring later in life. 
The National Children's Study, currently under way, is designed to 
assess the effects of such environmental exposures during pregnancy and 
early childhood on many other aspects of health and disease later in 
life.
    In sum, the Barker Hypothesis, now 20 years old, has led to 
numerous productive lines of research which have relevance to many NIH 
Institutes, including the NICHD, NIDDK, NCI, NINDS, NHLBI, NIEHS, NINR, 
NIDA, NIAAA, NIAID and the NIMH.

                        WELLNESS AND PREVENTION

    Senator Harkin. I'm just curious. What Institutes would be 
the lead?
    Dr. Kington. Child health, I know, has funded. Aging has 
funded some, as well, because some of the early studies--the 
intriguing idea was that something happening in the uterus 
would be manifest in old age and some of the interesting 
studies focused on that element of this relationship.
    Senator Harkin. Do you have any idea about when we might be 
able to really get some body of evidence or something that we 
could rely on to say for prevention, we ought to be doing this 
and that pre-natal care and pregnant women ought to take 
certain factors into account?
    I don't know that we have enough to go on right now. I 
don't know. Do we?
    Dr. Kington. That's the point. I don't think we've resolved 
the scientific question enough to translate into a different 
way of doing what we're doing now, which is a lot of the things 
that you noted, good nutrition, all the prevention things that 
we know, pre-natal care, the social environment of pregnant 
women, all the things that we know are very important for 
having healthy babies.
    I don't think that the science is at a point where that 
would tell us to do something different or beyond what we know 
now as best practice. I think we're still ahead of the curve on 
that, but we're funding research and interesting ideas. It's 
been bandied about for a couple decades now and the evidence 
base was growing, not uniform support, but an evidence base and 
an interesting problem and question.
    Maybe Dr. Nabel might want to comment, as well.
    Dr. Nabel. Yes, I think the Barker Hypothesis raises in a 
broader term the concept of when should we begin prevention 
measures. I think that's probably one of the points you're 
getting to.
    From the cardiovascular and from the diabetes and obesity 
literature, we do know that the intrauterine environment makes 
a distinct difference in terms of predisposition toward 
subsequent diabetes and obesity in the newborn, but it also 
raises the fact that there's growing recognition among 
physicians, healthcare providers, that rather than waiting 
until middle age to focus on risk factor detection and 
prevention, we've got to shift much earlier and initially we 
shifted to the young adulthood but now we're increasingly more 
and more shifting to adolescence and childhood.
    In fact, the American Academy of Pediatrics has put out 
guideline recommendations for detection of cardiovascular risk 
factors, for example, in pediatric population.
    So there's growing recognition. Much of that recognition is 
built on the science base, that we're beginning to see, 
serendipitously, risk factors appearing in the pediatric 
office. When we go back and do natural history studies or 
observational studies then we can detect it on a scientific 
level.
    So yes, we know that these risk factors are appearing much 
earlier in life and that now is leading to action programs for 
detection and risk factor management.
    Senator Harkin. Very good. This is the last one, I promise, 
but I did want to get this in.
    Dr. Kington. You may ask as many questions as you like.

                   COMPARATIVE EFFECTIVENESS RESEARCH

    Senator Harkin. It has to do with comparative 
effectiveness. Dr. Nabel, this is probably to you.
    We provided $1.1 billion for comparative effectiveness in 
the Recovery Act. I have to admit, I did that and I have a lot 
of people asking about that. We put $400 million in there and 
that money is going to be used by NIH.
    We also created the Federal Coordinating Council for 
Comparative Effectiveness Research (CER), which will recommend 
priorities for this research and I understand you're a member 
of this Council.
    Again, can you tell me something about NIH's plans for the 
$400 million? What kinds of activities might fall into the 
category of comparative effectiveness research as far as NIH is 
concerned? What are you looking at and what are you going to 
use that money for?
    Dr. Nabel. Terrific. Well, thank you, Senator, for the 
question.
    As you know, the NIH has supported work that now fits the 
definition of comparative effectiveness research for many 
years, but we're delighted to have this additional money to 
again do things that we normally could not do or to jumpstart 
or accelerate other programs.
    Dr. Richard Hodes, the Director of the Aging Institute, and 
I co-direct the NIH Comparative Effectiveness Research 
Coordinating Committee. This is a committee that has brought 
together senior leadership, Institute Director leadership and 
deputy director leadership from across the agency to develop 
plans for that $400 million and again we're enormously 
grateful.
    We are looking at opportunities now that meet the 
definition of CER and would allow us to conduct research that 
again will either--something that we normally couldn't do or 
would jumpstart.
    We are looking at several possible mechanisms for 
supporting that research. One are payline expansions, so 
studies that Institutes have had to leave on the table because 
they simply did not have enough funds to initiate it. We're 
looking at the possibility of supplements that could accelerate 
enrollment in a trial or add an ancillary study or accelerate a 
trial in another way.
    We anticipate that over the summer we will have a broad 
number of Challenge Grants because in fact CER was one of the 
Challenge Grant topics. We anticipate we will have applications 
in CER, and we also anticipate there may be some GO 
applications that also meet the definition of CER.
    So we continue to meet on a regular basis. We are 
coordinating our work with the work of AHRQ and the Federal 
Coordinating Committee. We are working toward one common 
definition of CER for the department which we anticipate using 
and we are very cognizant of the fact that we want to make good 
use of this money. We want to get it right.
    We see this as a downpayment toward many CER activities 
that we would like to continue in the future.
    Senator Harkin. I wanted to get that on the record and 
thank you very much for your response on that.
    I have no further questions. Do you have anything else that 
any of you would like to bring up before we close this down?
    Well, let me just say thank you to all of you and to all of 
you in the row in the back and to all the Directors of the 
Institutes.
    Again, NIH is just one of our shining examples, I think, of 
good public policy and what we're using taxpayer dollars for 
and for all the years I've been privileged to associate with 
you, I just think you're doing an outstanding job at NIH, all 
of you.
    I thank you very much for your commitment to public service 
and to public health and to the research that we do at NIH and 
I always like to continue to say for the record that this is 
the National Institute of Health. It's not the National 
Institute of Basic Research. Basic research is important, but 
we always have to keep in mind we are looking at increasing the 
health of our people and of humankind in general. It's not just 
geared toward the American people, and so with all of that 
research we have to keep thinking about, what's that 
translational research, what's it going to translate into? 
Better health for people and I think NIH has done an 
outstanding job in that through all its years.
    So again, my thanks for your public service. I would again 
say, Dr. Kington, that I just repeat what I said earlier, I'm 
hopeful that this fall I will have healthcare reform behind us, 
maybe a little bit more time. It would be my intention and my 
desire and my intention to reprise again what we did a couple 
years ago. I'd love to have the Institute Directors down, two 
or three at a time, for some in-depth look at what the research 
is doing.

                     ADDITIONAL COMMITTEE QUESTIONS

    I think it's not only good for the record but I think it's 
good for us to know, me and the staff and the others who are 
charged with the responsibility of making some of these 
decisions to know exactly where we are and where some of the 
new research avenues that are going on in all these different 
Institutes. So I hope to be able to do that some time this 
fall.
    [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 Tom Harkin
                           pancreatic cancers
    Question. Dr. Niederhuber, one of the deadliest forms of cancer--
pancreatic cancer--also seems to be one of lowest priorities of the 
National Cancer Institute (NCI). Pancreatic cancer research accounts 
for less than 2 percent of the Institute's budget. Last year, the 
subcommittee asked for a report on how resources will be used to 
address this problem. Would you tell us what, if anything, is being 
done to expand the research portfolio for this lethal form of cancer?
    Answer. NCI is committed to pursuing a broad research effort for 
pancreatic cancer. In 2001, NCI convened a Pancreatic Cancer Progress 
Review Group (PRG) to identify priority areas for research. Since that 
time, NCI's support for pancreatic cancer research has grown 
significantly. Based on the recommendations in the PRG report, NCI 
expanded its portfolio of pancreatic cancer research from $21.8 million 
in fiscal year 2001 to $87.3 million in fiscal year 2008. Part of this 
growth came about through planned actions and funding opportunities 
specific to pancreatic cancer, and part grew out of an increasingly 
larger pool of pancreatic cancer researchers successfully competing for 
general funding opportunities and unsolicited research grants.
    In the past 7 years, the number of investigators funded through the 
standard principal investigator-funding R01 awards has more than 
doubled, increasing from 34 to 93. The total number of research awards 
with a pancreatic cancer focus has more than tripled since fiscal year 
2000, increasing from 85 projects in fiscal year 2000 to 271 projects 
in fiscal year 2007.
    NCI has also increased the number of Specialized Program of 
Research Excellence (SPORE) grants with pancreatic cancer components, 
increasing the investment from one award in fiscal year 2000 to a total 
of six in fiscal year 2008. SPORE grants support specialized centers 
that promote interdisciplinary research, moving basic research findings 
from the laboratory to clinical settings while also bringing clinical 
findings back to the laboratory environment. SPORE investigators work 
collaboratively to plan, design, and implement research programs that 
may impact cancer prevention, detection, diagnosis, and treatment. Five 
of these SPORE grants were initially awarded shortly after the PRG 
meetings were held, with the sixth SPORE newly awarded in fiscal year 
2008.
    NCI continues to support pancreatic cancer research training awards 
for graduate students, postdoctoral trainees, clinical researchers, and 
junior faculty, as well as career transition and development awards for 
established investigators. In fiscal year 2005, an estimated 23 
distinct training projects were relevant to pancreatic cancer research 
and approximately $2.2 million was spent on these projects. In fiscal 
year 2006, an estimated 31 distinct training projects were relevant to 
pancreatic cancer research and approximately $2.7 million was spent on 
these projects. In fiscal year 2007, an estimated 36 distinct training 
projects were relevant to pancreatic cancer research and approximately 
$2.8 million was spent on these projects.
    NCI implemented a policy in fiscal year 2002 of increasing its 
payline (percentage of applications that are funded) for research that 
is related to pancreatic cancer. Initially, NCI's policy called for a 
50 percent higher payline for investigator-initiated R01 grant 
applications with 100 percent relevance to pancreatic cancer. Since 
fiscal year 2004, grant applications with 50 percent or greater 
pancreatic cancer relevance were given special consideration for 
exception funding.
    NCI has also developed pancreatic cancer-focused initiatives, 
including the Pilot Studies in Pancreatic Cancer and the Pancreatic 
Cancer Cohort Consortium. The Pilot Studies promote innovative 
multidisciplinary research to increase our understanding of pancreatic 
cancer biology, etiology, detection, prevention, and treatment. The 
Pancreatic Cancer Cohort Consortium is a group of investigators from 12 
prospective epidemiologic cohorts and 1 case-control study who conducts 
whole genome scans of common genetic variants in order to identify 
markers of susceptibility to pancreatic cancer. Pancreatic cancer 
studies have also been funded within the Mouse Models of Human Cancers 
Consortium, Novel Technologies for In Vivo Imaging, Cancer 
Nanotechnology Platform Partnerships, and the Early Detection Research 
Network.
    The Pancreatic Cancer Research Map is a Web-based tool developed 
for tracking pancreatic cancer research, clinical trials, and 
investigators. By providing a way to search the pancreatic research 
portfolio for funding opportunities, investigators, and developments in 
pancreatic research, the map facilitates and expedites collaborations 
and networking among researchers focuses on this disease.
    Recently, as part of the restructuring of the NCI Clinical Trials 
Enterprise, NCI formed the Gastrointestinal Intergroup. Pancreatic 
cancer is one of the gastrointestinal cancers that the group will be 
looking at as they harmonize an efficient, cost-effective, science-
driven, and transparent process that will identify and promote the 
``Best Science'' in gastrointestinal cancer clinical research by 
addressing the design and prioritization of large phase II studies and 
phase III trials in these cancers.
       progress in treatment and prevention of pancreatic cancer
    The number of therapeutic trials that can be conducted in any 
cancer type depends upon scientific opportunity, frequency of the 
disease, and its outcome. NCI has been able to test a large number of 
drugs intended to treat pancreatic cancer in small trials. 
Unfortunately, as you know, to date pancreatic cancer has proven to be 
unresponsive to most drugs and radiation therapies. Less than 20 
percent of patients with pancreatic cancer are candidates for surgery, 
because the disease is often detected in the late stages. Gemcitabine 
has been a standard treatment for patients with advanced and inoperable 
pancreatic cancer for a decade. New findings support use of the 
chemotherapy drug in the adjuvant setting, and patients who received 
the drug gemcitabine after surgery for pancreatic cancer lived 2 months 
longer than patients who had surgery alone. This study shows that this 
treatment improves a patient's survival and more than doubles the 
overall survival 5 years after treatment.
    Another study has shown that a new drug combination tested in mice 
may target the cells responsible for driving some pancreatic tumors. 
The combination of gemcitabine and the experimental drug tigatuzumab 
eliminated populations of cancer stem cells and reduced tumor growth in 
a mouse model of pancreatic cancer. The results provide a rationale for 
testing the promising combination in patients with this deadly disease. 
Tigatuzumab is also being tested in a phase II clinical trial with 
patients who have inoperable, untreated pancreatic cancer.
    Ultimately, only a better understanding of the genetics and biology 
of pancreatic cancer is likely to yield improved therapies. These 
fundamental breakthroughs are likely to be produced by basic and 
genetic research into the mechanisms of cancer risk, initiation, 
growth, and resistance, in which NCI is heavily invested. One such 
investment is PanScan, a project made up of 12 cohort and 8 case-
control studies primarily supported by NCI. The goal of PanScan is to 
identify the genetic variants that increase the risk of developing 
pancreatic cancer and refine our understanding of the interactions of 
tobacco and other nongenetic risk factors with the genetic variants 
that increase pancreatic cancer risk.
    NCI anticipates that these studies will provide fundamental new 
insights into the genetic underpinnings of pancreatic cancer similar to 
the recent discoveries resulting from the genome-wide scans of prostate 
and breast cancers. These findings will inform further biological 
research that is likely to have clinical applications, including the 
detection of molecular targets for preventive, diagnostic, and 
therapeutic interventions. It is expected that the initial findings 
this study will be published later this year.
    NCI is also involved in the Pancreatic Cancer Genetic Epidemiology 
(PACGENE) Consortium which was developed to identify susceptibility 
genes in familial pancreatic cancer. The Consortium consists of seven 
data collection centers, a statistical genetics core, and a pathology/
archival genotyping core. PACGENE recruits people with two or more 
affected blood relatives found through incident pancreatic 
adenocarcinoma cases, physician referrals, as well as Internet 
recruitment. Accrual to a database containing core clinical, 
demographic, lifestyle and family history information from 
questionnaires is ongoing, along with biospecimen collection. The 
shared goals and methodologies of data collection of this Consortium 
will facilitate and accelerate our understanding of the genetic basis 
of pancreatic cancer.
    In addition to genetic research, NCI is also supporting pancreatic 
cancer research that utilizes nanotechnology. Cancer Nanotechnology 
Platform Partnerships, a component of NCI's Alliance for Nanotechnology 
in Cancer, are developing technologies for new products in such areas 
as molecular imaging and early detection. One partnership is studying 
the use of nano particles in the diagnosis and therapy of pancreatic 
cancer, and developing and testing nano particles that will deliver 
imaging and therapeutic agents to pancreatic tumors.
                               prevention
    There are presently no effective ways to detect early signs of 
pancreatic cancer. One way to discover susceptibility genes for an 
inherited disease is to analyze DNA from large families with many 
affected members. But this strategy does not work with inherited forms 
of pancreatic cancer, because the disease is so deadly that there are 
very few large families with adequate numbers of samples.
    Researchers at the Johns Hopkins Kimmel Cancer Center have shown 
for the first time that sequencing the genes in both the normal and the 
cancer cells of a single patient can reveal genes that are altered in 
both types of cells. Some of these changes can help identify 
susceptibility genes.
    This strategy offers a new way to find hereditary susceptibility 
genes, and in the future, these genes could be part of a panel used to 
evaluate patients with familial pancreatic cancer. A test for 
predisposing mutations could help identify people at high risk of the 
disease who could be monitored for precancerous changes, enrolled in 
screening programs and potentially prevent them from getting pancreatic 
cancer.
    Question. In addition to pancreatic cancer, would you tell us how 
NCI plans to attack some the other deadly cancers--ones where survival 
rates remain low?
    Answer. In terms of other deadly cancers, the following are the 
ones with the lowest percentage for 5-year relative survival rate (30 
percent or lower).
                             ovarian cancer
    The high-mortality rate stems from an overall lack of early 
symptoms or screening methods for the disease. As a result, most 
ovarian cancer patients are diagnosed with advanced stage disease. For 
fiscal year 2009, NCI is funding 5 SPORE program grants, and the 
relatively low incidence of this disease, as well as the team concept 
of the SPORE program, has resulted in a number of Inter-SPORE 
activities aimed at developing much needed early detection, screening, 
prevention, and therapeutic tools for ovarian cancer. These 
supplemental activities are being performed in collaboration with a 
number of other NCI programs, including Avon Progress for Patients 
Partnership, the Cancer Genetics Network, the Early Detection Research 
Network, the Division of Cancer Prevention's Prostate, Lung, Colon, and 
Ovarian Cancer (PLCO) Screening Trial and the NCI Intramural Program.
    The Cancer Genome Atlas (TCGA) is assessing the feasibility of 
systematically identifying the major genomic changes involved in cancer 
using state-of-the-art genomic analysis technologies. Ovarian cancer is 
one of the first cancer types to be studied in the TCGA pilot phase. 
Early results are revealing genetic changes that could be used to 
identify those women who may be at risk for developing ovarian cancer, 
as well as pointing to markers for early detection of the disease when 
there is a better potential for successful therapy.
    NCI's Cancer Nanotechnology Platform Partnerships are developing 
technologies for several key areas including studies focused on 
developing multifunctional nanoparticles that can deliver light-
activated anticancer compounds specifically to ovarian cancer cells 
through a partnership at the Massachusetts General Hospital.
    The New Drug Combination for Ovarian and Primary Peritoneal Cancers 
clinical trial is testing the combination of cisplatin, a drug 
containing platinum, and flavopiridol, which blocks the activity of 
proteins that help cancer cells grow and spread, in women with ovarian 
or peritoneal cancer resistant to platinum-based chemotherapy. 
Flavopiridol can increase the platinum concentrations in cells when 
administered with cisplatin, and researchers believe that this may lead 
to a reversal of platinum resistance.
    The National Ovarian Cancer Early Detection Program.--Screening and 
Genetic Study is determining effective screening and genetic testing 
methods to identify women at increased risk of ovarian cancer. The 
study is also designed to develop markers for early detection and novel 
therapies.
                       liver and bile duct cancer
    Primary liver and bile duct cancers are the fifth most common cause 
of cancer death in men and the ninth most common cause of cancer death 
in women. More than 90 percent of all cases occur in men and women age 
45 or older. Liver cancer is closely associated with hepatitis virus 
infections, especially hepatitis B.
    A clinical trial, Hepatic Arterial Infusion of Melphalan with 
Hepatic Perfusion in Treating Patients with Unresectable Liver Cancer, 
is evaluating the effectiveness of hepatic arterial infusion 
(delivering chemotherapy directly to the liver) of the drug melphalan 
combined with hepatic perfusion (delivering chemotherapy to a blood 
vessel) in patients with liver cancer
    The Etiology, Prevention, and Treatment of Hepatocellular Carcinoma 
program supports research on the etiology of liver cancer, development 
of animal models, novel prevention approaches, identification of 
reliable predictors of disease progression, and ways to minimize the 
morbidity and mortality associated with this disease.
    The Tumor Microenvironment Network is exploring the role of the 
microenvironment, the cells and blood vessels that feed a tumor cell, 
in tumor initiation and progression. Network investigators are 
examining the role of inflammation and the microenvironment in the 
development of liver cancer.
                           esophageal cancer
    The Prevention Agents Program provides scientific and 
administrative oversight for chemoprevention agent development from 
preclinical research to early Phase I studies. The program is currently 
supporting research on several agents for potential chemoprevention of 
esophageal cancer.
    The interdisciplinary scientists of the Network for Translational 
Research: Optical Imaging is accelerating translational research in 
optical imaging and/or spectroscopy. Current efforts include the 
development of techniques to identify molecular markers for detecting 
esophageal neoplasia and understanding basic disease mechanisms.
    The Cancer Prevention Research Small Grant Program is supporting 
several research projects focused on esophageal cancer, including 
studies on esophageal cancer biomarkers, a mouse model of esophageal 
adenocarcinoma, and the molecular mechanisms involved in the 
development of Barrett esophagus. The latter is a condition in which 
the cells lining the lower part of the esophagus have changed or been 
replaced with abnormal cells that could lead to cancer of the 
esophagus. The backing up of stomach contents (reflux) may irritate the 
esophagus and, over time, cause Barrett esophagus.
                              lung cancer
    Lung cancer is the second most common cancer and the most common 
cause of cancer-related death in both men and women in the United 
States.
    Seven lung cancer-specific Specialized Programs of Research 
Excellence (SPOREs) are promoting interdisciplinary research and moving 
basic research results from the laboratory to the clinical setting.
    TCGA is assessing the feasibility of systematically identifying the 
major genomic changes involved in cancer using state-of-the-art genomic 
analysis technologies. Lung cancer is one of the first cancer types to 
be studied in the TCGA pilot phase.
    PLCO Cancer Screening Trial is determining whether certain cancer 
screening tests reduce deaths from prostate, lung, colorectal, and 
ovarian cancers.
    NCI's Lung Cancer Program supports research on early detection and 
treatment. The Lung Cancer Biomarkers Group is developing sets of 
specimens that can be used to test biomarkers for the early detection 
or diagnosis of lung cancer.
    The Mouse Models of Human Cancers Consortium is developing models 
of lung cancer to aid in our understanding of lung tumor biology and to 
facilitate the development and testing of novel therapeutic approaches 
and methods for early diagnosis.
                             stomach cancer
    The overall incidence of stomach cancer in the United States has 
declined in the past 75 years. Five gastrointestinal cancer-specific 
SPOREs are moving results from the laboratory to the clinical setting.
    The Tumor Microenvironment Network is exploring the role of the 
microenvironment, the cells and blood vessels that feed a tumor cell, 
in tumor initiation and progression. Network investigators are studying 
the role of inflammation and the tumor microenvironment in stomach 
cancer.
    NCI's Infections and Immunoepidemiology Branch conducts high-impact 
epidemiologic research on infectious agents and cancer. Researchers are 
investigating why stomach cancer risk is low in Africa, despite high 
rates of Helicobacter pylori infection, as well as genetic factors 
associated with stomach cancer risk.
    The Community Clinical Oncology Program (CCOP) and the Minority-
Based Community Clinical Oncology Program (MB-CCOP) are comprehensive 
clinical trial mechanisms that disseminate the latest cancer prevention 
and treatment research findings to the community. Several CCOP and MB-
CCOP groups currently participate in stomach cancer clinical trials.
                                myeloma
    Myeloma, also known as multiple myeloma or plasma cell myeloma is 
the second most common blood cancer in the United States. The myeloma-
specific SPORE is moving results from the laboratory to the clinical 
setting. This program is studying novel myeloma therapies and 
identifying new markers of this disease.
    The Multiple Myeloma Prevention Study is evaluating the use of 
nonsteroidal anti-inflammatory drugs to modulate biomarkers associated 
with monoclonal gammopathy of undetermined significance, a condition 
that sometimes precedes the development of myeloma.
    The Quick-trials for Novel Cancer Therapies and Prevention.--
Exploratory Grants program expedites clinical translation of basic 
research discoveries in cancer biology through the development of novel 
anti-cancer drugs, diagnostic tools, treatments, and prevention 
strategies. This program currently supports two projects focused on 
immunotherapy and on improving the effectiveness of stem cell 
transplants in myeloma patients.
    Question. Is NCI considering a plan to specifically and 
comprehensively address these lethal cancers?
    Answer. Nearly half of the over 500,000 expected cancer deaths this 
year will be caused by 8 forms of cancer with 5-year relative survival 
rates of less than 50 percent-lung, liver, pancreatic, ovarian, brain, 
stomach, esophagus cancers and myeloma-and most of these cancers 
disproportionately affect minorities and under-served subgroups in the 
United States. These cancers are often difficult to diagnose early. 
Cancers of high lethality pose a significant research challenge. These 
aggressive tumors are usually diagnosed late in their disease course, 
making the study of early disease progression and promotion, as well as 
the impact of genetic and environmental exposures, especially 
difficult.
    NCI proposes to increase research on highly lethal cancers by 
expanding its investment into molecular epidemiological approaches such 
as the Cohort Consortium-of which the Pancreatic Cancer Cohort 
Consortium (PanScan) is one component--TCGA and genome-wide association 
studies to accelerate a fuller understanding of cancer causation and 
provide scientific direction of early detection, prevention and 
targeted therapeutic strategies. Molecular interrogation will generate 
data that can be used to evaluate profiles across the disease spectrum 
as well as among ethnic and racial populations.
                            nih medline plus
    Question. This subcommittee has long supported increased efforts by 
the NIH to provide the public important health information based on the 
results of the medical research their taxpayer monies support. At my 
urging, the NLM has increased its commitment to boost the distribution 
of the NIH MedlinePlus magazine. It is my understanding that a new 
bilingual version of the magazine, NIH MedlinePlus Salud, has been 
tested. What steps can be taken to substantially increase the public's 
access to these publications by getting them to all physician offices, 
community health clinics, and libraries?
    Answer. Distribution of the magazines has increased from 50,000 
copies of each issue in 2006 to over 500,000 copies of the English and 
Spanish versions in 2008. We estimate that the magazines now enjoy a 
readership of approximately 5 million nationwide. In February 2009, NLM 
created improved online versions of both magazines, which makes it easy 
for people to find, use, and email individual articles from the 
complete set of issues.
    To increase distribution of the magazines still further, NLM, other 
NIH Institutes and Centers, and the Friends of the National Library of 
Medicine are forming partnerships with other Government agencies and 
private organizations which have an interest in supporting and enabling 
distribution of high-quality health information to their respective 
audiences. For example, the Peripheral Arterial Disease (PAD) Coalition 
supported the distribution of an additional 250,000 copies of one 2008 
issue. In addition, the National Alliance for Hispanic Health is 
helping to support the production and distribution of NIH MedlinePlus 
Salud, which is an English/Spanish version. The pilot issue featured 
Cuban American journalist Cristina Saralegui, who is well known for her 
Univision talk show, The Cristina Show, as well as her work on behalf 
of health and wellness causes.
    Question. Is this something that could be done with stimulus 
funding?
    Answer. NIH is extremely grateful for the opportunities and funding 
provided in the American Recovery and Reinvestment Act of 2009 (ARRA) 
to preserve and create jobs and promote economic recovery by spurring 
technological advances in science and health. NLM is investigating how 
it may best use ARRA dollars to support the spirit of the Recovery Act, 
including increasing the distribution of the NIH MedlinePlus and NIH 
MedlinePlus Salud magazines.
                         interstitial cystitis
    Question. According to NIH's recently revised methods for 
calculating support levels for various disease research areas, the 
amount dedicated to interstitial cystitis (IC) is less than half of 
what NIH previously believed it to be. (NIH originally estimated the 
fiscal year 2007 funding for IC research to be $23 million; new 
calculations show that the actual amount was just $10 million.) This is 
disappointing, given that this condition afflicts more than 8 million 
Americans.
    What are the agency's plans to further basic and clinical research 
in this area?
    Answer. NIH's shift to a new and more consistent process--requested 
by the Congress--to report on certain diseases and conditions through 
the Research, Condition, and Disease Categorization (RCDC) system, has 
indeed led to changes in reported funding levels for a variety of 
conditions, including IC. There are a number of reasons for these 
differences, including precise ``definitions'' for some disease 
reporting categories under the new system. More information is 
available on our RCDC Web site, at http://report.nih.gov/rcdc/reasons/. 
We began using RCDC to report actual funding levels in fiscal year 
2008. To ensure transparency during the transition to RCDC, the NIH 
disease funding table provides a side-by-side comparison of the actual 
fiscal year 2007 levels produced using the prior method and the levels 
that would have resulted if RCDC had been implemented that year--
thereby illustrating the effect of the RCDC methodology and clarifying 
the changes between fiscal year 2007 and fiscal year 2008 resulting 
from use of this new process. For example, while the actual amount of 
funding reported for IC in fiscal year 2007 was $23 million, the RCDC 
analysis of the fiscal year 2007 portfolio reflected annual funding 
support of $10 million. The actual funding level reported for fiscal 
year 2008 of $10 million is comparable with the amount identified for 
fiscal year 2007 using the new RCDC methodology. While the impact of 
this change has in some instances resulted in significant one-time 
adjustments, it is important to note that they do not reflect a change 
in the NIH's commitment to research on IC and other conditions, and 
will ultimately result in more accurate, consistent reporting across 
NIH. Research that can lead to improved detection, treatment, or cure 
for IC remains a high priority for NIH.
                                 ______
                                 
            Questions Submitted by Senator Daniel K. Inouye
                            pharmacy program
    Question. Dr. Sidney McNairy, Director of the Division of Research 
Infrastructure, met with the University of Hawaii at Hilo faculty and 
administrative staff in December 2008. What are we doing or should we 
be doing to help the new University of Hawaii at Hilo's new pharmacy 
program meet the objectives set by Dr. McNairy's site visit?
    Answer. One of the objectives set forth during Dr. McNairy's visit 
was to facilitate an expanded role of the University of Hawaii at Hilo 
in the Institutional Development Award (IDeA) Program's IDeA Networks 
of Biomedical Research Excellence (INBRE) initiative within National 
Center for Research Resources (NCRR), a component of the National 
Institutes of Health (NIH). The long-term objective is to facilitate 
the development of the research infrastructure in the School of 
Pharmacy at Hilo and foster collaboration with the Manoa campus.
    Subsequent to this visit, Dr. McNairy and his staff set up several 
teleconferences with the Dean of the School of Medicine at the Manoa 
campus and the Dean of the School of Pharmacy at Hilo to discuss plans 
for the development of a joint application to compete for support via 
the INBRE initiative. As a result, these institutions are developing an 
application that includes core research facilities and instrumentation 
at the Hilo campus; support for research projects for junior faculty 
investigators at Hilo aimed at transitioning them to independent 
research support; and alterations and renovations at the Hilo campus. 
The Hawaii INBRE application will also include collaborations with 
several community colleges and 4-year institutions. Interactions with 
these latter institutions will provide the School of Pharmacy with an 
expanded pool of potential candidates for entry into the pharmacy 
program.
    Question. What is being done to anchor these activities and help 
assure success?
    Answer. NCRR staff participates in teleconferences with the 
Principal Investigator of the proposed Hawaii INBRE to review the 
details of the funding opportunity announcement (PAR-08-150), answer 
questions, and provide programmatic advice during the development of 
the application. The institutions are working toward the submission of 
this application in fiscal year 2009.
    Question. Many initiatives and programs that have recently been 
launched by the National Cancer Institute (NCI) appear to be based on 
mechanisms that utilize center-based models. Large awards or 
cooperative agreements are made to large, well-established institutions 
and individual researchers. One criticism of such a model has been that 
it detracts from an already depleted investigator-initiated pool of 
grants for funding cancer and biomedical research. What steps is the 
NCI taking to ensure that adequate resources in the form of 
investigator-initiated research project grants continue to be made 
available to not only individual investigators but to young and/or new 
investigators?
    Answer. The allocation to investigator-initiated research continues 
to represent the largest component of the NCI budget. That is a strong 
demonstration of the commitment the Institute has to investigator-
initiated research. Equally strong is the Institute's commitment to 
first-time investigators. NCI allocated $74 million to pay new 
competing grant applications from first time investigators in fiscal 
year 2007 and raised that to $82 million in fiscal year 2008. Research 
Project Grants (RPGs) represent 44 percent of NCI's fiscal year 2009 
budget. NCI intends to increase the number of first-time investigators 
in fiscal year 2009 using additional American Recovery and Reinvestment 
Act funds to support the first 2 years of their research project and 
then continuing their support in years 3-5 with appropriated funds.
              innovative approaches and novice researchers
    Question. What efforts are currently underway to stimulate and 
support new, novel, and innovative approaches to the detection, 
treatment, and diagnosis of cancer?
    Answer. NIH supports innovative approaches to the detection, 
treatment, and diagnosis of cancer. NCI established the Innovative 
Molecular Analysis Technologies (IMAT) program to support the 
development, technical maturation, and dissemination of novel and 
potentially transformative next-generation technologies through an 
approach of balanced, but targeted innovation. The IMAT program 
utilizes a variety of investigator-initiated research project grant 
mechanisms while retaining a strong commitment to diversity and to the 
training of scientists and clinicians in cross-cutting, research-
enabling disciplines.
    Nanotechnology represents a large number of advanced technologies 
that promise to change all aspects of 21st century medicine, especially 
cancer medicine. This is an area that brings scientists from physics, 
chemistry, mathematics, and engineering together with cancer biologists 
and oncologists to develop new cancer interventions. NCI launched the 
Alliance for Nanotechnology for Cancer program in 2004 to capitalize on 
these technologies. These centers are developing and translating novel 
nanotechnology-enabled diagnostic, imaging, and therapeutic platforms 
into clinical practice--which is required to capitalize on our prior 
investments in the molecular sciences. The original program produced 
several nano platforms that are currently in preclinical evaluation 
with a few already in clinical trials. The Alliance is a magnet for 
young creative scientists. Trained in the molecular sciences, 
bioinformatics, and physics, these centers have attracted the best--
bringing Nobel Prize winners together with scientists that are early in 
their careers. Together they are creating new training and research 
opportunities that are driving this emerging field.
    Question. Through what mechanisms are such programs funded, and is 
there a percentage or grant category designated to support the 
development of novice researchers?
    Answer. NCI allocated 17 percent of the competing RPG budget to 
select grant applications that were identified as filling gaps in the 
research portfolio or representing novel approaches to research 
problems. We often refer to the grants funded with that pool as 
``exceptions'' to the regular payline. One-third of that exception pool 
was allocated to supporting first-time investigators. Those exceptions 
are used across the portfolio, including in the areas of detection, 
treatment, and diagnosis.
    The NCI Alliance for Nanotechnology in Cancer program, for example, 
utilizes several mechanisms, including the U54 center mechanism, R25 
training center mechanism, K99/R00 fellowships mechanism, and U01 
investigator-initiated research project mechanism. Based on comparison 
of landscape before and after the initial program, there is a clear 
trend of increased interest in cancer nanotechnology training as NIH 
fellowship applications supported by the original program (F32/F33) 
increased significantly since the program began. Postdoctoral students 
are the largest group participating in the alliance and, in fact, 
dominate the annual meeting where their research is presented. A 
similar increasing trend for NCI is seen in both individual training 
awards (K99) and institutional training awards (T32, R25). When the 
Alliance for Nanotechnology in Cancer began, the Institute supported a 
total of 4 individual-initiated grants in the field; that number has 
increased to 48 (excluding Alliance awardees) during the 5 years that 
the Alliance has been in place, and the Alliance shows signs of further 
expansion as more young people enter this new field.
                          military researchers
    Question. The National Institute of Nursing Research (NINR) lists 
(1) Integrating Biological and Behavioral Science for Better Health; 
(2) Adopting, Adapting and Generating New Technologies for Better 
Health Care; (3) Improving Methods for Future Scientific Discoveries; 
and (4) Developing Scientists for Today and Tomorrow as its 2006-2010 
Strategic Goals, with a research emphasis on Promoting Health and 
Preventing Disease, Improving Quality of Life, Eliminating Health 
Disparities, and Setting Directions for End-of-Life Research. 
Historically, military nurse researchers have been unable to compete 
for funds due to the uniqueness of the population they serve. 
Considering the ongoing status of conflict in the Middle East and other 
countries, what efforts are being taken to allow military nurse 
researchers to actively compete for these funds?
    Answer. The NINR strongly encourages all scientists to apply for 
funding within the NINR areas of research emphasis. There are no 
funding exclusions based on military status. Currently, the NINR is 
sponsoring a research initiative entitled, ``Improving Quality of Life 
of Patients and Family Following a War-Related Traumatic Injury'' to 
develop and test personalized interventions to prevent complications in 
persons with war-related traumatic injuries during the post 
hospitalization transition period, with the ultimate goal of improving 
the health and quality of life of individuals and families following a 
war-related traumatic injury. NINR is actively involved in the 
collaboration between the NIH and the Center for Neuroscience and 
Regenerative Medicine at the Uniformed Services University of the 
Health Sciences (USHUS) to answer difficult research questions and 
improve medical care for service members with brain injuries and Post-
Traumatic Stress Disorder. Through this collaboration, there are 
valuable training opportunities for nurse scientists. Other Federal 
partners collaborating in this effort are the Defense Centers of 
Excellence for Psychological Health and Traumatic Brain Injury, Army 
Medical Research Command labs, Navy labs, and the Walter Reed National 
Military Medical Center.
    NINR also has a long-standing relationship with the TriService 
Nursing Research Program at USHUS to facilitate collaboration and to 
consult on matters relevant to military nursing research. One of the 
members of the National Advisory Council for Nursing Research (NACNR) 
is Capt. Maggie Richard, Ph.D., MSN, NC, USN. Captain Richard is the 
director of the Human Research Protection Program in the Bureau of 
Medicine and Surgery, the Department of the Navy. She has served more 
than 20 years in the Navy Nurse Corps, and is the former head of the 
Nursing Research Service at the Bethesda National Naval Medical Center. 
As a member of the NACNR, Captain Richard provides the second level of 
review of grant applications, and recommends to the Institute Director 
which applications should be approved and considered for funding.
    NINR remains dedicated to supporting clinical and basis research to 
help improve the health of the Nation, including members of the 
military service.
                              nci and cis
    Question. While the NCI intends to retain the information service 
arm of the Cancer Information Service (CIS) (i.e., 1-800-4CANCER 
service, the Internet, and instant messaging), NCI leadership has 
decided not to continue funding the CIS Partnership Program beyond the 
current contract period, ending January 15, 2010. What is NCI's plan 
for responding to the cancer information, training and technical 
assistance needs of remote, medically underserved communities and the 
organizations that serve them, such as those located in Hawaii and the 
U.S.-Associated Pacific Island jurisdictions?
    Answer. Rather than renew the Partnership Program, we have 
reassessed how NCI can most effectively and efficiently disseminate 
important cancer information, and engage communities in order to 
realize an impact in the lives of those we serve. NCI will actively 
align its community outreach with its community-based research programs 
and build capacity in communities for the effective delivery of cancer 
information to their members. Building on the success of projects such 
as the Imi Hale-Native Hawaiian Cancer Network and the American Samoa 
Community Cancer Network, as well as the partnership between the 
University of Hawaii and the University of Guam, NCI will support 
community-based research programs that will build capacity to meet the 
needs of the underserved populations.
    Beginning in January 2010, NCI will augment community-based 
research projects to include a community outreach structure that will 
specifically employ community outreach staff. While it is expected that 
these staff members will service the outreach needs for those funded 
projects, NCI is also expecting them to perform activities to address a 
broader area of needs identified by NCI. The funded projects that will 
initiate this new model of outreach include the Community Networks 
Program-II (CNP-II), the Minority Institution/Cancer Center Partnership 
(MI/CCP), and the NCI Community Cancer Center's Program (NCCCP), 
representing a total of 66 sites initially.
    The establishment of a coordinated outreach network that works 
within established NCI-supported research programs will provide 
national geographic coverage for outreach to all populations. The 
proposed Community Outreach Core within the CNP-II concept will employ 
health education/community outreach staff to foster activities 
supporting the community and community partners. A similar approach 
within the MI/CCP and NCCCP would further augment and reinforce this 
national outreach network. Within the MI/CCP, for example, all 
partnerships are encouraged to have outreach programs and activities 
linking scientific discoveries and implementation of scientific 
breakthroughs in high-risk populations, and some partnerships are also 
increasing enrollment of racial/ethnic minorities in clinical trials. 
The outreach and partnership components of the CIS partnerships can be 
successfully integrated and absorbed within the existing community 
outreach cores of NCI funded research initiatives to enhance and 
strengthen NCI's ability to educate and engage communities in 
addressing cancer health disparities within diverse, high-risk 
populations. NCI will also examine the feasibility of expanding this 
model to other NCI-funded programs.
    NCI already has an outreach and dissemination infrastructure within 
its Office of Communications and Education that will provide these 
grantees the necessary technical assistance for communication, 
dissemination, and outreach. This infrastructure supports the current 
CIS Partnership Program. They are prepared to provide this national 
outreach network guidance in the use of best practices, the development 
of shared resources and tools, and the provision of training and 
technical assistance to community outreach coordinators in 
comprehensive cancer control and the delivery of evidence-based 
outreach activities.
    In addition to the establishment of this national outreach network 
through NCI-funded programs, NCI is already in the process of planning 
a concept for dissemination, community outreach, and communication. 
This process, which has been described in responses to previous 
inquiries on this matter, utilizes a public health planning approach 
which examines the scientific evidence across areas of cancer control 
and engages the community throughout the process in feedback loops, and 
will ultimately yield a concept that aims to reduce the impact of 
cancer in the most vulnerable communities. Greater details on the 
planning process for this can be provided upon request.
                                 ______
                                 
                Question Submitted by Senator Herb Kohl
            increasing funding and greater number of awards
    Question. Dr. Kington, I was pleased to see that funding sources 
for the National Institutes of Health Clinical and Translational 
Science Awards (CTSA) were increased this year, through both the fiscal 
year 2009 omnibus appropriations bill and the American Reinvestment and 
Recovery Act. I am aware that several institutions applying for awards 
this year, including applicants in my home State of Wisconsin, have 
received ``outstanding'' application ratings. Will this increase in 
funding allow for a greater number of awards to be distributed?
    Answer. The funding provided in the Omnibus Appropriations Act, 
2009, will support new CTSAs in fiscal year 2009 as the program moves 
closer to a goal of 60 CTSAs.
    The American Recovery and Reinvestment Act (ARRA) funding is being 
used to allow existing CTSAs to compete for resources to supplement 
their current activity, plus support other researchers who may apply to 
leverage current CTSA activities. However, since normal CTSA funding is 
for 5 years and ARRA funds are limited to 2 years the funding is not 
able to support new awards.
                                 ______
                                 
            Questions Submitted by Senator Mary L. Landrieu
small business innovation research (sbir) and small business technology 
                        transfer (sttr) programs
    Question. When the American Recovery and Reinvestment Act (ARRA) 
passed in February, it contained a short sentence that directly hurt 
small businesses by exempting two important small business programs. 
The provision, which provided $8.2 billion to the National Institutes 
of Health's (NIH), exempted the NIH from the statutory requirement that 
2.8 percent of extramural research and development (R&D) money be used 
for the Small Business Innovation Research (SBIR) and the Small 
Business Technology Transfer (STTR) programs. As the chair of the 
Senate Small Business Committee, and as a member of this appropriations 
subcommittee, I was never consulted or notified about the exemption 
language which was added in conference. My staff has been told by NIH 
officials and others that NIH directly requested the exemption. As a 
result of the exemption, the NIH is not required to award up to $200 
million from the ARRA funds to small businesses for research and 
development. This exemption went directly counter to the principles and 
goals of ARRA. The recovery effort was supposed to be about creating 
high-quality jobs, spurring innovation, and giving a boost to 
businesses across the board. Instead, this language singled out small 
businesses and slashed the relatively tiny amount they are normally 
guaranteed. I have several questions for Dr. Kington regarding NIH's 
request and the exemption: Specifically, who at the NIH requested that 
ARRA be exempt from funding the SBIR and STTR programs? Was this 
request first cleared through you?
    Answer. NIH was concerned about the decreasing number of SBIR 
applications. We had seen nearly a 40 percent decrease in applications 
during the fiscal years 2004 through 2008. Although the NIH is not 
required by this law to provide a set amount of ARRA funds toward the 
SBIR/STTR programs, it is important to note that small businesses are 
able to apply for and will receive funds. NIH remains committed to the 
small business community and has been encouraging small businesses to 
apply for stimulus funds through various funding opportunity 
announcements that have been released.
    Question. From your experience at NIH, would you agree that the 
SBIR and STTR programs play a vital role in NIH's extramural R&D 
because of the high levels of innovation that come out of these two 
programs?
    Answer. NIH has supported and continues to support small business 
and efforts to bring innovations from biomedical research to the 
taxpayer. NIH research is driving a vibrant community of American small 
businesses and entrepreneurs in the health enterprise. NIH-funded 
research leads to patents and spin-off companies across the Nation. 
Through the SBIR and STTR programs, the NIH helps nurture entrepreneurs 
as they bring products to the international market that improve health 
and well-being. Small businesses supported by NIH grants help maintain 
American economic leadership.
    For example, Kinetic Muscles, a small business in Arizona, has 
developed the Hand Mentor ProT, which is a device designed for 
neurological rehabilitation of the hand and wrist for people who have 
suffered strokes or other brain injuries. In partnership with their 
exclusive distributor, Columbia Scientific, the Hand Mentor ProT is now 
being used in select HealthSouth rehabilitation hospitals.
    Biopsy Sciences of Florida has developed the Bio-SealT and recently 
sold the technology to Angiotech Pharmaceutics, Inc. (a global 
specialty pharmaceutical and medical device company). This novel 
technology was designed to reduce the incidence of postoperative 
pneumothorax (collapsed lung) in patients who undergo lung biopsy 
procedures. The technology involves placement of an expanding hydrogel 
plug along the biopsy needle track during the procedure, closing off 
the track to subsequent influx of air into the chest during respiration 
after the biopsy needle is withdrawn. The seal is airtight and the plug 
is absorbed into the body after healing of the puncture site has 
occurred.
    These are only a few examples of the high level of innovation and 
the many products that have been developed with NIH SBIR/STTR funding.
    Question. From your experience at NIH, would you agree that small 
businesses doing extramural R&D for the NIH have a proven record of 
creating jobs?
    Answer. Small businesses have long been the engine of U.S. economic 
growth, generating a significant proportion of new jobs annually, and 
we believe NIH's SBIR/STTR programs assist with the creation of high-
quality jobs. NIH has invested in excess of $5 billion in more than 
19,000 projects to over 5,000 small businesses. Past studies of the 
SBIR program conducted by the NIH and the National Research Council 
(NRC) have shown small businesses are seen as sources of economic 
vitality and are especially important as a source of new employment.
    Question. Could you please provide, in detail, the steps NIH is 
taking to make sure small businesses receive an adequate share of ARRA 
funds?
    Answer. NIH has taken several steps to ensure small businesses 
receive an adequate share of the ARRA funds appropriated to NIH. 
Outreach efforts have been stepped up to alert small companies of ARRA 
opportunities. In the last few months, eight SBIR/STTR presentations 
have been given throughout the country at life science or SBIR/STTR 
conferences in New Jersey, Indiana, Kentucky, New York, Maryland, 
Washington, DC, and California. NIH's 11th Annual SBIR/STTR Conference 
was held at the end of June 2009 in Omaha, Nebraska, and with 
attendance typically in the hundreds, this was another excellent 
opportunity to disseminate information about specifically targeted ARRA 
opportunities to this small business audience.
    During the past few months, NIH has strongly encouraged small 
businesses to apply for several of its funding opportunity 
announcements (FOAs) that were supported by ARRA, including:
  --The NIH Challenge Grants in Health and Science Research or 
        ``Challenge Grants'' http://grants.nih.gov/grants/guide/rfa-
        files/RFA-OD-09-003.html
    This opportunity focuses on specific knowledge gaps, new 
technologies, data generation, or research methods that would benefit 
from an influx of funds to quickly advance the area in significant 
ways.
  --Research and Research Infrastructure ``Grand Opportunities'' or 
        ``GO Grants'' http://grants.nih.gov/grants/guide/rfa-files/RFA-
        OD-09-004.html
    This opportunity focuses on developing and implementing critical 
research innovations to advance their research enterprises, stimulate 
future growth and investments, and advance public health and health 
care delivery.
    In June, NIH released two additional announcements that explicitly 
targeted the private sector commercial research community. These 
included:
  --Recovery Act Limited Competition: Biomedical Research, Development, 
        and Growth to Spur the Acceleration of New Technologies (BRDG-
        SPAN) Pilot Program, http://grants.nih.gov/grants/guide/rfa-
        files/RFA-OD-09-008.html
    This FOA is a pilot program that focuses on the funding gap between 
promising research and development and transitioning to the market by 
contributing to the critical funding needed to pursue the next 
appropriate milestone(s) toward ultimate commercialization. Any U.S.-
owned, for-profit enterprise/commercial organization is encouraged to 
apply for this funding. Please note that applications received under 
this FOA may be given funding priority if the applicant is associated 
with an enterprise or commercial organization that is of small size 
and/or has limited resources.
  --Recovery Act Limited Competition: Small Business Catalyst Awards 
        for Accelerating Innovative Research, http://grants.nih.gov/
        grants/guide/rfa-files/RFA-OD-09-009.html
    This opportunity specifically targets the SBIR research community 
and focuses on accelerating innovation through high- risk, high-reward 
research and development that has commercial potential and is relevant 
to the NIH mission. It seeks to encourage fresh research perspectives 
and approaches and focuses on early-stage ideas that promise to lead to 
major leaps forward rather than incremental improvements of existing 
technologies. Only U.S. small business concerns are eligible to submit 
Phase I SBIR applications, and first-time applicants to NIH may receive 
funding priority.
    In addition to releasing these funding opportunity announcements, 
the pay-lines at various NIH Institutes and Centers have been extended 
to reach more meritorious research grants, including those submitted by 
small businesses. Finally, in March 2009, NIH offered three 
administrative supplement and competitive revision opportunities for 
those with active research project grants (including SBIR and STTR). 
The supplements provided additional funding to accelerate the tempo of 
scientific research on active grants. Revision awards support a 
significant expansion of the scope or research protocol of approved and 
funded projects. Administrative supplements were also offered to 
provide summer research experiences for students and science educators. 
SBIR and STTR projects successfully competed. At this time, over 20 
SBIR/STTR grantees have been selected to receive administrative 
supplements to provide summer research experiences for students and/or 
science educators.
    Question. My staff has been told by NIH officials that you are 
setting up a Pilot program for small businesses with your discretionary 
ARRA funds. Can you please report to the Senate Small Business 
Committee on the nature and progress of this Pilot program?
    Answer. You are correct, NIH recently announced the ARRA-funded 
BRDG-SPAN Pilot Program to focus on the gap between research and 
development and transitioning to the market.
    Only U.S.-owned for-profit enterprise/commercial organizations may 
apply, and although not explicitly limited to small businesses, most of 
the applications are expected to be submitted by small businesses. 
Applications received under this funding opportunity may be given 
funding priority if the applicant is associated with an enterprise/
commercial organization that is of small size and/or of limited 
resources.
    In addition, we have another ARRA-funded small business program 
called the Catalyst Awards, and only U.S. small business concerns are 
eligible to submit SBIR applications.
    Question. I have looked at a number of legislative vehicles, 
including the fiscal year 2010 Labor HHS Appropriations bill, to make 
up for the loss of money to small businesses that was created by the 
small business exemption in ARRA. Can you give me your thoughts on how 
this money can be made up, whether it be legislatively or through 
proactive actions by the NIH?
    Answer. NIH's current commitments to small business research 
instill confidence that this research community will receive a fair 
portion of NIH's extramural funding. This is already in evidence, since 
a large number of applications were received from small businesses in 
response to our initial ARRA-supported FOAs, and applications are still 
being received from small businesses in response to ARRA FOAs that 
remain open.
                                 ______
                                 
              Questions Submitted by Senator Arlen Specter
                maternal fetal medicine research network
    Question. I am aware of the critical research conducted by the 
National Institute of Child Health and Human Development (NICHD) 
Maternal Fetal Medicine Research Network in the area of preterm birth 
and maternal complications. What are your plans for this Network in the 
fiscal year 2010 budget?
    Answer. The Maternal Fetal Medicine Units Network (MFMU) is one of 
the landmark research networks within NICHD. Conducting research that 
may affect pregnant women and their offspring can present some critical 
health and ethical issues. Yet improvements in clinical practice and 
care are dependent on evidence-based research, and the Network was 
created in response to this need. This research mechanism permits 
large-scale clinical studies that provide the necessary information to 
allow healthcare professionals to translate the findings into everyday 
clinical practice.Specifically, the MFMU Network conducts clinical 
trials and observational studies in obstetrics to improve maternal and 
neonatal outcomes. It is essential for each Network participant to 
conduct this work in the same manner (i.e. following the same protocol) 
in order to have comparable results that can be applied across the 
Nation and for different population groups. In addition, preventive 
measures and interventions can be tested to find out if they work, or 
just as important, if they do not.
    NICHD has spent approximately $170 million since the MFMU Network's 
inception in 1986. It is re-competed every 5 years to ensure that only 
the best scientists are funded to do this work. The existing network 
will expire in fiscal year 2011. The networks scientific success 
supports considering a new competition in fiscal year 2011. As is 
typical, decisions regarding extending the Network will be made during 
development of the 2011 budget. Current projections for fiscal year 
2010 are $12.6 million in NICHD funding. Along with a projected 
$700,000 contribution from NINDS in fiscal year 2010, the total support 
level comes to $13.3 million.
                          salivary diagnostics
    Question. Dental schools, and I have one in my State, are doing 
some rather exciting research in the area of saliva as a diagnostic 
tool. Where does this research stand at this point?
    Answer. Saliva is a complex mixture of water, antibodies, and other 
specialized protective proteins, important for maintaining oral health, 
function, and comfort. It has long been recognized that saliva acts as 
a mirror of the body's health, in that it contains the full repertoire 
of proteins, hormones, antibodies, and other substances that are 
frequently measured in standard blood tests to monitor health and 
disease. Saliva is easy to collect, even repeatedly if needed, and 
poses none of the risks, fears, or invasiveness of blood tests.
    Saliva has already been used reliably to detect a number of 
diseases, including HIV, as well as viral hepatitis A, B, and C. It 
also can be used to monitor a variety of drug levels, including those 
of marijuana, cocaine, and alcohol. The National Institute of Dental 
and Craniofacial Research (NIDCR) is supporting efforts to identify and 
validate biomarkers, and to also support technology to overcome 
barriers to the widespread use of salivary diagnostics. For example 
researchers are focused on developing microchip assays for point-of-
care delivery, and are making impressive progress at achieving high-
sensitivity, high-specificity, miniaturization, automation, 
portability, low cost, speed, and the ability to assay a large number 
of samples and biomarkers concurrently.
    Last year, scientists funded by NIDCR completed the first full 
catalogue of proteins present in saliva. This protein dictionary will 
serve as an essential reference point as scientists continue to 
validate saliva as a diagnostic fluid. This resource also complements 
our growing ability to leverage DNA and RNA as biomarkers. For example, 
in October 2008, NIDCR-supported scientists reported that they could 
use a panel of 5 RNA biomarkers to accurately detect oral squamous cell 
carcinoma, a form of oral cancer, more than 90 percent of the time.
    Question. Is progress being made?
    Answer. Yes, progress is being made. The field of salivary 
diagnostics combines the power of mathematics, biology, genomics, 
proteomics, engineering, computer science, and other areas, with the 
goal of using saliva as a diagnostic fluid for a variety of conditions, 
from AIDS to cancer to diabetes. Several NIDCR grantees are now working 
to develop and assemble tiny ``labs on a chip'' that can precisely 
measure levels of the various antibodies, antigens, and nucleic acids 
present in saliva, all of which may indicate a developing disease or 
condition. In contrast to existing blood tests which require painful 
needle sticks, salivary tests could be performed on the spot and 
rapidly scan oral fluids for the presence or absence of multiple 
proteins linked to various systemic diseases and conditions. NIDCR is 
currently supporting the development of devices that will detect 
infectious diseases, cancer, renal diseases, steroid hormones, and 
inflammatory markers for cardiovascular and pulmonary diseases. The 
technologies being developed also will be effective for tracking new, 
as-yet unidentified biomarkers.
    As an illustration of progress in this area, NIDCR scientists 
recently reported clinical success in detecting C-reactive protein in 
human saliva with an ultrasensitive microchip assay system. C-reactive 
protein, a serum protein indicative of inflammation, is elevated in 
people with periodontal disease and may be predictive of developing 
heart disease.
    Question. Will we be able to go to our dentist and undergo this 
noninvasive diagnostic test to detect early markers of diseases, such 
as Alzheimer's disease, pancreatic, and breast cancer?
    Answer. This is part of our vision for the future; saliva is easy 
to collect and poses none of the risks, fears, or invasiveness of blood 
tests. The miniaturization of detection devices may allow placement of 
the sentinel device directly in the mouth, yielding real-time 
surveillance of hundreds of biomarkers that could alert individuals to 
consult with their health professionals at the earliest moment of 
disease, or to monitor the progression and recurrence of diseases in 
patients undergoing treatment. This will enable oral healthcare 
professionals to assume a more prominent role in primary care and 
disease prevention that will assume increasing importance as the 
American population ages. NIDCR will continue to support ongoing 
studies, as well as new studies including those made possible by 
American Recovery and Reinvestment Act funding, that will examine the 
feasibility of developing salivary diagnostic testing for the early 
markers of a number of diseases, including Alzheimer's disease and 
several cancers. The recent success of NIDCR-supported researchers in 
identifying salivary markers for primary Sjogren's syndrome, a chronic 
autoimmune condition of the salivary and tear glands that affects about 
2 million Americans, mainly women, is another example of progress in 
this area.
    Salivary diagnostics could have benefits far beyond medicine and 
dentistry as well. For example, law enforcement agencies could employ 
saliva tests both forensically and 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.
                nih budget with presidential initiatives
    Question. The budget presented provides an increase of $174 million 
for all research except cancer. Will this essentially flat budget 
funding be sufficient to meet the important research work being 
conducted by the National Institutes of Health (NIH)?
    Answer. We believe that the fiscal year 2010 NIH funding priorities 
are sound and will ensure the rapid translation of science from the 
laboratory to the bedside. The budget supports more than 9,800 
competing Research Project Grants in addition to exponentially funding 
cancer as an initiative.
    NIH's research categories are not mutually exclusive and individual 
research projects can be included in multiple categories as in cancer 
research; we have seen progress in one disease often comes from 
unrelated areas of investigation, and through the mutual synergy of 
such research that transformational findings occur. NIH will continue 
to fund high-quality research in all areas of its portfolio and will 
continue to effectively use every resource we receive in support of 
biomedical research.
                               stem cells
    Question. What do you think is necessary in terms of time and 
funding to make research breakthroughs in stem cell research?
    Answer. The NIH has been clear that the best way to make 
breakthroughs in stem cell research is to pursue all avenues of stem 
cell research simultaneously as: (1) it is impossible to predict which 
type of stem cell research (e.g., adult or human embryonic) will 
ultimately yield the most successful approach in any given stem cell 
application; and (2) work in both adult and embryonic stem cells 
continues to inform and facilitate progress in stem cell research.
    It is difficult to predict a timeline for scientific breakthroughs 
or determine a budget that will achieve these breakthroughs for stem 
cell research or any other type of research. Since 2001, NIH has been 
the lead Federal agency supporting and conducting human embryonic stem 
cell (hESC) research, spending over $262 million on hESC research 
during this period. This research has significantly enhanced our 
understanding of the basic biology of these unique cells. For example, 
the genes required for maintaining pluripotency were determined by 
studying hESCs which led in 2007 to the breakthrough discovery of 
human-induced pluripotent stem cells. These cells are now being studied 
along with adult and hESCs to elucidate the unique characteristics and 
potential uses of each cell type.
    As you are aware, President Barack Obama signed Executive Order 
13505 on March 9, 2009, which requires NIH to establish new guidelines 
for Federal funding of human embryonic stem cell (hESC) research. NIH 
will issue the final guidelines by July 7, 2009. These new guidelines 
should increase ethical oversight and the number of responsibly derived 
hESC lines eligible for Federal funding. We anticipate that NIH will be 
able to provide support for research using many new hESC lines that 
were not previously eligible for Federal funding. It is our expectation 
that the expansion of the number of human embryonic stem cell lines 
available to scientists funded by NIH will hasten stem cell 
breakthroughs.
    As you know, there has never been a cap on how much NIH could 
potentially spend on stem cell research, adult or embryonic. Instead, 
the amount spent depends on the number of highly meritorious stem cell 
grants that are submitted by the scientific community. The scientific 
community has told us about additional research that will be enabled by 
the increase in the number of human embryonic stem cell lines eligible 
for Federal funding that will result from the new policy. Once the new 
Guidelines are in place, NIH will assess the research needs and 
opportunities in stem cell biology and will develop initiatives that 
meet those needs to capitalize on these opportunities.
                              lower lp(a)
    Question. Several years ago, I asked Dr. L'Enfant about your 
research for a medication to lower Lp(a). Is there anything new that 
you can tell me about the status of research toward a medication that 
lowers Lp(a)?
    Answer. Of all the drugs we currently use to treat abnormal 
lipoproteins, the one that most consistently lowers Lp(a) levels is a 
drug that has been around quite a while--niacin. Although the National 
Heart, Lung and Blood Institute (NHLBI) does not ordinarily sponsor 
drug development, as that is the province of the pharmaceutical 
companies, we are currently supporting a very important randomized 
clinical trial called AIM-HIGH. The trial is testing whether an 
extended release form of niacin (Niaspanr) will improve outcomes in 
3,300 patients who have cardiovascular disease and ``atherogenic 
dyslipidemia,'' a fairly common constellation of lipoprotein 
abnormalities associated with high cardiovascular risk that often 
includes high Lp(a) levels. We have funded an ancillary study to the 
AIM-HIGH trial specifically to learn more about how niacin affects 
lipoproteins, including Lp(a), and to determine the extent to which the 
effects may explain any observed improvement in cardiovascular 
outcomes. The information this study will provide about the role of 
Lp(a)in cardiovascular disease may help inform subsequent drug 
development efforts.
                             curing cancer
    Question. The cancer community has indicated that $335 billion over 
the next 15 years is necessary to make real progress toward cancer 
cures. What do you think is necessary in terms of time, funding, and 
research breakthroughs to make a real difference in curing cancer?
    Answer. The National Cancer Institute (NCI) is currently working 
with the other Institutes and Centers at NIH to develop an NIH cancer 
research strategic plan for the proposed plan by President Obama to 
double cancer research funding over the next 8 years. The strategic 
plan recognizes that most advances in the field will be made because of 
the knowledge that cancer is a disease of genomic alterations and of 
tumor cell evolution.
    The NCI is developing a personalized cancer care platform--based 
upon the knowledge that cancer is a disease of altered genes--that will 
encompass and enable a drug development platform, from discovery of 
genetic changes to translation to man. Advanced genome sequencing 
technology will soon make it possible to completely sequence both 
normal and disease tissue of individual patients. NCI is developing a 
comprehensive approach to translate raw genetic information into an 
intimate understanding of the function of the genetic pathways which 
can then be used to clearly define targets for manipulating those 
pathways to inform the development of new targeted interventions. NCI 
is taking steps to create the first of a small national network of 
tumor characterization centers that will match a genetically 
characterized patient's tumor to appropriate and optimal therapeutic 
solutions. This 21st century vision for personalized medicine will 
connect individuals, organizations, institutions, and the concomitant 
information in a cycle of discovery, development, and clinical care.
    As the leader of the National Cancer Program, NCI is building on 
its history of research success and wisely spending every dollar it 
receives in a continual effort to foster the best research and to 
connect the public, private, and academic sectors for effective 
translation of these discoveries. With the significant funding 
increases proposed by the President, NCI could realize the promise of 
personalized cancer care more rapidly by significantly shortening the 
path between making an innovative discovery in the laboratory to having 
an effective impact on a patient in the clinic.
    In this new era of post-human-genome science, it is clear that 
multiple new agents will be necessary to target multiple cancer 
pathways in each unique patient. Small molecules will penetrate cancer 
cells. New agents will energize the body's immune system to fight 
tumors. Still other agents will target the seemingly normal tissue of 
the tumor microenvironment or the tumor initiator cells with ``stem-
like'' characteristics that may lead to cancer's deadly spread. 
Consequently, we will need to continue to expand discovery of the 
underlying genetic signatures of cancer and to develop individual 
recipes of therapy, often using multiple drugs from multiple 
manufacturers.
    It is in the area of developing orphan drugs or combination 
therapies where industry--concerned about marketability, intellectual 
property, competition, and liability issues--often fears to tread. NCI 
must fill that void:
  --Through increased funding of the Developmental Therapeutics Program 
        and other allied programs, NCI could greatly expand a cohesive 
        effort to produce small quantities of new agents and begin 
        first-in-human testing, which would, in turn, lead to 
        commercialization at a more rapid pace.
  --Through a well-financed, coordinated plan, NCI could importantly 
        restructure how it conducts clinical trials, creating an 
        electronically connected system capable of bringing early phase 
        clinical research to millions more patients, in their home 
        communities.
  --Through strategically placed characterization centers, NCI could 
        conduct the intensely technological and specialized testing 
        necessary in an era of targeted agents. This effort could 
        create the standards of tumor analysis required in this new 
        age, and could more effectively address the demands of rapidly 
        changing technology. Examples of needed programs include early 
        phase pharmacodynamic studies, a U.S. oncology tissue bank and 
        certified centralized tumor characterization laboratories.
  --Additional development of advanced technologies will allow us 
        further develop nanoparticles designed to penetrate tumors and 
        conduct greater research into the telltale proteins in the body 
        that could be used to enhance early diagnosis. Enhancing 
        technology development in clinical proteomics, systems biology, 
        and increasing our biomedical computing capabilities would 
        accelerate progress against cancer, but could also be applied 
        to understanding other diseases.
  --Through greater development of imaging, science could refine and 
        improve the capacity to look inside cells, revealing biological 
        processes in real time. This effort could develop the next 
        generation of tools for early diagnosis, at a time when there 
        are only a few million cancer cells in a patient's body.
                                 ______
                                 
              Questions Submitted by Senator Thad Cochran
                              sarcoidosis
    Question. Sarcoidosis is a systemic inflammatory disease and one of 
the most common causes of fibrotic lung disease in the United States. 
Sarcoidosis can cause chronic debilitating or life-threatening heart, 
neurological, and internal organ disease and has no safe, effective 
treatments. In North America, African Americans are about five times 
more likely to have sarcoidosis than whites, representing a significant 
national health disparity. Despite the substantial burden of this 
illness on many (tens of) thousands of Americans of all races, and 
significant recent progress in our understanding of the illness, the 
National Institutes of Health (NIH) has supported disproportionately 
little research for this disease relative to its burden of disease, a 
disparity that has been increasing over the past decade. What do you 
believe are the reasons for this disparity and how can it be corrected?
    Answer. The National Heart, Lung and Blood Institute (NHLBI) has 
had a long-standing commitment to funding research on the causes and 
treatment of sarcoidosis and on genetic predisposition to developing 
it. In recent years the Institute developed several new initiatives 
specifically addressing sarcoidosis, including a solicitation on 
granulomatous inflammation in sarcoidosis that resulted in funding of 
11 new research projects. The Institute currently supports exciting 
programs in genomics of sarcoidosis and a new clinical trial on 
atorvastatin as a disease-modifying agent in pulmonary sarcoidosis. One 
reason for the funding disparity may be the small numbers of 
investigators in the country who are interested in conducting research 
in this complex and multi-organ disease. In addition, applications 
submitted have not competed well. Some steps we are taking to address 
this disparity include increasing visibility of sarcoidosis through 
activities such as radio spots on the disease; developing new research 
initiatives to address specific aspects of the disease; and working 
with the Trans NIH Sarcoidosis Working Group, which coordinates 
sarcoidosis research activities across the NIH. One of its recent 
activities has been promotion of a workshop on the genetics of 
sarcoidosis that was held last summer. Workshop recommendations, which 
have been posted on the NHLBI Web site, include initiation of a 
community-based study of sarcoidosis that would develop a registry of 
clinical information about the disease and might also include 
collection of patient samples for genetic studies. Other 
recommendations were to promote collaboration on sarcoidosis with 
NHLBI-funded investigators and the scientific community in Europe and 
other parts of the world, and to launch a genome-wide association study 
(GWAS) based on available samples from ACCESS and other existing 
cohorts. NHLBI staff are following up on these recommendations. Via the 
NIH solicitation for Challenge grants under the American Recovery and 
Reinvestment Act (ARRA), the NHLBI requested GWAS on rare lung 
diseases, including sarcoidosis.
    Question. What are the plans of the NHLBI for closing this gap and 
improving the clinical care and treatment for patients with 
sarcoidosis?
    Answer. Our plan is to support ongoing and new meritorious research 
through both ARRA and traditional investigator-initiated applications; 
re-issue an NIH-wide sarcoidosis program announcement, which seeks to 
stimulate research on the multi-organ manifestations of the disease; 
continue support of the NHLBI atorvastatin clinical trial; and consider 
future initiatives based on the NHLBI workshop on genetics of 
sarcoidosis that was held last summer. A new initiative under 
consideration addresses cardiac dysfunction associated with 
sarcoidosis. We are optimistic that these efforts will lead to advances 
in understanding the origin and pathogenesis of this disease and will 
improve our ability to diagnose and treat affected individuals.
                                 ______
                                 
            Questions Submitted by Senator Richard C. Shelby
                    clinical and transational awards
    Question. The Clinical and Translational Science Awards (CTSA) is 
designed to transform how clinical and translational research is 
conducted, ultimately enabling researchers to provide new treatments 
more efficiently to patients. Tremendous effort has brought 
institutions together to rally around this program, yet current funding 
levels make it difficult for the programs to succeed. Key to the 
success of the CTSA is the development of cost sharing for use of 
infrastructure services. An example of this mechanism is the General 
Clinical Research Centers (GCRC), which allowed institutes to reduce 
their research budgets by having investigators use the GCRC when 
clinical care such as inpatient stays, lab tests, and nursing staff was 
made available at no additional cost. Today, individual investigators 
must provide funds for clinical care cost sharing from grants funded 
from other National Institutes of Health (NIH) Institutes. As research 
becomes more expensive and private capital dries up, it becomes even 
more critical to ensure support for translational research, that is, 
research that moves a potential therapy from development to the market. 
Will the NIH provide the financial resources necessary to maximize the 
potential of this critical program?
    Answer. The CTSA program is providing substantially more funding 
for clinical research than was available under the GCRC program. The 
CTSA allows the institution to continue activities that were conducted 
in the GCRC and add new activities. With a minimum total funding level 
of $4 million per year, all CTSAs will be able to offer clinical 
investigators a substantial diversity of resources. The prioritization 
of resources offered within an institution is determined locally, as 
are any needs for cost sharing to ensure adequate support for a wide 
range of activities.
    National Center for Research Resources (NCRR) expects to fulfill 
the charge to transform clinical and translational research within the 
current overall budget for the program. At $500 million per year when 
fully implemented, the CTSA program represents a significant increase 
in infrastructure support over the $340 million allocated to pre-
existing NIH clinical research resources (i.e., NCRR K12, GCRC M01, NIH 
K30, and Roadmap T32 and K12 programs). To reach the critical mass 
necessary to transform clinical and translational research, NCRR 
projects that 60 CTSAs are needed throughout the United States. 
Diversity in the size, scope, and geographic location of participating 
institutions will strengthen the CTSA consortium and enhance its 
national and regional collaborations

                         CONCLUSION OF HEARINGS

    Senator Harkin.So again, I thank you all very much, and 
with that the subcommittee will stand recessed.
    Dr. Kington. Thank you.
    [Whereupon, at 11:49 a.m., Thursday, May 21, the 
subcommittee was recessed, to reconvene subject to the call of 
the Chair.]
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